Tanshinone regulated gut microbiota and TMAO to improve high-fat diet induced atherosclerosis in APOE(-/-) mice

丹参酮通过调节肠道菌群和三甲胺氧化物(TMAO)改善APOE(-/-)小鼠高脂饮食诱导的动脉粥样硬化

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Abstract

BACKGROUND: Atherosclerosis is the main pathogenic factor of cardiovascular and cerebrovascular diseases, but the current effective treatment drugs are limited. The search for an effective treatment is urgent. The objective of this research was to examine the potential role of tanshinone in the treatment of atherosclerosis through the modulation of gut microbiota and Trimethylamino-n-oxide (TMAO), which is expected to provide a new therapeutic strategy and target for clinical treatment. RESULTS: In APOE(-/-) mice disease models, tanshinone alleviates atherosclerosis. Analysis through 16 S rRNA gene sequencing revealed a significant increase in lactobacillus within the tanshinone-treated group, while a notable decrease in lachnospiraceae was observed. Conversely, in the model group, lactobacillus levels diminished, whereas proteobacteria and lachnospiraceae levels increased. The primary functional enrichment of species in both groups was closely associated with lipid metabolism, with a more pronounced enhancement of lipid metabolism noted in the tanshinone group. The concentration of TMAO in the high-fat diet treated group was significantly greater than that observed in both the control group and the tanshinone group. Furthermore, the expression of NF-κB, IL-1β,TNF-α in the tanshinone group indicated a reduction by WB or RT-qPCR analyses relative to the high-fat diet treated group. CONCLUSION: Tanshinone has the potential to ameliorate atherosclerosis induced by a high-fat diet by promoting the proliferation of lactobacillus, reducing the abundance of lachnospiraceae, enhancing lipid metabolism, and diminishing the production of TMAO.

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