Indigenous wisdom of a Kwatha to treat NASH: An insight into the mechanism.

Nonalcoholic fatty liver disease (NAFLD) is the most common severe liver disease globally, progressing further into nonalcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC). Vasaguduchyadi Kwatha (VK) is an Ayurvedic formulation traditionally used to treat liver diseases and other metabolic complications. This study is an ethnopharmacological approach to unravel this indigenous remedy. We aimed to discover the probable mechanism of action of VK against NASH in this study, using network pharmacology, molecular docking, in vitro study, and preclinical investigation. Among the 55 components identified, 10 were confirmed based on mass, elution charecteristics, MS/MS analysis data, and fragmentation rules. Computational study indicated 92 targets involved in the central pathways of NASH, out of which only 15 targets and 9 VK constituents have significant docking scores. In vitro and in vivo analysis results showed that VK significantly reduces weight gain and improves insulin sensitivity, dyslipidemia, steatohepatitis and overall histological features of NASH compared to saroglitazar (SGZR). Our detailed study yielded three signalling pathways related to NASH on which VK has maximum effect, bringing up a probable alternative treatment for NASH. [Display omitted] • Imbalance in lipid metabolism, inflammation and oxidative stress foster NASH progression. • Vasaguduchyadi Kwatha, traditionally used to treat liver ailments. • This formulation improved insulin sensitivity, dyslipidaemia and steatohepatitis. • Combination of network pharmacology and systems biology ushers in new targets. [ABSTRACT FROM AUTHOR]