Frontiers in Pharmacology (Nov 2021)
Sanqi Oral Solution Mitigates Proteinuria in Rat Passive Heymann Nephritis and Blocks Podocyte Apoptosis via Nrf2/HO-1 Pathway
- Xiaowan Wang,
- Xiaowan Wang,
- Xiaowan Wang,
- Xiaowan Wang,
- Jinchu Liu,
- Jinchu Liu,
- Ruimin Tian,
- Ruimin Tian,
- Ruimin Tian,
- Ruimin Tian,
- Bidan Zheng,
- Chuang Li,
- Chuang Li,
- Chuang Li,
- Chuang Li,
- Lihua Huang,
- Lihua Huang,
- Lihua Huang,
- Lihua Huang,
- Zhisheng Lu,
- Zhisheng Lu,
- Jing Zhang,
- Jing Zhang,
- Wei Mao,
- Wei Mao,
- Wei Mao,
- Wei Mao,
- Bo Liu,
- Bo Liu,
- Bo Liu,
- Kun Bao,
- Kun Bao,
- Kun Bao,
- Kun Bao,
- Peng Xu,
- Peng Xu,
- Peng Xu,
- Peng Xu
Affiliations
- Xiaowan Wang
- State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
- Xiaowan Wang
- Department of Nephrology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China
- Xiaowan Wang
- Guangdong Provincial Key Laboratory of Chinese Medicine for Prevention and Treatment of Refractory Chronic Diseases, Guangzhou, China
- Xiaowan Wang
- Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, China
- Jinchu Liu
- State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
- Jinchu Liu
- Department of Nephrology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China
- Ruimin Tian
- State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
- Ruimin Tian
- Department of Nephrology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China
- Ruimin Tian
- Guangdong Provincial Key Laboratory of Chinese Medicine for Prevention and Treatment of Refractory Chronic Diseases, Guangzhou, China
- Ruimin Tian
- Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, China
- Bidan Zheng
- State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
- Chuang Li
- State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
- Chuang Li
- Department of Nephrology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China
- Chuang Li
- Guangdong Provincial Key Laboratory of Chinese Medicine for Prevention and Treatment of Refractory Chronic Diseases, Guangzhou, China
- Chuang Li
- Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, China
- Lihua Huang
- State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
- Lihua Huang
- Department of Nephrology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China
- Lihua Huang
- Guangdong Provincial Key Laboratory of Chinese Medicine for Prevention and Treatment of Refractory Chronic Diseases, Guangzhou, China
- Lihua Huang
- Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, China
- Zhisheng Lu
- State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
- Zhisheng Lu
- Department of Nephrology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China
- Jing Zhang
- State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
- Jing Zhang
- Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, China
- Wei Mao
- State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
- Wei Mao
- Department of Nephrology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China
- Wei Mao
- Guangdong Provincial Key Laboratory of Chinese Medicine for Prevention and Treatment of Refractory Chronic Diseases, Guangzhou, China
- Wei Mao
- Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, China
- Bo Liu
- State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
- Bo Liu
- Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, China
- Bo Liu
- Guangzhou Key Laboratory of Chirality Research on Active Components of Traditional Chinese Medicine, Guangzhou, China
- Kun Bao
- State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
- Kun Bao
- Department of Nephrology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China
- Kun Bao
- Guangdong Provincial Key Laboratory of Chinese Medicine for Prevention and Treatment of Refractory Chronic Diseases, Guangzhou, China
- Kun Bao
- Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, China
- Peng Xu
- State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
- Peng Xu
- Department of Nephrology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China
- Peng Xu
- Guangdong Provincial Key Laboratory of Chinese Medicine for Prevention and Treatment of Refractory Chronic Diseases, Guangzhou, China
- Peng Xu
- Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, China
- DOI
- https://doi.org/10.3389/fphar.2021.727874
- Journal volume & issue
-
Vol. 12
Abstract
Idiopathic membranous nephropathy (IMN) is the most common pathological type in adult nephrotic syndrome where podocyte apoptosis was found to mediate the development of proteinuria. Sanqi oral solution (SQ), an effective Chinese herbal preparation clinically used in treatment of IMN for decades, plays an important role in reducing proteinuria, but the underlying mechanisms have not been fully elucidated yet. The current study tested the hypothesis that SQ directly lessens proteinuria in IMN by reducing podocyte apoptosis. To investigate the effects of SQ, we established the experimental passive Heymann nephritis (PHN) rat model induced by anti-Fx1A antiserum in vivo and doxorubicin hydrochloride (ADR)-injured apoptotic podocyte model in vitro. SQ intervention dramatically reduced the level of proteinuria, together with the rat anti-rabbit IgG antibodies, complement C3, and C5b-9 deposition in glomerulus of PHN rats, accompanied by an elevation of serum albumin. Protein expression of synaptopodin, marker of podocyte injury, restored after SQ administration, whereas the electron microscopic analysis indicated that fusion of foot processes, and the pachynsis of glomerular basement membrane was markedly diminished. Further studies showed that SQ treatment could significantly inhibit podocyte apoptosis in PHN rats and ADR-injured podocytes, and protein levels of Cleaved Caspase-3 or the ratio of Bax/Bcl-2 were significantly decreased with SQ treatment in vivo or in vitro. Moreover, we found that the nuclear factor erythroid 2–related factor-2/heme oxygenase 1 (Nrf2/HO-1) pathway mediated the anti-apoptosis effective of SQ in podocyte. Thus, SQ mitigates podocyte apoptosis and proteinuria in PHN rats via the Nrf2/HO-1 pathway.
Keywords
- Sanqi oral solution
- passive Heymann nephritis
- podocyte apoptosis
- proteinuria
- Nrf2/HO-1 signaling pathway