College of Pharmacy, Xinjiang Medical University, Urumqi, 830054, China.
Department of Pharmacy, The Fifth Affiliated Hospital, Xinjiang Medical University, Urumqi, 830011, China.
Food Funct. 2023 Apr 24;14(8):3488-3508. doi: 10.1039/d2fo03110h.
Cognitive impairment is the main central nervous system complication of diabetes, affecting the quality of life of patients. is a homologous plant widely used as a health food and therapeutic drug. Verbascoside, a signature component of , has anti-diabetic and neuroprotective effects. However, it is quickly metabolized by the gut microbiota, and the mechanism of its neuroprotection and improvement of learning and memory remains unclear. We investigated the effectiveness and potential mechanisms of verbascoside on cognitive dysfunction in db/db mice using a 16S rRNA microbiome and serum metabolomics approach. We found that 12-week treatment with verbascoside significantly inhibited insulin resistance, reduced blood glucose and lipids, and improved cognitive deficits. In addition, verbascoside increased the gut microbiota diversity, improved intestinal dysbiosis, attenuated intestinal barrier disruption, reduced the levels of inflammatory factors, regulated the expression of the metabolites associated with cognitive function, and enhanced the central insulin sensitivity and hippocampal synaptogenesis signaling. We revealed that verbascoside induced the enrichment of , , and in the gut, suppressed the abundance of -, increased the serum levels of gamma-aminobutyric acid, L-glutamic acid, and L-lysine, and decreased taurine expression. Finally, a strong association between gut microbes, serum metabolites, and cognitive performance affected by verbascoside was observed. Our research suggests that alterations in gut microbes/metabolites are involved in the development of diabetic cognitive dysfunction, which is alleviated by verbascoside in the db/db mice through restructuring the gut microbiota composition, ameliorating diabetic metabolic disorders, and attenuating pathological brain damage.
认知障碍是糖尿病的主要中枢神经系统并发症，影响患者的生活质量。列当属植物是一种广泛用作保健品和治疗药物的同源植物。毛蕊花糖苷是列当属的标志性成分，具有抗糖尿病和神经保护作用。然而，它在肠道微生物群中很快被代谢，其神经保护作用和改善学习记忆的机制仍不清楚。我们使用 16S rRNA 微生物组和血清代谢组学方法研究了毛蕊花糖苷对 db/db 小鼠认知功能障碍的有效性及其潜在机制。我们发现，12 周的毛蕊花糖苷治疗显著抑制了胰岛素抵抗，降低了血糖和血脂，并改善了认知障碍。此外，毛蕊花糖苷增加了肠道微生物多样性，改善了肠道失调，减弱了肠道屏障破坏，降低了炎症因子水平，调节了与认知功能相关的代谢物的表达，并增强了中枢胰岛素敏感性和海马突触发生信号。我们揭示了毛蕊花糖苷诱导了肠道中、和的富集，抑制了-的丰度，增加了血清中γ-氨基丁酸、L-谷氨酸和 L-赖氨酸的水平，并降低了牛磺酸的表达。最后，观察到受毛蕊花糖苷影响的肠道微生物、血清代谢物与认知表现之间存在很强的关联。我们的研究表明，肠道微生物群/代谢物的改变参与了糖尿病认知功能障碍的发生，毛蕊花糖苷通过重塑肠道微生物群组成、改善糖尿病代谢紊乱和减弱病理性脑损伤来缓解 db/db 小鼠的糖尿病认知功能障碍。
