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Hibiscus acid from Hibiscus sabdariffa (Malvaceae) has a vasorelaxant effect on the rat aorta
Abstract
Hibiscus sabdariffa (Malvaceae) is a plant that is widely recognised for its antihypertensive properties; however the constituent(s) responsible for this biological activity are presently unknown. The aim of this study was to identify the potential compounds that are responsible for the vasorelaxant activity of H. sabdariffa. Thereafter, the mechanisms involved in producing the vasorelaxation were investigated. The plant was extracted consecutively with hexane, ethyl acetate and methanol. The methanolic extract was subjected to bioassay-guided fractionation in order to isolate pure compounds that possessed vasorelaxant activity. The vascular effects of the pure compounds were studied on the rat aorta in vitro using myography techniques. Hibiscus acid produced a concentration-dependent relaxation of the rat aorta pre-contracted with either phenylephrine (3 μM) or KCl (60 mM), irrespective of the presence of the endothelium. When the tissue was pre-contracted with phenylephrine, the concentration required to produce 50% relaxation (IC50), was 0.09 ± 0.01 mg/ml. Hibiscus acid had no effect on the phasic contraction induced by phenylephrine in Ca²⁺-free physiological solution; but it did affect the component of the contraction that is due to Ca²⁺ influx. In parallel studies, garcinia acid, a diastereoisomer of hibiscus acid, was found to have an almost identical vasorelaxant effect. The vasorelaxant action of both compounds is most likely due to the inhibition of Ca²⁺ influx via voltage-dependent Ca²⁺ channels.
... Taken together, these results emphasize the PKA-and PKG-dependent antiplatelet effect of HSCE. Because the antiplatelet effects of HSCE appear to be attributed to its ability to modulate the NO-cGMP-PKG pathway, recent studies show that HSCE has vasorelaxant effects [27,28]. Therefore, we sought to understand the effects of HSCE on the NO-cGMP pathway in aortic rings isolated from mice using different experimental approaches (i.e. using NOS inhibitors, oxidizing agent of guanylyl cyclase, and aortic rings with and without endothelium). ...
... The results showed that HSCE induces relaxation in a concentration-dependent manner, corroborating what was observed in a series of in vitro studies [12,27,30]. Furthermore, the relaxation of isolated aortic rings was significantly affected by HSCE in assays with intact or denuded endothelium, or pre-incubated with inhibitors or alkylating agents of sGC. ...
... A possible explanation for the observed effect is the reduction of calcium mobilization and, consequently, of the activation of the K + channel. Additional support for this mechanism of action is provided by data shown on platelet aggregation that showed a reduction in calcium mobilization similar to that reported previously by Zheoat et al. who demonstrated that the vasorelaxant effect of HSCE seems to be associated with the inhibition of Ca 2+ influx in rat aortic rings [27]. ...
Hibiscus sabdariffa L. is a worldwide component for tea and beverages, being a natural source of anthocyanins, which are associated with cardiovascular activities. To investigate this relationship, we explored different methods of aqueous extraction on the anthocyanin content and antioxidant activity of H. sabdariffa L. calyx extract (HSCE). Pharmacological effects via platelet aggregation, calcium mobilization, cyclic nucleotide levels, vasodilator-stimulated phosphoprotein Ser157 and Ser239, and on the vasomotor response of aortic rings isolated from mice are studied herewith. We found that the application of ultrasonic turbolization, 20 min, combined with acidified water was significantly more effective in the extraction process, providing extracts with the highest levels of anthocyanins (8.73 and 9.63 mg/100 g) and higher antioxidant activity (6.66 and 6.78 μM trolox/g of sample). HSCE significantly inhibited (100–1000 μg/mL) arachidonic acid-induced platelet aggregation, reduced calcium mobilization, and increased cAMP and cGMP levels with VASPSer157 and VASPSer239 phosphorylation. Vasorelaxation reduction was confirmed by the aortic rings and endothelium assays treated with nitric oxide synthase inhibitors, soluble guanylyl cyclase (sGC) oxidizing agent, or Ca²⁺-activated K⁺ channel inhibitor. The increasing of cGMP levels could be understood considering the sGC stimulation by HSCE compounds in the specific stimulus domain, which allows an understanding of the observed antiplatelet and vasorelaxant properties of H. sabdariffa L. calyx extract.
... Regarding flavonoids, 18 compounds were identified, headed by glycosidic derivatives (ID: [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32]. The presence of compounds derived from flavonoids, such as anthocyanins and anthocyanidins, specifically delphinidin-3-sambubioside, was also found, cyanidin-3-glucoside and delphinidin (ID: [33][34][35]. ...
... PC2 on the positive axis was highly influenced by glycosides such as leucoside, and aglycones such as ellagic acid, and naringenin (ID: 18,25,32). On the other hand, PC1 negative axis comprises compounds that were quantified at relatively low levels (ID: 19,20,22,28,29,30,33,34,35). However, these compounds improve the profile of BC in the hibiscus beverage. ...
... Hibiscus acid has a direct vasorelaxant effect on the rat aorta, through the inhibition of VDCCs (voltage-dependent calcium channels), inhibiting the influx of extracellular Ca 2+ (a component of the contractile response). Then, this compound may be the constituent responsible for the vascular activity of this plant [33]. It was also found in a recent study that hibiscus acid presents anti-microbial activity against some pathogenic bacteria, concluding that it was one of the compounds responsible for the anti-microbial effect of Hibiscus calyxes [34]. ...
Hibiscus sabdariffa possess great versatility to be used as an ingredient for a whole range of products with natural-based ingredients, which are growing in popularity due to the health benefits of bioactive compounds (BC). Therefore, the objective of this study was to characterize the BC content in Hibiscus beverages and to evaluate their in vitro bioaccessibility. Results showed significant differences (p < 0.05) in the total contents of BC prior to the in vitro intestinal digestion. Hibiscus acid was the most abundant compound identified. Thirty-five compounds were identified in the Hibiscus beverage at the initial stage, while a maximum of 15 compounds were quantified in the different fractions of gastrointestinal digestion. After digestion, significant differences were found compared with the initial content of BC. That phenolic acids were the less bioaccessible group, while flavonoids were the most diverse. Principal components analysis showed different clusters and changes in the profiles of BC present at the initial stage and those bioaccessible, showing that intestinal digestion significantly affects the BC profile of the beverage.
... Several in vitro and in vivo (often murine modelled) biological activities of HS have been reported in literature, including antioxidant [35,55], antihypertensive [34], antidiabetic [56], vasorelaxant [57], cardioprotective [58], antibacterial [59], antiviral [60], antiproliferative [61], cytotoxic [59], neuroprotective [62], sedative [63], antianxiety [64], antidepressant [64], hepatoprotective [65], antihyperinsulinemic [66], anti-obesity [67], anti-inflammatory [68], antianemic [69], and anti-ulcer activities [70], among others, associated with the presence of bioactive compounds, as shown in Figure 2. Table 2 lists some in vitro and in vivo studies on the biological and beneficial health effects of HS calyxes. [57] diabetic Aqueous IC50 of 25.2 and 187 µg/mL, respectively α-amylase and α-glucosidase inhibition assay ...
... Several in vitro and in vivo (often murine modelled) biological activities of HS have been reported in literature, including antioxidant [35,55], antihypertensive [34], antidiabetic [56], vasorelaxant [57], cardioprotective [58], antibacterial [59], antiviral [60], antiproliferative [61], cytotoxic [59], neuroprotective [62], sedative [63], antianxiety [64], antidepressant [64], hepatoprotective [65], antihyperinsulinemic [66], anti-obesity [67], anti-inflammatory [68], antianemic [69], and anti-ulcer activities [70], among others, associated with the presence of bioactive compounds, as shown in Figure 2. Table 2 lists some in vitro and in vivo studies on the biological and beneficial health effects of HS calyxes. [57] diabetic Aqueous IC50 of 25.2 and 187 µg/mL, respectively α-amylase and α-glucosidase inhibition assay ...
... The antihypertensive effects of HS have been evaluated by angiotensin-converting enzyme (ACE) inhibitory assay, where the anthocyanin compounds can inhibit the ACE activity by mode of competitive action [34]. Moreover, the antihypertensive activity of HS extract was also carried out on rat aorta, exhibiting a vasorelaxant effect [57]. Regarding the antidiabetic potential of HS, α-amylase and α-glucosidase inhibitory assays have been used to evaluate bioactivity [56]. ...
Hibiscus sabdariffa Linn. Malvaceae (HS) is characterized by its edible calyxes. The HS calyxes are widely used for cosmetic, food, and medicinal applications. According to ethnobotanical evidence, decoction, infusion, or maceration extracts from HS calyxes have been used in folk medicine to treat many ailments. Moreover, several in vitro and in vivo studies have demonstrated the pharmacological properties and potential human health benefits of HS consumption. On the other hand, the evaluation of the physiological effects and health benefits of HS in clinical studies is most challenging. Therefore, this narrative review summarizes and discusses the physiological effects and health benefits of HS calyxes reported in clinical trials. Preparations obtained from HS calyxes (extracts, infusions, decoction, teas, beverages, capsules, and pills) are used as non-pharmacological therapies to prevent/control diverse chronic non-communicable diseases. The most-reported HS health benefits are its antihypertensive, antidyslipidemic, hypoglycemic, body fat mass reduction, nephroprotective, antianemic, antioxidant, anti-inflammatory, and anti-xerostomic activities; these effects are associated with the phytochemicals found in HS. Moreover, no adverse effects were reported during the clinical trials. However, clinical studies exhibited some limitations; thus, further studies are required to validate the clinical efficacy of HS in large-scale studies with higher doses and a good experimental design
... The anthocyanins-rich fraction (mainly delphinidin-3-O-sambubioside and cyanidin-3-Osambubioside) was found to inhibit the angiotensin-converting enzyme (ACE) activity by competing with the active site in a dose-dependent manner [7]. The hibiscus acid-rich fraction exhibits a vasorelaxant effect on rat aorta through an anti-calcic mechanism [8]. Anthocyanins and hibiscus acid appear as the active compounds responsible for the antihypertensive effect of the HS calyx. ...
... The ELSD detection showed a very intense peak assigned to hibiscus acid (4). This compound, described for its vasorelaxant effect on the rat aorta [8], was also quantified by NMR. These analyses showed that this compound is present in a very large quantity in decoction with contents of 2.13 g (21.3%) and 3.23 g (21.5%) from 10 g and 15 g of HS, respectively. ...
... Even presented in very small amounts, it was showed that the anthocyanin-rich fraction of HS (mainly delphinidin-3-O-sambubioside and cyanidin-3-O-sambubioside) inhibit the angiotensin-converting enzyme (ACE) activity by competing with the active site in a dose-dependent manner [7]. The large amount of 2130 mg of hibiscus acid (4) in 10 g of HS might also help explain the hypotensive effect, as the vasorelaxant activity of pure hibiscus acid via blockade of voltage-dependent Ca2 + channels has been shown [8]. Finally, the presence of chlorogenic acid (2), even in trace amounts, is also remarkable since this compound demonstrated a reduction of blood pressure in spontaneously hypertensive rats in a dose-dependent manner when administered orally [14]. ...
In Iraq, in 2019, there were about 1.4 million Internally Displaced Persons (IDP); medical treatments were often interrupted. The feasibility of using Hibiscus sabdariffa (HS) decoction to curb hypertension was evaluated. A multicentric comparative pilot intervention for 121 participants with high blood pressure (BP) (≥140/90 mmHg) was conducted. Participants of the intervention group (with or without conventional medication) received HS decoction on a dose regimen starting from 10 grams per day. BP was measured five times over six weeks. The major active substances were chemically quantified. Results: After 6 weeks, 61.8% of participants from the intervention group (n = 76) reached the target BP < 140/90 mmHg, compared to 6.7% in the control group (n = 45). In the intervention group, a mean (±SD) reduction of 23.1 (±11.8) mmHg and 12.0 (±11.2) for systolic and diastolic BP, respectively, was observed, while in the control group the reduction was 4.4 (±10.2)/3.6 (±8.7). The chemical analysis of the starting dose indicated a content of 36 mg of total anthocyanins and 2.13 g of hibiscus acid. The study shows the feasibility of using HS decoction in IDP’s problematic framework, as hibiscus is a safe, local, affordable, and culturally accepted food product.
... The ethanolic extract of H. sabdariffa analyzed by Borrás-Linares et al. [15] presented organic acids like hibiscus acid, hydroxycitric acid, citric acid, and protocatechuic acid, among which the hibiscus acid was also identified in our study. Hibiscus acids are derived from (2S,3R)-2-hydroxycitric acid, whose biosynthetic pathway has not yet been unraveled, since hibiscus acid(-derived) substances are not synthesized by all plants [84]. Notwithstanding, the hibiscus acid has been pointed out as a fulcral organic acid for the bioactivity of H. sabdariffa extract [14,15,36]. ...
... Anthocyanins have been frequently identified in extracts of H. sabdariffa and/or within the Hibiscus genus, being the major responsible compounds for the hibiscus pigment. The often detected anthocyanins are delphinidin-3-glucoside, cyanidin-3-glucoside, delphinidin-3sambubioside and cyanidin-3-sambubioside [36,84,[88][89][90][91]. Similarly, our ethanolic extract presented derivative compounds, such as cyaniding-3,5-O-diglucoside, petunidin-3-Oglucoside, delphinidin, and delphinidin-3-O-sambubioside ( Table 3). ...
Philasterides dicentrarchi is an histophagous parasite that infects flatfish, namely turbot (Scophthalmus maximus), and cause significant losses in aquaculture units. The available measures for P. dicentrarchi control have limited efficiency, and some cause harm to fish. Hence, sustainable and natural control strategies are urgently needed. This study evaluated the in vitro bioactivity of the ethanol extract of Hibiscus sabdariffa calyces on P. dicentrarchi population growth rate (PGR), oxidative stress biomarkers (glutathione-S-transferases (GST), glutathione reductase (GR), glutathione peroxidase (GPx), total glutathione (TG) and catalase (CAT), neurotoxicity (acetylcholinesterase, AChE), activity and gene expression of proteases as major virulence factors. H. sabdariffa extract inhibited parasite PGR (IC50 = 1.57 mg mL−1), and caused significant changes in the activity of antioxidant enzymes (LOEC = 0.22 mg mL−1), especially GPx, TG, and CAT. The activity of proteases was also severely inhibited (IC50 = 0.76 mg mL−1), and gene expression of catepsin 90 and leishmanolysin proteases was downregulated. Organic acids and phenolic phytochemicals in hibiscus extract are potentially responsible for the antiprotozoal bioactivity herein determined. Therefore, H. sabdariffa extract can be a promising disease-control alternative against the ciliate proliferation, cellular defense mechanisms and pathogenicity. Still, its applicability in aquaculture settings, and potential effects on farmed fish, should be further elucidated.
... RAW 264.7 cell lines. Inhibition of α-amylase, lipid, cholesterol metabolism, pancreatic lipase, and adipogenesis [106,[114][115][116] Cornflower Inhibitory activity of angiotensin converting enzyme (ACE). HRBC (human red blood cell) membrane stabilization. ...
... [96,118] Anti-hypertensive activity has been examined in roselle (Hibiscus sabdariffa) and cornflower (Centaurea cyanus L.) through the inhibitory activity of angiotensin converting enzyme (ACE) and vasorelaxant activity by block of Ca 2+ channels depending on the voltage. This activity has been attributed to several compounds, such as: hibiscus acid, [114] ascorbic acid, neochlorogenic acid, cryptochlorogenic acid, and anthocyanins [delphinidin-3-O-sambubioside and cyanidin-3-O-sambubioside], [115] and chlorogenic acid. [96,115] At the same time, anti-inflammatory activity has been studied in roselle flowers (Hibiscus sabdariffa), calendula (Calendula officinalis L.) and Japanese rose (Rosa rugosa), using different models (Table 4), and the research have been focused on the inhibition of production of inflammatory mediators, production of nitric oxide (NO), inhibition of proinflammatory cytokines, COX-2, and the prostaglandins synthesis. ...
