Yi Shen An, a Chinese traditional prescription, ameliorates membranous glomerulonephritis induced by cationic bovine serum albumin in rats

Pharm Biol. 2022 Dec;60(1):163-174. doi: 10.1080/13880209.2021.2021947.

Abstract

Context: Yi Shen An (YSA) is an investigational composite of traditional Chinese medicine (Reference: 2010L000974) for the treatment of renal disease.

Objective: To investigate the protective effects of YSA against membranous glomerulonephritis (MGN).

Materials and methods: 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.

Results: YSA-1 g/kg significantly lowered urinary protein from 68.37 to 30.74 mg (p < 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 (p < 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.

Discussion and conclusions: 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.

Keywords: Nephritis; circulating immune complex; podocytes; proteinuria.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antigen-Antibody Complex / metabolism*
  • Cations
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drugs, Chinese Herbal / administration & dosage
  • Drugs, Chinese Herbal / pharmacology*
  • Glomerulonephritis, Membranous / drug therapy*
  • Immunoglobulin G / blood
  • Male
  • Prednisone / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Serum Albumin, Bovine
  • Superoxide Dismutase / metabolism

Substances

  • Antigen-Antibody Complex
  • Cations
  • Drugs, Chinese Herbal
  • Immunoglobulin G
  • Serum Albumin, Bovine
  • Superoxide Dismutase
  • Prednisone

Grants and funding

This work was financially supported by the General Program of Applied Basic Research of Yunnan Province [2019FB116], introduced talents grant of Yunnan University (to Xiao-Dong Luo), Yunnan Major Science and Technology Project [2019ZF003, 2019FY003004], the National Key Research and Development Program of China [2017YFC1704007], and the National Science-Technology Support Plan Projects of China [2013BAI11B00].