Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, PR China.
Simcere Pharmaceutical Group Limited, Nanjing 210042, PR China.
Int J Biol Macromol. 2024 Jun;270(Pt 1):132121. doi: 10.1016/j.ijbiomac.2024.132121. Epub 2024 May 6.
Diabetic encephalopathy (DE), characterized by cognitive impairment, currently lacks targeted treatment. Previous studies have shown that Sarcandra glabra extracted residue polysaccharide (SERP) exhibited hypoglycemic effects either in vitro or in streptozotocin-induced diabetes mice. However, the therapeutic effect of SERP on DE was not elucidated. This study investigated the therapeutic effect of SERP on DE and its underlying mechanism. Our results revealed that SERP regulates glucose and lipid metabolism, improves cognitive function, and exhibits diminished activity post-antibiotic intervention. Importantly, we discovered a novel mechanism by which SERP modulates the gut microbiota, specifically enriching Bacteroidales S24-7, resulting in elevated levels of butyric acid in the intestine. This regulation modulates the intestinal endocrine cell lipid metabolism level, restores damaged intestinal barriers and neural epithelial circuits, thus exhibiting cure effects. Our findings suggest that SERP could become a candidate for treating DE, potentially involving the regulation mechanism of the "microbiota-gut-brain axis". This study underscores the unique therapeutic efficacy of SERP in managing DE, offering fresh drug candidates and innovative treatment strategies for this challenging condition.
糖尿病脑病(DE)的特征是认知障碍,目前缺乏针对性的治疗方法。先前的研究表明,肿节风提取残渣多糖(SERP)在体外或链脲佐菌素诱导的糖尿病小鼠中均表现出降血糖作用。然而,SERP 对 DE 的治疗效果尚不清楚。本研究探讨了 SERP 对 DE 的治疗作用及其潜在机制。我们的结果表明,SERP 可调节糖脂代谢,改善认知功能,减少抗生素干预后的活性。重要的是,我们发现了 SERP 调节肠道微生物群的新机制,特别是使拟杆菌门 S24-7 丰富,导致肠道中丁酸水平升高。这种调节调节肠道内分泌细胞的脂代谢水平,恢复受损的肠道屏障和神经上皮回路,从而表现出治疗效果。我们的研究结果表明,SERP 可能成为治疗 DE 的候选药物,可能涉及“微生物群-肠道-大脑轴”的调节机制。本研究强调了 SERP 在治疗 DE 方面的独特治疗效果,为这种挑战性疾病提供了新的药物候选物和创新的治疗策略。