Traditionally, edible flowers have been used in alternative medicine by several cultures around the world. Recently, they have gained in popularity as a new trend in worldwide gastronomy because they have been added as ingredients in food and beverages since they have important organoleptic properties and beneficial health effects. In fact, edible flower consumption has increased in the last years, and many works have demonstrated that they are essential sources of macronutrients, vitamins, and antioxidant compounds, which give benefits like prevention against illness associated with oxidative stress, some cardiovascular illness, and cancers, among others. Nowadays, the main studies about edible flowers are focused on their nutritional, functional, antioxidant, antimicrobial, and anti-inflammatory properties. This review summarizes relevant information about the properties and bioactive compounds content of edible flowers, likewise, the acceptance and security risks of their consumption, highlighting the importance of their incorporation in human nutrition and the main biological activities. According to the revision process, the consumer acceptability of edible flowers and their inclusion in the human diet have been increased due to their positive health effects.
... Following a chemical workflow described in the Methods section, a major component in the fractions that retained the ability to inhibit Salmonella motility was detected, which showed to be the HA, as the obtained NMR data corresponded with those by Portillo-Torres and colleagues [22]. Despite the fact that many studies have been carried out with the extract (either organic or aqueous) of H. sabdariffa L. [18][19][20]28,29], only a few studies have been focused on HA [30][31][32][33][34]. In a few reports, it was shown to have inhibitory activity against α-amylase and α-glucosidase and also an anti-hypertensive effect in eukaryotes [30,32,33]. ...
... Despite the fact that many studies have been carried out with the extract (either organic or aqueous) of H. sabdariffa L. [18][19][20]28,29], only a few studies have been focused on HA [30][31][32][33][34]. In a few reports, it was shown to have inhibitory activity against α-amylase and α-glucosidase and also an anti-hypertensive effect in eukaryotes [30,32,33]. At first glance, these activities do not seem to have a relationship with either the biogenesis of either the fT3SS, the T3SS-1, or the motility, which might explain the effect shown by the results described here. ...
Extracts of Hibiscus sabdariffa L. (commonly called Rosselle or “Jamaica flower” in Mexico) have been shown to have antibiotic and antivirulence properties in several bacteria. Here, an organic extract of H. sabdariffa L. is shown to inhibit motility in Salmonella enterica serovars Typhi and Typhimurium. The compound responsible for this effect was purified and found to be the hibiscus acid. When tested, this compound also inhibited motility and reduced the secretion of both flagellin and type III secretion effectors. Purified hibiscus acid was not toxic in tissue-cultured eukaryotic cells, and it was able to reduce the invasion of Salmonella Typhimurium in epithelial cells. Initial steps to understand its mode of action showed it might affect membrane proton balance.
... Hibiscus acid has already been isolated and crystallized from H. sabdariffa [27]. The vascular effects of pure hibiscus acid on the rat aorta was studied in vitro [29]. It was discussed that the observed vasorelaxant effect of hibiscus acid potentially explains the antihypertensive properties of H. sabdariffa [29]. ...
... The vascular effects of pure hibiscus acid on the rat aorta was studied in vitro [29]. It was discussed that the observed vasorelaxant effect of hibiscus acid potentially explains the antihypertensive properties of H. sabdariffa [29]. ...
Red mature calyces of Hibiscus sabdariffa were collected from 16 different locations in Meghalaya, India. Samples were processed using shade drying (SD) and tray drying (TD). NMR spectroscopy was used to assess the metabolic composition of the calyces. In this study, 18 polar metabolites were assigned using 1D and 2D NMR spectra, and 10 of them were quantified. Proximate analysis showed that the TD method is more efficient at reducing moisture and maintaining the ash content of the Hibiscus biomass. NMR metabolomics indicates that the metabolite composition significantly differs between SD and TD samples and is more stable in TD plant processing. The differences in post-harvest drying has a greater impact on the metabolite composition of Hibiscus than the plant location.
... Hibiscus sabdariffa L. (Roselle) has a diversity in its folk uses as being a hypotensive, diuretic, mild laxative, used in gastrointestinal ailments, antimicrobial, emollient, antipyretic, besides sedative effects [14]. Chemical characterization of H.sabdariffa showed the abundance of flavonoids as well as phenolic acids [15][16][17][18] justifying its folk use worldwide. Many biological activities have been demonstrated as an antioxidant [19], chemopreventive [20], cytotoxic and anti-inflammatory [21] anti-obesity [17], hypolipidemic [22], anti-anxiety, antidepressant [16], antihypertensive [23], as well as having a vasorelaxant effect [18]. ...
... Chemical characterization of H.sabdariffa showed the abundance of flavonoids as well as phenolic acids [15][16][17][18] justifying its folk use worldwide. Many biological activities have been demonstrated as an antioxidant [19], chemopreventive [20], cytotoxic and anti-inflammatory [21] anti-obesity [17], hypolipidemic [22], anti-anxiety, antidepressant [16], antihypertensive [23], as well as having a vasorelaxant effect [18]. ...
Many researches have been undergone to hasten the natural wound healing process. In this study, several Hibiscus species (leaves) were extracted with petroleum ether, methanol, and their mucilage was separated. All the tested species extracts were assessed for their viability percentage using the water-soluble tetrazolium. H.syriacus was the plant of choice to be incorporated in a new drug delivery system and evaluated for its wound healing activity. H.syriacus petroleum ether extract (PEE) showed a high percentage of palmitic and oleic acids while its mucilage demonstrated high glucosamine and galacturonic acid. It was selected to be formulated and pharmaceutically evaluated into three different composite sponges using chitosan in various ratios. Fourier-transformed infrared spectroscopy investigated the chemical interaction between the utilized sponges’ ingredients. Morphological characteristics were evaluated using scanning electron microscopy. H.syriacus composite sponge of mucilage: chitosan (1:5) was loaded with three different concentrations of PEE. Medicated formulations were assessed in rat model of excision wound model. The wound healing ability was clearly proved by the clinical acceleration, histopathological examination, and modulation of correlated inflammatory parameters as tumor necrosis factor in addition to vascular endothelial growth factor suggesting a promising valuable candidate that supports the management of excision wounds using single-dose preparation.
... Several hypotheses have been suggested to explain the mechanism(s) involved in the reduction of arterial blood pressure, such as angiotensin-converting enzyme inhibition, the diuretic effect, or the direct vasorelaxant effect [21], but none have been clearly established. In some studies, it has been suggested that the relaxation is either endothelium dependent and/or endothelium independent due to inhibition of Ca 2+ influx or activation of K + channels [14,16,22], but no electrophysiological study has been performed to bring direct evidence. ...
... In accordance with previous work that studied hibiscus acid, which is a water extract component of H. sabdariffa, on aorta [22], our results showed that there was no significant difference in relaxation achieved in either endothelium-intact or endothelium-denuded vessels. Therefore, the relaxation of mesenteric artery rings to H. sabdariffa AF seems to be endothelium-independent. ...
Background/objectives:
Hibiscussabdariffa L. (H.sabdariffa (HS)) extract has a vascular relaxant effect on isolated rat thoracic aorta, but data on small resistance arteries, which play an important role on the development of hypertension, are still missing. The purposes of this study were (1) to assess the effect on isolated mesenteric arteries (MA) from normotensive (Wistar and Wistar-Kyoto (WKY)) and spontaneous hypertensive rats (SHR); (2) to elucidate the mechanism(s) of action underling the relaxant effect in light of bioactive components.
Methods:
Vascular effects of HS aqueous fraction (AF) on isolated MA rings, as well as its mechanisms of action, were assessed using the contractility and intracellular microelectrode technique. The patch clamp technique was used to evaluate the effect of HS AF on the L-type calcium current. Extraction and enrichment of AF were carried out using liquid-liquid extraction, and the yield was analyzed using HPLC.
Results:
The HS AF induced a concentration-dependent relaxant effect on MA rings of SHR (EC50 = 0.83 ± 0.08 mg/mL), WKY (EC50 = 0.46 ± 0.04 mg/mL), and Wistar rats (EC50 = 0.44 ± 0.08 mg/mL) pre-contracted with phenylephrine (10 µM). In Wistar rats, the HS AF maximum relaxant effect was not modified after endothelium removal or when a guanylate cyclase inhibitor (ODQ, 10 µM) and a selective β2-adrenergic receptor antagonist (ICI-118551, 1 µM) were incubated with the preparation. Otherwise, it was reduced by 34.57 ± 10.66% when vascular rings were pre-contracted with an 80 mM [K+] solution (p < 0.001), which suggests an effect on ionic channels. HS AF 2 mg/mL significantly decreased the peak of the L-type calcium current observed in cardiac myocytes by 24.4%. Moreover, though the vasorelaxant effect of HS, AF was reduced by 27% when the nonselective potassium channels blocker (tetraethylammonium (TEA) 20 mM) was added to the bath (p < 0.01). The extract did not induce a membrane hyperpolarization of smooth muscle cells, which might suggest an absence of a direct effect on background potassium current.
Conclusion:
These results highlight that the antihypertensive effect of HS probably involves a vasorelaxant effect on small resistance arteries, which is endothelium independent. L-type calcium current reduction contributes to this effect. The results could also provide a link between the vasorelaxant effect and the bioactive compounds, especially anthocyanins.
... The peaks were Molecules 2020, 25, 2307 3 of 15 assigned using an in-house Hibiscus metabolite database, according to the retention time and parent masses. Identification of metabolites was based also on the comparison of acquired mass spectra with previously published data on Hibiscus [10,[13][14][15][16]. ...
... In vivo clinical trials showed that a daily consumption of H. sabdariffa tea decreased the blood pressure compared to the control placebo, with no significant adverse clinical effects [28]. The proposed mechanism of Hibiscus antihypertensive activity could be attributed to its vasorelaxant effect through increasing nitric oxide production, Ca 2+ channel blocking activity as well as angiotensin converting enzyme (ACE) inhibitor activity [8,10,16]. Additionally, Hibiscus extract has been shown, next to its blood pressure lowering effect, to reduce the heart rate via a negative chronotropic action salt-sensitive hypertension and hypertension due to chronic NOS inhibition in animal models [29]. ...
Hibiscus species (Malvaceae) have been long used as an antihypertensive folk remedy. The aim of our study was to specify the optimum solvent for extraction of the angiotensin-converting enzyme inhibiting (ACEI) constituents from Hibiscus sabdariffa L. The 80% methanol extract (H2) showed the highest ACEI activity, which exceeds that of the standard captopril (IC50 0.01255 ± 0.00343 and 0.210 ± 0.005 µg/mL, respectively). Additionally, in a comprehensive metabolomics approach, an ultra-performance liquid chromatography (UPLC) coupled to the high resolution tandem mass spectrometry (HRMS) method was used to trace the metabolites from each extraction method. Interestingly, our comprehensive analysis showed that the 80% methanol extract was predominated with secondary metabolites from all classes including flavonoids, anthocyanins, phenolic and organic acids. Among the detected metabolites, phenolic acids such as ferulic and chlorogenic acids, organic acids such as citrate derivatives and flavonoids such as kaempferol have been positively correlated to the antihypertensive potential. These results indicates that these compounds may significantly contribute synergistically to the ACE inhibitory activity of the 80% methanol extract.
... Probably, this scarce scientific attention is attributed to the fact that hibiscus acid is not commercially available and is a chiral compound and diastereomer of garcinia acid (extracted from Garcinia cambogia); which is commercially available. Practically, the most representative evidence on their extraction, properties and/or chemical characteristics have been analyzed by Zheoat et al., (2019) [37] and Portillo-Torres et al., (2019) [69]; who mention that their empirical formula is C6H6O7•H2O. Through crystallographic analysis and X-ray spectroscopy confirmed that HA is a five-membered lactone ring (similar to HCA), with four carbon atoms and one oxygen atom. ...
... Regarding its antihypertensive effect, Zheoat et al., (2019) [37] conducted a comparative study between a crude extract of Hibiscus sabdariffa and the HA derived from the same extract on the direct vasorelaxant effect in the Sprague-Dawley rat aorta. At the end of the study, they confirmed that HA was more potent and effective, attributing its vasorelaxant action to the inhibition of Ca 2+ influx via voltage-dependent Ca 2+ channels (an identical mechanism observed in garcinia acid; Ha diastereoisomer). ...
Roselle (Hibiscus sabdariffa L.), also known as jamaica in Spanish, is a perennial plant that grows in tropical and subtropical regions, including China, Egypt, Indonesia, Mexico, Nigeria, Thailand, and Saudi Arabia. It has a long history of uses, mainly focused on culinary, botanical, floral, cosmetic, and medicinal uses. The latter being of great impact due to the diuretic, choleretic, analgesic, antitussive, antihypertensive, antimicrobial, immunomodulatory, hepatoprotective, antioxidant, and anti-cancer effects. These therapeutic properties have been attributed to the bioactive compounds of the plant, mainly phenolic acids, flavonoids, anthocyanins, and organic acids (citric, hydroxycitric, hibiscus, tartaric, malic, and ascorbic). Most literature reviews and meta-analyses on the therapeutic potential of Hibiscus sabdariffa L. (Hs) compounds have not adequately addressed the contributions of its organic acids present in the Hs extracts. This review compiles information from published research (in vitro, in vivo, and clinical studies) on demonstrated pharmacological properties of organic acids found in Hs. The intent is to encourage and aid researchers to expand their studies on the pharmacologic and therapeutic effects of Hs to include assessments of the organic acid components.
... In addition, Baena-Santillan et al. (2022) reported that hibiscus acid is not toxic. Other authors have also mentioned that hibiscus acid is not toxic (Zheoat et al. 2019;Sedillo-Torres et al. 2022). ...
... Hibiscus acid (HA), HCA, TA, MA, CTA, SA, and QA were used as standards for organic acid quantitation. There was no commercially available reference standard for HA, so a diastereomer (GCA) was used (Zheoat et al., 2019). The stock solutions were prepared by dissolving ∼10 mg of the standards in 10 mL of 0.1% FA water, to reach a final concentration of ∼1 mg/mL. ...
Hibiscus sabdariffa has gained increasing attention from consumers as a natural, healthy food ingredient, leading to a myriad of available products, yet there is a lack of understanding of the quality and chemical diversity among commercially available hibiscus products. Here, we conducted a survey on the chemistry of 29 hibiscus products (calyces, beverages, and extracts). UHPLC‐DAD and UHPLC‐QQQ/MS methods with high sensitivity and selectivity were developed to evaluate the chemical profiles pertaining to the sensory attributes (color and taste). Two major anthocyanins (delphinidin‐3‐sambubioside and cyanindin‐3‐sambubioside), eight organic acids, and 23 phenolic acids were identified and quantified in hibiscus market products. The results showed that hibiscus samples contained < 0.001–2.372% of total anthocyanins, 0.073–78.002% of total organic acids, and 0.001–1.041% of total phenolic acids, and demonstrated significant variations in market products. This is the first time that an in‐depth organic acid profiling was conducted on hibiscus products using UHPLC‐QQQ/MS. This method can also be extended to chemical profiling, sensory analysis, quality control, authentication, and standardization of other natural products.
... As for the results of KEGG for HA, while the results suggest it has an impact on pathways associated with the nervous system and others like PPAR, to date, there is little to no information regarding tests in the areas of most of the pathways described for HA. However, there has been some research regarding the impact of HA on rats and their results have shown some potential therapeutic effect (26,27). ...
The historical and cultural use of food as a remedy for diseases is evident in societies, such as using Hibiscus sabdariffa to address conditions like hypertension and high blood glucose. The natural biocompounds in this plant, including Delphinidin-3-Sambubioside (DS3), Quercetin (QRC), and Hibiscus Acid (HA), have been linked to various health benefits. Despite individual attention, molecular targets for these compounds remain unclear. In this study, in-silico analysis employed bioinformatic tools; including Swiss Target Prediction, ShinnyGo 0.77, KEGG, and Stringdb, to identify molecular targets, pathways, and hub genes. A PubMed literature search complemented the results. DS3 demonstrated potential modifications in genes related to nitrogen and glucose metabolism, inflammation, angiogenesis, and cell proliferation, particularly affecting the PI3K-AKT pathway. QRC displayed interconnected targets across multiple pathways, with overlap with DS3 and a focus on cancer-related pathways. HA showed distinct targets, particularly associated with nervous system-related pathways. These findings highlight the need for targeted research on the molecular effects of DS3, QRC, and HA, providing valuable insights into potential therapeutic pathways.
