Wang Rong, Yang Kuan, Liu Xuefeng, Zhang Yiye, Chen Yunmei, Wang Nana, Yu Lili, Liu Shaojing, Hu Yaqi, Qin Bei
Xi'an Key Laboratory for Research and Development of Innovative Multi-Target Anti-Hypertensive Drugs, Xi'an Medical University, Xi'an 710021, China.
Xi'an Innovative Anti-Hypertensive Drugs International Science and Technology Cooperation Base, Xi'an Medical University, Xi'an 710021, China.
Curr Issues Mol Biol. 2025 Jul 12;47(7):543. doi: 10.3390/cimb47070543.
The progression of type 2 diabetes mellitus (T2DM) is shaped by a multifaceted interplay among genetic, behavioral, and environmental factors, alongside gut dysbiosis. Cinnamon, being abundant in polyphenols and flavonoids, shows significant antioxidant effects. Studies have substantiated that cinnamon contributes to the management of glucose and lipid metabolism. However, the anti-diabetic efficacy of cinnamon is not completely understood. The objective of this research was to clarify the anti-diabetic mechanism associated with cinnamon extract through a combination of chemical profiling, network pharmacology, and in vivo investigations. The results indicated that 32 chemical ingredients, including quercetin, were identified through UPLC-Q-TOF-MS. Network pharmacology revealed that 471 targets related to 14 compounds were screened. The analysis of GO enrichment revealed that the primary pathways were notably enhanced in the metabolism of insulin and glucose. In vivo analyses showed that cinnamon could effectively alleviate hyperglycemia, insulin resistance, and lipid metabolism abnormalities via increased relative abundance of and at the genus level and a decreased Firmicutes/Bacteroidetes ratio at the phylum level. Moreover, cinnamon reduced the serum levels of lipopolysaccharide (LPS) and proinflammatory cytokines (IL-6 and TNF-α) and significantly increased the colon Zonula occludens-1 (ZO-1) and occludin protein levels. It was also observed that cinnamon improved the fecal SCFA levels (acetic, propionic, butyric, valeric and caproic acid), while also modifying the bile acid (BA) profile and increasing the conjugated-to-unconjugated BA ratio. The Western blotting analysis further demonstrated that cinnamon activated intestinal FXR/FGF15 and hepatic PI3K/AKT signaling pathways. In summary, the finding confirmed that cinnamon ameliorated glucose and lipid metabolism disorders by safeguarding the intestinal barrier and modulating the gut microbiota and metabolites, thereby activating intestinal FXR/FGF15 and hepatic PI3K/AKT signaling pathways.
2型糖尿病（T2DM）的进展受到遗传、行为和环境因素以及肠道菌群失调之间多方面相互作用的影响。肉桂富含多酚和黄酮类化合物，具有显著的抗氧化作用。研究证实，肉桂有助于调节葡萄糖和脂质代谢。然而，肉桂的抗糖尿病功效尚未完全明确。本研究的目的是通过化学表征、网络药理学和体内研究相结合的方法，阐明肉桂提取物的抗糖尿病机制。结果表明，通过超高效液相色谱-四极杆飞行时间质谱（UPLC-Q-TOF-MS）鉴定出32种化学成分，包括槲皮素。网络药理学显示，筛选出与14种化合物相关的471个靶点。基因本体（GO）富集分析表明主要途径在胰岛素和葡萄糖代谢中显著增强。体内分析表明，肉桂可通过增加属水平上 和 的相对丰度以及降低门水平上的厚壁菌门/拟杆菌门比值，有效缓解高血糖、胰岛素抵抗和脂质代谢异常。此外，肉桂降低了血清脂多糖（LPS）和促炎细胞因子（IL-6和TNF-α）水平，并显著提高了结肠紧密连接蛋白1（ZO-1）和闭合蛋白水平。还观察到肉桂提高了粪便短链脂肪酸水平（乙酸、丙酸、丁酸、戊酸和己酸），同时改变了胆汁酸（BA）谱并增加了结合型与非结合型BA比值。蛋白质免疫印迹分析进一步证明，肉桂激活了肠道法尼醇X受体（FXR）/成纤维细胞生长因子15（FGF15）和肝脏磷脂酰肌醇-3激酶（PI3K）/蛋白激酶B（AKT）信号通路。总之，该研究结果证实，肉桂通过保护肠道屏障、调节肠道微生物群和代谢产物，从而激活肠道FXR/FGF15和肝脏PI3K/AKT信号通路，改善了葡萄糖和脂质代谢紊乱。
