Ursolic acid alleviates liver injury in diabetic mice induced by high-fat diet combined with streptozotocin via the NLRP3 signaling pathway

TL;DR

Ursolic acid helps protect the liver in diabetic mice with fatty liver disease by reducing inflammation and oxidative stress through the NLRP3 pathway.

Contribution

This study is the first to systematically investigate ursolic acid's protective effects in T2DM combined with NAFLD via the NLRP3 signaling pathway.

Findings

Ursolic acid reduced hepatic lipid deposition and serum ALT/AST levels in diabetic mice.

UA inhibited oxidative stress by increasing SOD, CAT, and GSH-Px activities in liver tissues.

Ursolic acid suppressed NLRP3 inflammasome activation, reducing IL-1β and TGF-β1 expression.

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a type of metabolic stress-induced liver injury that is closely related to type 2 diabetes mellitus (T2DM). Ursolic acid (UA), a natural pentacyclic triterpenoid compound, has anti-inflammatory, hypoglycemic and liver-protective effects. However, its role in regulating liver injury through the NLRP3 inflammasome pathway in a T2DM combined with NAFLD model has not been systematically elucidated. This study systematically evaluated the protective effect of UA on NAFLD and its molecular mechanism through in vivo (STZ + high-fat diet-induced NAFLD mouse model) and in vitro (high glucose + palmitic acid-induced LO2 cell oxidative stress model) experiments. The results showed that UA significantly improved hepatic lipid deposition, reduced serum ALT/AST levels, and effectively alleviated oxidative stress, as indicated by decreased malondialdehyde (MDA) content and increased activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in liver tissues. Further mechanism studies revealed that UA could significantly down-regulate the expression levels of pro-inflammatory factor IL-1β and pro-fibrotic factor TGF-β1 by inhibiting NLRP3 inflammasome activation, and simultaneously reduce the deposition of type IV collagen. This study demonstrated that ursolic acid (UA) has a protective effect on T2DM combined with NAFLD, and its mechanism of action may be related to the regulation of the NLRP3 signaling pathway by UA, which inhibits oxidative stress, inflammation and fibrosis.

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