... Penghambat aliran kalsium pada penderita hipertensi dapat menghambat influks kalsium pada sel otot polos pembuluh darah dan otot jantung sehingga terjadi relaksasi dan vasodilatasi yang mengakibatkan menurunnya tekanan darah. Adapun pada otot jantung juga akan terjadi pengurangan kontraktilitas otot [17]. Senyawa dari bunga rosela yang bertanggung jawab sebagai penghambat aliran kalsium yaitu kuersetin, hibiscus acid, dan antosianin. ...
Hipertensi merupakan suatu penyakit yang ditandai dengan tingginya tekanan darah berupa tekanan sistolik lebih dari 140 mmHg dan tekanan diastolik lebih dari 90 mmHg. Tingginya tekanan darah dapat menyebabkan beragam komplikasi serius apabila bersifat persisten dan tidak ditangani dengan terapi. Bunga rosela merupakan salah satu bahan pengobatan berbasis bahan alam yang berpotensi sebagai anti-hipertensi. Penulisan sistematik review artikel ini dilakukan untuk mengetahui gambaran senyawa pada bunga rosela yang berkontribusi terhadap aktivitas anti-hipertensi serta mekanisme kerjanya. Pencarian literatur komperhensif dilakukan melalui database elektronik berupa Pubmed, Google Scholar, Scopus dan Science Direct dengan kata kunci spesifik serta operator Boolean. Sebanyak 329 artikel ditemukan pada pencarian awal kemudian diseleksi kembali berdasarkan kriteria inklusi dan eksklusi sehingga didapatkan sebanyak 21 artikel. Hasil review artikel menunjukkan bahwa bunga rosela mengandung senyawa flavonoid (antosianin, gossypetin, hibiscetin, kaempferol dan kuersetin), fenolik (asam klorogenat dan asam fenolat), asam organik (hibiscus acid, asam hidroksisitrat dan asam askorbat), polisakarida dan asam linoleat yang bertanggung jawab sebagai agen anti-hipertensi. Mekanisme anti- hipertensi dari bunga rosela yaitu dengan penghambatan ACE yang merubah angiotensin I menjadi angiotensin II, efek diuretik, penghambatan aliran kalsium ke otot jantung, peningkatan sekresi NO serta modulator aksi aldosteron. Berdasarkan studi literatur, maka dapat disimpulkan bahwa bunga rosela memiliki mekanisme kerja yang efektif untuk pengobatan hipertensi. Studi lebih lanjut dibutuhkan untuk mengetahui efek samping dan toksisitas dari bunga rosela.
... The vasorelaxant potential of canagli ozin was signi cantly diminished in denuded aortic ring preparations showing the participation of endothelium in canagli ozin-induced vasorelaxation. The agents claimed to have vasorelaxant effects have shown a similar response as canagli ozin (29,30). Canagli ozin in cumulative fashion prevented high K (80 mM K) induced thoracic aortic ring contractions signi cantly. ...
Canagliflozin is a sodium-glucose cotransporter 2 inhibitor (SGLT2i) an oral hypoglycemic agent. The present study was performed to determine the vasorelaxant response of canagliflozin along with the underlying mechanism. In diabetes-associated complications, those involving blood vessels remain a high cause of morbidity. The diabetes-related cardiovascular complications should be treated with newer drugs that could cure both complications concurrently. The study was conducted on the aortic rings of Wistar rats of either sex. Canagliflozin (10 ⁻⁸ -10 ⁻⁴ M) induces relaxation in phenylephrine (PE 100 µM) and 80 mM KCl pre-contracted rings significantly in a cumulative manner acquiring endothelium. The canagliflozin mechanism of vasorelaxant was established by incubating endothelium intact aortic rings for 30 minutes before PE with; nitro-L-arginine methyl ester (L-NAME 100 µM), methylene blue (10 µM), barium chloride (BaCl 2 : 10 µM), glibenclamide (1 µM) and indomethacin (10 µM). To estimate the role of calcium (Ca + 2 ), cumulative Ca ²⁺ (0.01- 10.0 mM) was added in a bath containing Ca + 2 free Krebs-Henseleit solution. It was repeated by pre-incubating strips with nifedipine (1 µM) and canagliflozin (1 µM, 10 µM and 100 µM) respectively. The relaxant response of canagliflozin involves the release of nitric oxide, cyclic guanosine monophosphate, prostacyclin, and membrane hyperpolarization from endothelium as pretreatment with L-NAME (IC 50 : 2.166 × 10 − 7 ± 7 M ), methylene blue (IC 50 : 1.738 × 10 − 7 ± 7 M), indomethacin (IC 50 : 2.269 × 10 − 7 ± 7 M), BaCl 2 (IC 50 : 3.320 × 10 − 6 ± 7 M) and glibenclamide (IC 50 : 3.960 × 10 − 7 ± 7 M) diminished the response. Additionally, canagliflozin relaxing effects include both decreased Ca + 2 influx and release from sarcoplasmic reserves. Thus, canagliflozin is a possible adjuvant in diabetes with concurrent hypertension.
... The enterohepatic recirculation could justify the accumulative effect observed for hibiscus acid dimethyl ether and favoring the time of permanence in our body and benefit for our health (Ávila-Román et al., 2021). Hibiscus acid has shown a beneficial effect on the blood vessels when administered at deficient concentrations in a murine model, being these vessels contracted with phenylephrine (3 µM), confirming its potential impact on cardiovascular disease (Zheoat et al., 2019). ...
... incluindo o intestino, bexiga e útero(Zheoat et al., 2019). O Hibiscus sabdariffa, como pode ser observado, é conhecido por sua delicadeza e propriedades medicinais, que tem vários benefícios para a saúde (Riaza e Chopra. ...
... The production of eicosanoids through the metabolism of AA is important in the renal system, since it participates in the maintenance of the proper relaxation and contraction of the renal vasculature in the glomeruli, thin limb of the loop of Henle, connecting tubule, collecting ducts, and mesangial cells [17,18]. The traditional medicinal herb, HSL, has been used to treat different pathologies of the renal system such as urinary bladder and kidney stones, and as a diuretic [19]. Its beneficial effects have been attributed mainly to the antioxidants it contains and to its activity on the ACE. ...
The renal system is engaged in metabolic syndrome (MS) and metabolites of arachidonic acid (AA) participate in renal homeostasis and disruption of functionality. Hibiscus sabdariffa L (HSL) is used as a diuretic and could improve renal function. The aim of this study was to assess if treatment with HSL at 2% improves renal function in MS through the metabolites of AA. A total of 24 male Wistar rats were divided into four groups: Group 1, control (C); Group 2, MS with 30% sucrose in drinking water, Group 3, MS plus HSL infusion at 2% (MS+HSL); and Group 4, C+HSL. We evaluated the perfusion pressure changes (∆-PP), the activities of cyclooxygenases (COXs), the percentage of AA, the expressions of PLA2, COX2, COX1, 5-LOX, TAXS and CYP450, and the concentrations of prostaglandins in the kidney from rats with MS. There was a decrease in the ∆-PP, in the activities of COXs, and the expressions of COX2 and CYP450 (p ≤ 0.03, respectively)as well asPGE2, TxB2, and LKB4 (p ≤ 0.01, respectively). However, the percentage of AA and expressions of PLA2 and PGE1 (p = 0.01, respectively) were increased in C and MS+HSL. The HSL treatment improved the function and anatomical structure of the kidneys in the MS rats, through antioxidant molecules, and inhibited the pathways that metabolize the AA including that of PLA2, COX2, 5-LOX, TAXS, and CYP450 while favoring the COX1 pathway. This improves the vascular resistance of renal arterioles.
... Hibiscus sabdariffa L. belongs to the Malvaceae family, is used worldwide as a food and local medicine for a variety of illnesses including hypertension, diabetes, urinary problems and for cardiovascular complications [13,14]. Phytochemical studies on the calyces have shown that they are a major source of flavonoids (anthocyanins, anthocyanidins, quercetin), phenolic compounds (protocatechuic acid, eugenol), polysaccharides, organic acids (maleic, citric, oxalic, tartaric, ascorbic, hibiscus acid), vitamins (ascorbic acid, thiamine, riboflavin), and β-carotene [13,15,16]. Previous scientific reports have proven the use in traditional medicines of H. sabdariffa extract in the treatment of diabetes in animal models [17,18]. ...
Plants are known to possess relatively high efficacy in the treatment of several chronic diseases with fewer adverse effects. In the recent years, numerous medicinal plants have been reported to be effective in treating diabetes. Hence, the present study aims to evaluate the antidiabetic property of hydroalcoholic extract of Hibiscus sabdariffa (HS) calyces in diabetic rats. Diabetes was induced by single intraperitoneal injection of alloxan (150 mg/kg, b.w), in male Wistar rats. Diabetic rats were administered daily oral doses of HS (100, 200 and 400 mg/kg body weight) and Glibenclamide (10 mg/kg) for 21 days. Then, blood glucose levels, oral glucose tolerance test and lipid profiles were determined. Treatment with HS resulted in a significant dose dependent reduction of blood glucose levels accompanied by a significant improvement in body weight. The extract also enhanced the glucose tolerance and significantly decreased cholesterol, triglycerides, and low-density lipoproteins levels while the high-density lipoproteins level significantly increased. From the results obtained, it can therefore be concluded that Hibiscus sabdariffa has an antidiabetic effect in alloxan-induced diabetic rats.
... Additionally, these previous studies also investigated the composition of TPC levels in the various kenaf tissues including leaves, stems, roots, flowers, and seeds, which showed the highest TPC levels in leaves or flowers according to the extract solvents. Hibiscus acid, as a dimethyl sulfoxide monosolvate, is widely found in the Malvaceae family and has therapeutic and pharmacological properties including α-amylase inhibitory [29], antihypertensive [30], and antimicrobial effects [31]. However, these studies were carried out on roselle (Hibiscus sabdariffa), and studies on hibiscus acid in kenaf are limited. ...
The biochemical compounds in kenaf leaves and flowers mainly consist of flavonoids, including flavonoid glycosides and floral anthocyanins. In the present study, we performed comparative transcriptome analysis using RNA-sequencing and identified putative genes involved in flower coloration in different flower developmental stages of three kenaf mutants including Baekma (white flower), Jangdae (ivory flower), and Bora (purple flower). A total of 36.1 Gb reads were generated for two kenaf accessions and 38,601 representative transcripts with an average length of 1350 bp were yielded, of which 33,057 (85.64%) were annotated against two databases. Expression profiling of the transcripts identified 1044 and 472 differentially expressed genes (DEGs) among three mutants in the young bud and full bloom stages, respectively. KEGG enrichment analysis of these DEGs revealed that the representative pathway was “biosynthesis of secondary metabolites”, including phenylpropanoid biosynthesis and flavonoid biosynthesis. Consequently, we investigated genes related to the phenylpropanoid pathway, which included 45 DEGs from a total of 1358. Our results provide useful information for understanding gene functions of flower coloration in kenaf, which will be useful in further studies.
... It blocks the voltage-dependent calcium channels in smooth muscle and leads to inhibition of the influx of extracellular calcium. This may reduce the blood pressure level (65). In addition, H. sabdariffa extracts have an antihypertensive effect in the condition of salt-induced hypertension and hypertension due to chronic nitric oxide synthase (NOS) inhibition (66). ...
Hibiscus sabdariffa L., belonging to the Malvaceae family, has been long used as herbal medicine, food, beverage, flavouring, and colouring agents. This study aims to review and document the evidence regarding the potential use of H. sabdariffa as ethnomedicine in some countries and its bioactive constituents and therapeutic properties. The electronic databases were used to search for the relevant information to the aims of this review up to March 2022. The high usage of H. sabdariffa as traditional medicine is due to its easy accessibility and low price. The plant is often used to treat intestinal problems, stomach disorders, and blood or liver toxicities. The plant contains phenolic compounds, including anthocyanins, flavonoids, and phenolic acids. The in vivo, in vitro, and clinical studies provide evidence that H. sabdariffa possesses therapeutic effects such as antihypertensive, antihyperlipidemic, antioxidants, antimicrobial, and antitumor activities. The studies provided scientific evidence for the statement of H. sabdariffa and its bioactive constituents in treating various diseases.
... The normal histopathological sections in rabbits treated with H. sabdariffa extract could be attributable to the antioxidant effect of the extract that can protect the aorta from the oxidative damage and prevent development of atherosclerotic lesions (Zheoat et al., 2019;Zainalabidin et al., 2018;Yusof et al., 2018). On the other hand, a mild histopathological changes observed in starvation group that can be attributable to intracellular lipid mobilization as a result of utilizing the fat as a source of energy (Kartin et al., 1944). ...
The objective of the study conducted here was to investigate effect of Hibiscus sabdariffa extract on the body weight, complete blood count (CBC), liver function, and lipid profile in rabbits. A total of 20 local male rabbits were randomly divided into four experimental groups, including five rabbits in each group: (i) control; (ii) starvation; (iii) H. sabdariffa extract; and (iv) H. sabdariffa extract and starvation. Blood samples were collected directly from the heart at the end of the experiment (day 28) and used for complete blood count and estimation of cholesterol, triglycerides, ALT, and AST. Aorta and liver sections were histopathologically examined. Results indicated that the Body weight at the end of the study was significantly decreased in starvation, extract, and starvation and extract groups, compared to the beginning of the study for each group. There was no difference in the body weight between groups at the end of the study. Rabbits in the extract group showed significant increase in lymphocytes, RBC, hemoglobin, and platelets, compared to those in control and in starvation groups. ALT activity significantly increased in starvation, extract, and starvation and extract groups, compared to those in control group. AST activity significantly increased in both extract and starvation and extract group, compared to those in control and starvation groups. Cholesterol and triglycerides decreased in starvation, extract, and starvation and extract groups, compared to those in control group. Histopathological sections indicated simple changes in aorta layers in starvation group rabbits including few number foam cells in tunica media. Liver sections from starvation group rabbits showed coagulative necrosis of hepatocytes, hyperplasia of bile duct endothelia, dilation and congestion of central veins. In extract group there was dilation of central veins, vacuolar degeneration of the hepatocytes, infiltration of inflammatory cells and hepatic artery congestion. Similar changes were revealed in liver sections from starvation and extract group. In conclusion, aqueous H. sabdariffa can decrease the body weight as alternative to the starvation, decrease blood cholesterol and triglycerides, and increase the immunity; however, daily consumption can have impact on the liver.
... A number of biological activities are attributed to these organic acids. For example, hibiscus acid was shown to have antihypertensive activity as it demonstrated to be a potent vasorelaxant in a rat aorta [18]. Moreover, hibiscus acid was also found to have antibacterial activity against multidrug resistant bacteria [19]. ...
Roselle ( Hibiscus sabdariffa L.) has been shown to have various bioactivities with therapeutic benefits. These bioactivities are owing to the different kinds of phytochemicals, which include anthocyanins, phenolic acids, and flavonoids. This mini review aims to summarize the reported antibacterial activity of roselle phytochemicals in the literature in the past decade (2011-2021). The results revealed that roselle extracts from various extraction methods were shown to have antibacterial activity against clinical isolates and food pathogens, including multidrug resistant bacteria. Furthermore, there is evidence that roselle extract showed potential synergy with antibiotics. Overall, phytochemicals in roselle have the potential as an antibacterial for different beneficial applications.
... On the other hand, HS extracts have been shown to have several effects on blood vessel endothelial cells to induce blood pressure. These mechanisms include: -Vasorelaxation effect (Zheoat et al., 2019): Hibiscus acid has a vasorelaxation effect in the aorta, due to the inhibition of Ca 2+ influx via voltage-dependent Ca 2+ channels. A similar effect has been observed with garcinia acid of Garcinia cambogia, which is an isomer of hibiscus acid. ...
