Xu Meng, Li Wanggao, Xu Yuan, Zhang Jiachao, Xue Hui, Du Juan, Hu Xiaosong
School of Food Science and Engineering, Key Laboratory of Food Nutrition and Functional Food of Hainan Province, Hainan University, Haikou, China.
Collaborative Innovation Center of One Health, Hainan University, Haikou, China.
Mol Nutr Food Res. 2025 May;69(9):e70015. doi: 10.1002/mnfr.70015. Epub 2025 Mar 23.
Arecoline, the main alkaloid in areca nut, has shown potential in modulating metabolism and gut microbiota. This study aimed to evaluate its therapeutic effects on glucose and lipid metabolism, inflammation, liver function, and potential mechanisms in a Type 2 diabetes mellitus (T2DM) mouse model.
T2DM was established in mice with a high-fat, high-sugar diet, and streptozotocin injections. Arecoline significantly reduced fasting blood glucose, enhanced glucose tolerance, and increased insulin sensitivity. Serum lipid profiles showed marked decreases in total cholesterol, triglycerides, and LDL-C levels. Systemic inflammation, as measured by serum levels of IL-1β, IL-6, and MCP-1, decreased significantly. Improvements in liver function were observed, as indicated by reductions in ALT and AST levels. Liver transcriptomic analysis revealed modulation of pathways related to glutathione metabolism, MAPK signaling, and cAMP signaling, which were involved in insulin signaling and oxidative stress response. Additionally, arecoline mitigated gut dysbiosis by restoring microbial diversity, altering gut microbiota composition, and regulating key pathways involved in NAD biosynthesis and fatty acid β-oxidation, which were critical for maintaining energy homeostasis.
Arecoline improves glucose metabolism, lipid profiles, and liver function, while modulating gut microbiota and liver metabolic pathways, showing potential as a therapeutic agent for T2DM.
槟榔碱是槟榔中的主要生物碱，已显示出调节代谢和肠道微生物群的潜力。本研究旨在评估其在2型糖尿病（T2DM）小鼠模型中对葡萄糖和脂质代谢、炎症、肝功能的治疗作用及其潜在机制。
通过高脂高糖饮食和注射链脲佐菌素在小鼠中建立T2DM模型。槟榔碱显著降低空腹血糖，增强葡萄糖耐量，并提高胰岛素敏感性。血清脂质谱显示总胆固醇、甘油三酯和低密度脂蛋白胆固醇水平显著降低。通过血清白细胞介素-1β、白细胞介素-6和单核细胞趋化蛋白-1水平测定，全身炎症显著降低。观察到肝功能有所改善，谷丙转氨酶和谷草转氨酶水平降低表明了这一点。肝脏转录组分析揭示了与谷胱甘肽代谢、丝裂原活化蛋白激酶信号传导和环磷酸腺苷信号传导相关的途径的调节，这些途径参与胰岛素信号传导和氧化应激反应。此外，槟榔碱通过恢复微生物多样性、改变肠道微生物群组成以及调节参与烟酰胺腺嘌呤二核苷酸生物合成和脂肪酸β氧化的关键途径来减轻肠道菌群失调，这些途径对于维持能量稳态至关重要。
槟榔碱改善葡萄糖代谢、脂质谱和肝功能，同时调节肠道微生物群和肝脏代谢途径，显示出作为T2DM治疗药物的潜力。
