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Many Premna species have been used in traditional medicine to treat hypertension and cardiac insufficiency, and as a tonic for cardiac-related problems. Some have been reported to possess cardiovascular protective activity through several possible mechanisms, but not Premna foetida. In the present study, the methanol extract of P. foetida leaves (P...
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... resulted in lower IC50 value of the CHCl3 fraction (3.95 µ g/mL) than the MeOH fraction (5.77 µ g/mL). Most of the flavonoids isolated in this study were obtained from the CHCl3 fraction ( Figure 4). Thus it is deduced that the rich aglycon-flavonoid content present in the fraction might be responsible for such phenomenon. ...
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... A growing body of evidence supports the efficacy of flavonoid aglycones in treating thrombosis. Flavonoids isolated from Leuzea carthamoides, Premna foetida, and Ginkgo biloba have demonstrated strong antiplatelet effects [38][39][40]. Previous data indicated inhibitory effects of isolated flavonoid aglycones, including luteolin, myricetin, quercetin, eriodictyol, kaempferol, and apigenin, on platelet activation induced by various agonists [38,[41][42][43][44]. Noteworthy, the antiplatelet effect of aglycones was stronger in comparison with the effects exhibited by flavonoid glycosides [35]. ...
Flavonoid aglycones are secondary plant metabolites that exhibit a broad spectrum of pharmacological activities, including anti-inflammatory, antioxidant, anticancer, and antiplatelet effects. However, the precise molecular mechanisms underlying their inhibitory effect on platelet activation remain poorly understood. In this study, we applied flow cytometry to analyze the effects of six flavonoid aglycones (luteolin, myricetin, quercetin, eriodictyol, kaempferol, and apigenin) on platelet activation, phosphatidylserine externalization, formation of reactive oxygen species, and intracellular esterase activity. We found that these compounds significantly inhibit thrombin-induced platelet activation and decrease formation of reactive oxygen species in activated platelets. The tested aglycones did not affect platelet viability, apoptosis induction, or procoagulant platelet formation. Notably, luteolin, myricetin, quercetin, and apigenin increased thrombin-induced thromboxane synthase activity, which was analyzed by a spectrofluorimetric method. Our results obtained from Western blot analysis and liquid chromatography–tandem mass spectrometry demonstrated that the antiplatelet properties of the studied phytochemicals are mediated by activation of cyclic nucleotide-dependent signaling pathways. Specifically, we established by using Förster resonance energy transfer that the molecular mechanisms are, at least partly, associated with the inhibition of phosphodiesterases 2 and/or 5. These findings underscore the therapeutic potential of flavonoid aglycones for clinical application as antiplatelet agents.
... Moreover, most astringent phenolic compounds (caffeic acid, myricetin, coumaric acid, ellagitannins, and so on) played an important role in hepatoprotective via alleviating oxidative stress, inflammation, and hepatic apoptosis (Feng et al., 2018). Astringent phenolic compounds also protect the cardiovascular through reducing low-density lipoprotein cholesterol (LDL-C), plasma glucose, oxidation, and inflammation and maintaining the high-density lipoprotein cholesterol (HDL-C) level (Gao et al., 2019;Dianita & Jantan, 2019) (Fig. 3). It was noteworthy that salivary proteins -phenolic compounds complexes with a low degree of polymerization could be disrupted (or a part of them) by gastric digestion, releasing some biological activities of phenolic compounds or could be degraded into small phenolic molecules by the intestinal microflora which contributed to the gastrointestinal health (Huang et al., 2021;Morzel et al., 2022;Soares et al., 2015). ...
Astringency as the complex sensory of drying or shrinking can be perceived from natural foods, including abundant phenolic compounds. Up to now, there have been two possible astringency perception mechanisms of phenolic compounds. The first possible mechanism involved chemosensors and mechanosensors and took salivary binding proteins as the premise. Although piecemeal reports about chemosensors, friction mechanosensor's perception mechanisms were absent. There might be another perception way because a part of astringent phenolic compounds also triggered astringency although they could not bind with salivary proteins, however, the specific mechanism was unclear. Structures caused the differences in astringency perception mechanisms and intensities. Except for structures, other influencing factors also changed astringency perception intensity and aimed to decrease it, which probably ignored the health-promoting effects of phenolic compounds. Therefore, we roundly summarized the chemosensor's perception processes of the first mechanism. Meanwhile, we speculated that friction mechanosensor's probably activated Piezo2 ion channel on cell membranes. Phenolic compounds directly binds with oral epithelial cells, activating Piezo2 ion channel probably the another astringency perception mechanism. Except for structure, the increase of pH values, ethanol concentrations, and viscosity not only lowered astringency perception but were beneficial to improve the bioaccessibility and bioavailability of astringent phenolic compounds, which contributed to stronger antioxidant, anti-inflammatory, antiaging and anticancer effects.
