Mahuang Lianqiao Chixiaodou Decoction and its active components inhibit alternative pathway complement activation in rat model of IgA nephropathy.
10.19540/j.cnki.cjcmm.20241107.706
- Author:
Ting SONG
1
;
Guang-Yu SHENG
1
;
Wei RUAN
1
;
Ya-Heng ZHANG
1
;
Xue-Jun YANG
1
Author Information
1. Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine Shanghai 201203, China Institute of Traditional Chinese Medicine Nephrology, Shanghai University of Traditional Chinese Medicine Shanghai 201203, China Key Laboratory of Hepatorenal Diseases of Ministry of Education,Shanghai University of Traditional Chinese Medicine Shanghai 201203, China Shanghai Key Laboratory of Traditional Chinese Clinical Medicine Shanghai 201203, China.
- Publication Type:Journal Article
- Keywords:
IgA nephropathy;
Mahuang Lianqiao Chixiaodou Decoction;
complement C3;
complement activation;
inflammatory response
- MeSH:
Animals;
Drugs, Chinese Herbal/administration & dosage*;
Glomerulonephritis, IGA/genetics*;
Rats;
Male;
Disease Models, Animal;
Rats, Wistar;
Complement Activation/drug effects*;
Kidney/immunology*;
Humans
- From:
China Journal of Chinese Materia Medica
2025;50(6):1626-1636
- CountryChina
- Language:Chinese
-
Abstract:
This study aims to investigate the mechanism of Mahuang Lianqiao Chixiaodou Decoction(MHLQ) and its main active components in treating immunoglobin A nephropathy(IgAN). The rat model of IgAN was established by a combination of measures including gavage of bovine serum albumin, subcutaneous injection of carbon tetrachloride, and tail vein injection of lipopolysaccharide. The modeled rats were randomized into model, low-, medium-, and high-dose(1.773, 3.545, and 7.090 g·kg~(-1), respectively) MHLQ, phillyrin(PHI, 0.020 g·kg~(-1)), pseudoephedrine(PSE, 0.020 g·kg~(-1)), and losartan potassium(LP, 9.003 mg·kg~(-1)) groups, and Wistar rats were used as the control. Rats were administrated with corresponding drugs by gavage, and those in the control and model groups received an equal volume of normal saline. All the groups were treated for 4 consecutive weeks. Urine, serum, liver, and kidney samples were collected from rats in each group at the end of drug administration. The 24 h urine protein and renal function were examined, and staining was performed to observe the pathological changes in the renal tissue. The immunofluorescence assay was employed to detect the expression of IgA and complement C3/C3b/C3c in the renal tissue. Electron microscopy was employed to observe the ultrastructure of the renal tissue. Enzyme-linked immunosorbent assay was performed to determine the expression of complement C3 and sublytic C5b-9 in the serum and renal tissue. Western blot was performed to determine the expression levels of hepatic and renal complement C3/C3b/C3c, C5/C5a, C5b-9, and complement factor B(CFB). Immunohistochemistry(IHC) was employed to measure the expression of complement C3 in the renal tissue. The results showed that compared with the control group, the model group had elevated levels of blood urea nitrogen and serum creatinine, proliferation of glomerular mesangial cells and extracellular matrix, and glomerular deposition of IgA immune complexes or electron-dense material. In addition, the model group showcased increased serum C3 levels and up-regulated expression of CFB, C3/C3b/C3c, C5/C5a, and C5b-9 in the renal tissue and C3/C3b/C3c and C5b-9 in the hepatic tissue. After treatment with MHLQ and its active components, all of the above indexes were reversed. In conclusion, MHLQ and its active components can improve the renal function and reduce the deposition of immune complexes and pathological damage in the renal tissue of the rat model of IgAN by inhibiting the alternative pathway complement activation.
