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目的 探讨黄连-乌梅药对最佳活性部位(CMNBP)中活性成分的抗糖尿病作用及机制。方法 采用大剂量链脲佐菌素(STZ)诱导糖尿病小鼠模型，随机分为Normal组，Model组，Metformin组，石油醚部位低、中、高剂量组(CMPEP-L组、CMPEP-M组、CMPEP-H组)，正丁醇部位低、中、高剂量组(CMNBP-L组、CMNBP-M组、CMNBP-H组)及水部位低、中、高剂量组(CMWP-L组、CMWP-M组、CMWP-H组)。系统评估不同部位提取物对血糖、生化指标及组织病理学的影响。基于网络药理学预测CMNBP的作用机制，并采用免疫组化技术验证胰腺组织中肿瘤坏死因子-α(TNF-α)、STAT3及CASP3的蛋白表达。结果 与Normal组相比，Model组小鼠体重显著降低，并出现高血糖、糖脂代谢紊乱及炎症因子升高(P<0.05)。CMNBP干预能有效改善这些代谢异常，减轻胰腺和肝脏组织病理损伤。网络药理学从黄连-乌梅药对中筛选出29个活性成分，发现其通过GAPDH、TNF、STAT3等核心靶点调控胰岛素信号通路与β细胞凋亡。免疫组化证实CMNBP可显著抑制胰腺组织中TNF-α、STAT3和CASP3的过度表达(P<0.05)。结论 CMNBP通过调控AGE-RAGE通路与TNF-α/STAT3/CASP3信号轴，发挥抗炎、保护β细胞及抗凋亡等多靶点治疗作用。
Abstract：Objective To determine the multi-target mechanism underlying the antidiabetic effects of bioactive components from the optimal active fraction of Coptis chinensis Franch.-Prunus mume (Sieb.) Sieb.et Zucc.herb pair (CMNBP).Methods A diabetic mouse model was established by a high-dose streptozotocin (STZ) injection.The mice were randomly assigned to the following groups:a Normal group,a Model group,a Metformin group,and low-,mid-,and high-dose groups of the petroleum ether (CMPEP),n-butanol (CMNBP),and aqueous (CMWP) fractions.We systematically evaluated the effects of these fraction extracts on the blood glucose levels,biochemical parameters,and histopathological changes.The mechanism of CMNBP was predicted with network pharmacology,and the protein expression of TNF-α,STAT3,and CASP3 in the pancreatic tissue was verified via immunohistochemical techniques.Results Compared with the Normal group,mice in the Model group showed significantly reduced body weight,glucolipid metabolic disorders,and elevated pro-inflammatory cytokines (P <0.05),and developed hyperglycemia.CMNBP intervention effectively ameliorated these metabolic abnormalities and alleviated the histopathological damage in the pancreatic and hepatic tissues.Network pharmacology identified 29 active constituents and found that the core targets such as GAPDH,TNF,and STAT3 modulated the insulin signaling pathways and β-cell apoptosis.Immunohistochemical tests confirmed that CMNBP greatly suppressed the overexpression of TNF-α,STAT3,and CASP3 in the pancreatic tissues (P<0.05).Conclusion CMNBP exerts multi-target therapeutic effects through modulation of the AGE-RAGE pathway and TNF-α/STAT3/CASP3 signaling axis,to display anti-inflammation,β-cell protection,and anti-apoptosis effect.
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基本信息:
中图分类号:R285.5
引用信息:
[1]张盼盼,彭琴,林园,等.黄连-乌梅药对抗糖尿病活性部位筛选及作用机制探索[J].中南药学,2026,24(03):54-62.
基金信息:
国家中医药管理局高水平重点学科建设项目(No.zyyzdxk-2023202)
2026-03-19
2026-03-19