β-Amyrin,an active compound of Bryophyllum pinnatum,alleviates alcoholic liver disease by regulating AKT1 expression and enhancing antioxidant defense.

Abstract

Bryophyllum pinnatum (L. f.) Oken (BP), a traditional hepatoprotective herb, has demonstrated therapeutic potential in managing liver disorders. However, the specific bioactive compounds of BP and its mechanisms against alcoholic liver disease (ALD) remain unclear. In this study, the bioactive compounds of BP were screened by database mining and their targets were predicted. A compound-target-disease network was constructed to identify core targets, followed by molecular docking and molecular dynamics simulation to validate the binding of β-Amyrin with AKT1. The hepatoprotective efficacy and mechanism were finally verified in ethanol-exposed HepG2 cells. A database screening process has identified four bioactive compounds (β-Amyrin, Astragalin, α-Amyrin and Bryophyllin A). Network pharmacology analyses revealed 138 common targets, primarily associated with lipid metabolism, hepatitis B and C, and the PI3K/AKT signaling pathway, and core targets included AKT1, CCND1, EGFR, HIF1A and SRC. Notably, in vitro experiments using ethanol-exposed HepG2 cells demonstrated that β-Amyrin significantly reduced transaminase (ALT, AST), total cholesterol (TC) and triglyceride (TG). Additionally, β-Amyrin enhanced antioxidant defense (SOD, CAT, GSH) and suppressed malondialdehyde (MDA) accumulation. Furthermore, β-Amyrin alleviated intracellular lipid accumulation as evidenced by Oil Red O staining. Mechanistically, β-Amyrin restored the expression of total AKT1 and its phosphorylation level (p-AKT1), which could be abolished by AKT1-specific inhibitor MK2206. This is the first study to identify β-Amyrin as the key bioactive compound of BP against ALD, and these findings provide compelling evidence for BP's potential as a therapeutic strategy for ALD.

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