荆条黄酮通过调控 NF-κB 通路介导的炎症反应和 TGF-β1/Smad/CTGF 相关的纤维化改善 2 型糖尿病肾病。
Lupenone improves type 2 diabetic nephropathy by regulating NF-κB pathway-mediated inflammation and TGF-β1/Smad/CTGF-associated fibrosis.
机构信息
School of pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang 550025 Guizhou, PR China.
School of Chinese Ethnic Medicine, Guizhou Minzu University, Guiyang 550025 Guizhou, PR China.
出版信息
Phytomedicine. 2023 Sep;118:154959. doi: 10.1016/j.phymed.2023.154959. Epub 2023 Jul 11.
BACKGROUND
Type 2 diabetic nephropathy is a common diabetic complication and the main cause of death in patients with diabetes. Research has aimed to find an ideal drug with minimal side effects for treating this disease. Banana peel has been shown to be anti-diabetic, with lupenone isolated from banana peel exhibiting antidiabetic and anti-inflammatory activities; However, the effects of lupenone on type 2 diabetic nephropathy are largely unknown.
PURPOSE
This study aimed to investigate the ameliorative effect of lupenone on type 2 diabetic nephropathy, and its mechanism from both anti-inflammatory and anti-fibrotic perspectives.
METHODS
Spontaneous type 2 diabetic nephropathy db/db mouse models were given three levels of lupenone (24 or 12 or 6 mg/kg/d) via intragastric administration for six weeks, and irbesartan treatment was used for the positive control group. We explored the effects and mechanism of lupenone action using enzyme-linked immunosorbent assay, automatic biochemical analyzer, hematoxylin-eosin and Masson staining, real time-PCR, and western blotting. Concurrently, a high-sugar and high-fat diet combined with a low-dose streptozotocin-induced type 2 diabetic nephropathy rat model was used for confirmatory research.
RESULTS
Lupenone administration maintained the fasting blood glucose; reduced glycosylated hemoglobin, insulin, and 24 h proteinuria levels; and markedly regulated changes in biochemical indicators associated with kidney injury in serum and urine (including 24 h proteinuria, micro-albumin, N-acetyl-β-d-glucosaminidase, α1-micro-globulin, creatinine, urea nitrogen, uric acid, total protein, and albumin) of type 2 diabetic nephropathy mice and rats. Hematoxylin-eosin and Masson staining as well as molecular biology tests revealed that inflammation and fibrosis are the two key processes affected by lupenone treatment. Lupenone protected type 2 diabetic nephropathy kidneys by regulating the NF-κB-mediated inflammatory response and TGF-β1/Smad/CTGF pathway-associated fibrosis.
CONCLUSION
Lupenone has potential as an innovative drug for preventing and treating diabetic nephropathy. Additionally, it has great value for the utilization of banana peel resources.
背景
2 型糖尿病肾病是一种常见的糖尿病并发症，也是糖尿病患者死亡的主要原因。研究旨在寻找一种副作用最小的理想药物来治疗这种疾病。香蕉皮已被证明具有抗糖尿病作用，从香蕉皮中分离出的 lupenone 具有抗糖尿病和抗炎作用；然而，lupenone 对 2 型糖尿病肾病的影响在很大程度上尚不清楚。
目的
本研究旨在探讨 lupenone 对 2 型糖尿病肾病的改善作用及其从抗炎和抗纤维化两个方面的作用机制。
方法
采用自发性 2 型糖尿病肾病 db/db 小鼠模型，通过灌胃给予 lupenone 三个剂量（24 或 12 或 6mg/kg/d），为期 6 周，并用厄贝沙坦治疗作为阳性对照组。通过酶联免疫吸附试验、自动生化分析仪、苏木精-伊红和 Masson 染色、实时 PCR 和 Western blot 法来探讨 lupenone 的作用及机制。同时，采用高糖高脂饮食联合小剂量链脲佐菌素诱导的 2 型糖尿病肾病大鼠模型进行验证性研究。
结果
lupenone 给药可维持空腹血糖；降低糖化血红蛋白、胰岛素和 24 小时尿蛋白水平；并显著调节血清和尿液中与肾脏损伤相关的生化指标的变化（包括 24 小时尿蛋白、微量白蛋白、N-乙酰-β-D-氨基葡萄糖苷酶、α1-微球蛋白、肌酐、尿素氮、尿酸、总蛋白和白蛋白）。苏木精-伊红和 Masson 染色以及分子生物学试验表明，炎症和纤维化是 lupenone 治疗影响的两个关键过程。lupenone 通过调节 NF-κB 介导的炎症反应和 TGF-β1/Smad/CTGF 通路相关的纤维化，保护 2 型糖尿病肾病肾脏。
结论
lupenone 有望成为预防和治疗糖尿病肾病的创新药物。此外，它对于香蕉皮资源的利用具有重要价值。
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