Many patients with stage 1 hypertension have difficulties to achieve lifestyle changes to avoid the progression of the disease. The use of natural alternatives with demonstrated blood pressure-regulating properties is instrumental at this stage, avoiding the side effects found in some pharmaceutical drugs. In this context, previous studies have indicated the possibility that a botanical nutraceutical product based on the combination of Lippia citriodora and Hibiscus sabdariffa extracts has hypotensive properties in overweight and obese individuals. Therefore, we aimed to evaluate the antihypertensive properties of this dietary supplement, as well as the effect on anthropometric and circulating parameters in pre-hypertensive and early stage 1 hypertensive patients (n = 84). The nutraceutical product, rich in polyphenolic compounds, has been assessed in a 6-week randomized, double-blind, placebo-controlled trial with pre-hypertensive and early stage 1 hypertensive (non-medicated) individuals. Participants consumed early in the morning in fasting conditions 2 capsules/day containing each one 250 mg of the polyphenolic extracts. Anthropometric and blood parameters as well as punctual and continuous blood pressure monitoring were determined in placebo and experimental groups. As a result and compared to baseline values, volunteers showed a significant reduction of average daily systolic/diastolic blood pressure as well as in daytime diastolic/systolic, nighttime diastolic blood pressure and in % dipper. Intergroup analysis revealed that the consumption of the plant extract resulted in a significant reduction of body fat content (−1.26%; p
... An aqueous extract of the petals of HS was shown to have a vaso-relaxant effect on rat aortic rings through endothelium-dependent and independent mechanisms (88). Fouda, Mohamad (89) reported an inhibition of rat bladder and uterine contractility by an aqueous calyx extract of HS through mechanisms unrelated to local or remote autonomic receptors or calcium channels as previously suggested in a study of the effects of HS on the GIT (90,91). ...
Hibiscus sabdariffa (HS) is a plant from the Malvaceae family that is grown widely in most of Asia and tropical Africa. The various parts of the plant are used traditionally as food in form of beverages or salads and as medicine. In folklore, HS has been used to treat many ailments including cardiac and nerve ailments, induction of diuresis and lactation among others. Scientific studies have also demonstrated the antihypertensive, antidiabetic, anti-obesity and anti-hyperlipidaemic properties of HS. These biological activities are thought to be as a result of the battery of phytochemicals in HS that have strong antioxidant activity and that inhibit α-amylase, α-glucosidase, angiotensin converting enzyme, calcium channel blockage and direct vasorelaxant effects. Some of the phytochemicals that are thought to be responsible for these biological effects include anthocyanins, flavonoids and organic acids.There is however the need for more robust researches including controlled clinical trials to validate these biological activities with a view to bringing the benefits closer to the bedside.
... The dominant structure of anthocyanins in red cabbage was cyanidin-3diglucoside-5-glucoside (Charron et al., 2009). On the other hand, roselle (Hibiscus sabdariffa) belongs to the Malvaceae family, which is a species of Hibiscus widely cultivated in tropical and subtropical regions (Zheoat et al., 2019). Roselle calyx is rich in colours, flavour, and micronutrients such as vitamin C, B 1 and B 2 (Yaacob et al., 2006). ...
Response surface methodology (RSM) was employed for optimising the formulation and processing parameters of red cabbageroselle
mixed drink. In this study, four independent variables namely red cabbage-roselle extracts concentration (30 to 70%),
stingless honey concentration (1–10%), pasteurisation temperature (70–90°C), and pasteurisation time (30–300 s) were studied
in order to determine the effect of the formulation (ingredients) and processing parameters towards the colour and anthocyanins
content of the mixed drinks. Thirty different experimental combinations generated by RSM design were studied on the responses
i.e. colour values (L*, a*, b*) and total anthocyanin content of red cabbage-roselle mixed drink. The optimal formulation and
processing condition were obtained with a 70% combination of red cabbage-roselle extracts concentration and 1% of stingless
honey concentration, with pasteurisation temperature, and time of 70.01°C and 284.07 s, respectively. In order to verify the
models, the experimental values were compared with the predicted values to check the adequacy of the models. The experimental
values were found to be in agreement with those predicted, thus, indicating the suitability of the models used by RSM to
optimise the formulation and processing parameters of mixed drinks made from red cabbage and roselle extracts.
... Studies have shown that anthocyanins hypotensive effect could be explained by two main mechanisms: the modulation of aldosterone activity and the inhibitory effect of the angiotensin converting enzyme [11,[14][15][16]. Also, the hibiscus acid may have a vasorelaxant activity [17]. ...
Hibiscus sabdariffa L. (local names: bissap, karkade) and Combretum micranthum (kinkeliba) are widely known in traditional medicines and popular beliefs for their antihypertensive effect. This study assessed the clinical effectiveness of these two plants in the galenic forms of tablet and brew (decoction) in noncomplicated hypertensive patients. In total, 219 hypertensive patients with systolic blood pressure (SBP) between 140 and 180 mmHg and/or diastolic blood pressure (DBP) between 90 and 110 mmHg, without cardiovascular or renal complications, were involved in a multicentric randomized clinical trial in Senegal comparing five treatment regimens: bissap tablets (2 × 375 mg/day), bissap brew (10 g of calyx/day), kinkeliba tablets (2 × 200 mg/day), kinkeliba brew (10 g of leaves/day), and captopril (2 × 50 mg/day) as control. During the 6 months' follow-up, a significant and equivalent decrease of SBP was observed with the herbal drug approach (-19.5 ± 16.1 mmHg, p < 0.001) and control group (-19.7 ± 16.7, p < 0.001). Regarding the galenic forms, the brews tended to be slightly more effective than tablets (reduction of SBP: -20.7 ± 15.1 mmHg vs -18.7 ± 16.7). The rates of clinically significant effectiveness (decrease in SBP ≥ 10 mmHg) were 75%, 67%, and 65% with bissap, kinkeliba, and captopril, respectively. After 6 months, target blood pressure of <140/90 mmHg was attained by 49% of patients with bissap, 51% with kinkeliba and 40% with captopril. Bissap and kinkeliba appeared, at doses utilized, to be as effective as captopril over the 6 months' follow-up. In subsequent studies, brews might be started with a lower dosage.
... An aqueous extract of the petals of HS was shown to have a vaso-relaxant effect on rat aortic rings through endothelium-dependent and independent mechanisms (88). Fouda, Mohamad (89) reported an inhibition of rat bladder and uterine contractility by an aqueous calyx extract of HS through mechanisms unrelated to local or remote autonomic receptors or calcium channels as previously suggested in a study of the effects of HS on the GIT (90,91). ...
Hibiscus sabdariffa (HS) is a plant from the Malvaceae family that is grown widely in most of Asia and tropical Africa. The various parts of the plant are used traditionally as food in form of beverages or salads and as medicine. In folklore, HS has been used to treat many ailments including cardiac and nerve ailments, induction of diuresis and lactation among others. Scientific studies have also demonstrated the antihypertensive, antidiabetic, anti-obesity and anti-hyperlipidaemic properties of HS. These biological activities are thought to be as a result of the battery of phytochemicals in HS that have strong antioxidant activity and that inhibit α-amylase, α-glucosidase, angiotensin converting enzyme, calcium channel blockage and direct vasorelaxant effects. Some of the phytochemicals that are thought to be responsible for these biological effects include anthocyanins, flavonoids and organic acids.
There is however the need for more robust researches including controlled clinical trials to validate these biological activities with a view to bringing the benefits closer to the bedside.
... Traditionally, it is used in Ayurveda and Chinese herbal medicine for the treatment of hypertension, hypercholesterolemia, hyperlipidemia, diarrhoea and many other diseases. Beside, roselle extracts exhibited powerful protective effects against neurotoxicity [10], hepatotoxicity [11], diabetes-related complexities [12] and exhibited immunomodulatory [13] and vasorelaxant effects [14] in experimental animals. However, the investigation for its anti-cancerogenesis potential started only at the beginning of the decade and encouraging results were recorded. ...
Hibiscus sabdariffa or roselle tea is popular around the globe for its antioxidant capability along with various other health benefits. Besides, it has uses in Ayurvedic and Chinese herbal medicines for the treatment of several diseases. However, the investigation for the anticancer potential of the plant began roughly in the last decade that emerged with encouraging results. Both crude extracts and pure compounds of the plant were reported to induce chemoprevention, selective cytotoxicity, cell cycle arrest, apoptosis, autophagy and anti-metastasis effects in varied types of human cancer cells. The plant contains a high quantity of polyphenolic compounds and at least two of them were proven to induce potent anticancer effects. Although, the molecular mechanism underlying the anticancer activity was roughly estimated in several studies. The present review aimed to assemble all ambiguous information to report the molecular evidence establishing the potent anticancer activity of Hibiscus sabdariffa and its implication for cancer therapy. This study suggests that Hibiscus sabdariffa is an ideal candidate to investigate its role as a herbal supplement for cancer prevention and treatment. With excellent safety and tolerability record, polyphenolic compounds from the plant need better designed clinical trials.
... In addition, studies have been dedicated to hibiscus acid and garcinia acid, to the flavonoid myricetin and to the glucosides of the anthocyanins delphinidin and cyanidin (Fig. 3). The two acids exert vasorelaxant action likely due to the inhibition of Ca 2+ influx via voltage-dependent Ca 2+ channels (Zheoat et al., 2019). Myricetin has been proved to significantly inhibit atherogenesis (Sasaki et al., 2018) and it could prevent the development of high blood pressure induced by a diet rich in fructose (Godse et al., 2010). ...
Hypertension has become the leading risk factor for worldwide cardiovascular diseases. Conventional pharmacological treatment, after both dietary and lifestyle changes, is generally proposed. In this review, we present the antihypertensive properties of phytocomplexes from thirteen plants, long ago widely employed in ethnomedicines and, in recent years, increasingly evaluated for their activity in vitro and in vivo, also in humans, in comparison with synthetic drugs acting on the same systems. Here, we focus on the demonstrated or proposed mechanisms of action of such phytocomplexes and of their constituents proven to exert cardiovascular effects. Almost seventy phytochemicals are described and scientifically sound pertinent literature, published up to now, is summarized. The review emphasizes the therapeutic potential of these natural substances in the treatment of the 'high normal blood pressure' or 'stage 1 hypertension', so-named according to the most recent European and U.S. guidelines, and as a supplementation in more advanced stages of hypertension, however needing further validation by clinical trial intensification.
... Furthermore, hibiscus acid was demonstrated to have a vasorelaxant effect on the rat's aorta [30]. ...
The anti-microbial properties of acetone extracts from Hibiscus sabdariffa calyces, fractions isolated by silica gel chromatography and hibiscus acid purified from some of these fractions and additionally identified by nuclear magnetic resonance spectroscopy, mid-infrared spectroscopy and X-ray diffraction, were studied against both multidrug-resistant Salmonella strains and pathogenic Escherichia coli bacteria. Gel diffusion was used to determine the anti-microbial effects. The mode of action of hibiscus acid was determined by crystal violet assay. Hibiscus acid and 17 of the 25 chromatographic fractions obtained, displayed an anti-microbial effect against all bacterial strains tested. Hibiscus acid showed a greater anti-microbial effect than the acetone extract against most of the bacteria strains, while chromatographic fractions IX–XIV exerted the greatest anti-microbial effect against all bacteria. The minimum inhibitory concentration of the acetone extract was 7 mg/mL, and the minimum bactericidal concentration was 10 mg/mL, while the corresponding values for hibiscus acid were 4–7 and 7 mg/mL, respectively. The results of the crystal violet assay indicate that hibiscus acid alters membrane permeability. Hibiscus acid is a potential alternative to control multidrug-resistant bacteria. Due to its ready availability and easy extraction from H. sabdariffa, hibiscus acid is potentially useful in the food industries.
... The results are similar to those obtained by related lavonoid glycosides [7]. Kinetic determinations suggested that these compounds inhibit the enzyme activity by competing with the substrate for the active site [8]. ...
... In vitro, in vivo studies and clinical trials have shown that Roselle aqueous, methanolic and ethanolic extracts rich in EPP have antihyperlipidemic, antiobesity, antihypertensive, anti-inflammatory, and antimicrobial effects (Riaz & Chopra, 2018). Some of these health beneficial effects have been attributed not only to EPP but also to organic acids such as hydroxycitric and hibiscus acids, which produce vasorelaxant effects (Zheoat et al., 2019), inhibit triglyceride synthesis and promote lipolysis (Peng et al., 2018). However, studies evaluating the health effects of grounded Roselle calyces are limited. ...
The aim of the present study was to evaluate extractable (EPP), non-extractable polyphenols (NEPP) and organic acid in Roselle by-product, as well as its potential health beneficial effects in obesity control and their complication in rats fed with high caloric diet. Roselle by-product showed a higher content of dietary fiber and NEPP than Roselle calix, which was was a better source of EPP (P < .05). The UPLC-QTOF MSE analysis allowed the tentative identification of 34 EPP, and 3 hydrolysable polyphenols (NEPP), and 2 organic acids in calyx and by-product. Rats fed with a high caloric diet supplemented with 4% of dietary fiber from by-products and Roselle calyx powder generated a reduction in body weight gain (10% and 14%), adipocytes hypertrophy (17% and 13%) and insulin resistance (48% and 59%) and hepatic steatosis (15% and 25%; respectively) compared with rats fed with a high caloric diet alone. Interestingly, even though Roselle by-product has low EPP contents showed comparable beneficial health effects than Roselle calyces. These effects could be associated with high content of dietary fiber and NEPP. Together, the results of the present study indicate that Roselle by-products could be a potential ingredient to develop functional foods against obesity and its complications.
... This indicated that the observed cardiac inhibitory effect of the plant extract might be causing a decrease in cardiac output and ultimately a decrease in the blood pressure. When tested in pre-contracted rat aortic preparations, the plant's extract inhibited both high K + and phenylephrine (PE) induced vasoconstriction by blockage of Ca 2+ influx through voltage-dependent channels and receptor-operated channels caused by high K + and PE, respectively [85]. In addition, when the control responses of PE were taken in Ca 2+ free medium, the crude extract inhibited the PE-induced peaks, indicating that the inhibition of Ca 2+ release from internal stores through inositol-1,4, 5-trisphosphate-sensitive sarcoplasmic reticulum mechanism [86,87]. ...
Hypertension is highly prevalent among the Lebanese adult population and is indeed the major cause of mortality in Lebanon. Traditional use of antihypertensive medicinal plants has long been practiced. The aim of this study is to document this traditional knowledge and clinically test the antihypertensive capacity of three of the most commonly used wild plant species Mentha longifolia, Viola odorata and Urtica dioica. Ethno-pharmacological data was collected by personal interviews with herbalists and traditional healers using a semi structured survey questionnaire and assessing relative frequency of citation (RFC). The clinical study was conducted by a randomized, blind, placebo-controlled trial in 29 subjects with mild hypertension distributed in four groups, three plant extract treatments and one placebo. Systolic (SBP) and diastolic blood pressures (DBP) as well as mean arterial blood pressures (MAP) were monitored at weeks 4, 8, 12 and 16 during the treatment with 300 mL/day of plant extract. Results showed that M. longifolia, U. dioica and V. odorata exhibited the highest values of RCF (0.95) followed by Allium ampeloprasum (0.94), Apium graveolens (0.92) and Crataegus azarolus (0.90). The clinical trial revealed dose-and duration-dependent significant reductions in SBP, DBP and MAP of subjects treated with M. longifolia, U. dioica or V. odorata. Our findings indicate that extracts of these plants present an effective, safe and promising potential as a phyto-therapuetical approach for the treatment of mild hypertension. More research on the phytochemistry, pharmacological effects and the underlying mechanisms is necessary.
