Department of Traditional Chinese Medicine, Peking Union Medical College Hospital, Beijing, China.
College of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China.
Phytomedicine. 2024 Dec;135:156100. doi: 10.1016/j.phymed.2024.156100. Epub 2024 Oct 1.
Type 2 diabetes is a complex metabolic disorder characterized by insulin resistance and impaired insulin secretion, with growing evidence highlighting the critical role of the gut-microbiota-brain axis in modulating glucose and lipid metabolism.
To evaluate the effects of Jiang Tang San Hao Formula (JTSHF) on blood glucose control in type 2 diabetic mouse model and to explore its mechanism through the gut- microbiota-brain axis.
A type 2 diabetes model was established using six-week-old male C57BL6/J mice, induced by a high-fat diet combined with streptozotocin injection. The diabetic mice then randomly assigned to the model group, metformin (Glucophage) group and JTSHF group, receiving 11 weeks of treatment by gavage. Body weight and fasting blood glucose were monitored biweekly. The oral glucose tolerance test was performed during the fifth and 10th weeks of the intervention. The measurements of body composition were conducted pre- and post-treatment. After the intervention, serum insulin, lipid levels, glucagon like peptide-1 (GLP-1), peptide YY, ghrelin, and leptin were detected. The fresh feces of mice were collected before sacrifice for gut microbiota analysis and short chain fatty acids quantification. The colon tissues of mice in each group were collected to observe the morphological structure and to measure the expression levels of GPR41 and GPR43. The hypothalamus was collected to assess the expression of POMC, AgRP and NPY.
JTSHF significantly boosted sugar and lipid metabolism and contributed to weight reduction in diabetic mice (p < 0.05). At the genus level, JTSHF increased the relative abundance of Bacteroides, Prevotella, and Parabacteroides, and decreased Clostridium, Lactobacillus, and Oscillibacter in the gut microbiota. JTSHF enhanced the content of short chain fatty acids, improved the expression level of GPR43/41 in colonic tissue (p < 0.05), and increased POMC expression while decreasing AgRP and NPY expression in the hypothalamus (p < 0.05). Serum GLP-1 was increased, and ghrelin was decreased significantly after JTSHF intervention (p < 0.05).
By affecting the composition, relative abundance, and metabolites of gut microbiota, JTSHF regulates various gut brain peptides, affects the hypothalamic feeding center, improves glucose and lipid metabolism, and thus plays the anti-diabetic role. The study provides novel insights into how traditional Chinese medicine modulates the gut-brain connection to exert anti-diabetic effects, highlighting the innovative potential of JTSHF in metabolic disease management.
2 型糖尿病是一种以胰岛素抵抗和胰岛素分泌受损为特征的复杂代谢紊乱，越来越多的证据强调了肠道微生物群-脑轴在调节葡萄糖和脂质代谢中的关键作用。
评估降糖三号方（JTSHF）对 2 型糖尿病小鼠模型血糖控制的影响，并通过肠道微生物群-脑轴探讨其作用机制。
采用 6 周龄雄性 C57BL6/J 小鼠，给予高脂饮食联合链脲佐菌素注射诱导 2 型糖尿病模型。将糖尿病小鼠随机分为模型组、二甲双胍（Glucophage）组和 JTSHF 组，通过灌胃进行 11 周的治疗。每两周监测一次体重和空腹血糖。在干预的第 5 周和第 10 周进行口服葡萄糖耐量试验。在治疗前和治疗后进行身体成分测量。干预结束后，检测血清胰岛素、血脂水平、胰高血糖素样肽-1（GLP-1）、肽 YY、胃饥饿素和瘦素。收集各组小鼠的新鲜粪便进行肠道微生物分析和短链脂肪酸定量。收集各组小鼠的结肠组织，观察形态结构，检测 GPR41 和 GPR43 的表达水平。收集下丘脑，评估 POMC、AgRP 和 NPY 的表达。
JTSHF 显著改善了糖尿病小鼠的糖脂代谢，有助于减轻体重（p<0.05）。在属水平上，JTSHF 增加了肠道微生物群中拟杆菌属、普雷沃氏菌属和副拟杆菌属的相对丰度，降低了梭菌属、乳杆菌属和 Oscillibacter 的相对丰度。JTSHF 增加了短链脂肪酸的含量，改善了结肠组织中 GPR43/41 的表达水平（p<0.05），增加了下丘脑 POMC 的表达，同时降低了 AgRP 和 NPY 的表达（p<0.05）。JTSHF 干预后血清 GLP-1 增加，胃饥饿素显著降低（p<0.05）。
JTSHF 通过影响肠道微生物群的组成、相对丰度和代谢物，调节各种肠道脑肽，影响下丘脑摄食中枢，改善糖脂代谢，从而发挥抗糖尿病作用。该研究为肠道微生物群与脑连接的中医调节提供了新的见解，强调了 JTSHF 在代谢性疾病管理中的创新潜力。
