Mechanism research of Bu-Shen-Huo-Xue formula against renal fibrosis in rats with 5/6 nephrectomy via E-cadherin, α-SMA, and TGF-β1

Lu, Jianrao; Han, Hepeng; Hu, Jing; Zhang, Chuanfu; Chen, Jie; Chen, Xiufeng; Wang, Xinhua; Pan, Ronghua

doi:10.5414/cn109298

Cited by 11 publications

(8 citation statements)

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“…LRP is a cell surface receptor recognized by several growth factors, including CTGF (Mason, 2013; Wujak et al, 2017), that maintains the integrity of blood vessels, partially by modulating CTGF expression (Muratoglu et al, 2013). The α-SMA, an actin isoform, plays an important role in fibrogenesis (Zeniya et al, 2017) and can reflect the degree of renal fibrosis (Lu et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Time Course of the Effects of Buxin Yishen Decoction in Promoting Heart Function and Inhibiting the Progression of Renal Fibrosis in Myocardial Infarction Caused Type 2 Cardiorenal Syndrome Rats

et al. 2019

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This study aimed to investigate the therapeutic effect of traditional Chinese medicine-Buxin Yishen decoction (BXYS) on type 2 cardiorenal syndrome (CRS) caused by myocardial infarction and explore the possible mechanism BXYS works. A chronic heart failure (CHF) rat model induced by left anterior descending coronary artery ligation was used and five groups were created that included a sham group, a CHF model group, a fosinopril group, a BXYS (0.4 g/kg) group and a BXYS (0.8 g/kg) group. Heart function, renal hemodynamics, neuroendocrine factors, serum, and urine concentration of soluble form connective tissue growth factor (sCTGF), expression of CTGF mRNA, CTGF, α-smooth muscle actin (α-SMA), and low-density lipoprotein receptor-related protein (LRP) in renal tissues were evaluated after 28 days and 60 days of drug administration. Histological analysis of kidney tissues was also performed. In vitro experiments were designed to verify the results of in vivo experiments by detecting factors including CTGF, α-SMA, in NRK-52E cells. Rats with CHF showed obvious pathophysiological changes including: altered renal hemodynamic parameters; dysregulated heart function; changes to serum concentrations of angiotensin II (AngII), cyclic guanosine monophosphate (cGMP), serum creatinine (Scr), blood urea nitrogen (BUN), C-reactive protein (CRP), brain natriuretic peptide (BNP); high serum and urine sCTGF concentration; high CTGF mRNA, CTGF, α-SMA and LRP expression in renal tissues; increased extracellular matrix (ECM) deposition and fibrosis in renal tissues. Treatment of BXYS was correlated with a restoration of heart function and improvement of renal hemodynamics, lower serum and urine sCTGF, lower CTGF mRNA, CTGF, α-SMA and LRP expression in renal tissues and lower ECM deposition. In addition, in vitro experiments showed that treatment with BXYS reduced the α-SMA and LRP concentration in NRK-52E cells, which were similar in vivo experiments. In conclusion, the current study provided evidences that BXYS played a role in improving heart function and delaying the progress of renal fibrosis. Meanwhile, the CTGF-LRP pathway might be one of the therapeutic targets for myocardial infarction caused type 2 CRS which showed a positive change after BXYS treatment and is worthy of further exploration.

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Section: Discussionmentioning

confidence: 99%

Time Course of the Effects of Buxin Yishen Decoction in Promoting Heart Function and Inhibiting the Progression of Renal Fibrosis in Myocardial Infarction Caused Type 2 Cardiorenal Syndrome Rats

et al. 2019

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“…TGF- β 1 (transforming growth factor beta1) signaling pathway via the phosphorylation of Smads protein can activate the expression of airway smooth muscle cell protein α -SMA and promote airway remodeling and fibrosis. Therefore, the inhibition of TGF- β 1/Smads signaling pathway can reduce the expression of α -SMA and the deposition of extracellular matrix and alleviate airway fibrosis [8]. The traditional Chinese medicine E-Zhu is also known as Curcuma zedoaria , which is the dry rhizome of the ginger plants [9].…”

Section: Introductionmentioning

confidence: 99%

Curcumin and Curcumol Inhibit NF-κB and TGF-β₁/Smads Signaling Pathways in CSE-Treated RAW246.7 Cells

Liu

et al. 2019

Evidence-Based Complementary and Alternative Medicine

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E-Zhu (Curcuma zedoaria) is known as a classical traditional Chinese medicine and widely used in the treatment of cancers, cardiovascular disease, inflammation, and other diseases. Its main components include curcumol and curcumin, which have anti-inflammatory and antifibrosis effects. Here we established an in vitro inflammatory injury model by stimulating RAW246.7 cells with cigarette smoke extract (CSE) and detected the intervention effects of curcumin and curcumol on CSE-treated Raw246.7 macrophage cells to explore whether the two compounds inhibited the expression of inflammatory cytokines by inhibiting the NF-κB signaling pathway. We detected the antifibrosis effects of curcumin and curcumol via TGF-β1/Smads signaling pathways. The model of macrophage damage group was established by CSE stimulation. Curcumol and curcumin were administered to Raw246.7 macrophage cells. The efficacy of curcumol and curcumin was evaluated by comparing the activation of proinflammatory factors, profibrotic factors, and NF-κB and TGF-β1/Smads signaling pathway. In addition, CSE-treated group was employed to detect whether the efficacy of curcumol and curcumin was dependent on the NF-κB signaling via the pretreatment with the inhibitor of NF-κB. Our findings demonstrated that curcumol and curcumin could reduce the release of intracellular ROS from macrophages, inhibit the NF-κB signaling pathway, and downregulate the release of proinflammatory factor. Curcumol and curcumin inhibited the TGF-β1/Smads signaling pathway and downregulated the release of fibrotic factors. Curcumin showed no anti-inflammatory effect in CSE-treated cells after the inhibition of NF-κB. Curcumol and curcumin showed an anti-inflammatory effect by inhibiting the NF-κB signaling pathway.

