Ferulic acid from Angelica sinensis (Oliv.) Diels ameliorates lipid metabolism in alcoholic liver disease via AMPK/ACC and PI3K/AKT pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Angelica sinensis (Oliv.) Diels is a well-known traditional medicinal plant. In China, it is a common blood tonic drug that has been inherited for thousands of years. There is a consensus that Angelica sinensis (Oliv.) Diels has a protective effect against various liver diseases. However, the effects and mechanisms of Angelica sinensis (Oliv.) Diels and its active components on alcoholic liver disease (ALD) have not been clearly defined yet.

AIM OF THE STUDY: The aim of this study is to evaluate the effect and explore the mechanism of ferulic acid (FA) from Angelica sinensis (Oliv.) Diels ameliorates lipid metabolism in ALD.

METHODS: C57BL/6 mice were fed ethanol-containing liquid feeds to establish ALD model in vivo. The lipid metabolism-related indexes were detected by kits, H&E staining and oil red O staining were used to analyze liver histopathological changes and fat deposition, to evaluate the protective effect of water extraction and ethanol precipitation of Angelica sinensis radix (WEEPAS) on ethanol-induced liver injury. The active components and potential targets of Angelica sinensis (Oliv.) Diels for ALD were screened by network pharmacology and molecular docking. Ethanol was co-incubated with HepG2 cells to construct the ALD model in vitro, then the same approaches were used to explore the effect of FA for ALD in vivo and in vitro. The levels of proteins and mRNA related to AMPK/ACC and PI3K/AKT pathways were detected by Western Blotting and RT-qPCR.

RESULTS: WEEPAS could protect mice from ethanol-induced liver tissues injury by ameliorating fat deposition and inhibiting oxidative stress response. Network pharmacology and molecular docking results suggested that FA might be the main bioactive component in Angelica sinensis (Oliv.) Diels for ALD, and its mechanism might be related to the regulation of AMPK and PI3K/AKT signaling pathways. In vitro and in vivo experiments further demonstrated that FA regulated lipid metabolism via AMPK/ACC and PI3K/AKT pathways, thereby ameliorating ethanol-induced liver tissues injury and lipid metabolism disorders in HepG2 cells and mice, which were consistent with the network pharmacology results.

CONCLUSION: In summary, the results indicated that FA from Angelica sinensis (Oliv.) Diels was able to ameliorate ethanol-induced ALD. The mechanism may be related to the regulation of lipid metabolism via AMPK/ACC and PI3K/AKT pathways.