Guangdong Engineering Research Center of Natural Products and New Drugs, Guangdong Provincial University Engineering Technology Research Center of Natural Products and Drugs, Guangdong Pharmaceutical University, Guangzhou 510006, China.
Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China, Guangdong TCM Key Laboratory for Metabolic Diseases, Guangdong Pharmaceutical University, Guangzhou 510006, China.
Int J Mol Sci. 2024 Jun 6;25(11):6280. doi: 10.3390/ijms25116280.
Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases in the world, which begins with liver lipid accumulation and is associated with metabolic syndrome. Also, the name chosen to replace NAFLD was metabolic dysfunction-associated steatotic liver disease (MASLD). We performed focused drug screening and found that Cilostazol effectively ameliorated hepatic steatosis and might offer potential for NAFLD treatment. Our aim was to investigate the therapeutic effects of Cilostazol on the glycolipid metabolism and intestinal flora in NAFLD mice and explore the specific mechanism. In this study, 7-week-old male C57BL/6J mice were fed a high-fat diet (HFD) for 8 weeks to induce NAFLD, and then treated with intragastric administration for 12 weeks. The results showed that Cilostazol inhibited liver lipid de novo synthesis by regulating the AMPK-ACC1/SCD1 pathway and inhibited liver gluconeogenesis by the AMPK-PGC1α-G6P/PEPCK pathway. Cilostazol improved the intestinal flora diversity and intestinal microbial composition in the NAFLD mice, and specifically regulated Desulfovibrio and Akkermansia. In addition, Cilostazol increased the level of short-chain fatty acids in the NAFLD mice to a level similar to that in the blank Control group. Cilostazol reduces liver lipid accumulation in NAFLD mice by improving glucose and lipid metabolism disorders and intestinal dysfunction, thereby achieving the purpose of treating NAFLD.
非酒精性脂肪性肝病（NAFLD）是世界上最常见的慢性肝病之一，它始于肝脏脂质堆积，并与代谢综合征有关。此外，取代 NAFLD 的名称是代谢功能障碍相关脂肪性肝病（MASLD）。我们进行了有针对性的药物筛选，发现西洛他唑有效改善了肝脂肪变性，可能为 NAFLD 的治疗提供了潜力。我们的目的是研究西洛他唑对 NAFLD 小鼠糖脂代谢和肠道菌群的治疗作用，并探讨其具体机制。在这项研究中，7 周龄雄性 C57BL/6J 小鼠用高脂肪饮食（HFD）喂养 8 周以诱导 NAFLD，然后用灌胃法治疗 12 周。结果表明，西洛他唑通过调节 AMPK-ACC1/SCD1 通路抑制肝脏脂质从头合成，通过 AMPK-PGC1α-G6P/PEPCK 通路抑制肝脏糖异生。西洛他唑改善了 NAFLD 小鼠的肠道菌群多样性和肠道微生物组成，并特异性调节脱硫弧菌和阿克曼氏菌。此外，西洛他唑增加了 NAFLD 小鼠短链脂肪酸的水平，使其达到与空白对照组相似的水平。西洛他唑通过改善糖脂代谢紊乱和肠道功能障碍来减少 NAFLD 小鼠肝脏脂质堆积，从而达到治疗 NAFLD 的目的。
