Astragalus Polysaccharide Reduces Blood Pressure, Renal Damage, and Dysfunction Through the TGF-β1-ILK Pathway

Zheng, Wei; Huang, Tao; Tang, Qizhen; Li, Shi; Qin, Jie; Chen, Feng

doi:10.3389/fphar.2021.706617

Cited by 15 publications

(9 citation statements)

References 38 publications

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“…It has been shown that single herbs (Liu et al, 2022;Qian et al, 2022), herbal extracts (Yu, 2020;Zheng et al, 2021;Cong et al, 2022;Ma et al, 2022), and Chinese medicine compounds (Chen et al, 2022a;Chen et al, 2022b;Wu et al, 2022;Zhao et al, 2022) have made great progress in the prevention and even treatment of renal fibrosis (Xu et al, 2021). They regulate multiple signaling pathways such as Wnt/β-catenin (Zhao et al, 2022), TGF-β1/Smad (Mao et al, 2019;Wu et al, 2022), Akt/mTOR (Lian et al, 2022), CX3CL1-RAF/MEK/ ERK (Hu et al, 2022b), mTORC1/p70S6K (Chen et al, 2019), SIRT1-NF-κB (Wang et al, 2018b), and interfere with different cytokine or inflammatory factors expression to regulate the development and progression of renal fibrosis.…”

Section: Discussionmentioning

confidence: 99%

Heidihuangwan alleviates renal fibrosis in rats with 5/6 nephrectomy by inhibiting autophagy

Tian

Pan

et al. 2022

Front. Pharmacol.

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Renal fibrosis is a common pathway for the progression of various chronic kidney diseases (CKD), and the formation and deterioration will eventually lead to end-stage renal failure, which brings a heavy medical burden to the world. HeidihuangWan (HDHW) is a herbal formulation with stable and reliable clinical efficacy in the treatment of renal fibrosis. However, the mechanism of HDHW in treating renal fibrosis is not clear. In this study, we aimed to investigate the mechanism of HDHW to improve renal fibrosis. Wistar rats were randomly divided into the normal control group, 5/6 Nephrectomy group, astragaloside IV (AS-IV) group, HDHW group, and HDHW + IGF-1R inhibitor (JB1) group. Except for the normal control group, the rat renal fibrosis model was established by 5/6 nephrectomy and intervened with drugs for 8 weeks. Blood samples were collected to evaluate renal function. Hematoxylin-Eosin (HE), Periodic Acid-Schiff (PAS), Modified Masson’s Trichrome (Masson) staining were used to evaluate the pathological renal injury, and immunohistochemistry and Western blotting were used to detect the protein expression of renal tissue. The results showed that HDHW was effective in improving renal function and reducing renal pathological damage. HDHW down-regulated the levels of fibrosis marker proteins, including α-smooth muscle actin (α-SMA), vimentin, and transforming growth factors–β(TGF-β), which in turn reduced renal fibrosis. Further studies showed that HDHW down-regulated the expression of autophagy-related proteins Beclin1 and LC3II, indicating that HDHW inhibited autophagy. In addition, we examined the activity of the class I phosphatidylinositol-3 kinase (PI3K)/serine-threonine kinase (Akt)/mTOR pathway, an important signaling pathway regulating autophagy, and the level of insulin-like growth factor 1 (IGF-1), an upstream activator of PI3K/Akt/mTOR. HDHW upregulated the expression of IGF-1 and activated the PI3K/Akt/mTOR pathway, which may be a vital pathway for its inhibition of autophagy. Application of insulin-like growth factor 1 receptor (IGF-1R) inhibitor further confirmed that the regulation of autophagy and renal fibrosis by HDHW was associated with IGF-1-mediated activation of the PI3K/Akt/mTOR pathway. In conclusion, our study showed that HDHW inhibited autophagy by upregulating IGF-1 expression, promoting the binding of IGF-1 to IGF-1R, and activating the PI3K/Akt/mTOR signaling pathway, thereby reducing renal fibrosis and protecting renal function. This study provides support for the application and further study of HDHW.

