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Isolated and identified chemical compounds of the hexane fraction of Piper glabratum. The chromatographic to silica gel column eluted with increasing concentrations of AcOEt in hexane, and preparative thin layer chromatography eluted in 95% hexane and 5% acetate system. The compounds were identified by Nuclear Magnetic Resonance Spectrometer (RMN) 1D and 2D. Fitol (1), stigmasterol (2) and β-sitosterol (3) in a mixture.
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In the state of Mato Grosso do Sul, Brazil, Piper glabratum leaves are used as a popular medicine for pain and inflammation. We performed a phytochemical analysis and evaluated the effects of ethanolic extract (EEPG) obtained from leaves of P. glabratum on toxicity as well as the effects of application of the hexanic fraction (HXPG) and the hydroal...
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... The genus Piper, belonging to the Piperaceae family, is popularly known as "pimenta", "pariparoba caapeba" and "falso jaborandi" [1][2][3][4]. This genus has about 2000 species geographically distributed in tropical and subtropical regions [2,3,5]. ...
... One of the species of this genus is Piper glabratum Kunth. This species, which occurs in Mato Grosso do Sul, Brazil, is popularly used in that state to treat pain and inflammation [4]. ...
... However, Branquinho et al. (2017) [3] demonstrated the anti-inflammatory effects of the essential oil from the leaves of P. glabratum evaluated in Swiss mice, confirming the ethnopharmacological indication of this plant. Later, Leitão et al. [4] showed that the ethanolic extract of the leaves of this species, particularly the hexane fraction, has antihyperalgesic and anti-inflammatory properties. ...
Piper glabratum Kunth is a plant traditionally used to treat pain and inflammation in the Mato Grosso do Sul, Brazil. Even pregnant women consume this plant. Toxicology studies of the ethanolic extract from the leaves of P. glabratum (EEPg) could establish the safety of popular use of P. glabratrum. Thus, the effects of the ethanolic extract of leaves of P. glabratum (EEPg) on the reproductive performance and embryofetal development of Swiss mice were evaluated. Pregnant female mice were treated with 100, 1000 and 2000 mg/kg throughout the gestational period by gavage (p.o). The control group received the EEPg vehicle (Tween 80–1%) in the proportion of 0.1 mL/10 g (p.o.). The results demonstrated that EEPg has low maternal toxic potential and does not alter the reproductive performance of females. However, it altered embryofetal development and caused fetal weight reduction (increasing the frequency of small-for-gestational-age fetuses) at the two highest doses. In addition, it interfered with placental weight, placental index and placental efficiency. The frequency of visceral malformations increased by 2.8 times for the lowest dose of EEPg, and skeletal malformations increased by 2.48, 1.89 and 2.11 times for doses of 100, 1000 and 2000 mg/kg of EEPg, respectively. It is noteworthy that 100% of the offspring treated with EEPg showed changes in the ossification process. Thus, it is considered that the EEPg has low maternal toxic potential; it does not alter the reproductive performance of females. However, it is teratogenic and interferes, mainly, in the ossification process, and therefore its use is contraindicated in the gestational period.
... The known compounds 7-29 were identified by comparison of their spectroscopic data with values reported in the literature as: 2′,4′-dihydroxy-3,6′-dimethoxychalchone (7) [22], 2′,4′-dihydroxy-6′-methoxychalchone (8) [26], 2′-hydroxy-3,4′,6′-trimethoxychalchone (9) [27], 2′,4′-dihydroxy-3,3′,6′-trimethoxychalcone (10) [16], 2′,3′,5-trihydroxy-4′,6′,3-trimethoxychalcone (11) [16], 2′,3′-dihydroxy-4′,6′-dimethoxychalchone (12) [28], 2′,4′,3,4-tetrahydroxy-6′-methoxychalchone (13) [29], 2′,4′,4-trihydroxy-3,6′-dimethoxychalchone (14) [30], 2′,3,4-trihydroxy-4′,6′-dimethoxychalchone (15) [31], uvangoletin (16) [32], 7,5′-dihydroxy-5,3′-dimethoxyflavanone (17) [16], pinocembrin (18) [26], alpinetin (19) ...
