Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, Yunnan Provincial Center for Research & Development of Natural Products, School of Chemical Science and Technology, Yunnan University, Kunming, P. R. China.
New Drug R&D Department of Kunming Institute of Kidney Disease, Kunming, P. R. China.
Pharm Biol. 2022 Dec;60(1):163-174. doi: 10.1080/13880209.2021.2021947.
Yi Shen An (YSA) is an investigational composite of traditional Chinese medicine (Reference: 2010L000974) for the treatment of renal disease.
To investigate the protective effects of YSA against membranous glomerulonephritis (MGN).
Male Sprague-Dawley rats were injected with cationic bovine serum albumin (C-BSA) to create a model of MGN. Then, rats were orally treated with YSA at doses of 0.25, 0.5, 1 and 2 g/kg for 35 successive days; prednisone (5 mg/kg) was used as a positive control. At the end of the experimental period, we performed a series of tests, including 24 h urinary protein, and biochemical, immunological, antioxidative, coagulation indices, and histopathological examination.
YSA-1 g/kg significantly lowered urinary protein from 68.37 to 30.74 mg ( < 0.01). Meantime, total protein (TP) and albumin (ALB) recovered from 66.26 and 20.51 g/L to 76.08 and 35.64 g/L ( < 0.01), respectively. YSA removed the deposition of immunoglobulin G (IgG) and complement 3c (C3c), prevented inter-capillary cell hyperplasia on the glomerular basement membrane (GBM), and reduced electron-dense deposits and fusion of podocytes. In addition, serum IgG and superoxide dismutase were significantly elevated. In contrast, malondialdehyde, total cholesterol, triglyceride, circulating immune complex (CIC), and immunoglobulin M decreased in the YSA-treated group. Moreover, the blood coagulation dysfunction was adjusted.
These findings indicate YSA may exert a therapeutic effect against MGN through the inhibition of CIC formation, and the removal of IgG and C3c deposition from the GBM, thus supporting the development of further clinical trials.
益肾安(YSA)是一种中药复方制剂(参考文献:2010L000974),用于治疗肾病。
探讨益肾安对膜性肾小球肾炎(MGN)的保护作用。
雄性 Sprague-Dawley 大鼠注射阳离子牛血清白蛋白(C-BSA)建立 MGN 模型。然后,大鼠连续 35 天口服 YSA 剂量为 0.25、0.5、1 和 2g/kg;强的松(5mg/kg)作为阳性对照。实验期末,进行一系列检测,包括 24 小时尿蛋白和生化、免疫、抗氧化、凝血指标及组织病理学检查。
YSA-1g/kg 可显著降低尿蛋白从 68.37 至 30.74mg( <0.01)。同时,总蛋白(TP)和白蛋白(ALB)从 66.26 和 20.51g/L 恢复到 76.08 和 35.64g/L( <0.01)。YSA 清除 IgG 和补体 3c(C3c)在肾小球基底膜(GBM)上的沉积,阻止毛细血管内细胞在 GBM 上增生,减少电子致密沉积物和足细胞融合。此外,血清 IgG 和超氧化物歧化酶明显升高。相反,丙二醛、总胆固醇、甘油三酯、循环免疫复合物(CIC)和免疫球蛋白 M 在 YSA 治疗组中降低。此外,凝血功能障碍得到调整。
这些发现表明,益肾安可能通过抑制 CIC 形成,以及从 GBM 清除 IgG 和 C3c 沉积,从而发挥治疗 MGN 的作用,支持进一步开展临床试验。