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Section: Discussionmentioning

confidence: 99%

Heidihuangwan alleviates renal fibrosis in rats with 5/6 nephrectomy by inhibiting autophagy

Tian

Pan

et al. 2022

Front. Pharmacol.

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“…Frontiers in Pharmacology frontiersin.org Furthermore, APS inhibits the expression of MMP-2 and downregulates the expression of TIMP-1, TNF-α, and AngII (Lu and Wei, 2014;Sun et al, 2021). In addition, AS-IV inhibits multiple signaling pathways, including P38MAPK (Chen and Xie, 2019), TGF-β1/1-ILK (Zheng et al, 2021), and JAK/STAT (Guo et al, 2018). It also reduces the phosphorylation of P65 protein and effectively inhibits immune inflammation, apoptosis, and degradation of the extracellular matrix (ECM) in the renal tubular epithelium.…”

Section: Renal Tubular Epithelial Cellsmentioning

confidence: 99%

Fufang shenhua tablet, astragali radix and its active component astragaloside IV: Research progress on anti-inflammatory and immunomodulatory mechanisms in the kidney

et al. 2023

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Background: Given the limited treatment options available for kidney disease, a significant number of patients turn to alternative therapies, including traditional Chinese medicine. Among these therapies, the Fufang Shenhua tablet (SHT) has garnered attention for its effectiveness in addressing the most common deficiency of Qi and Yin in chronic glomerulonephritis. Notably, the sovereign drug of SHT is Astragali Radix (AR), with the most abundant and effective component being Astragaloside IV (AS-IV). AS-IV has been shown to possess anti-inflammatory and immunomodulatory properties, and it is extensively used in treating kidney diseases. Nevertheless, the molecular mechanisms underlying its action are numerous and intricate, and a comprehensive understanding is yet to be achieved.Aim of the review: Thus, we have thoroughly examined the existing research and outlined the advancements made in investigating the anti-inflammatory and immunomodulatory mechanisms of SHT, AR and its active component AS-IV, in relation to kidney health. This serves as a dependable foundation for conducting more comprehensive investigations, evaluating efficacy, and making further improvements in the future.Materials and methods: We conducted a comprehensive literature search utilizing multiple globally recognized databases, including Web of Science, Google Scholar, PubMed, ScienceDirect, Wiley, ACS, Springer, and CNKI. The search keywords used in this study were “Fufang Shenhua tablet,” “Astragali Radix,” “Astragaloside IV,” and “Anti-inflammatory” or “Immunity.”Results: The mechanism of inflammation inhibition by SHT, AR and its active component AS-IV is mainly related to the signaling pathways such as NF-κB, TLRs, PI3K/AKT, Wnt/β-catenin, and JAK-STAT. Immunomodulation exerts not only activating, stimulating, and regulating effects on macrophages and dendritic cells, but also on immune organs, T-lymphocytes, B-lymphocytes, and a myriad of cytokines. Moreover, the SHT, AR and its active component AS-IV also demonstrate regulatory effects on renal cells, including glomerular mesangial cells, tubular epithelial cells, and podocytes.Conclusion: To summarize, SHT, AR and its active component AS-IV, exhibit notable therapeutic effects in kidney-related ailments, and their molecular mechanisms for anti-inflammatory and immunomodulatory effects have been extensively explored. However, further standard clinical trials are necessary to evaluate their safety and efficacy in the adjunctive treatment of kidney-related diseases. Moreover, in-depth studies of unverified chemical components and regulatory mechanisms in SHT are required. It is our belief that with continued research, SHT, AR and its active component AS-IV are poised to pave the way for enhancing therapeutic outcomes in kidney-related ailments.

