Rhodiola rosea L. extract ameliorates ethanol-induced gastric ulcer in rats by alleviating oxidative stress and inflammation via NF-κB pathway inhibition

Abstract

Rhodiola rosea L. is a traditional plant that has been found to exhibit a wide range of biological activities, however, there is a lack of research regarding its potential anti-ulcer activity. In this study, the plant’s anti-ulcer activity has been evaluated in detail for the first time. R. rosea methanolic extract anti-ulcer activity was investigated against ethanol-induced ulcer rats. The results showed that administering the extract to ulcerated rats reduced gastric acidity and ulcer index while improving nitric oxide (NO) and cytoprotective prostaglandin E2 (PGE2), as well as anti-oxidants glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD). On the other hand, the extract decreased malondialdehyde (MDA) and myeloperoxidase (MPO) levels. Further, ELISA assays showed that R. rosea extract decreased pro-inflammatory cytokines IL-1β, IL-6, IL-8, and TNF-α levels in ulcerated rats. Western blot analysis confirmed the ELISA results, indicating that the extract decreased IL-6 and TNF-α protein expression and inhibited the NF-κB signalling pathway. Macroscopic and histological investigations on ulcerated rats verified the extract's anti-ulcer effects. The extract’s anti-ulcer activity was dose-dependent with the 600 mg/kg/day dose showing superior activity across all assays. GCMS analysis identified the extract’s major constituents as bicyclo [4.1.0] heptane, 7-pentyl (50.784 %) followed by 2-heptadecenal (33.2 %), and it is thought that these compounds play a crucial role in the extract’s bioactivity. Finally, in silico studies showed that the most abundant molecule, bicyclo [4.1.0] heptane, 7-pentyl, demonstrated the highest binding affinity in its interaction with H⁺, K⁺-ATPase. Taken together, the extract’s mode of action might include the inhibition of H⁺, K⁺-ATPase by bicyclo [4.1.0] heptane, 7-pentyl, followed by NF-κB pathway inhibition and subsequent regulation of cytokines and other inflammatory biomarkers. This innovative finding has the potential to lead to a successful anti-ulcer medicine, which might be followed by additional clinical trials or bioguided isolation research.