The bio-derived material acacetin ameliorated hyperlipidemia and intestinal barrier damage in mice by modulating gut microbiota

Abstract

The increasing incidence of hyperlipidemia has been linked to disruptions in gut flora. The bio-derived material, acacetin, is a naturally flavonoid compound extracted from various plants that has been shown to protect the liver and lowers blood lipid levels, its potential to mitigate gut barrier damage caused by a high-fat diet (HFD) has not been fully explored. This work aimed to investigate the effects of acacetin on HFD-induced intestinal barrier disruption and its potential interaction with gut microbiota regulation. Forty-eight female ICR mice were divided into three groups: control group (standard diet containing 6% daily energy from fat), HFD group (45% of daily energy from fat), and the acacetin (AC) group (HFD with acacetin 30 mg/kg body weight). The test period lasted for eight weeks. In addition to lipid metabolism parameters, serum lactate dehydrogenase (LDH) activity, diamine oxidase (DAO) activity, and lipid metabolism, we used the real-time fluorescence quantitative method to measure the expression of zonula occludens 1 (ZO-1) and occludin genes. The microorganisms were analyzed by 16 s RNA and functional gene prediction analysis. The results indicated that acacetin treatment could alter serum biochemical parameters and reduce body weight, liver weight gain, and abdominal fat accumulation. Furthermore, acacetin increased the expression levels of ZO-1 and occludin in HFD mice. In addition, acacetin altered the structure, diversity, and function of intestinal flora, characterized by the restoration of the Firmicutes/Bacteroidetes ratio. Additionally, the species abundance were significant correlation with lipid factors, DAO, and LDH. Alistipes and Acetatifactor were the prevalent genus in the AC group. Acacetin downregulated HFD-induced Facultative_anaerobic phenotypes related to Clostridium according to the BugBase analysis. The KEGG study revealed that acacetin altered the functional composition of microorganisms, as evidenced primarily by variations in the abundance of metabolic pathways involved in lipid metabolism and intestinal epithelial injury. The COG category showed acacetin increased the abundance of Cytoskeleton associated with the intestinal barrier. Overall, acacetin ameliorated HFD-induced hyperlipidemia and intestinal barrier damage in mice by modulating intestinal bacteria, exhibited a good clinical application prospect.