Tripterygium and its extracts for diabetic nephropathy: Efficacy and pharmacological mechanisms

Huang, Weijun; Liu, Weijing; Zheng, Huaiping; Xiao, Yao; Jia, Qi; Jiang, Hanxue; Zhu, Zebing; Xia, Chenhui; Han, Xueting; Ruixi, Sun; He, Ning; Feng, Zheng-dong; Wang, Shidong; Zhao, Jinxi

doi:10.1016/j.biopha.2019.109599

Cited by 35 publications

(28 citation statements)

References 71 publications

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“…However, its toxicity limits its clinical application. With the development of various biotechnologies, TW and its extracts have been recognized as a key alternative intervention measures for the treatment of DN in the 2014 Consensus on Prevention of Diabetic Nephropathy in China, and its efficacy has been confirmed in many experiments ( Huang et al, 2020 ). Evidence-based medicine research shows that TW can effectively reduce proteinuria, serum creatinine, and blood urea nitrogen levels, and increase the effective rate ( Hong et al, 2016 ; Wang D. et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Study of the Active Components and Molecular Mechanism of Tripterygium wilfordii in the Treatment of Diabetic Nephropathy

Wang

Yang

et al. 2021

Front. Mol. Biosci.

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We aimed to explore the active ingredients and molecular mechanism of Tripterygium wilfordii (TW) in the treatment of diabetic nephropathy (DN) through network pharmacology and molecular biology. First, the active ingredients and potential targets of TW were obtained through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and related literature materials, and Cytoscape 3.7.2 software was used to construct the active ingredient-target network diagram of TW. Second, the target set of DN was obtained through the disease database, and the potential targets of TW in the treatment of DN were screened through a Venn diagram. A protein interaction network diagram (PPI) was constructed with the help of the String platform and Cytoscape 3.7.2. Third, the ClueGO plug-in tool was used to enrich the GO biological process and the KEGG metabolic pathway. Finally, molecular docking experiments and cell pathway analyses were performed. As a result, a total of 52 active ingredients of TW were screened, and 141 predicted targets and 49 target genes related to DN were identified. The biological process of GO is mediated mainly through the regulation of oxygen metabolism, endothelial cell proliferation, acute inflammation, apoptotic signal transduction pathway, fibroblast proliferation, positive regulation of cyclase activity, adipocyte differentiation and other biological processes. KEGG enrichment analysis showed that the main pathways involved were AGE-RAGE, vascular endothelial growth factor, HIF-1, IL-17, relaxin signalling pathway, TNF, Fc epsilon RI, insulin resistance and other signaling pathways. It can be concluded that TW may treat DN by reducing inflammation, reducing antioxidative stress, regulating immunity, improving vascular disease, reducing insulin resistance, delaying renal fibrosis, repairing podocytes, and reducing cell apoptosis, among others, with multicomponent, multitarget and multisystem characteristics.

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Section: Discussionmentioning

confidence: 99%

Study of the Active Components and Molecular Mechanism of Tripterygium wilfordii in the Treatment of Diabetic Nephropathy

Wang

Yang

et al. 2021

Front. Mol. Biosci.

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“…Also, it is widely recognized that MAPKs signaling pathway can be activated by HG or diabetes, thus contributing to DN 27,28 . It has been reported in a number of studies that a variety of natural products, including tripterygium 29 , ginsenoside 30 , and oridonin 31 , could inhibit inflammatory response in DN through the downregulation of MAPKs pathway. Herein, it was demonstrated that ISL inhibited the MAPKs pathways activated in STZ-induced DN and HG-challenged NRK-52E cells (Figs.…”

Section: Discussionmentioning

confidence: 99%

Isoliquiritigenin prevents hyperglycemia-induced renal injuries by inhibiting inflammation and oxidative stress via SIRT1-dependent mechanism

