Huangqi Guizhi Wuwu Decoction attenuates Podocyte cytoskeletal protein damage in IgA nephropathy rats by regulating AT1R/Nephrin/c-Abl pathway

Liu, Weiwei; Shi, Liqiang; Wan, Qiang; Wu, Yansheng; Huang, Di; Ou, Jiaoying; Liu, Qiuyu; Guan, Xiangdong; Yu-lin, Yang; Zhang, Xiaotian; Gao, Jiandong

doi:10.1016/j.biopha.2021.111907

Cited by 13 publications

(16 citation statements)

References 37 publications

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“…e urinary protein level was the highest, the renal function was the worst, and the pathological damage was the most severe in IgAN patients with spleen-kidney Yang-deficiency syndrome [18,21]. Huangqi Guizhi Wuwu decoction, a classic prescription, with the functions of supplementing Qi, warming Yang, removing blood stasis, and dredging collaterals, had also been proved to alleviate proteinuria and protect renal function in IgAN patients with spleen-kidney Yang-deficiency syndrome [22]. Traditional Chinese medicine believed that Yang Qi can stimulate and promote the physiological functions of human tissues and organs and promote the production and operation of blood, as well as the production, distribution, and excretion of body Evidence-Based Complementary and Alternative Medicine fluid.…”

Section: Discussionmentioning

confidence: 99%

Relationship between Traditional Chinese Medicine Syndrome Elements and Prognosis of Patients with IgA Nephropathy

Duan

Liu

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Objective. It is not clear which Traditional Chinese Medicine- (TCM-) related elements affect primary IgA nephropathy (IgAN) progression. Here, we explored the risk factors, based on TCM syndrome elements, related to the prognosis of primary IgAN patients. Methods. We analyzed patients with newly diagnosed, biopsy-proven IgAN at a single institution from December 2013 to September 2021. Basic clinical and pathological characteristics were assessed at the time of renal biopsy. The study endpoint was end-stage renal disease (ESRD: eGFR <15 ml/min per 1.73 m2, dialysis, or kidney transplantation) and/or eGFR decreased by >30% from baseline. Kaplan‒Meier survival analysis was used to explore the role of TCM syndrome elements in IgAN progression. Multivariate Cox regression analysis with adjustment for traditional risk factors was performed to explore TCM syndrome elements that may influence patient prognosis. The factors correlated with TCM syndrome elements in IgAN patients were further evaluated by logistic regression analysis. Results. During a median follow-up of 22.0 months, 53 (12.5%) of the 423 included IgAN patients reached the study endpoint. The main IgAN disease location elements were the kidney, liver, and spleen. The main IgAN disease nature elements were Yin-deficiency and Qi-deficiency, dampness, Yang-deficiency, phlegm, and Blood-deficiency. Kaplan‒Meier analysis identified three disease locations (liver, spleen, and kidney) and four disease natures (Qi-deficiency, Yang-deficiency, phlegm, and dampness) as elements associated with poor renal survival in IgAN patients. In multivariate Cox regression analysis, baseline Yang-deficiency was an independent risk predictor of poor prognosis in primary IgAN patients (hazard ratio 2.338; 95% confidence interval [CI]: 1.208–4.525; P = 0.012 ) after adjustment for traditional risk factors. Furthermore, logistic regression analysis identified being female (odds ratio [OR] 2.518; 95% CI: 1.538–4.122; P < 0.001 ), older age (OR 1.043; 95% CI: 1.022–1.065; P < 0.001 ), low hemoglobin levels (OR 0.984; 95% CI: 0.971–0.996; P = 0.013 ), and cellular/fibrocellular crescents (OR 1.706; 95% CI: 1.068–2.728; P = 0.026 ) as factors affecting Yang-deficiency in IgAN patients. Conclusions. Yang-deficiency independently predicts the risk of poor prognosis in primary IgAN patients. Being female, older age, low hemoglobin levels, and cellular/fibrocellular crescents were independently associated with Yang-deficiency in IgAN patients.

