Bergenia ciliata, a Himalayan medicinal herb with Chinese ethnobotanical roots, alleviates L-arginine-induced acute pancreatitis through modulation of inflammation and oxidative stress: Insights from in Silico and in Vivo studies

Abstract

Acute pancreatitis (AP) is an inflammatory disorder of the exocrine pancreas, where oxidative stress and inflammatory cytokines play a key role in the induction and progression of the disease. The present study aims to examine the in-vivo effect of methanol extract of Bergenia ciliata rhizome (MEBCR) on L-arginine induced AP in mice and to identify novel drug candidates as alternative therapeutic options in the management of acute pancreatitis. Various markers for pancreatic function, inflammation, oxidative stress, and histological parameter were assessed. Our results indicate that mice treated with MEBCR was able to control the L-arginine-induced changes in pancreatic enzymes, oxidative stress markers (MDA, GSH and nitrite), pancreatic inflammatory markers (MPO, IL-1β, TNF-α and IL-6) as well as histological changes in the pancreatic and liver tissues. MEBCR dose dependently decreases the pro-inflammatory cytokines levels such as TNF-α, IL-6, and IL-1β. MEBCR improved the antioxidant defence by improving Nrf-2 and SOD-1 expression. When considered collectively, our findings indicate that MEBCR pretreatment inhibits AP. These outcomes may be related to the antioxidant activity of the antioxidant enzyme, which was brought about by the Nrf2/ARE signaling pathway being activated. Thus, up-regulating the expression of antioxidant enzymes and activating the endogenous antioxidant pathway Nrf2/ARE may represent viable treatment targets for MEBCR during AP. In our in silico analysis, chelidonine demonstrated favourable pharmacological properties and a notable binding affinity of −11.0 kcal/mol towards the Keap1 protein, and the chelidonine-Keap1 complex remained stable through 100 ns simulation with GROMACS without undergoing major fluctuations.