... The consumption is not limited to ceremonial gatherings owing to the awareness of its functional capability. The functional use of H. sabdariffa includes as antidiabetic, antihypertensive, hypolipidemic, antimetabolic syndrome, anticancer metastasis, neuroprotective hepatoprotective, and vasorelaxant (Ajiboye et al., 2011;Ajiboye, Raji, et al., 2016;Griffin et al., 2018;Igoli, Drummond, Ferro, Zheoat, & Gray, 2019;Jabeur et al., 2017;Su, Wang, et al., 2018). The chemical components of H. sabdariffa responsible for these activities are catechin, gallic acid, caffeic acid, and protocatechuic acid (Da-Costa- Rocha, Bonnlaender, Sievers, Pischel, & Heinrich, 2014). ...
We isolated and identified gallic and protocatechuic acids as the antidiabetic principles in Hibiscus sabdariffa using solvent extraction, column chromatographic fractionation, and nuclear magnetic resonance (NMR) spectroscopy. Ethylacetate fraction of the aqueous extract of H. sabdariffa inhibited α‐amylase and α‐glucosidase with IC50 of 411.73 and 433.93 μg/ml, respectively. Furthermore, fractions I and II obtained from column chromatography inhibited α‐amylase with IC50 of 27.03 and 20.12 μg/ml, and α‐glucosidase with IC50 of 24.30 and 22.29 μg/ml, respectively. In addition, the principles reduced the serum glucose and lipid peroxide levels of diabetic rats and with an improvement in the rat lipid profiles and antioxidant defenses. Fractions I and II were identified as protocatechuic acid and gallic acid, respectively, using ¹H and ¹³C NMR. Protein–ligand docking showed that these compounds form multiple favorable interactions with the active‐site residues of the two glycosidases. Overall, protocatechuic and gallic acids emerge as natural antidiabetic agents.
Practical applications
Hibiscus sabdariffa (Zoborodo) is a refreshment drink for ceremonial gatherings in Nigeria. Also, its pharmacological use includes diabetes, hypertension, hyperlipidemia, metabolic syndrome, and hepatoprotection. The consumption of this food drink could improve diabetes, hypertension, dyslipidemia, metabolic syndrome, and liver disease. Furthermore, the inhibition of α‐amylase and α‐glucosidase could prevent diabetic complications associated with postprandial glucose. Developing the extract of H. sabdariffa calyx as food supplement could be used in managing diabetes and its associated complications such as dyslipidemia, hypertension, and metabolic syndrome.
The anti-microbial properties of acetone extracts from Hibiscus sabdariffa calyces, fractions isolated by silica gel chromatography and hibiscus acid purified from some of these fractions and additionally identified by nuclear magnetic resonance spectroscopy, mid-infrared spectroscopy and X-ray diffraction, were studied against both multidrug-resistant Salmonella strains and pathogenic Escherichia coli bacteria. Gel diffusion was used to determine the anti-microbial effects. The mode of action of hibiscus acid was determined by crystal violet assay. Hibiscus acid and 17 of the 25 chromatographic fractions obtained, displayed an anti-microbial effect against all bacterial strains tested. Hibiscus acid showed a greater anti-microbial effect than the acetone extract against most of the bacteria strains, while chromatographic fractions IX-XIV exerted the greatest anti-microbial effect against all bacteria. The minimum inhibitory concentration of the acetone extract was 7 mg/mL, and the minimum bactericidal concentration was 10 mg/mL, while the corresponding values for hibiscus acid were 4-7 and 7 mg/mL, respectively. The results of the crystal violet assay indicate that hibiscus acid alters membrane permeability. Hibiscus acid is a potential alternative to control multidrug-resistant bacteria. Due to its ready availability and easy extraction from H. sabdariffa, hibiscus acid is potentially useful in the food industries.
Medicinal plants have been the keystone of health care since ancient time. Their
innumerable uses have been documented and transformed through the generation for
over more than 4000 years. In the early 19th century, as soon as the scientific
investigations began, numerous plant based drugs have been made available to cure
large number of global diseases. The 21st century started with exploration of these
traditional remedies to meet patient needs. Now we are in the era where science and
technologies have evolved to elucidate the safety and efficacy of traditional
medicines. Even though much more information on uses of plant/plant parts in various
health practices is still unrecorded. This book will present an overall illustration of
some selected medicinal plants and their medico biological application. It will also
throw light on critical areas of ongoing research, transforming the information on
medicinal plants and their recent applications.
We aimed to assess the efficacy of hibiscus sabdariffa in patients with mild to moderate hypertension or metabolic syndrome (MetS) by comparing it against placebo, antihypertensive drugs, or other herbal products.Four databases were searched for randomized clinical trials (RCTs) examining the efficacy of hibiscus sabdariffa in patients with mild to moderate hypertension or hypertension associated with MetS. Data on the change in systolic blood pressure (SBP) and diastolic blood pressure (DBP) were extracted and analyzed using Review Manager Version 5.3.A total of 13 RCTs (1205 participants) were analyzed. Hibiscus sabdariffa significantly reduced both SBP and DBP compared to placebo (MD -6.67, P=0.004 and -4.35 mmHg, P=0.02). Subgroup analysis showed that change in SBP and DBP was statistically significant in patients with only hypertension while not significant in patients with hypertension associated with MetS. When hibiscus sabdariffa was compared to active controls (antihypertensive drugs or other herbals), the change in SBP and DBP was not statistically significant (all P>0.05).Hibiscus sabdariffa is effective in reducing the SBP and DBP in patients with mild to moderate hypertension but was neither effective in those with MetS nor superior to antihypertensive drugs. Further RCTs are required to determine the long-term efficacy of hibiscus sabdariffa and to describe patients who would benefit most from this treatment.
According to the World Health Organization, cardiovascular diseases are the main cause of death worldwide. They may be caused by various factors or combinations of factors. Frequently, endothelial dysfunction is involved in either development of the disorder or results from it. On the other hand, the endothelium may be disordered for other reasons, e.g., due to infection, such as COVID-19. The understanding of the role and significance of the endothelium in the body has changed significantly over time—from a simple physical barrier to a complex system encompassing local and systemic regulation of numerous processes in the body. Endothelium disorders may arise from impairment of one or more signaling pathways affecting dilator or constrictor activity, including nitric oxide–cyclic guanosine monophosphate activation, prostacyclin–cyclic adenosine monophosphate activation, phosphodiesterase inhibition, and potassium channel activation or intracellular calcium level inhibition. In this review, plants are summarized as sources of biologically active substances affecting the endothelium. This paper compares individual substances and mechanisms that are known to affect the endothelium, and which subsequently may cause the development of cardiovascular disorders.
Hibiscus sabdariffa Linn. comumente denominada no Brasil de vinagreira, é um membro da família das malváceas. Esta espécie é largamente utilizada na medicina tradicional, sendo rica em compostos biativos, que apresentam inúmeras propriedades farmacológicas já comprovadas cientificamente como antioxidante, anti-inflamatório, antidiabético, entre outros. Assim, no presente artigo foram apresentados estudos de compostos bioativos presentes no H. sabdariffa, de caráter bibliográfico descrevendo no fluxo de trabalhos em relação à composição química e os efeitos biológicos. O objetivo do estado da arte foi descrever um apanhado de informações científicas e evidências farmacológicas sobre a espécie que apoiam seu uso, buscando responder quais os aspectos e dimensões que vêm sendo destacados e priorizados no que se refere à composição química e as atividades biológicas da espécie, visando ressaltar novas perspectivas com sugestões cogentes de pesquisa sobre a espécie. O estado da arte foi realizada com base nos bancos de dados eletrônicos que disponibilizam publicações de pesquisas (SciELO, Google Acadêmico, NCBI), com dados eletrônicos pesquisados de 2005 até 2019, empregando as palavras-chave: Hibiscus sabdariffa, fitoquímicos e polifenóis, que foram selecionadas através do software VOSviewer, mapeando palavras-chave de maior frequência com dados do repositório da Scopus. Nesta perspectiva, conclui-se que o estado da arte agrupou um grande número de informações que aprimorará o conhecimento em relação à espécie estudada, fazendo o detalhadamente de constituintes presentes e das propriedades biológicas, constatando-se que são poucos os estudos relacionados às atividade farmacológicas frente aos feitos adversos ligados ao consumo da espécie, além de serem poucos os estudos que viabilizam a produção dessa espécie de forma sustentável garantindo uma produção regular desses constituintes químicos e a utilização de técnicas biotecnológicas associadas à ferramentas de metabolômicas que poderiam fornecer estratégias para produção e identificação, respectivamente, de metabólitos responsáveis pelos efeitos farmacológicos, sendo as sugestões necessárias para maiores publicações que envolvam essas perspectivas de forma plausível e sólida. Palavras-Chave: Hibiscus, constituintes químicos, malvaceae, vinagreira, metabolômica.
The anti-hypertensive activity of aqueous calyx extract of Hibiscus sabdariffa on salt induce hypertensive albino rats was investigated for 28 days using the non invasive method. The extract and drug treated groups showed a significant (P < 0.01) reduction in diastolic and systolic blood pressure when compared to the normotensive and hypertensive rats. There was no significant difference (P < 0.05) between the drug treated group and the extract treated group during this treatment. Thus, this study further supports previous findings and the use of H. sabdariffa calyx extract in the treatment of hypertension.
The biologically active title compounds have been isolated from Hibiscus sabdariffa plants, hibiscus acid as a dimethyl sulfoxide monosolvate [systematic name: (2 S ,3 R )-3-hydroxy-5-oxo-2,3,4,5-tetrahydrofuran-2,3-dicarboxylic acid dimethyl sulfoxide monosolvate], C 6 H 6 O 7 ·C 2 H 6 OS, (I), and hibiscus acid dimethyl ester [systematic name: dimethyl (2 S ,3 R )-3-hydroxy-5-oxo-2,3,4,5-tetrahydrofuran-2,3-dicarboxylate], C 8 H 10 O 7 , (II). Compound (I) forms a layered structure with alternating layers of lactone and solvent molecules, that include a two-dimensional hydrogen-bonding construct. Compound (II) has two crystallographically independent and conformationally similar molecules per asymmetric unit and forms a one-dimensional hydrogen-bonding construct. The known absolute configuration for both compounds has been confirmed.
This study was aimed at investigating the cardiovascular effects of an Olea europea L. leaf extract (OEE), of a Hibiscus sabdariffa L. flower extract (HSE), and of their 13 : 2 w/w mixture in order to assess their cardiac and vascular activity. Both extracts were fully characterized in their bioactive compounds by HPLC-MS/MS analysis. The study was performed using primary vascular endothelial cells (HUVECs) to investigate the antioxidant and cytoprotective effect of the extracts and their mixture and isolated guinea-pig left and right atria and aorta to evaluate the inotropic and chronotropic activities and vasorelaxant properties. In cultured HUVECs, OEE and HSE reduced intracellular reactive oxygen species formation and improved cell viability, following oxidative stress in dose-dependent manner. OEE and HSE exerted negative inotropic and vasorelaxant effects without any chronotropic property. Interestingly, the mixture exerted higher cytoprotective effects and antioxidant activities. Moreover, the mixture exerted an inotropic effect similar to each single extract, while it revealed an intrinsic negative chronotropic activity different from the single extract; its relaxant activity was higher than that of each single extract. In conclusion OEE and HSE mixture has a good potential for pharmaceutical and nutraceutical application, thanks to the synergistic effects of the single phytochemicals.
Hibiscus sabdariffa L. (Hs, roselle; Malvaceae) has been used traditionally as a food, in herbal drinks, in hot and cold beverages, as a flavouring agent in the food industry and as a herbal medicine. In vitro and in vivo studies as well as some clinical trials provide some evidence mostly for phytochemically poorly characterised Hs extracts. Extracts showed antibacterial, anti-oxidant, nephro- and hepato-protective, renal/diuretic effect, effects on lipid metabolism (anti-cholesterol), anti-diabetic and anti-hypertensive effects among others. This might be linked to strong antioxidant activities, inhibition of α-glucosidase and α-amylase, inhibition of angiotensin-converting enzymes (ACE), and direct vaso-relaxant effect or calcium channel modulation. Phenolic acids (esp. protocatechuic acid), organic acid (hydroxycitric acid and hibiscus acid) and anthocyanins (delphinidin-3-sambubioside and cyanidin-3-sambubioside) are likely to contribute to the reported effects.
More well designed controlled clinical trials are needed which use phytochemically characterised preparations. Hs has an excellent safety and tolerability record.
About more than half of the drugs currently in use are chiral compounds and near 90% of the last ones are marketed as racemates consisting of an equimolar mixture of two enantiomers. Although they have the same chemical structure, most isomers of chiral drugs exhibit marked differences in biological activities such as pharmacology, toxicology, pharmacokinetics, metabolism etc. Some mechanisms of these properties are also explained. Therefore, it is important to promote the chiral separation and analysis of racemic drugs in pharmaceutical industry as well as in clinic in order to eliminate the unwanted isomer from the preparation and to find an optimal treatment and a right therapeutic control for the patient. In this article, we review the nomenclature, pharmacology, toxicology, pharmacokinetics, metabolism etc of some usual chiral drugs as well as their mechanisms. Different techniques used for the chiral separation in pharmaceutical industry as well as in clinical analyses are also examined.
In vitro studies show Hibiscus sabdariffa L., an ingredient found in many herbal tea blends and other beverages, has antioxidant properties, and, in animal models, extracts of its calyces have demonstrated hypocholesterolemic and antihypertensive properties. Our objective in this study was to examine the antihypertensive effects of H. sabdariffa tisane (hibiscus tea) consumption in humans. A randomized, double-blind, placebo-controlled clinical trial was conducted in 65 pre- and mildly hypertensive adults, age 30-70 y, not taking blood pressure (BP)-lowering medications, with either 3 240-mL servings/d of brewed hibiscus tea or placebo beverage for 6 wk. A standardized method was used to measure BP at baseline and weekly intervals. At 6 wk, hibiscus tea lowered systolic BP (SBP) compared with placebo (-7.2 +/- 11.4 vs. -1.3 +/- 10.0 mm Hg; P = 0.030). Diastolic BP was also lower, although this change did not differ from placebo (-3.1 +/- 7.0 vs. -0.5 +/- 7.5 mm Hg; P = 0.160). The change in mean arterial pressure was of borderline significance compared with placebo (-4.5 +/- 7.7 vs. -0.8 +/- 7.4 mm Hg; P = 0.054). Participants with higher SBP at baseline showed a greater response to hibiscus treatment (r = -0.421 for SBP change; P = 0.010). No effects were observed with regard to age, gender, or dietary supplement use. These results suggest daily consumption of hibiscus tea, in an amount readily incorporated into the diet, lowers BP in pre- and mildly hypertensive adults and may prove an effective component of the dietary changes recommended for people with these conditions.
In this study, we suggested characterizing the vasodilator effects and the phytochemical characteristics of a plant with food usage also used in traditional treatment of arterial high blood pressure in Senegal.
Vascular effects of crude extract of dried and powdered calyces of Hibiscus sabdariffa were evaluated on isolated thoracic aorta of male Wistar rats on organ chambers. The crude extract was also enriched by liquid-liquid extraction. The various cyclohexane, dichloromethane, ethyl acetate, butanol extracts obtained as well as the residual marc were subjected to Sephadex LH-20 column chromatography. The different methanolic eluate fractions were then analyzed by Thin Layer (TLC) and High Performance Liquid Chromatography (HPLC) and their vascular effects also evaluated.
The H. Sabdariffa crude extract induced mainly endothelium-dependent relaxant effects. The endothelium-dependent relaxations result from NOS activation and those who not dependent to endothelium from activation of smooth muscle potassium channels. The phytochemical analysis revealed the presence of phenolic acids in the ethyl acetate extract and anthocyans in the butanolic extract. The biological efficiency of the various studied extracts, in term of vasorelaxant capacity, showed that: Butanol extract > Crude extract > Residual marc > Ethyl acetate extract. These results suggest that the strong activity of the butanolic extract is essentially due to the presence of anthocyans found in its fractions 43-67.
These results demonstrate the vasodilator potential of hibiscus sabdariffa and contribute to his valuation as therapeutic alternative.
