The active components of the Danshen-Shanzha herb-pair exert a protective effect on MASLD by synergistically promoting fatty acid oxidation via the activation of PPARα, Plin-5 and Plin-2.

ETHNOPHARMACOLOGICAL RELEVANCE: The Danshen (root of Salvia miltiorrhiza Bge.) and Shanzha (fruit of Crataegus pinnatifida Bge. var. major N.E.Br.) (SD) herb combination is a commonly used traditional Chinese medicine with potential for treating cardiovascular diseases. This study aimed to evaluate the anti-MASLD efficacy of SD and the potential mechanism of synergistic treatment of MASLD with its active ingredients.

MATERIALS AND

METHODS

The chemical composition of SD was elucidated using high-resolution mass spectrometry. A mouse model of MASLD was developed to assess therapeutic efficacy of SD. An integrated method, combining network pharmacology and multi-omics, was utilized to explore the anti-MASLD effects and mechanisms of SD. Additionally, molecular docking, Western blotting (WB), and other methodologies were employed to investigate the synergistic intervention mechanisms of SD's active ingredients in MASLD.

RESULTS

SD can substantially mitigate liver lipid accumulation and inflammation in MASLD mice. We identified 92 components in SD, of which 55 were recognized as potential active ingredients. Notably, four chemical constituents-rutin, quercetin, salvianolic acid B, and hyperoside-have been identified as the active compounds responsible for the anti-MASLD effects of SD. Rutin, hyperoside and salvianolic acid B interacts with the Plin-5, facilitating the recruitment of lipid droplets to the mitochondria. Subsequently, salvianolic acid B, rutin and hyperoside activates PPARα, thereby promoting the oxidation of fatty acids. Concurrently, rutin, hyperoside and quercetin modulates Plin-2 to mitigate excessive fatty acid oxidation, thereby reducing the risk of oxidative stress.

CONCLUSIONS

Our research preliminarily confirms the anti-MASLD effects and the mechanism of synergistic intervention by SD's active ingredients, providing valuable evidence to support the use of TCM formulae for treating MASLD.