... In another study, apigenin was isolated from the chloroform extract from the leaves of Premna foetida Renw. ex Blume (Lamiaceae family) [27]. It was also identified in the methanol extract (19.0 µg/mL) by the RP-HPLC method using a gradient system of H 2 O:ACN. ...
Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality worldwide. As a result, pharmaceutical and non-pharmaceutical interventions modifying risk factors for CVDs are a top priority of scientific research. Non-pharmaceutical therapeutical approaches, including herbal supplements, have gained growing interest from researchers as part of the therapeutic strategies for primary or secondary prevention of CVDs. Several experimental studies have supported the potential effects of apigenin, quercetin, and silibinin as beneficial supplements in cohorts at risk of CVDs. Accordingly, this comprehensive review focused critically on the cardioprotective effects/mechanisms of the abovementioned three bio-active compounds from natural products. For this purpose, we have included in vitro, preclinical, and clinical studies associated with atherosclero-sis and a wide variety of cardiovascular risk factors (hypertension, diabetes, dyslipidemia, obesity, cardiac injury, and metabolic syndrome). In addition, we attempted to summarize and categorize the laboratory methods for their isolation and identification from plant extracts. This review unveiled many uncertainties which are still unexplored, such as the extrapolation of experimental results to clinical practice, mainly due to the small clinical studies, heterogeneous doses, divergent constituents, and the absence of pharmacodynamic/pharmacokinetic analyses.
... Some active ingredients widely present in a variety of traditional Chinese medicines may also inhibit platelet activation by inhibiting the ADP pathway. For example, studies on apigenin have confirmed its ability to resist platelet aggregation induced by arachidonic acid (AA) and ADP [30]. Moreover, quercetin and resveratrol inhibit thrombin-induced platelet ADP and adenosine triphosphate (ATP) secretion in a concentrationdependent manner [31]. ...
Ischemic heart disease is a significant risk factor that threatens human health, and antiplatelet drugs are routinely used to treat cases in clinical settings. Chinese medicine for promoting blood circulation and removing blood stasis (PBCRBSCM) can often be combined with antiplatelet drugs to treat ischemic heart disease. PBCRBSCM can inhibit platelet adhesion, activation, and aggregation; moreover, PBCRBSCM in combination with antiplatelet drugs exerts antiplatelet effects. The mechanism is related to several factors, including the inhibition of platelet activation and aggregation, improvement of the hemodynamic status and coagulation function, and correction of metabolism and inflammation. PBCRBSCM can also regulate the absorption and metabolism of conventional antiplatelet drugs and protect the gastric mucosal epithelial cells against damage induced by conventional antiplatelet drugs. Randomized controlled trials have confirmed that PBCRBSCM preparations and the active ingredients in these preparations can reduce resistance to aspirin and clopidogrel so that the combination of these drugs can exert their antiplatelet effects. In the perioperative treatment of patients with stable angina pectoris, unstable angina pectoris, and acute coronary syndrome undergoing percutaneous coronary intervention therapy, preparations of the active ingredients of PBCRBSCM combined with antiplatelet drugs and other conventional Western medicine treatments have been proven effective. The efficacy and safety of such combinations have also been extensively verified. Considerable progress has been made to understand the antiplatelet mechanism of PBCRBSCM. However, most clinical studies had problems, such as limited sample size and inappropriate research design, which has limited the translational use of PBCRBSCM in antiplatelet therapy. A large-scale, multicenter, randomized controlled study with cardiovascular events as the endpoint is still to be conducted to provide evidence for the combined application of PBCRBSCM and antiplatelet drugs in the prevention and treatment of ischemic heart disease.
... All digested extracts from black nightshade and spinach also did not inhibit the oxidation of LDL. Flavonoids can inhibit LDL oxidation by reducing the copper-binding site on the LDL molecule, hence, preventing the ion from oxidizing the LDL; also, flavonoids can act by neutralizing radicals such as aldehydes during oxidation (Dianita & Jantan, 2019). ...