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Section: Discussionmentioning

confidence: 99%

Relationship between Traditional Chinese Medicine Syndrome Elements and Prognosis of Patients with IgA Nephropathy

Duan

Liu

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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“…The blood and urine samples were submitted to Shuguang Hospital for accurate measurement of serum urea, serum creatinine (SCr), uric acid (UA) and urinary protein concentrations using the Beckman Coulter AU5800 automated analyzer (Beckman Coulter, Inc.). The 24-h urine protein was calculated by urinary protein concentration x urinary volume [ 19 ].…”

Section: Methodsmentioning

confidence: 99%

TNF-α-mediated podocyte injury via the apoptotic death receptor pathway in a mouse model of IgA nephropathy

Wan

Zhou

et al. 2022

Renal Failure

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Background IgA nephropathy (IgAN) is the most common primary glomerular disease worldwide and it is characterized by mesangial IgA deposits. Proteinuria is a common clinical feature of IgAN, which has a critical connection to podocyte injury and has been used as a clinical prognostic factor for IgAN. Evidence has shown that TNF-α released from mesangial cells may lead to podocyte apoptosis. Methods Forty male BALB/c mouse were randomly divided into the control group and IgAN group. A mice model of IgAN was developed by oral administration of bovine serum albumin (BSA) combined with Staphylococcus Enterotoxin B (SEB) tail vein injection. Urinary protein concentrations, renal function, renal morphological, IgA deposition, apoptosis situation, and the mRNA and protein expression of nephrin, podocin, TNF-α, TNFR1, caspase-8 and caspase-3, were detected after 12 weeks. Results BSA and SEB can successfully establish an IgAN mouse model, and the main pathological changes are the IgA immune complex deposition in the mesangial area. The gene and protein expression levels of nephrin and podocin were found to be downregulated, and death receptor pathway-related indicators were upregulated, and they were involved in TNF-α-activated podocyte injury and apoptosis in IgAN mice. Conclusion TNF-α may play an important role in the pathogenesis of podocyte apoptosis in IgAN, and its effects may be mediated through the apoptotic death receptor pathway.

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“…Huaiqihuang Granule upregulates the expression of nephrin and podocin in rats with adriamycin nephropathy and maintains the integrity of podocyte synovium and cytoskeleton ( Sun et al, 2011 ). Huangqi Guizhi Wuwu Decoction upregulates the expression of the cytoskeletal proteins nephrin, podocin, and ACTN4 in podocytes through the AT1R–nephrin–c-Abl pathway and downregulates the expression levels of TNF-α, AT1R, and c-Abl to alleviate the damage of cytoskeletal proteins in podocytes ( Liu et al, 2021b ).…”

Section: Protective Effects Of Traditional Chinese Medicine and Activ...mentioning

confidence: 99%

Traditional Chinese Medicine in Treating Primary Podocytosis: From Fundamental Science to Clinical Research

Tian

Ren

et al. 2022

Front. Pharmacol.

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Podocytes form a key component of the glomerular filtration barrier. Damage to podocytes is referred to as “podocyte disease.” There are many causes of podocyte injury, including primary injury, secondary injury, and gene mutations. Primary podocytosis mostly manifests as nephrotic syndrome. At present, first-line treatment is based on glucocorticoid administration combined with immunosuppressive therapy, but some patients still progress to end-stage renal disease. In Asia, especially in China, traditional Chinese medicine (TCM) still plays an important role in the treatment of kidney diseases. This study summarizes the potential mechanism of TCM and its active components in protecting podocytes, such as repairing podocyte injury, inhibiting podocyte proliferation, reducing podocyte apoptosis and excretion, maintaining podocyte skeleton structure, and upregulating podocyte-related protein expression. At the same time, the clinical efficacy of TCM in the treatment of primary podocytosis (including idiopathic membranous nephropathy, minimal change disease, and focal segmental glomerulosclerosis) is summarized to support the development of new treatment strategies for primary podocytosis.

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Huangqi Guizhi Wuwu Decoction attenuates Podocyte cytoskeletal protein damage in IgA nephropathy rats by regulating AT1R/Nephrin/c-Abl pathway

Cited by 13 publications

References 37 publications

Relationship between Traditional Chinese Medicine Syndrome Elements and Prognosis of Patients with IgA Nephropathy

Relationship between Traditional Chinese Medicine Syndrome Elements and Prognosis of Patients with IgA Nephropathy

TNF-α-mediated podocyte injury via the apoptotic death receptor pathway in a mouse model of IgA nephropathy

Traditional Chinese Medicine in Treating Primary Podocytosis: From Fundamental Science to Clinical Research

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