To compare the antihypertensive effectiveness of sour tea (ST; Hibiscus sabdariffa) with black tea (BT) infusion in diabetic patients, this double-blind randomized controlled trial was carried out. Sixty diabetic patients with mild hypertension, without taking antihypertensive or antihyperlipidaemic medicines, were recruited in the study. The patients were randomly allocated to the ST and BT groups and instructed to drink ST and BT infusions two times a day for 1 month. Their blood pressure (BP) was measured on days 0, 15 and 30 of the study. The mean of systolic BP (SBP) in the ST group decreased from 134.4+/-11.8 mm Hg at the beginning of the study to 112.7+/-5.7 mm Hg after 1 month (P-value <0.001), whereas this measure changed from 118.6+/-14.9 to 127.3+/-8.7 mm Hg (P-value=0.002) in the BT group during the same period. The intervention had no statistically significant effect on the mean of diastolic BP (DBP) in either the ST or BT group. The mean pulse pressure (PP) of the patients in the ST group decreased from 52.2+/-12.2 to 34.5+/-9.3 mm Hg (P-value <0.001) during the study, whereas in the BT group, it increased from 41.9+/-11.7 to 47.3+/-9.6 mm Hg (P-value=0.01). In conclusion, consuming ST infusion had positive effects on BP in type II diabetic patients with mild hypertension. This study supports the results of similar studies in which antihypertensive effects have been shown for ST.
Biochemical events associated with activation of smooth muscle contraction were studied in neurally stimulated bovine tracheal smooth muscle. A latency period of 500 ms preceded increases in isometric force and myosin light chain phosphorylation. However, stimulation resulted in the rapid hydrolysis of inositol phospholipids as demonstrated by increases in inositol phosphates by 500 ms. Inositol trisphosphate increased 2-fold with no significant change in inositol tetrakisphosphate. The apparent activation state of myosin light chain kinase was assessed indirectly through measurements of the fractional activation of a second calmodulin-dependent enzyme, cyclic nucleotide phosphodiesterase. The fractional activation of cyclic nucleotide phosphodiesterase increased after neural stimulation to a maximal extent by 500 ms and remained at this level for at least 4 s. The monophosphorylation of myosin light chain increased after 500 ms and reached a maximum value by 2 s. Diphosphorylation also occurred but to a much lesser extent. Fractional activation of cyclic nucleotide phosphodiesterase and myosin light chain phosphorylation both decreased after 10 min continuous stimulation, although the force response remained at a maximal level. These observations demonstrate that inositol trisphosphate formation and activation of cyclic nucleotide phosphodiesterase (and hence most likely myosin light chain kinase) by calmodulin precede myosin light chain phosphorylation and that these events are sufficiently rapid to mediate the contractile response of neurally stimulated tracheal smooth muscle.
Considering the high prevalence of hypertension, its debilitating end organ damage, and the side effects of chemical drugs used for its treatment, we conducted this experimental study to evaluate the effect of sour tea (Hibiscus sabdariffa) on essential hypertension. For this purpose, 31 and 23 patients with moderate essential hypertension were randomly assigned to an experimental and control group, respectively. Patients with secondary hypertension or those consuming more than two drugs were excluded from the study. Systolic and diastolic blood pressures were measured before and 15 days after the intervention. In the experimental group, 45% of the patients were male and 55% were female, and the mean age was 52.6 +/- 7.9 years. In the control group, 30% of the patients were male, 70% were female, and the mean age of the patients was 51.5 +/- 10.1 years. Statistical findings showed an 11.2% lowering of the systolic blood pressure and a 10.7% decrease of diastolic pressure in the experimental group 12 days after beginning the treatment, as compared with the first day. The difference between the systolic blood pressures of the two groups was significant, as was the difference of the diastolic pressures of the two groups. Three days after stopping the treatment, systolic blood pressure was elevated by 7.9%, and diastolic pressure was elevated by 5.6% in the experimental and control groups. This difference between the two groups was also significant. This study proves the public belief and the results of in vitro studies concerning the effects of sour tea on lowering high blood pressure. More extensive studies on this subject are needed.
The antihypertensive effect of aqueous extracts of the calyx of Hibiscus sabdariffa (HS) has been investigated in anaesthetized rats. Hibiscus sabdariffa caused a dose-dependent decrease in mean arterial pressure (MAP) of the rats. Sectioning of the right and left vagi nerves did not have a significant effect on the fall in MAP produced by HS. Cholinergic blockade with 0.2 mgkg-1 atropine and histaminergic blockade with 1 mgkg-1 cimetidine and 15 mgkg-1 promethazine significantly attenuated the hypotensive response to HS. Pretreatment of the rats with 20 mgkg-1 HS extract did not have a significant effect on increase in blood pressure induced by bilateral carotid occlusion (48.05 +/- 6.83 mmHg vs 46.53 +/- 7.49 mmHg). The cumulative addition of HS to noradrenaline precontracted aortic rings produced dose-dependent relaxation of the rings. The maximum relaxation response was 86.96 +/- 5.20% and this was observed at the dose of 1.70 mgml-1. These findings suggest that the antihypertensive effect of the extracts of calyx of HS is not mediated through inhibition of the sympathetic nervous system but it could be mediated through acetylcholine-like and histamine-like mechanisms as well as via direct vaso-relaxant effects.
This review examines the properties and roles of the four types of K+ channels that have been identified in the cell membrane of arterial smooth muscle cells. 1) Voltage-dependent K+ (KV) channels increase their activity with membrane depolarization and are important regulators of smooth muscle membrane potential in response to depolarizing stimuli. 2) Ca(2+)-activated K+ (KCa) channels respond to changes in intracellular Ca2+ to regulate membrane potential and play an important role in the control of myogenic tone in small arteries. 3) Inward rectifier K+ (KIR) channels regulate membrane potential in smooth muscle cells from several types of resistance arteries and may be responsible for external K(+)-induced dilations. 4) ATP-sensitive K+ (KATP) channels respond to changes in cellular metabolism and are targets of a variety of vasodilating stimuli. The main conclusions of this review are: 1) regulation of arterial smooth muscle membrane potential through activation or inhibition of K+ channel activity provides an important mechanism to dilate or constrict arteries; 2) KV, KCa, KIR, and KATP channels serve unique functions in the regulation of arterial smooth muscle membrane potential; and 3) K+ channels integrate a variety of vasoactive signals to dilate or constrict arteries through regulation of the membrane potential in arterial smooth muscle.
Enantiomers as a optically active forms of drugs now have a big impact on most areas of pharmacotherapy. They arouse a large interest in the field of psychiatry and especially in the treatment of depression. This is due to the fact that enantiomers (chiral forms) of many drugs may have a different pharmacokinetic, pharmacological or pharmacogenetic profiles. Therefore, in many cases the use of a single enantiomer of the drug may have huge advantages over previously used forms and lead to strong improvement of the current treatments. An example is the stereoselective property of such a psychotropic drug fluoxetine as belonging to a group of selective serotonin reuptake inhibitors (SSRI).
The mechanism by which aqueous extracts of Hibiscus sabdariffa (HS) relaxes the vascular smooth muscle has been investigated. We used 2 mm ring segments of isolated aorta of rat mounted in organ baths containing physiological salt solution (PSS). Cumulative addition of HS (0.02—0.96 mg/ml) had a significant (p < 0.05) relaxation effect on noradrenaline precontracted rings but not on potassium chloride (KCl) precontracted rings. Similarly, HS significantly attenuated the contractile response to calcium chloride (CaCl2) in noradrenaline stimulated rings while it has no effect on KCl-stimulated rings. HS also significantly reduced the magnitude of noradrenaline phasic contraction. The results of this study suggest that HS relaxes vascular smooth muscle via a mechanism that is associated with an inhibition of Ca2+ influx through receptor operated channels and also on inhibition of Ca2+ release from intracellular stores.
The complete spectroscopic data and other physical constants of two naturally occuring, diastereomeric, optically active γ-lactones derived from inexpensive 2-hydroxycitric acids, namely garcinia acid [(2S,3S)-tetrahydro-3-hydroxy-5-oxo-2,3-furandicarboxylic acid] and hibiscus acid [(2S,3R)-tetrahydro-3-hydroxy-5-oxo-2,3-furandicarboxylic acid] and related derivatives have been described for the first time.
The principal acid in the highly acidic fruits of Garcinia cambogia has been identified as (−)-hydroxycitric acid. This acid has not been encountered in nature before. Fruits of two other species of Garcinia were found to contain the same acid, and the leaves of Hibiscus cannabinus, (+)-allo-hydroxycitric acid, an isomer reported earlier in Hibiscus sabdariffa. Wide occurrence of hydroxycitric acid in nature is thus indicated.
Introduction:
The use of herbal medicines including different types of tea is among the different strategies for preventing and controlling the side-effects of diabetes. The aim of the present study was to compare the effect of sour tea and green tea on mildly hypertensive patients with diabetes.
Methods:
The present study was a randomized clinical trial in which 100 mildly hypertensive patients with diabetes were randomly assigned into sour tea group (ST) and green tea group (GT). They were instructed to drink sour tea and green tea infusion, respectively, three times a day 2 hr after each meal for 4 weeks. The participants' blood pressure was measured at days 1, 15, and at the end of study.
Results:
The systolic pressure of both groups statistically decreased at the end of the study; it decreased from 123.1 ± 15.5 to 116.8 ± 16.3 mmHg in the ST and from 119.4 ± 15.1 to 114.8 ± 15.9 mmHg in the GT. The diastolic pressure of both groups statistically decreased by the end of the study; it decreased from 79.4 ± 11.1 to 74.5 ± 9.3 mmHg in the ST and from 78.9 ± 8.3 to 75.3 ± 7.7 mmHg in the GT. The therapeutic effectiveness of tea drinking by the end of intervention was 43.5% in the ST and 39.6% in the GT compared to the beginning.
Conclusions:
The present study revealed that mildly hypertensive type 2 diabetic individuals who drink three glasses of green or sour tea daily for 4 weeks show significant decreased systolic and diastolic blood pressures.
Abstract A water extract of the petals of Hibiscus sabdariffa (HS) has been tested for vascular smooth muscle contractile activity by applying cumulative concentrations on isolated rat aortic rings under baseline tension. Relaxation responses to HS were also tested on tissues precontracted with 100−7M noradrenaline (NA). Relaxation experiments were conducted on endothelium-intact, methylene blue-treated, and endothelium-denuded tissues. In the concentration range of 0.02-7.68 mg/ml, HS did not show a measurable contractile effect on the rat aorta. In contrast, in tissues with NA-induced tone, vasorelaxation was observed with cumulative concentrations of HS and reached a mean of 91 ± 4% at a concentration of 1.70 mg/ml, with an EC50 of 0.53 ± 0.06 mg/ml. This relaxation response was significantly attenuated by removal of the endothelium, since endothelium-denuded rings showed a mean relaxation of 28 ± 1% at 1.70 mg/ml, with an EC50 of 2.53 ± 0.09 mg/ml (p<0.05). Moreover, endothelium-intact rings which were pretreated with 106M methylene blue showed significantly attenuated relaxation to threshold concentrations of HS, with EC10 values of 0.25 ± 0.01 mg/ml and 0.15 ± 0.01 mg/ml (p<0.05) with and without methylene blue treatment, respectively. The effect of methylene blue was not significant, however, at higher concentrations of HS. Thus, HS-induced relaxation of rat aortic smooth muscle occurs by both endothelium-dependent and -independent mechanisms. Since the endothelium-dependent response was largely unaffected by methylene blue treatment, this component of r's activity does not appear to involve EDRF.
This review is concerned with the mechanisms by which substances, many of them neurotransmitters, produce their effects on smooth muscle cells. It is concerned primarily with those that exert effects within seconds of their application to the muscle - effects most easily studied in vitro with the smooth muscle cells bathed in physiological salt solutions. Those substances, such as hormones or other trophic agents, that have a long-term effect are not considered here. An examination is presented of the strength of the experimental support for some simple concepts about how stimulant or inhibitory chemicals affect the contractility of smooth muscle. This review concentrates particularly on the effects of drugs, and substances found naturally in the body, on the permeability of the smooth muscle cell membrane and how these changes might increase or decrease tension in the contractile proteins.
We examined the interactions of two Ca2+ channel activators, (S)-Bay K 8644 and FPL 64176, on smooth muscle L-type Ca2+ channels. FPL 64176 (300 nM) caused a sustained contraction of rat tail artery strips. This contractile response was inhibited by approximately 70% by (S)-Bay K 8644 (EC50 = 14 nM). (S)-Bay K 8644 (100 nM) increased whole-cell Ca2+ currents in A7r5 smooth muscle cells but effectively blocked further stimulation by 1 microM FPL 64176. When added alone, 1 microM FPL 64176 increased Ca2+ channel current amplitude, slowed current activation, and prolonged tail current duration. Furthermore, no inactivation of current during step depolarizations was observed in the presence of FPL 64176. After subsequent addition of (S)-Bay K 8644, Ca2+ channel current activation was accelerated and tail current duration was shortened. Additionally, pronounced inactivation of the Ca2+ channel current became apparent. These results are consistent with a negative allosteric interaction between the (S)-Bay K 8644 binding site and that of FPL 64176, in smooth muscle.
Recent studies suggest endothelium to be involved in the vasorelaxation of calcium antagonists of the 1,4-dihydropyridine type, which may at least in part be mediated by endothelium-derived relaxing factor (EDRF = NO). To study this effect further, the influence of L-NG-nitro arginine (L-NNA), a specific inhibitor of EDRF-synthesis, on nitrendipine-induced vasorelaxation was examined in different isolated porcine arteries. Coronary, basilary, and tail arteries were bathed in Krebs-Henseleit solution and endothelial function was verified by means of substance P, an EDRF releasing neuropeptide. Vasorelaxation of nitrendipine in PGF2 alpha-precontracted arteries was studied in the presence and absence of L-NNA. Nitrendipine-induced vasorelaxation was markedly reduced by the addition of L-NNA in all vessels studied. Tachyphylactic effects of nitrendipine could be excluded. The obtained results may be explained by an enhancement of nitrendipine action by basally released EDRF, alternatively, by an increased EDRF-release induced by this calcium antagonist. Therefore, in a second series of experiments the release of EDRF was studied in isolated coronary arteries under cumulative application of nitrendipine. Using the nitric oxide scavenging properties of oxyhemoglobin, EDRF release was measured spectrophotometrically by means of methemoglobin formation. The application of nitrendipine resulted in a concentration-dependent increase in the extinction rate, indicating an increased release of NO which could be inhibited by preincubation with L-NNA. It may be concluded that, in functionally intact vessels, vasorelaxation induced by nitrendipine may additionally be mediated by an increased release of EDRF.
The mechanisms involved in the contraction of rat aorta induced by the activation of α 1 ‐adrenoceptors were studied. Phenylephrine induced a phasic contraction in the aorta incubated in Ca ²⁺ ‐free medium containing 0.5 m m EGTA. Subsequent addition of Ca ²⁺ induced a tonic contraction, which exhibited a stepwise development, an initial phase lasting 3 to 6 min (tonic‐I) followed by a superimposing second phase (tonic‐II).
2‐Nitro‐4‐carboxyphenyl‐N,N‐diphenylcarbamate, which has been reported to inhibit phosphatidylinositol turnover, and H‐7, a protein kinase C inhibitor, inhibited the tonic‐I phase more effectively than the tonic‐II phase. On the other hand, the tonic‐II phase was more sensitive to nifedipine and cromakalim.
The rate of ⁴⁵ Ca ²⁺ influx during the tonic‐I phase in phenylephrine‐treated muscles was not different from that in untreated muscles, while that during the tonic‐II phase was significantly greater. Nifedipine inhibited the increased ⁴⁵ Ca ²⁺ influx during the tonic‐II phase, whereas H‐7 did not affect the uptake during either phase.
These results suggest that the tonic contraction of rat aorta following α 1 ‐adrenoceptor activation involves two different mechanisms: one is directly related to consequences of the polyphosphoinositide cascade, probably to protein kinase C, and the other dependent on Ca ²⁺ influx through nifedipine‐sensitive Ca ²⁺ channels.
