Total Extract of Folium Rhododendri Daurici alleviate MASLD by regulating PPAR and TNF signaling pathways.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE: MASLD is the most prevalent chronic liver disease globally, with inflammation being a prominent characteristic. Folium Rhododendri Daurici is a traditional Chinese medicinal herb mainly used for acute and chronic bronchitis and pharyngitis, with broad-spectrum anti-inflammatory potential. However, the effect of Folium Rhododendri Daurici on MASLD remains unclear. AIM OF THE STUDY: This study aimed to elucidate the therapeutic effects of the total Folium Rhododendri Daurici extract (TFRE) on MASLD and to uncover the underlying molecular mechanisms involved. MATERIALS AND METHODS: UHPLC-Q-Orbitrap HRMS was employed to identify and characterize the active compounds in TFRE, while its potential therapeutic mechanisms against MASLD were predicted via network pharmacology analysis. Experimental models included OA&#xa0;+&#xa0;PA-stimulated HepG2 cells and mice with MASLD fed by a high-fat diet. RESULTS: Twelve constituents with a high probability of being present in TFRE were identified and subjected to network pharmacology analysis. Using network pharmacology, we found that PPAR and TNF pathway may be relevant for treatment of MASLD by TFRE. The ability of TFRE to mitigate lipid accumulation and inflammation was demonstrated in vitro and in vivo. Notably, in the animal model, TFRE treatment significantly reduced hepatic TG content by70.8&#xa0;% (P < 0.01), serum ALT activity by 41.9&#xa0;% (P < 0.01), and TNF-&#x3b1; concentration by 41.1&#xa0;% (P < 0.01) compared to the HFD group. It also effectively reduced malondialdehyde (MDA) levels and increased glutathione (GSH) levels in MASLD mice to alleviate hepatic oxidative stress. Additionally, Western blotting confirmed that TFRE may affect PPAR and TNF signaling pathways in HepG2 cells and MASLD mice liver tissues. CONCLUSIONS: TFRE exerts therapeutic effects against MASLD, potentially via the PPAR and TNF signaling pathways.