Evaluating the inhibitory potential ofWithania somniferaon platelet aggregation and inflammation enzymes: Anin vitroandin silicostudy

Abstract

Context Withania somnifera (L.) Dunal is traditionally used for treating various ailments, but lacks scientific evaluation. Objective This study evaluates Withania somnifera (WS) for its effect on platelet activity and inflammatory enzymes. Materials and methods Aqueous and ethanolic (1:1) leaf extracts were subjected to in vitro indirect haemolytic activity using Naja naja venom, human platelet aggregation was quantified for lipid peroxidation using arachidonic acid (AA) as agonist and 5-lipoxygenase (5-LOX) levels were determined using standard spectrometric assays. Further, molecular docking was performed by the ligand fit method using molegro software package (Molegro ApS, Aarhus, Denmark). Results The study found that aqueous and ethanol extracts have very negligible effect (15%) with an IC 50 value of 13.8 mg/mL on PLA 2 from Naja naja venom. Further, extracts of WS also had very little effect (18%) with an IC 50 value of 16.6 mg/mL on malondialdehyde (MDA) formation. However, a 65% inhibition of 5-LOX with an IC 50 value of 0.92 mg/mL was observed in 1:1 ethanol extracts. The same was evident from SAR model with the active ingredient withaferin A binding predominantly on Phe 77, Tyr 98, Arg 99, Asp 164, Leu 168, Ser 382, Arg 395, Tyr 396 and Tyr 614 with an atomic contact energy value of À128.96 compared to standard phenidone (À103.61). Thus, the current study validates the application of WS for inflammatory diseases. Conclusion This study reveals the inhibitory potential of W. somnifera on inflammatory enzymes and platelet aggregation. Thus, WS can serve as a newer, safer and affordable medicine for inflammatory diseases. ARTICLE HISTORY

Covalent Ligand Discovery against Druggable Hotspots Targeted by Anti-cancer Natural Products

“…For this study, we have chosen to investigate the proteome-wide reactivity and targets of the natural product withaferin A, a steroidal lactone from the Ayurvedic plant Withania somnifera, which has been shown to possess anti-inflammatory, anti-diabetic, and anti-cancer activity (Dar et al, 2015; Lee and Choi, 2016; Lee et al, 2016; M et al, 2016). Withaferin A bears a Michael acceptor that may react with cysteine nucleophilic hotspots in protein targets (Fig.…”

An Adaptogen: Withaferin A Ameliorates in Vitro and in Vivo Pulmonary Fibrosis by Modulating the Interplay of Fibrotic, Matricelluar Proteins, and Cytokines

“…Withaferin A is a natural steroidal lactone, rejuvenating tonifier, immunomodulator and a pre-dominant bioactive constituent obtained from Withania somnifera (Ashwagandha) which exhibits an array of potential biological activities including anti-inflammatory, anti-invasive, pro-apoptotic, and anti-fibrotic effects and is remarkably safe ( Vanden Berghe et al, 2012 ; Hahm et al, 2014 ; Madhusudan et al, 2016 ; Kim et al, 2017 ). WFA exhibits potent anti-inflammatory effect by downregulating central inflammatory mediator, nuclear factor kappa light chain enhancer of activated B cells (NF-κB) and other cytokines which has been well-elucidated in vitro and in vivo studies ( Heyninck et al, 2014 ).…”

In silico Exploration of Bioactive Compounds from Withania somnifera as Inhibitor for Alpha Delta Bungarotoxin of Bungarus candidus Venom

“…In addition, it was also reported that Withania somnifera has anti-edema and anti-myotoxic activity in cobras. Anti-hyaluronidase activity was also reported to inhibit Naja naja venom and Daboia russelii [25,26,27].…”