The pharmacological, radioligand binding, and electrophysiological properties of FPL 64176, a new nondihydropyridine Ca2+ channel activator, were studied in rat tail artery, cardiac membranes, and A7r5 smooth muscle cells. FPL 64176 induced a contractile response, with an EC50 value of 2.11 x 10(-7) M. The maximum tension response to FPL 64176 was approximately 2-fold higher than that to (S)-Bay K 8644. FPL 64176 showed no significant inhibitory activity at concentrations up to 10(-5) M. The Ca2+ channel antagonists nifedipine, verapamil and diltiazem noncompetitively antagonized and completely relaxed the responses induced by FPL 64176. IC50 values of these three drugs were 5.22 x 10(-9), 1.31 x 10(-7), and 1.95 x 10(-7) M, respectively, for relaxing submaximum contractile responses to FPL 64176 (5 x 10(-7) M). The washout time for FPL 64176 was about 40 min, which was much longer than that for (S)-Bay K 8644 (within 1 min). FPL 64176 weakly inhibited (+)-[3H]PN 200-110, [3H]D888, and [3H]TA-3090 binding in rat cardiac membranes, with IC50 values of 1.04 x 10(-5) M and 7.03 x 10(-6) M for inhibition of (+)-[3H]PN 200-110 and [3H]TA-3090 binding, respectively, and with 23% inhibition of [3H]D888 binding at a FPL 64176 concentration of 1 x 10(-5) M. Dissociation kinetics of the three radioligands were allosterically accelerated by FPL 64176. Electrophysiological studies on the A7r5 smooth muscle cell line directly confirmed a large (approximately 14-fold) stimulatory effect on L-type Ca2+ current amplitude. The results suggest that FPL 64176 is a new type of Ca2+ channel activator with higher efficacy and a mechanism and site of action that are distinct from those for (S)-Bay K 8644.
Vascular endothelium modulates the effect of various vasoconstricting mediators as well as the affinity of dihydropyridine-type calcium entry blockers. To further investigate this influence, vasoconstriction by PGF2 alpha as opposed to KCl and the affinity of nitrendipine and some related 3-ester side-chain derivatives were determined in isolated porcine basilar arteries in the presence and in the absence of intact endothelium, as well as in the presence of methylene blue. Treatment with methylene blue or mechanical endothelial damage increased the contractile work of basilar arteries stimulated by PGF2 alpha and reduced the affinity of the dihydropyridines in such precontracted vessels. Both experimental conditions resulted in nearly the same effect. In addition, the degree of intact endothelium, as determined by substance-P-induced vasodilation, significantly correlated with the corresponding efficacy of all dihydropyridines examined. In contrast, KCl-mediated contractions remained unchanged. It is suggested that the endothelium (probably due to the production and release of endothelium-derived vasorelaxing factors, such as EDRF and/or prostacyclin) may attenuate PGF2 alpha-induced transmembrane calcium influx through receptor operated calcium channels, whereas potential operated calcium channels seems to be unaffected.
The effectiveness of the calcium antagonist, 1,4‐dihydropyridine nisoldipine, as an inhibitor of contraction and ⁴⁵ Ca entry evoked by noradrenaline in rat aorta has been investigated and correlated with binding characteristics in intact artery.
Contractions evoked by noradrenaline were concentration‐dependently depressed by nisoldipine (0.3–300 n m ). About 60% of the response was resistant to inhibition, while KCl‐induced contractions could be completely blocked. Noradrenaline‐induced contractions were also less sensitive to nisoldipine inhibition than were KCl‐induced contractions.
Preincubation of the aorta with nisoldipine in high KCl depolarizing solution increased the inhibition of the contraction evoked by a short application of noradrenaline or KCl to a similar extent.
The inhibition by nisoldipine of ⁴⁵ Ca influx evoked either by KCl depolarizing solution or by noradrenaline correlated well with the inhibition of the contractile responses. However, while KCl‐stimulated ⁴⁵ Ca influx was totally abolished by nisoldipine (300 n m ), 38% of the noradrenaline‐stimulated ⁴⁵ Ca influx was resistant to inhibition by nisoldipine (300 n m ).
The study of [ ³ H]‐(+)‐PN 200‐100 ([ ³ H]‐(+)‐isradipine) binding in intact aorta showed the presence of a homogeneous population of specific binding sites. K D values were dependent on the KCl concentration in the bath while B max was unaffected. Binding of [ ³ H]‐(+)‐isradipine was also increased in tissue exposed to noradrenaline; in the presence of 10 ⁻⁵ m noradrenaline, binding parameters of [ ³ H]‐(+)‐isradipine were close to the values obtained in aorta bathed in 20 m m KCl solution.
Displacement of [ ³ H]‐(+)‐isradipine specific binding by nisoldipine was determined in segments of mesenteric artery and of aorta. The potency of nisoldipine was dependent on the incubation conditions applied to the vessel, as follows: KCl (100 m m ) depolarizing solution > noradrenaline (10 ⁻⁵ m ) = KCl (25 m m ) solution > physiological solution. The K i value measured in aorta exposed to noradrenaline (10 ⁻⁵ m ) was close to the IC 50 value of nisoldipine on the noradrenaline‐evoked contraction.
The membrane potential value of rat aorta was estimated by the distribution of [ ³ H]‐tetraphenylphosphonium bromide ([ ³ H]‐TPP ⁺ ). [ ³ H]‐TPP ⁺ uptake concentration‐dependently decreased when the KCl concentration in the bath was increased from 5.9 to 130 m m . Noradrenaline also concentration‐dependently decreased [ ³ H]‐TPP ⁺ uptake; the maximum effect (1–10 μ m noradrenaline) was comparable in amplitude to the effect of 25 m m KCl solution.
It is concluded that in rat aorta, noradrenaline activates voltage‐operated calcium channels that contain the specific, voltage‐sensitive binding sites for calcium antagonistic dihydropyridines. The existence of a fraction of noradrenaline‐stimulated ⁴⁵ Ca entry that is resistant to nisoldipine blockade suggests that another Ca ²⁺ entry pathway is also opened by the agonist.
The mechanisms of pinacidil-induced direct vasodilation were studied in vitro in RMA and RAO. In RMA, pinacidil produced dose-dependent relaxations of norepinephrine (5 microM)-induced contractions with an IC50 of 0.2 microM. This component of pinacidil relaxation appeared to be dependent on K+ conductance because pretreatment with tetraethylammonium (10 mM), Ba++ (0.5 mM), glyburide (1 microM) and 20 mM K+ all caused a rightward shift of the pinacidil dose-response curve (DRC) and a corresponding increase in the pinacidil IC50. However, additional relaxation effects of pinacidil were still evident in the presence of various K+ channel blockers. Pinacidil also showed a relaxation DRC under the condition of 80 mM K+ contraction in both RMA and RAO with IC50 values of 27 and 50 microM, respectively. Pinacidil could also produce maximal relaxation in RMA and RAO remained unaffected in 145 mM K+ (zero Na+) depolarizing solution suggesting a lack of dependence on Na(+)-Ca++ exchange mechanism for this action of pinacidil. Studies using 1 or 3 min pulse labeling with 45Ca showed an absence of an inhibitory effect of pinacidil (at 50 and 100 microM) on unidirectional 45Ca influx stimulated by high-K+. Net 45Ca uptake studies showed that pinacidil inhibited high-K+ stimulated 45Ca uptake at 100 but not at 50 microM. Ryanodine (10-100 microM) was used as a tool to investigate the role of sarcoplasmic reticulum (SR) in this action of pinacidil. Under the condition in which ryanodine (10-100 microM) treatment was found to cause the SR to be nonfunctional, pinacidil relaxation DRC remained unaltered, suggesting a lack of a stimulatory effect of pinacidil on SR Ca++ accumulation. These data thus show that the K+ channel-independent effect of pinacidil does not involve to any significant degree an effect of pinacidil on plasmalemmal voltage-sensitive Ca++ channels, SR Ca++ stores, Na(+)-Ca++ exchange or membrane hyperpolarization.(ABSTRACT TRUNCATED AT 250 WORDS)
Addition of an aqueous extract of Hibiscus sabdariffa calyces (2.5 ml/bath approximately 125 mg of starting crude material) inhibited the tone of various isolated muscle preparations (rabbit aortic strip, rhythmically contracting rat uterus, guinea-pig tracheal chain and rat diaphragm). Other muscles were stimulated (quiescent rat uterus and frog rectus abdominis). Intravenous injection of the extract to anaesthetized cats lowered the blood pressure in a dose-response manner. The inhibitory effects were resistant to a number of standard receptor blockers but the hypotensive influence was partially blocked by atropine and the tonic effects on rat uterus were partially reduced by hydrocortisone and indomethacin.
This study describes a sensitive in vitro relaxation assay using isolated rabbit mesenteric artery to detect the activity of a vasodilator as a K(+)-channel activator. Thus, comparison of several known K(+)-channel activators was made with other vasodilators known to work via various cellular mechanisms. The vasodilators used were minoxidil sulfate (MNXS; 5 microM), BRL-34915 (cromakalim, 0.1 microM), nicorandil (10 microM), pinacidil (1 microM), diazoxide (100 microM), sodium nitroprusside (10 microM), forskolin (1 microM), D600 (0.5 and 10 microM), hydralazine (10 microM), and viprostal (PGE1 analog, 5 microM). The concentrations chosen were equipotent to produce greater than 80% relaxation of the maximal norepinephrine (NE) (5 microM) contraction. At these concentrations, MNXS, cromakalim, pinacidil, nicorandil, and diazoxide were found to be ineffective in producing relaxation of 80 mM K(+)-contractions. Subsequently, pretreatment of tissues with 20 mM K+ before NE contraction was found to attenuate relaxation significantly by these agents, but had not effect on the relaxations by forskolin or D600. These initial criteria helped to establish cromakalim, pinacidil, nicorandil, and diazoxide as compounds acting similarly to MNXS as K(+)-channel-dependent. In another set of experiments, the effects of tetraethylammonium (TEA) (10 mM), Ba2+ (0.5 mM), and glyburide (1 microM) as K(+)-channel blockers were examined. Again it was found that these blockers had the most inhibitory effect on the class of compounds identified as K(+)-channel activators. Additionally, it was found that these K(+)-channel activators were without any significant effect on the NE-sensitive intracellular Ca2+ release as studied by contraction in a Ca2(+)-free solution. Thus, this series of functional criteria clearly show that the profile of these K(+)-channel activators is distinctly different from the vasodilators working via other mechanisms such as cyclic AMP (cAMP) (forskolin), cyclic GMP (cGMP) (nitroprusside), and Ca2+ antagonists (D600). It is suggested that appropriately defined, systematic functional studies, such as the one described here, can provide a sensitive and reproducible vascular model to discover and delineate the role of pharmacologically relevant mechanisms for vasodilation.
Calcium may be considered as the final intracellular messenger of excitation-contraction coupling. In this report the main mechanisms involved in the cellular regulation of calcium movements are reviewed. Most of the pharmacological agents actually available for therapy interfere with the processes responsible for increase in cytoplasmic activator calcium. Study of the relation between contraction and calcium movements shows that blockade of calcium entry may cause inhibition of contraction. This has allowed to illustrate some of the characteristics of calcium channels in smooth muscle. Potential-operated channels are activated by changes in membrane potential, that can be evoked by K-rich solutions. They are completely blocked by calcium antagonistic dihydropyridines and diphenylpiperazines. This blockade shows (time-)-use-dependence. They are opened by calcium agonistic dihydropyridines. Receptor-operated channels are activated by the interaction of an agonist with its receptors; they are incompletely blocked by calcium antagonistic dihydropyridines and diphenylpiperazines. Endothelium appears to modulate the response of the adjacent smooth muscle to vasoconstrictors. This may be accounted for by modulation of calcium metabolism, both at the level of membrane channels and of intracellular stores. As a consequence, endothelium modulates the action of calcium entry blockers. Study of isolated human tissues illustrates difference in drug sensitivity between cardiac and smooth muscle. Human isolated coronary arteries are sensitive to nifedipine concentrations found in the blood of patients receiving therapeutic regimen. These concentrations do not alter the contractility of the isolated human myocardium. Differences between drugs may be explained assuming that they may interact with one of the states (closed, open, inactivated) of the Ca channels. This also helps the understanding of tissue selectivity of some compounds. A pharmacological classification of calcium entry blockers may be proposed. This classification is a rationale to differentiate between the various clinical indications of drugs affecting calcium movements.
The mechanism of vasoconstriction induced by endothelin was investigated in rat isolated aorta in comparison with the Ca++ agonist, Bay K 8644. Endothelin (EC50 = 4 nM) induced a slow and sustained contraction in control medium whereas the one elicited by Bay K 8644 (EC50 = 14 nM) necessitating a partly K+ depolarized medium was fast with superimposed rhythmic contraction. By opposition with Bay K 8644, endothelin contraction was not inhibited by the calcium antagonists (1 microM), nifedipine, diltiazem and D 600, and substantially persisted in Ca++ free medium or after depletion of intracellular Ca++ by phenylephrine (1 microM). These data show that endothelin does not act as an activator of potential dependent Ca++ channels but probably through specific receptor(s) as suggested by its mode of vasoconstriction.
Bay k 8644 is a structural analog of nifedipine with positive inotropic activity. The mechanism of drug action was evaluated by measuring the effects of Bay k 8644 on twitch tension, action potential configuration, and calcium channel currents in myocardial cells. Bay k 8644 increases twitch tension in guinea pig atria without changing the time course of tension development. The drug does not occlude the effect of isoproterenol on twitch tension. The effects of Bay k 8644 on atrial twitch tension are highly dependent on the frequency of stimulation. Maximal inotropic effects are observed at approximately 0.5 Hz, but no inotropic effect occurs at 0.003 Hz (a rested-state contraction). Since positive inotropic effects only occur with frequent electrical stimulation, they are not due to an intracellular action or to mechanisms that elevate cell calcium in quiescent muscle, such as inhibition of the Na,K-ATPase. Bay k 8644 increases the action potential duration of calf ventricular muscle and Purkinje fibers. Effects on action potential duration are occluded by 1 microM nisoldipine, which specifically blocks calcium channels. The interaction of Bay k 8644 with calcium channels in calf Purkinje fibers was studied using the two-microelectrode voltage clamp technique. Strontium was used as a charge carrier to minimize current through calcium-activated channels and to avoid changes in calcium conductance due to changes in intracellular calcium. Bay k 8644 increases strontium currents and alters the time- and voltage-dependence of channel opening. The greatest percent increase in strontium current occurs for weak depolarizations. For strong depolarizations, strontium current is increased most at the beginning of a test pulse. The drug-induced changes in calcium channel gating are inconsistent with a calcium- or cyclic adenosine monophosphate-mediated effect, and indicate a novel mechanism of action on calcium channels. Thus, Bay k 8644 is the first positive inotropic agent shown to act specifically and directly on calcium channels.
1. The influence of endothelium on the response of rat isolated aorta to α-adrenergic agonists has been studied by comparing the response of intact and denuded preparations before and after treatment with calcium entry blockers flunarizine and nifedipine.
2. Endothelium removal enhanced the response of the preparations, especially to α2-agonists that had a weak effect in intact preparations. In the absence of endothelium, about 80% of the maximum response to clonidine was blocked by calcium entry blockers, whereas only 25% of the maximum response to noradrenaline was sensitive to them. In contrast about 40% of maximum noradrenaline-evoked contractions was sensitive to calcium entry blockers in the presence of endothelium. This may be attributed to an increase in the intracellular exchangeable calcium fraction, likely to be due to a slight depolarization of smooth muscle membrane of denuded preparations, which are highly sensitive to the calcium agonist BAY K 8644.
3. The results indicate that a factor liberated by endothelial cells controls both calcium entry and calcium release evoked by α-adrenoceptor agonists in vascular smooth muscle.