Diarrhea diseases caused by the intestinal protozoan parasite Giardia intestinalis are a major global health burden. Moreover, there is an ongoing need for novel anti-Giardia drugs due to drawbacks with currently available treatments. This paper reports on the isolation and structural elucidation of six new flavonoids (1–6), along with twenty-three known ones (7–29) from the Piper species. Their structures were established by spectroscopic and spectrometric techniques. Flavonoids were tested for in vitro antiprotozoal activity against Giardia intestinalis trophozoites. In addition, structure-activity relationship (SAR) and in silico ADME studies were performed to understand the pharmacophore and pharmacokinetic properties of these natural compounds. Eight flavonoids from this series exhibited remarkable activity in the micromolar range. Moreover, compound 4 was identified as having a 40-fold greater antiparasitic effect (IC50 61.0 nM) than the clinical reference drug, metronidazole (IC50 2.5 µM). This antiprotozoal potency was coupled with an excellent selectivity index (SI 233) on murine macrophages and in silico drug-likeness. SAR studies revealed that the substitution patterns, type of functional group, and flavonoid skeleton played an essential role in the activity. These findings highlight flavonoid 4 as a promising candidate to develop new drugs for the treatment of Giardia infections.
... and pain parameters in mice. [33][34][35] The negative controls received a vehicle before the inoculation of either of the inflammatory stimuli mentioned. In two of the experimental models evaluated, a group named "naive" received only isotonic saline, instead of botryosphaeran or dexamethasone, and were inoculated with sterile isotonic saline instead of the inflammatory stimuli. ...
Several biological activities of the fungal exopolysaccharide (1 → 3)(1 → 6)-β-d-glucan (botryosphaeran) have been described in the literature, but its effects on inflammation have not been evaluated. This study aimed to investigate the action of botryosphaeran on experimental mice models of carrageenan-induced acute pleurisy and acute paw edema, and complete Freund's adjuvant-induced persistent paw edema. All botryosphaeran doses tested (1.0, 2.5, 5.0, and 10.0 mg/kg birth weight [b.w.], orally administered) reduced leukocyte recruitment, nitric oxide (NO) levels, and protein extravasation in the pleural cavity. Botryosphaeran (5 mg/kg b.w.) did not diminish edema and mechanical hyperalgesia in the paw within 4 h; however, cold allodynia was alleviated within the first 2 h. In the persistent paw inflammation model, the effects of daily oral administration of botryosphaeran (5 mg/kg b.w.) were evaluated over 3 and 7 days. The fungal β-glucan significantly reduced the levels of the cytokines, tumor necrosis factor(TNF)-α, interleukin (IL)-6), and IL-10, in the paw homogenates in both protocols, while paw edema and the levels of advanced oxidation protein products (AOPP) only diminished on Day 7. No effect in mechanical hyperalgesia was observed. Oral treatment for 3 or 7 days also decreased the plasma levels of NO, AOPP, TNF-α, and IL-10. On Day 7, the number of leukocytes in the blood was also reduced by this treatment. Importantly, botryosphaeran did not induce inflammation in mice when administered alone over 7 days. This study demonstrated the anti-inflammatory and antinociceptive potential of botryosphaeran in these experimental models, making this fungal β-glucan a new possibility for complementary treating acute and chronic inflammation.
... NF-κB not only participates in the process of immunity and inflammation but also causes apoptosis by regulating apoptotic genes [92]. Furthermore, because of the interactions of ROS with NF-κB and PI3K, the antioxidant activity of these active phytochemicals via the activation of the Nrf2 pathway can relieve inflammation and apoptosis [26,32,38,50,56,62,72,75,88]. The pleiotropic activities of the active phytochemicals indicate thus the safety of SHM when it is used alone or in combination with APAP. ...