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“…At present, it is believed that the essence of the progression of CRF is glomerulosclerosis and tubulointerstitial fibrosis under the alternating action of inflammatory and fibrogenic factors; however, still there is lacking of effective targeted prevention and treatment measures in clinic. In China, TCM has been in practice for thousands of years in the treatment of CRF and has showed number of remarkable results (Lu et al, 2018; Mei, Yang, Wang, & Wang, 2021). Buxu Xiaozheng recipe is a TCM preparation developed by famous and experienced TCM doctors, which previously reported to delay renal interstitial fibrosis progression by modulating the levels of inflammatory factors and oxidative stress in chronic kidney disease patients and rat mesangial cells (Ni, Zhong, & Cai, 2016; Zhong, Wei, & Xing, 2014).…”

Section: Discussionmentioning

confidence: 99%

Curcumenol improves renal function in 5/6 nephrectomy‐induced chronic renal failure rats via the SIRT1/NF‐κB pathway

Zhong

Cai

Wei

et al. 2022

The Anatomical Record

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The present work aimed to explore the protective effects of curcumenol and evaluate its pharmacological mechanisms in 5/6 nephrectomy‐induced chronic renal failure (CRF). Rats with CRF were administrated curcumenol and the effects on renal functions were investigated. Renal function examinations were carried out, whereas serum levels of inflammatory mediators, including NF‐κB, MCP‐1 and IL‐1β were analyzed by ELISA. The mRNA expression levels of SIRT1, p65 and IκBα were measured by qRT‐PCR, and the SIRT1 protein levels were analyzed by western blot and immunohistochemistry. Our results indicated that curcumenol significantly improved the renal functions in the CRF rats. Compared to the sham group, serum levels of NF‐κB, MCP‐1, IL‐1β, and the mRNA expression levels of p65 were significantly increased (p < 0.01), whereas the mRNA expression level of IκBα was significantly decreased (p < 0.01) and the SIRT1 levels were dramatically down‐regulated (p < 0.05) in the CRF groups. Treatment with curcumenol remarkably inhibited inflammatory responses as reflected by the reduced levels of inflammatory mediators (p < 0.01) and SIRT1 up‐regulation (p < 0.05). Our findings suggested that curcumenol could improve the renal function in 5/6 nephrectomy‐induced CRF rats, and the mechanisms might involve suppressing the associated inflammation and modulating the SIRT1 and NF‐κB signaling pathways.

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Mechanism research of Bu-Shen-Huo-Xue formula against renal fibrosis in rats with 5/6 nephrectomy via E-cadherin, α-SMA, and TGF-β1

Abstract: BSHX can effectively relieve the renal fibrosis in rats with 5/6 nephrectomy via the change of cell factor levels including enhancement of the expression of E-cadherin and depression of the levels of α-SMA and TGF-β1 expression. .

Cited by 11 publications

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Time Course of the Effects of Buxin Yishen Decoction in Promoting Heart Function and Inhibiting the Progression of Renal Fibrosis in Myocardial Infarction Caused Type 2 Cardiorenal Syndrome Rats

Time Course of the Effects of Buxin Yishen Decoction in Promoting Heart Function and Inhibiting the Progression of Renal Fibrosis in Myocardial Infarction Caused Type 2 Cardiorenal Syndrome Rats

Curcumin and Curcumol Inhibit NF-κB and TGF-β₁/Smads Signaling Pathways in CSE-Treated RAW246.7 Cells

Curcumenol improves renal function in 5/6 nephrectomy‐induced chronic renal failure rats via the SIRT1/NF‐κB pathway

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Mechanism research of Bu-Shen-Huo-Xue formula against renal fibrosis in rats with 5/6 nephrectomy via E-cadherin, α-SMA, and TGF-β1

Abstract: BSHX can effectively relieve the renal fibrosis in rats with 5/6 nephrectomy via the change of cell factor levels including enhancement of the expression of E-cadherin and depression of the levels of α-SMA and TGF-β1 expression. .

Cited by 11 publications

References 0 publications

Time Course of the Effects of Buxin Yishen Decoction in Promoting Heart Function and Inhibiting the Progression of Renal Fibrosis in Myocardial Infarction Caused Type 2 Cardiorenal Syndrome Rats

Time Course of the Effects of Buxin Yishen Decoction in Promoting Heart Function and Inhibiting the Progression of Renal Fibrosis in Myocardial Infarction Caused Type 2 Cardiorenal Syndrome Rats

Curcumin and Curcumol Inhibit NF-κB and TGF-β1/Smads Signaling Pathways in CSE-Treated RAW246.7 Cells

Curcumenol improves renal function in 5/6 nephrectomy‐induced chronic renal failure rats via the SIRT1/NF‐κB pathway

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Abstract: BSHX can effectively relieve the renal fibrosis in rats with 5/6 nephrectomy via the change of cell factor levels including enhancement of the expression of E-cadherin and depression of the levels of α-SMA and TGF-β1 expression. .

Curcumin and Curcumol Inhibit NF-κB and TGF-β₁/Smads Signaling Pathways in CSE-Treated RAW246.7 Cells