Huang

Shi²,

Chen

et al. 2020

Cell Death Dis

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Diabetic nephropathy (DN) as a global health concern is closely related to inflammation and oxidation. Isoliquiritigenin (ISL), a natural flavonoid compound, has been demonstrated to inhibit inflammation in macrophages. Herein, we investigated the effect of ISL in protecting against the injury in STZ-induced type 1 DN and in high glucose-induced NRK-52E cells. In this study, it was revealed that the administration of ISL not only ameliorated renal fibrosis and apoptosis, but also induced the deterioration of renal function in diabetic mice. Mediated by MAPKs and Nrf-2 signaling pathways, respectively, upstream inflammatory response and oxidative stress were neutralized by ISL in vitro and in vivo. Moreover, as further revealed by the results of molecular docking, sirtuin 1 (SIRT1) binds to ISL directly, and the involvement of SIRT1 in ISL-mediated renoprotective effects was confirmed by studies using in vitro models of SIRT1 overexpression and knockdown. In summary, by reducing inflammation and oxidative stress, ISL has a significant pharmacological effect on the deterioration of DN. The benefits of ISL are associated with the direct binding to SIRT1, the inhibition of MAPK activation, and the induction of Nrf-2 signaling, suggesting the potential of ISL for DN treatment.

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“…It not only lowers blood pressure but also reduces the proteinuria level [ 7 ]. Traditional Chinese medicine also has provided effective treatment for DN [ 8 ]. However, the therapeutic mechanism of DN remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Yiqi Huoxue Recipe Regulates Autophagy through Degradation of Advanced Glycation End Products via mTOR/S6K1/LC3 Pathway in Diabetic Nephropathy

Chen

Dai

Liu

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Background. Yiqi Huoxue recipe can delay the progression of diabetic nephropathy, but its treatment mechanism is still unclear. We aimed to explore the effects of Yiqi Huoxue recipe on autophagy in diabetic nephropathy and its underlying mechanism. Methods. All rats were randomly divided into seven groups. The body weight, kidney weight, blood glucose, glycated hemoglobin, urine protein, urine microprotein, creatinine, urea nitrogen, triglyceride, and lipoprotein were analyzed. HE, Masson, and periodic acid-Schiff staining were used to detect the severity of pathological changes in kidneys. The level of advanced glycation end products was assessed by the ELISA. Immunofluorescence staining was performed to check the expressions of podocin and nephrin. The expression levels of mTOR/S6K1/LC3 pathway-related proteins and mRNA were detected by qRT-PCR and western blotting. Results. Yiqi Huoxue recipe significantly elevated body weight and significantly decreased kidney weight and kidney index. Yiqi Huoxue recipe significantly affected the levels of biochemical indicators in diabetic nephropathy and showed a regulatory effect on kidney damage and lipid metabolism disorders. ELISA showed that Yiqi Huoxue recipe significantly reduced the level of advanced glycation end products. The expressions of nephrin and podocin increased significantly, depending on the dosage of Yiqi Huoxue recipe. Additionally, Yiqi Huoxue recipe regulated the expression levels of p-AKT, mTOR, S6K1, and LC3. Conclusion. Yiqi Huoxue recipe regulates podocyte autophagy to promote the degradation of advanced glycation end products through mTOR/S6K1/LC3 pathway. It has a certain guiding significance for the diagnosis and treatment of diabetic nephropathy.

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Tripterygium and its extracts for diabetic nephropathy: Efficacy and pharmacological mechanisms

Cited by 35 publications

References 71 publications

Study of the Active Components and Molecular Mechanism of Tripterygium wilfordii in the Treatment of Diabetic Nephropathy

Study of the Active Components and Molecular Mechanism of Tripterygium wilfordii in the Treatment of Diabetic Nephropathy

Isoliquiritigenin prevents hyperglycemia-induced renal injuries by inhibiting inflammation and oxidative stress via SIRT1-dependent mechanism

Yiqi Huoxue Recipe Regulates Autophagy through Degradation of Advanced Glycation End Products via mTOR/S6K1/LC3 Pathway in Diabetic Nephropathy

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