Osteoarthritis (OA), a highly prevalent chronic joint disease, involves a complex network of inflammatory mediators that not only triggers pain and cartilage degeneration but also accelerates disease progression. Traditional Chinese medicinal shenjinhuoxue mixture (SHM) shows anti-inflammatory and analgesic effects against OA with remarkable clinical efficacy. This study explored the mechanism underlying anti-OA properties of SHM and evaluated its efficacy and safety via in vivo experiments. Through network pharmacology and published literature, we identified the key active phytochemicals in SHM, including β-sitosterol, oleanolic acid, licochalcone A, quercetin, isorhamnetin, kaempferol, morusin, lupeol, and pinocembrin; the pivotal targets of which are TLR-4 and NF-κB, eliciting anti-OA activity. These phytochemicals can enter the active pockets of TLR-4 and NF-κB with docking score≤−3.86 kcal/mol, as shown in molecular docking models. By using surface plasmon resonance assay, licochalcone A and oleanolic acid were found to have good TLR-4-binding affinity. In OA rats, oral SHM at mid and high doses (8.72 g/kg and 26.2 g/kg) over 6 weeks significantly alleviated mechanical and thermal hyperalgesia (P
... The carrageenan was used in two acute in ammatory models to analyze the e cacy and potency of anti-in ammatory agents until 48 h [28] . When the carrageenan is administered into the mice paw the edema, mechanical and cold hyperalgesia can be measured [29] and when it is injected by intrapleural route the leukocyte and protein can be measured in pleural exudate [30] . In the present study the EESM showed to be effective against acute edema (2, and 4 h, Figure 1B and 1C), mechanical hyperalgesia (3 and 4 h, Figures 2A and 2B), however the cold hyperalgesia ( Figures 2C and 2D) was not inhibited in carrageenan paw in ammatory model. ...
Objectives: This study investigated the antimycobacterial, anti-inflammatory and antihyperalgesic effects of hydroalcoholic extract from leaves of S. marginata (EESM) in in vitro and in vivo models.
Methods and Results: EESM (0.98–1000 µg/ml) was evaluated in in vitro against Mycobacterium tuberculosis, M. bovis, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus epidermidis. The EESM oral administration (p.o.) (30, 100 and 300 mg/kg) and dexamethasone subcutaneous injection (s.c.) (1 mg/kg) were tested against the carrageenan-induced inflammatory paw edema and pleurisy in Swiss mice. The EESM (30 and 100 mg/kg, p.o.) and dexamethasone (1 mg/kg, s.c.) were tested against the CFA-induced paw inflammation and M. bovis (bacillus Calmette-Guerin - BCG)-induced pleurisy in C57bL6 mice. The minimum inhibitory concentration (MIC) of EESM in the presence of M. tuberculosis was 62.4 µg/ml. The values of MIC of EESM in the presence S. epidermidis, K. pneumoniae were 1000 µg/mL while EESM did not interfere against P. aeruginosa growth. EESM significantly inhibited paw edema/mechanical hyperalgesia in carrageenan induced paw inflammation and leukocytes migration/proteins exudation in carrageenan-induced pleurisy model. In the BCG-induced pleurisy model, the daily treatment for 7 days, with EESM inhibited the levels of IL-1β in blood and in pleural exudate. The EESM did not alter the mycobacterial growth in the cell culture from pleural lavage, spleen and liver samples collected from BCG-treated animals. The EESM significantly inhibited the persistent edema and mechanical hyperalgesia induced by CFA.
Conclusion: This study confirms the EESM anti-inflammatory property and showed that EESM has high potency in inducing inhibition of mycobaterial growth and low potency or no effects in relation to other microorganisms.
... Cholesterol, widely consisted in vivo, a precursor of neurosteroid biosynthesis, is an endogenous produced molecule that inhibits TRPV1 activity and plays an [53]. Increasing cholesterol content can inhibit the expression of PTGS2 and the secretion of PG [54], while decreasing cholesterol content can enhance p38 MAPK and inflammatory activity [55]. In molecular docking research, we found that cholesterol contained in GTF can stably target PTGS2, p38 MAPK, and TRPV1, which may play an analgesic role through MAPK and chemokine pathways. ...
