Multifunctional roles and pharmacological potential of ß-sitosterol: Emerging evidence toward clinical applications.

Currently, available therapeutic medications are both costly as well as not entirely promising in terms of potency. So, new candidates from natural resources are of research interest to find new alternative therapeutics. A well-known combination is a ß-sitosterol, a plant-derived nutrient with anticancer properties against breast, prostate, colon, lung, stomach, and leukemia. Studies have shown that ß-sitosterol interferes with multiple cell signaling pathways, including cell cycle, apoptosis, proliferation, survival, invasion, angiogenesis, metastasis, anti-inflammatory, anticancer, hepatoprotective, antioxidant, cardioprotective, and antidiabetic effects have been discovered during pharmacological screening without significant toxicity. The pharmacokinetic profile of ß-sitosterol has also been extensively investigated. However, a comprehensive review of the pharmacology, phytochemistry and analytical methods of ß-sitosterol is desired. Because ß-sitosterol is a significant component of most plant materials, humans use it for various reasons, and numerous ß-sitosterol-containing products have been commercialized. To offset the low efficacy of ß-sitosterol, designing ß-sitosterol delivery for "cancer cell-specific" therapy holds great potential. Delivery of ß-sitosterol via liposomes is a demonstration that has shown great promise. But further research has not progressed on the drug delivery of ß-sitosterol or how it can enhance ß-sitosterol mediated anti-inflammatory activity, thus making ß-sitosterol an orphan nutraceutical. Therefore, extensive research on ß-sitosterol as an anticancer nutraceutical is recommended.

In vivo analgesic effect of different extracts of Hopea odorata leaves in mice and in silico molecular docking and ADME/T property analysis of some isolated compounds from this plant.

Background The current study evaluates the analgesic effect of different extracts of Hopea odorata leaves in mice followed by molecular docking and absorption, distribution, metabolism, excretion, and toxicity (ADME/T) analysis of isolated compounds derived from the plant with the COX-1 enzyme. Methods In the present study, the dried leaves of H. odorata were subjected to extraction using methanol, ethanol, and water. In vivo analgesic activity was evaluated by using the acetic acid-induced writhing test and formalin-induced paw licking test, and in silico molecular docking and ADME/T study were performed using Schrödinger Maestro (version 11.1) and online-based tools, respectively, on eight isolated compounds. Results The results showed that the methanolic extract of leaves has highest significant dose-dependent analgesic activity at both 200 and 400 mg/kg followed by ethanolic extract of leaves. Among all the compounds, ampelopsin showed the best docking score of -7.055, ensuring strong binding affinity between the ligand and the receptor, and ADME/T analysis using Web-based tools ensures the compound has not violated Lipinski's rule of five indicating its safety consumption. Conclusions The result confirms the analgesic activity of H. odorata leaves in both in vivo and in silico assays. The data support ampelopsin to be a potent analgesic compound worthy of future clinical trials and its "drug-likeliness".

Antinociceptive Activity of Macaranga denticulata Muell. Arg. (Family: Euphorbiaceae): In Vivo and In Silico Studies.

Background: The present study was conducted to investigate the antinociceptive activity of methanol extract of Macaranga denticulata (Met.MD) in an animal model, followed by molecular docking analysis. Methods: Antinociceptive activity was determined by acetic acid-induced writhing and formalin-induced licking test in mice. Then, molecular docking study was performed to identify compounds having maximum activity against the COX-1 enzyme using Schrödinger Maestro (version 10.1) to determine docking fitness. Results: A preliminary phytochemical analysis of Met.MD revealed that it contained alkaloids, carbohydrates, phenols, flavonoids, tannins, and terpenoids. Met.MD exhibited a dose-dependent and statistically significant antinociceptive activity in the acetic acid and formalin test at the doses of 200 and 400 mg/kg. In addition, our docking study showed that macarangin had the best fitness score of -5.81 with COX-1 enzyme among six major compounds of M. denticulata. Conclusions: Results of the present study confirmed the potential antinociceptive activity of M. denticulata leaf extract in both in vivo and in silico models.