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“…AS regulates numb/Notch/TGF-β1 pathway ( Yongping et al, 2015 ). APS inhibits TGF-β1/ILK pathway to reduce inflammation ( Zheng et al, 2021 ). ATS modulates PGC-1α and Bax/Bcl2/caspase3 pathway to inhibit apoptosis ( Li et al, 2022 ).…”

Section: Effect Of Astragalus On Fibrotic Diseasesmentioning

confidence: 99%

“…Nearly all kidney disorders have a common ultimate pathway, and growing renal fibrosis is linked to functional impairment ( Nastase et al, 2018 ). In hypertensive mice, TGF-β1/integrin-linked kinase (ILK) signaling pathway is activated, while it is downregulated after Astragalus polysaccharide treatment, as evidenced by reduced IL (interleukin)-1β, IL-6, α-SMA, collagen I, and collagen III ( Zheng et al, 2021 ). Renal tubulointerstitial fibrosis is made worse by EMT.…”

Section: Effect Of Astragalus On Fibrotic Diseasesmentioning

confidence: 99%

“…In recent years, numerous studies have demonstrated the anti-fibrotic properties of Astragalus and its active components, including pulmonary, cardiac, liver, renal and peritoneal fibrosis. Mechanisms may be related to the inhibition of epithelial-mesenchymal transition (EMT), reactive oxygen species (ROS), transforming growth factor beta 1 (TGF-β1)/Smads, apoptosis, and inflammation pathways ( Yu et al, 2016 ; Qian et al, 2018 ; Zheng et al, 2021 ; Li et al, 2022 ). In this review, we summarized Astragalus ’s antifibrotic effects and mechanisms to provide a reference for the follow-up studies.…”

Section: Introductionmentioning

confidence: 99%

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Astragalus and its formulas as a therapeutic option for fibrotic diseases: Pharmacology and mechanisms

Zhu¹,

Chai

Xiao

et al. 2022

Front. Pharmacol.

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Fibrosis is the abnormal deposition of extracellular matrix, characterized by accumulation of collagen and other extracellular matrix components, which causes organ dysfunction and even death. Despite advances in understanding fibrosis pathology and clinical management, there is no treatment for fibrosis that can prevent or reverse it, existing treatment options may lead to diarrhea, nausea, bleeding, anorexia, and liver toxicity. Thus, effective drugs are needed for fibrotic diseases. Traditional Chinese medicine has played a vital role in fibrotic diseases, accumulating evidence has demonstrated that Astragalus (Astragalus mongholicus Bunge) can attenuate multiple fibrotic diseases, which include liver fibrosis, pulmonary fibrosis, peritoneal fibrosis, renal fibrosis, cardiac fibrosis, and so on, mechanisms may be related to inhibition of epithelial-mesenchymal transition (EMT), reactive oxygen species (ROS), transforming growth factor beta 1 (TGF-β1)/Smads, apoptosis, inflammation pathways. The purpose of this review was to summarize the pharmacology and mechanisms of Astragalus in treating fibrotic diseases, the data reviewed demonstrates that Astragalus is a promising anti-fibrotic drug, its main anti-fibrotic components are Calycosin, Astragaloside IV, Astragalus polysaccharides and formononetin. We also review formulas that contain Astragalus with anti-fibrotic effects, in which Astragalus and Salvia miltiorrhiza Bunge, Astragalus and Angelica sinensis (Oliv.) Diels are the most commonly used combinations. We propose that combining active components into new formulations may be a promising way to develop new drugs for fibrosis. Besides, we expect Astragalus to be accepted as a clinically effective method of treating fibrosis.

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Astragalus Polysaccharide Reduces Blood Pressure, Renal Damage, and Dysfunction Through the TGF-β1-ILK Pathway

Cited by 15 publications

References 38 publications

Heidihuangwan alleviates renal fibrosis in rats with 5/6 nephrectomy by inhibiting autophagy

Heidihuangwan alleviates renal fibrosis in rats with 5/6 nephrectomy by inhibiting autophagy

Fufang shenhua tablet, astragali radix and its active component astragaloside IV: Research progress on anti-inflammatory and immunomodulatory mechanisms in the kidney

Astragalus and its formulas as a therapeutic option for fibrotic diseases: Pharmacology and mechanisms

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