Hepatoprotective effects of a Cassia fistula fruit extract and molecular insights into its phytoconstituents’ interactions with Keap1

Cassia fistula L. (Fabaceae) is a plant indigenous to Bangladesh, India, Thailand, China and other South Asian countries. It has a long history of use in traditional medicine to treat various ailments including diabetes, skin and liver disorders. This study aimed to investigate the hepatoprotective activity of the ethanolic extract of Cassia fistula (EECF) fruits using a combination of in vivo and in silico analyses. The in vivo hepatoprotective activity was evaluated using an acetaminophen-induced hepatoxicity assay with oral administration of EECF to adult female non-pregnant white Sprague-Dawley albino rats at doses of 250, 500 and 750 mg/kg b.w and subsequent determination of AST, ALT, ALP, bilirubin, TG, TC, HDLc, LDLc, total protein and serum albumin levels. Molecular docking and molecular dynamic simulations were performed using the YASARA software to predict the binding affinities and molecular interactions of selected EECF phytoconstituents towards the target protein Keap1. HPLC analysis of EECF revealed the presence of (+) catechin, (–)-epicatechin, syringic acid and trans-ferulic acid. In the in vivo experiments, EECF showed significant hepatoprotective activity against acetaminophen-induced hepatotoxicity. (+)-Catechin showed a strong binding affinity towards Keap-1, suggesting its potential role in accelerating the Nrf2-Keap1 dissociation and subsequent activation of mechanisms that protect hepatocytes from oxidative stress and promote liver regeneration. Taken altogether these findings provide scientific evidence to justify, to some extent, the traditional use of C. fistula in liver disorders.