Fimbristylis aestivalis Vahl: a potential source of cyclooxygenase-2 (COX-2) inhibitors.

Cyclooxygenase-2 (COX-2) is an inducible enzyme that accelerates the biosynthesis of PGs during inflammation and has emerged as an important therapeutic target for anti-inflammatory drugs. Natural compounds may serve as a source of inspiration for pharmaceutical chemists and a foundation for developing innovative COX-2 inhibitors with fewer side effects. Therefore, the objective of this study was to identify the potent COX-2 inhibitor and anti-inflammatory activity of the Fimbristylis aestivalis whole plant extract (FAWE). The plant extract was found dominant with rosmarinic acid followed by catechin hydrate, syringic acid, rutin hydrate, (-) epicatechin, quercetin, myricetin, and catechol. FAWE exhibited considerable dose-dependent analgesic efficacy in all analgesic test models. FAWE also showed promising anti-inflammatory potential in carrageenan-induced inflammations in mice. This result was corroborated by molecular docking, revealing that the aforesaid natural polyphenols adopt the same orientation as celecoxib in the COX-2 active site. On the other hand, molecular dynamics (MD) simulations were performed between the most abundant components (rosmarinic acid, catechin hydrate, and syringic acid) and COX-2. Based on hydrogen bonding, RMSD, RMSF, radius of gyration, PCA, and Gibbs free energy landscape analysis, the results demonstrated that these compounds are very stable in the active site of COX-2, indicating substantial COX-2 inhibitory activity.

Rutin hydrate and extract from Castanopsis tribuloides reduces pyrexia via inhibiting microsomal prostaglandin E synthase-1.

Castanopsis tribuloides belongs to the oak species (Fagaceae) and it is commonly distributed in evergreen forests of Bangladesh, India, Myanmar, Nepal, China, and Thailand. Our present study aimed at uncovering the antipyretic potential of methanol extract of C. tribuloides bark (CTB) in the mice models. Baker's yeast pyrexia model was employed to determine the antipyretic potentials of the extract. Besides, molecular docking and dynamics simulation of CTB phenolic compounds were explored to validate the experimental results and gain insight into the possible antipyretic mechanism of action that can lead to the design and discovery of novel drugs against mPGES-1. The results revealed that CTB (400 mg/kg) significantly inhibited (P < 0.001) the elevated body temperature of mice since 0.5 h, which is more prominent than the standard. At dose 200 mg/kg, the bark extract also produced significant (P < 0.05) antipyretic activity since 2 h. HPLC-DAD analysis identified and quantified nine polyphenolic compounds from the extract, including rutin hydrate, (-) epicatechin, caffeic acid, catechin hydrate, catechol, trans-ferulic acid, p-coumaric acid, vanillic acid, and rosmarinic acid. Molecular docking study suggested probable competition of these phenolic compounds with glutathione, an essential cofactor for microsomal prostaglandin E synthase-1 (mPGES-1) activity. Additionally, RMSF, RMSD, Rg, and hydrogen bonds performed during MD simulations revealed that rutin hydrate (rich in CTB) bound to the mPGES-1 active site in a stable manner and thus inactivating mPGES-1. Therefore, it can be concluded that rutin hydrate reduces pyrexia in mice via downregulating PGE2 synthesis by inhibiting mPGES-1 activity.

Zingiber roseum Rosc. rhizome: A rich source of hepatoprotective polyphenols.

Zingiber roseum is native to Bangladesh and widely used in folk medicine. This present study was designed to assess the ameliorative potential of Zingiber roseum rhizome extract in carbon tetrachloride (CCl4) induced hepatotoxicity in mice model. Seven phenolic compounds were identified and quantified by HPLC analysis in the plant extract, including quercetin, myricetin, catechin hydrate, trans-ferulic acid, trans-cinnamic acid, (-) epicatechin, and rosmarinic acid. Hepatotoxicity was induced by administrating a single intraperitoneal injection of CCl4 (10 mL/kg) on 7th day of treatment. The results revealed that plant extract at all doses (100, 200 and 400 mg/kg) significantly reduced (p < 0.05) the elevated serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) concentrations, and these effects were comparable to that of standard drug silymarin. Histopathological examination also revealed the evidence of recovery from CCL4 induced cellular damage when pretreated with Z. roseum rhizome extract. The in-vivo hepatoprotective effects were further investigated by the in-silico study of the aforementioned compounds with liver-protective enzymes such as superoxide dismutase (SOD), peroxiredoxin, and catalase. The strong binding affinities (ranging from -7.3359 to -9.111 KCal/mol) between the phenolic compounds (except trans-cinnamic acid) and oxidative stress enzymes inhibit ROS production during metabolism. The compounds were also found non-toxic in computational prediction, and a series of biological activities like antioxidant, anticarcinogen, cardio-protectant, hepato-protectant have been detected.

Antidiabetic and hepatoprotective potential of whole plant extract and isolated compounds of Aeginetia indica.

BACKGROUND: Aeginetia indica, a perennial herb from the Orobanchaceae family, generally grows as a root parasite and is widely distributed in the forests of South and South-Asian countries. The plant has valuable uses in herbal medicine against various diseases, such as diabetes, liver diseases, and arthritis. AIM OF THE STUDY: The present study was designed to investigate the antidiabetic and hepatoprotective effects of the methanol extract of the whole plant of A. indica in a mouse model followed by the isolation of bioactive compounds and their in-silico studies. METHODS: The hepatoprotective effects were evaluated in a paracetamol-induced hepatotoxicity mouse model. The antidiabetic effects were examined by an oral glucose tolerance test and in an alloxan-induced diabetes mouse model. RESULTS: The plant extract, at a dose of 400 mg/kg, caused a significant reduction (p < 0.001) in liver enzyme concentrations, including alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase, similar to the effects of standard drug silymarin. The plant extract, at 400 mg/kg, also significantly reduced (p < 0.001) the fasting blood glucose concentration by 27.33 % after 3 h, compared with a reduction of 45.31 % in response to glibenclamide. In the alloxan-induced diabetes model mice, significant reductions (p < 0.05) in elevated glucose concentrations were observed on days 10 and 20 in mice treated with plant extract and glibenclamide. Chromatographic analyses and nuclear magnetic resonance (NMR) studies identified the presence of ß-sitosterol, stigmasterol, and oleic acid in the extract. The possible mechanism underlying the antidiabetic effects was revealed by molecular docking analyses examining the binding of ß-sitosterol and stigmasterol with sirtuin 4, an NAD-dependent deacylase enzyme that downregulates leucine-induced and glutamate dehydrogenase-induced insulin secretion. The binding affinities between sirtuin 4 and ß-sitosterol, stigmasterol, and NAD were found to be -8.6 kcal/mol, -7.2 kcal/mol and -9.5 kcal/mol, respectively, indicating the probable competition between NAD and the isolated components for sirtuin 4. CONCLUSION: The present study revealed that A. indica exerted protective effects against alloxan-induced diabetes and paracetamol-induced hepatotoxicity in mice, which supports the findings regarding the use of A. indica during traditional medical practice.