Gu-tong formula (GTF) has achieved good curative effects in the treatment of cancer-related pain. However, its potential mechanisms have not been explored. We used network pharmacology and molecular docking to investigate the molecular mechanism and the effective compounds of the prescription. Through the analysis and research in this paper, we obtained 74 effective compounds and 125 drug-disease intersection targets to construct a network, indicating that quercetin, kaempferol, and β-sitosterol were possibly the most important compounds in GTF. The key targets of GTF for cancer-related pain were Jun proto-oncogene (JUN), mitogen-activated protein kinase 1 (MAPK1), and RELA proto-oncogene (RELA). 2204 GO entries and 148 pathways were obtained by GO and KEGG enrichment, respectively, which proved that chemokine, MAPK, and transient receptor potential (TRP) channels can be regulated by GTF. The results of molecular docking showed that stigmasterol had strong binding activity with arginine vasopressin receptor 2 (AVPR2) and C-X3-C motif chemokine ligand 1 (CX3CL1) and cholesterol was more stable with p38 MAPK, prostaglandin-endoperoxide synthase 2 (PTGS2), and transient receptor potential vanilloid-1 (TRPV1). In conclusion, the therapeutic effect of GTF on cancer-related pain is based on the comprehensive pharmacological effect of multicomponent, multitarget, and multichannel pathways. This study provides a theoretical basis for further experimental research in the future.
Sixteen compounds were isolated from the whole herbs of Peperomia tetraphylla (Forst. F.) Hooker et Arnott by phytochemical methods, including eight flavonoids (1–3, 6, 7, 14–16), three lignans (8–10), three beta sitosterols (4, 5, 11), and two phenolic acids (12, 13). Their structures were identified by the analysis of NMR and MS, as well as the comparisons to the reported data. Among them, 2″-O-xylosylisoswertisin (14) was firstly isolated from the Piperaceae family, as well as ten compounds (1–4, 7, 10–11, 13, 15–16) were isolated from P. tytraphylla for the first time. Moreover, the chemotaxonomic significance of constituents isolated from P. tytraphylla was also discussed.
This study investigated the antimycobacterial, anti-inflammatory and antihyperalgesic effects of EESM in in vitro and in vivo models. EESM (0.98–1000 µg/ml) was evaluated in in vitro against Mycobacterium tuberculosis, M. bovis, Klebsiella pneumoniae , Pseudomonas aeruginosa , Staphylococcus epidermidis. The EESM oral administration (p.o.) (30, 100 and 300 mg/kg) and dexamethasone subcutaneous injection (s.c.) (1 mg/kg) were tested against the carrageenan-induced inflammatory paw edema and pleurisy in Swiss mice. The EESM (30 and 100 mg/kg, p.o.) and dexamethasone (1 mg/kg, s.c.) were tested against the CFA-induced paw inflammation and M. bovis (bacillus Calmette-Guerin - BCG)-induced pleurisy in C57bL6 mice. The minimum inhibitory concentration (MIC) of EESM in the presence of M. tuberculosis was 62.4 µg/ml. The values of MIC of EESM in the presence S. epidermidis, K. pneumoniae were 1000 µg/mL while EESM did not interfere with against P. aeruginosa growth. EESM significantly inhibited paw edema/mechanical hyperalgesia in carrageenan induced paw inflammation and leukocytes migration/proteins exudation in carrageenan-induced pleurisy model. In the BCG-induced pleurisy model, the daily treatment for 7 days, with EESM inhibited the levels of IL-1β in blood and in pleural exudate. The EESM did not alter the mycobacterial growth in the cell culture from pleural lavage, spleen and liver samples collected from BCG-treated animals. The EESM significantly inhibited the persistent edema and mechanical hyperalgesia induced by CFA. This study confirms the EESM anti-inflammatory property and showed that EESM has high potency in inducing inhibition of mycobaterial growth and low potency or no effects in relation to other microorganisms.