Solanum nigrum complex (black nightshade) is a wild leafy vegetable with phenolic antioxidant compounds related to the reduction of oxidative stress. Changes in phenolics and bioactivity due to cooking and gastrointestinal digestion of black nightshade were compared to spinach. Predominant compounds of black nightshade were myricetin, quercetin-3-O-robinoside, 3,4-dicaffeoylquinic acid, 3-caffeoylquinic acid, and rutin, which were improved after boiling but reduced after in vitro digestion. Phenolics were reduced after digestion of black nightshade and spinach; however, bioactivity was still retained, especially in preventing oxidative stress in Caco-2 cells. Hence, indicating their potential to reduce oxidative stress related diseases of the digestive tract.
... Quercetin and kaempferol glycosides are the main phenolic constituents of the crude extract and phenolic fraction from lentil aerial parts, so it is probable that they determine the antiplatelet properties of both preparations. Dianita and Jantan (2019) suggest that various flavonoids, especially kaempferol and quercetin, are the major constituents of Premma foetida extract responsible for anti-aggregation Fig. 5. Effects of the crude extract, the phenolic fraction and flavonoids from lentil aerial parts and commercial flavonoids on blood platelet aggregation stimulated by 10 μM ADP. Data represent mean ± SD of 6 healthy volunteers (each experiment performed in triplicate). ...
... In addition, BP and SO showed poor correlations between LDL oxidation and the FRAP assay at −0.277 and 0.0557. Flavonoids and other phenolics can protect LDL molecule from oxidation by decreasing the ability of copper to bind LDL (Dianita & Jantan, 2019 (Ma, Sun, Tian, Luo, & Zheng, 2015). Supercoiled, undamaged DNA, compared to open, circular and linear plasmid DNA, migrates more rapidly in an agarose gel, and therefore, the amount of damaged DNA can be quantified (Rahman et al., 2018). ...
Currently, the mainstay for treating endometriosis/adenomyosis consists in hormonal drugs. Aside from staying within the "therapeutic window" and cutting off the hormonal support to the ectopic endometrium, none of these treatments were developed with a pre-identified target. The current lack of innovation is humbling, especially considering that among over 34,000 PubMed-indexed publications on endometriosis or adenomyosis, ∼65% of them were published in the last two decades, many of them presumably with all the benefits of omics and molecular biology. One major reason for so many doomed research and development (R&D) projects on non-hormonal drugs is the failure to understand the natural history of the ectopic endometrium. Other reasons include, but are not limited to, the number of side-effects that these non-hormonal drug candidates presented, which the developers were either unaware of or simply had ignored when pursuing a too narrowly minded development---a common cognitive trap known as invisible gorillas. Unless we have a clear global picture with a good grasp of the natural history of ectopic endometrium, 'potholes' and 'blind alleys' in drug R&D are difficult to avoid. This review shall explore some new concepts in the progression of ectopic endometrium and explain how these new perspectives offer insights for devising better therapeutic options, explain why some drug R&D projects for endometriosis/adenomyosis have failed, provide a critical analysis of some issues encountered in everyday practice, expose knowledge gaps in need of further research, and, finally, offer possible ways to circumvent hurdles and potholes and avoid cul-de-sacs in non-hormonal drug R&D.
The SARS-CoV-2 outbreak has been one of the largest public health crises globally, while thrombotic complications have emerged as an important factor contributing to mortality. Therefore, compounds that regulate the processes involved in thrombosis could represent a dietary strategy to prevent thrombotic complications involved in COVID-19. In August 2022, various databases were consulted using the keywords "flavonoids", "antiplatelet", "anticoagulant", "fibrinolytic", and "nitric oxide". Studies conducted between 2019 and 2022 were chosen. Flavonoids, at concentrations mainly between 2 and 300 μM, are capable of regulating platelet aggregation, blood coagulation, fibrinolysis, and nitric oxide production due to their action on multiple receptors and enzymes. Most of the studies have been carried out through in vitro and in silico models, and limited studies have reported the in vivo and clinical effect of flavonoids. Currently, quercetin has been the only flavonoid evaluated clinically in patients with COVID-19 for its effect on D-dimer levels. Therefore, clinical studies in COVID-19 patients analyzing the effect on platelet, coagulant, fibrinolytic, and nitric oxide parameters are required. In addition, further high-quality studies that consider cytotoxic safety and bioavailability are required to firmly propose flavonoids as a treatment for the thrombotic complications implicated in COVID-19.