Tetraethylammonium chloride (TEA) at concentrations over 10(-3) mol/l produced a concentration-dependent contraction in the isolated canine coronary artery. We investigated mechanisms of the contractile response and the effects of various vasodilators on the contraction. While phentolamine, propranolol, guanethidine, atropine and tetrodotoxin did not affect the TEA response, the response was attenuated by a reduction in the extracellular potassium concentration and was augmented by an increase in the concentration of potassium. The response was also augmented by other potassium conductance blockers (CsCl and 4-AP). On the other hand, the contractile response to phenylephrine used as a control drug was not affected by the extracellular potassium concentration or by CsCl. Verapamil or removal of extracellular calcium abolished the TEA, but not the phenylephrine response. Nicorandil, isoproterenol, adenosine or glyceroltrinitrate produced an equipotent relaxation in the coronary arteries contracted by TEA and by phenylephrine, whereas acetylcholine relaxed to a lesser extent the arteries contracted by TEA than those contracted by phenylephrine. These results suggest that the TEA-induced contractions are strictly dependent on the reduction of potassium conductance and extracellular calcium while the phenylephrine-induced contractions are not and that the relaxing effects of tested vasodilators, except for acetylcholine, may not be affected by such different contractile mechanisms.
It appears that, in smooth muscle, there are two distinct types of Ca2+ channel, a voltage-dependent Ca2+ channel and a receptor-linked Ca2+ channel. The former is activated by decreases in membrane potential and the latter is regulated by drug-receptor interactions. These Ca2+ channels exist as separate channels in the aorta of the adult rabbit and of some rat strains; organic Ca2+ antagonists and sodium nitroprusside selectively inhibit each of these two respective channels. By examining the effects of these two specific antagonists, characterization of the Ca2+ channels in other types of smooth muscle was attempted. In a wide variety of vascular smooth muscle (except aorta of above-mentioned animals), however, these two Ca2+ channels showed some sensitivity to both types of inhibitor. It is proposed that in most types of vascular smooth muscle as well as in gastric fundus and corpus, the two types of Ca2+ channel are functionally not completely separated. These subtypes of Ca2+ channels are at least partly sensitive to both organic Ca2+ antagonists and sodium nitroprusside. Intestinal, genital, and tracheal smooth muscles also seem to have two types of Ca2+ channel. These subtypes of Ca2+ channels are, however, sensitive only to organic Ca2+ antagonists and are not affected by sodium nitroprusside.
Bay K8644 increased unidirectional Ca2+ influx and produced tension development in rabbit aorta. Both responses could be evoked in the tissue maximally stimulated with norepinephrine. When the arterial rings were maximally activated by high K+ depolarization, Bay K8644 was without effect. The tension evoked by high K+ and Bay K8644 was more sensitive to the dihydropyridine Ca2+ antagonist PY108-068 than norepinephrine induced tension. These results indicate that Bay K8644 activates only potential operated Ca2+ channels which are opened by high K+ depolarization.
Experiments were performed on isolated rat aorta and superior mesenteric artery in order to study the action of nifedipine on norepinephrine and K-depolarization-evoked contractions and transmembrane calcium fluxes. Concentration-dependent contractions were obtained with norepinephrine in physiological solution and with Ca++ in K-depolarizing solution. Nifedipine caused a concentration-dependent depression of the maximum response. When aorta was depolarized by 40 mM KCI (instead of usual 100 mM KCI concentration), high concentrations of Ca++ evoked a relaxation that was also blocked by nifedipine. The action of nifedipine has been examined on Ca influx and efflux in arteries stimulated by norepinephrine and K-depolarization. Norepinephrine-evoked Ca influx, but not Ca efflux, was reduced by nifedipine. Concentration inhibitory curves for Ca influx and contraction could be superimposed. K-depolarization-dependent Ca entry and Ca efflux were blocked by nifedipine at concentrations lower than those required to antagonize norepinephrine actions. The results suggest that the action of nifedipine on artery contractility can be related to blockade of calcium entry through channels opened during depolarization or receptor-response coupling.
The mechanism of diltiazem-induced inhibition of smooth muscle contractility was investigated by studying its effects on tension development and Ca++ fluxes in the rabbit aorta. Diltiazem caused a dose-dependent inhibiton of contractions as well as Ca++ influx stimulated by alpha adrenoceptor activation and high-K+ depolarization. Diltiazem was roughly equally potent in inhibiting contractions induced by high-K+ and a low concentration of norepinephrine (NE; 10(-8) M). The contractions induced by high concentrations (10(-6)-10(-5) M) of NE were more resistant to diltiazem inhibition. It was also observed that there was a close relationship between diltiazem inhibition of Ca++ influx and inhibition of contraction when either 40 mM K+ or 10(-8) M NE was applied, but not when 10(-6) M NE was used. Also, diltiazem produced a noncompetitive inhibition of Ca++-induced contractions of depolarized rabbit aorta. Furthermore, there was a lack of parallelism between the smooth muscle effects of removal of [Ca++]ex and of addition of diltiazem. It is suggested that diltiazem causes inhibition of stimulated Ca++ influx by interacting with the Ca++ pathway involved in excitation rather than competing with Ca++ for the entry.
This chapter discusses the stereochemistry and preparation of hydroxycitrate. In nonruminant mammals the acetyl-CoA used for lipogenesis is generated largely from citrate in a reaction catalyzed by ATP: citrate lyase. Hydroxycitrate is a competitive inhibitor of the reaction with respect to citrate. The de novo syntheses of long-chain fatty acids and 3-β-hydroxysterols are inhibited to about the same extent by hydroxycitrate. Both pathways are extramitochondrial and both use acetyl-CoA as a carbon source. In nonruminant mammals extramitochondrial acetyl-CoA is made predominantly via the citrate cleavage reaction. Hydroxycitrate can therefore be expected to inhibit both pathways. The degrees to which both pathways are inhibited will depend on the relative affinity of their acetyl-CoA-utilizing enzymes for acetyl-CoA. Metabolite analyses of perfused livers show that addition of either hydroxycitrate or oleate causes a crossover at the phosphofructokinase reaction. This indicates a slowing down of glycolysis, which is regulated through phosphofructokinase. It is found that ketone production by perfused livers from fed rats, which occurs at a considerably slower rate, is inhibited by hydroxycitrate.
The hypothesis that Ca2+ channel function is altered during pregnancy was tested by comparing responses to potassium chloride (KCl) and phenylephrine in aortic rings of virgin and term-pregnant rats under the influence of nifedipine and Bay K 8644. Maximum response to KCl was progressively reduced by increasing nifedipine concentrations (1.0-100 nM) in both groups of tissues. Nifedipine produced a smaller inhibition of KCl-induced contraction in aortic rings of pregnant than of virgin rats. It exerted little inhibition on the concentration-response curve to phenylephrine. The Ca2+ channel antagonist (100 nM) reduced the maximum response to the alpha-adrenoceptor agonist in rings from virgin rats, but had no effect in pregnant rats. Bay K 8644, a Ca2+ channel activator, potentiated the responses to low concentrations of both phenylephrine and KCl in the tissues of both virgin and pregnant rats, but did not affect maximum responses. It also induced concentration-dependent contractions in rings of virgin but not of pregnant rats. The effects of Bay K 8644 were markedly potentiated by precontracting the aorta with 10mM KCl. Nevertheless tissues from pregnant rats were still less responsive to Bay K 8644. However, when the strips were precontracted to the same level by different concentrations of KCl, the concentration-response curves to Bay K 8644 were identical in both groups. [3H]Nitrendipine binding to membrane preparations of the thoracic aorta was similar in virgin and pregnant rats.(ABSTRACT TRUNCATED AT 250 WORDS)
We investigated the effects of aranidipine, a dihydropyridine-type Ca2+ channel blocker, on contractile responses to KCl and spontaneous contractions in isolated rat portal veins in comparison with those of the Ca2+ channel blockers, nifedipine, nicardipine, nitrendipine, diltiazem, and verapamil, and of the K+ channel openers, cromakalim and nicorandil. All the Ca2+ channel blockers concentration-dependently inhibited contractions induced by KCl. Interestingly, aranidipine was more potent against the low K+ (20 mM)-induced contraction than the high K+ (80 mM)-induced contraction, whereas the other Ca2+ channel blockers were equally potent against contractions induced by either concentration of KCl. Cromakalim and nicorandil were effective only on the low K(+)-induced contraction. In addition, all the Ca2+ channel blockers and the K+ channel openers tested inhibited the amplitude of spontaneous contractions of isolated rat portal vein. Tetraethylammonium (TEA), a classic K+ channel blocker, significantly attenuated the effect of aranidipine but not of other Ca2+ channel blockers on the spontaneous contractions. The cromakalim-induced inhibition of spontaneous contractions was antagonized by TEA. Thus aranidipine was found to be different from the typical Ca2+ channel blockers and in part similar to the K+ channel openers in inhibiting mechanical responses of isolated rat portal vein, suggesting that activation of K+ channels may in part in part be involved in the aranidipine-induced vasodilation.
The LD(50) of roselle calyx extract and its effect on blood pressure were determined. The LD(50) was found to be above 5000 mg kg(-1). Roselle calyx infusion was found to lower significantly (p<0.05) both systolic and diastolic pressure in spontaneously hypertensive and normotensive Wistar-Kyoto rats at tested doses of 500 and 1000 mg kg(-1) body weight. The reduction in blood pressure in both groups was positively correlated with weight. Continuous consumption of the infusion at 1000 mg kg(-1) was discovered to lead to sudden death in spontaneously hypertensive rats but not in Wistar-Kyoto rats. Water intake was not significantly different (p>0.05) in the control groups of the two strains of rats used, neither was there a significant difference in their urine output. The water intake in the treated spontaneously hypertensive and normotensive rats was not different from the corresponding control groups. However the urine output of the treated spontaneously hypertensive rats was significantly higher. A significant decrease in serum creatinine, cholesterol, and glucose in the treated rats compared with the control as well as a significant increase in serum uric acid was observed. The serum proteins (albumin and total protein) in the treated rats when compared with the control groups was not changed significantly.
Recent studies have suggested that part of the vasorelaxation caused by nifedipine, a 1,4-dihydropyridine Ca(2+) antagonist, depends on the endothelium. To study the effect of endothelium-dependent vasorelaxation, the release of NO and superoxide (O(2)(-)) in the presence of nifedipine in isolated cultured rabbit endothelial cells was measured. Highly sensitive electrochemical microsensors were placed onto the cell membrane, and the kinetics of NO and O(2)(-) were measured simultaneously with time resolutions of 0.1 and 0.05 ms, respectively. Nifedipine at its therapeutical concentrations stimulated NO release and scavenged O(2)(-) in endothelial cells. The linear relationship between NO concentration and nifedipine concentration was observed in the range between 0.01 and 1 nmol/L. NO concentration reached a maximum of 200+/-10 nmol/L at 1.2 nmol/L of nifedipine. The NO concentration was approximately 50% and 30% of the concentration measured in the presence of receptor-dependent (acetylcholine) and the receptor-independent (Ca(2+) ionophore A23187) NO synthase (eNOS) agonists, respectively. NO release stimulated by eNOS agonists was followed by the generation of the NO scavenger superoxide. The concentration of O(2)(-) was significantly lower after stimulation with nifedipine (peak 5+/-0.5 nmol/L) than after stimulation with acetylcholine (15+/-1 nmol/L) and Ca(2+) ionophore (25+/-1 nmol/L). The average rate of NO release by nifedipine is relatively slow (17 nmol/L per second). This is in sharp contrast to the fast rate of NO release by acetylcholine and Ca(2+) ionophore (40 and 300 nmol/L per second, respectively). These experiments show that nifedipine, apart from its well-known Ca(2+) antagonistic properties in vascular smooth muscle cells, stimulates the release of significant concentration of NO in endothelium and also preserves NO concentration. Both these effects may be beneficial in the treatment of hypertension.
1. We characterized the mechanisms in vascular smooth muscle cells (VSMCs) that produce asynchronous, wave-like Ca2+ oscillations in response to phenylephrine (PE). Confocal imaging was used to observe [Ca2+]i in individual VSMCs of intact inferior vena cava (IVC) from rabbits. 2. It was found that the Ca2+ waves were initiated by Ca2+ release from the sarcoplasmic reticulum (SR) via inositol 1,4,5-trisphosphate-sensitive SR Ca2+ release channels (IP3R channels) and that refilling of the SR Ca2+ store through the sarcoplasmic-endoplasmic reticulum Ca2+-ATPase (SERCA) was required for maintained generation of the repetitive Ca2+ waves. 3. Blockade of L-type voltage-gated Ca2+ channels (L-type VGCCs) with nifedipine reduced the frequency of PE-stimulated [Ca2+]i oscillations, while additional blockade of receptor-operated channels/store-operated channels (ROCs/SOCs) with SKF96365 abolished the remaining oscillations. Parallel force measurements showed that nifedipine inhibited PE-induced tonic contraction by 27% while SKF96365 abolished it. This indicates that stimulated Ca2+ entry refills the SR to support the recurrent waves of SR Ca2+ release and that both L-type VGCCs and ROCs/SOCs contribute to this process. 4. Application of the Na+-Ca2+ exchanger (NCX) inhibitors 2′,4′-dichlorobenzamil (forward- and reverse-mode inhibitor) and KB-R7943 (reverse-mode inhibitor) completely abolished the nifedipine-resistant component of [Ca2+]i oscillations and markedly reduced PE-induced tone. 5. Thus, we conclude that each Ca2+ wave depends on initial SR Ca2+ release via IP3R channels followed by SR Ca2+ refilling through SERCA. Na+ entry through ROCs/SOCs facilitates Ca2+ entry through the NCX operating in the reverse mode, which refills the SR and maintains PE-induced [Ca2+]i oscillations. In addition some Ca2+ entry through L-type VGCCs and ROCs/SOCs serves to modulate the frequency of the oscillations and the magnitude of force development.
(-)-Hydroxycitric acid [(-)-HCA] is the principal acid of fruit rinds of Garcinia cambogia, Garcinia indica, and Garcinia atroviridis. (-)-HCA was shown to be a potent inhibitor of ATP citrate lyase (EC 4.1.3.8), which catalyzes the extramitochondrial cleavage of citrate to oxaloacetate and acetyl-CoA: citrate + ATP + CoA --> acetyl-CoA + ADP + P(i) + oxaloacetate. The inhibition of this reaction limits the availability of acetyl-CoA units required for fatty acid synthesis and lipogenesis during a lipogenic diet, that is, a diet high in carbohydrates. Extensive animal studies indicated that (-)-HCA suppresses the fatty acid synthesis, lipogenesis, food intake, and induced weight loss. In vitro studies revealed the inhibitions of fatty acid synthesis and lipogenesis from various precursors. However, a few clinical studies have shown controversial findings. This review explores the literature on a number of topics: the source of (-)-HCA; the discovery of (-)-HCA; the isolation, stereochemistry, properties, methods of estimation, and derivatives of (-)-HCA; and its biochemistry, which includes inhibition of the citrate cleavage enzyme, effects on fatty acid synthesis and lipogenesis, effects on ketogenesis, other biological effects, possible modes of action on the reduction of food intake, promotion of glycogenesis, gluconeogenesis, and lipid oxidation, (-)-HCA as weight-controlling agent, and some possible concerns about (-)-HCA, which provides a coherent presentation of scattered literature on (-)-HCA and its plausible mechanism of action and is provocative of further research.
Organic acids in fresh leaves, fruits, and dried rinds of Garcinia cowa (G. cowa) were determined by high-performance liquid chromatography. Fresh leaves, fruits, and dried rinds were extracted with water at 120 degrees C for 20-30 min under 15 lbs/in(2) pressure. Also, dried rinds were extracted with solvents (acetone and methanol) using a Soxhlet extractor at 60 degrees C for 8 h each. The samples were injected to HPLC under gradient elution with 0.01 M phosphoric acid and methanol with a flow rate of 0.7 mL/min using UV detection at 210 nm. The major organic acid was found to be (-)-hydroxycitric acid present in leaves, fruits, and rinds to the extent of 1.7, 2.3, and 12.7%, respectively. (-)-Hydroxycitric acid lactone, and oxalic and citric acids are present in leaves, fruits, and rinds in minor quantities. This is the first report on the composition of organic acids from G. cowa.