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熟地黄通过TLR4/MyD88/NF-κB信号通路改善Sprague-Dawley大鼠的糖尿病肾病。

Rehmannia glutinosa Libosch ameliorates diabetic nephropathy in Sprague-Dawley rats by the TLR4/MyD88/NF-κB signalling pathway.

作者信息

Quan Yiheng, Jia Fanfan, Hao Hao, Nie Yuhao, Xu Dingqiao, Kang Sirui, Feng Mingke, Chen Chen

机构信息

Chinese-German Joint Laboratory for Natural Product Research/Shaanxi Province Key Laboratory of Bio-resources/QinLing-Bashan Mountains Bioresources Comprehensive Development C. I. C./Qinba State Key Laboratory of biological resources and ecological environment, Shaanxi University of Technology, Hanzhong, Shaanxi 723000, China.

Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, Shaanxi University of Chinese Medicine, Xi'an, Shaanxi 712046, China.

出版信息

Fitoterapia. 2025 Jul;184:106595. doi: 10.1016/j.fitote.2025.106595. Epub 2025 May 5.

DOI:10.1016/j.fitote.2025.106595
PMID:40334822
Abstract

Diabetic nephropathy (DN) is the most common complication of type II diabetes. Rehmannia glutinosa (RG) is a traditional Chinese herb widely used in the treatment of diabetes and its complications; however, its pharmacological mechanism of action is incomplete. This study analysed the chemical composition of RG water extract (RGW) and RG ethanol extract (RGE) using UPLC-Q-TOF/MS and evaluated the in vitro activity. Moreover, a Sprague-Dawley rat model of DN was constructed using a high-fat diet and intraperitoneal injections of streptozotocin, followed by treatment of DN rats with RGW (250 and 500 mg/kg body weight) and observation of treatment effects. Water extraction of RG was efficient and had high total flavonoid and total polysaccharide contents. We identified 60 and 62 compounds from RGW and RGE, respectively, with RGW having the highest catalpol content. The combined antioxidant capacity of RGW was stronger than that of RGE, and the in vitro inhibitory activities of α-amylase and α-glucosidase were relatively high. RGW treatment resulted in reduced food intake, water intake, and blood glucose levels in DN rats. Furthermore, RGW improved blood lipid levels, improved kidney and hepatic function and antioxidant capacity, reduced inflammatory factor levels in DN rats, and improved pathological damage to the kidneys. The mRNA and protein expression levels of toll-like receptor 4, myeloid differentiation factor 88, and nuclear factor-κB p65 were all decreased. These results indicate that RG may be a potential therapeutic agent for improving DN, and its mechanism of action has been further clarified.

摘要

糖尿病肾病(DN)是II型糖尿病最常见的并发症。熟地黄(RG)是一种广泛用于治疗糖尿病及其并发症的传统中药;然而,其药理作用机制尚不完全清楚。本研究采用超高效液相色谱-四极杆-飞行时间质谱联用仪(UPLC-Q-TOF/MS)分析了熟地黄水提取物(RGW)和熟地黄乙醇提取物(RGE)的化学成分,并评估了其体外活性。此外,通过高脂饮食和腹腔注射链脲佐菌素构建了DN大鼠模型,随后用RGW(250和500mg/kg体重)治疗DN大鼠并观察治疗效果。熟地黄水提取效率高,总黄酮和总多糖含量高。我们分别从RGW和RGE中鉴定出60种和62种化合物,其中RGW的梓醇含量最高。RGW的联合抗氧化能力强于RGE,其体外α-淀粉酶和α-葡萄糖苷酶抑制活性较高。RGW治疗可降低DN大鼠的食物摄入量、饮水量和血糖水平。此外,RGW改善了血脂水平,改善了肾脏和肝脏功能以及抗氧化能力,降低了DN大鼠的炎症因子水平,并改善了肾脏的病理损伤。Toll样受体4、髓样分化因子88和核因子-κB p65的mRNA和蛋白表达水平均降低。这些结果表明,熟地黄可能是改善DN的潜在治疗药物,其作用机制得到了进一步阐明。

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