Intervention of non-alcoholic fatty liver disease by Ling Gui Zhu Gan Granules and its volatile components through the metabolism of intestinal microbiota and short-chain fatty acids.

Objectives: Ling Gui Zhu Gan (LGZG) Granules is a marketed traditional Chinese medicine compound granule, which is formulated to be consistent with the key quality attributes of the traditional LGZG Decoction. The volatile components are important parts of its preparation process.

Methods: A high-fat diet (HFD)-induced Non-alcoholic fatty liver disease (NAFLD) mouse model was established to evaluate the therapeutic effects of LGZG and preparation of LGZG's volatile components (IC-LGZG). Gut microbiota composition, Short-chain Fatty Acids (SCFA) levels, and intestinal parameters were assessed, and its correlations were analyzed. Lipopolysaccharide-induced RAW264.7 cells tested anti-inflammatory effects.

Key findings: LGZG and IC-LGZG significantly reduced HFD-induced body weight gain, improved lipid profiles and liver function, restored gut microbiota balance, increased beneficial bacteria (Akkermansia, Bacteroides, Parabacteroides, Dubosiella, and Bifidobacterium) that produce SCFAs, thereby enhancing SCFA concentrations (acetic acid, propionic acid, and butyric acid), decreased harmful bacteria abundance, and strengthened the intestinal barrier. In vitro studies showed that LGZG, IC-LGZG, and cinnamaldehyde exerted anti-inflammatory effects.

Conclusion: LGZG and its volatile components effectively alleviate the progression of NAFLD by modulating the gut microbiota homeostasis and SCFA levels, and can exert anti-inflammatory effects.