Sanqi Oral Solution Mitigates Proteinuria in Rat Passive Heymann Nephritis and Blocks Podocyte Apoptosis via Nrf2/HO-1 Pathway

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.

Baicalin Alleviates Contrast-Induced Acute Kidney Injury Through ROS/NLRP3/Caspase-1/GSDMD Pathway-Mediated Proptosis in vitro

“…A large number of studies have shown that traditional Chinese medicine and its active ingredients can effectively promote the remission of kidney disease. 18 , 19 Kidney is an important target organ for iohexol-induced cytotoxicity. Iohexol-induced AKI involves multiple pathophysiological mechanisms, including renal inflammation, pyroptosis, oxidative stress, proximal renal tubular injury, and vascular injury.…”

Activation of TRPC6 by AngⅡ Induces Podocyte Injury and Participates in Proteinuria of Nephrotic Syndrome

“…As a clinical symptom of NS, proteinuria is accompanied by the onset and development of NS. Proteinuria is mainly due to the destruction of the GFB, in which podocytes play an important role ( Wang et al, 2021 ). Podocytes have free and dispersed FPs, and adjacent FP bridges to form slit diaphragm, dynamically modified by the actin cytoskeleton ( Hu et al, 2020 ).…”

“…Therefore, TRPC6 may be a breakthrough point in elucidating the pathogenesis of NS. Most importantly, it was recently reported that AngⅡ-stimulated podocytes can significantly increase the expression of TRPC6 ( Wang et al, 2021 ). Therefore, the AngⅡ-TRPC6 targeting pathway may be a new strategy for modern NS treatment.…”

The efficacy and safety of Sanqi Qushi Granule in patients with idiopathic membranous nephropathy ——protocol of a multicenter, randomized control trial (SQ-AUTUMN)

“…Our previous basic studies have also shown that Sanqi formula could effectively help rat model of membranous nephropathy via reducing proteinuria, increasing serum albumin, ameliorating renal damage which is associated with the suppression of nuclear factor-kappa B (NF-κB) [ 41 ]. Besides, our studies reveal that Sanqi Oral Liquid protect podocyte as evidenced by effectively reducing podocytes apoptosis which is associated with nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway [ 42 ]. Our another experimental studies based on rat model of renal ischemia/reperfusion (I/R) injury demonstrated that Sanqi Oral Liquid has a significant effect on the immune system and exerts renoprotective effects by regulating apoptosis and autophagy, which may be linked to extracellular signal-regulated kinase (ERK)/mammalian target of rapamycin (mTOR) pathways [ 43 ].…”