Prediction of the Potential Mechanism of Triptolide in Improving Diabetic Nephropathy by Utilizing A Network Pharmacology and Molecular Docking Approach

An, Xiaofei; Fan, Decai; Yin, Zi; Zhang, Junhan; Zhou, Yan; Tian, Ruina; Yan, Mi

doi:10.31083/j.fbl2703094

Cited by 7 publications

(5 citation statements)

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“…Zhou et al [24] showed that CRT is more effective at reducing urinary proteins and delaying DN progression than irbesartan. Through network pharmacological analysis, An et al [12] found that the main component of CRT, regalcitonin, could improve DN through antinephritis, antirenal fibrosis, antioxidant, and podocyte-protective effects, which may elucidate the mechanism by which CRT improves DN renal function and reduces proteinuria. Zhou et al [9] demonstrated by High-Performance Liquid Chromatography that each CRT (0.18 g) contains 3.04 μg of triptolide (C20H24O6) and 0.13 mg of epicatechin (C35H14O6).…”

Section: Discussionmentioning

confidence: 99%

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Colquhounia Root Tablet Promotes Autophagy and Inhibits Apoptosis in Diabetic Nephropathy by Suppressing CD36 Expression In Vivo and In Vitro

Han

Wang

et al. 2023

Journal of Diabetes Research

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Background/Aims. Accumulating clinical evidence suggests that Colquhounia root tablet (CRT) has the potential to alleviate diabetic nephropathy (DN); however, the exact mechanism of action remains unclear. Here, we report the effects of CRT administration on apoptosis and autophagy and attempt to elucidate the underlying mechanisms in vivo and in vitro. Methods. Rat models of DN were established using streptozotocin (STZ). The primary metabolic parameters were assessed. The pathological changes of the rat kidney were investigated, and RNA sequencing was performed for each group. Renal tissue apoptosis was detected using the TUNEL assay. In rats and high glucose- (Hg-) induced HK-2 cells, RT-qPCR and western blot were used to analyze the expression of related genes and proteins. Hg medium was used to establish the diabetic kidney environment. The CCK-8 assay and flow cytometry were used to assess cell viability and apoptosis, respectively. Transmission electron microscopy was used to evaluate autophagy in vitro. Results. CRT treatment significantly reduced albuminuria and renal tissue damage in DN rats. Furthermore, CRT administration inhibited apoptosis and promoted autophagy in DN rat kidney tissues. CRT downregulated CD36 expression and activated the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway in DN rat kidney tissues. CRT intervention inhibited Hg-induced apoptosis and reversed autophagy in HK-2 cells. Moreover, overexpression of CD36 suppressed the beneficial effects of CRT. Conclusions. Our study is the first to report that CRT inhibited apoptosis and promoted autophagy in vivo and in vitro, which was achieved by reducing CD36 expression and activating the AMPK pathway. Therefore, CRT may be an effective drug to treat DN.

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Section: Discussionmentioning

confidence: 99%

“…CRT has shown good results in the treatment of rheumatic system diseases such as rheumatoid arthritis and systemic lupus erythematosus [ 11 ]. Growing evidence has shown the potential of CRT for alleviating DN [ 12 ]. In particular, Ma et al [ 13 ] reported that CRT can reverse the immune-inflammatory system imbalance to treat DN.…”

Section: Introductionmentioning

confidence: 99%

Colquhounia Root Tablet Promotes Autophagy and Inhibits Apoptosis in Diabetic Nephropathy by Suppressing CD36 Expression In Vivo and In Vitro

Han

Wang

et al. 2023

Journal of Diabetes Research

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“…Finally, AS targets were obtained by combining the disease targets from the three databases and removing duplicates. The targets for VO and AS were imported into Venny 2.1.0 to prepare Venn diagrams, and VO targets correlated with AS pathology were obtained ( An et al., 2022 ).…”

Section: Methodsmentioning

confidence: 99%

Key ingredients in Verbena officinalis and determination of their anti-atherosclerotic effect using a computer-aided drug design approach

Chen

Gan

et al. 2023

Front. Plant Sci.

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Lipid metabolism disorders may considerably contribute to the formation and development of atherosclerosis (AS). Traditional Chinese medicine has received considerable attention in recent years owing to its ability to treat lipid metabolism disorders using multiple components and targets. Verbena officinalis (VO), a Chinese herbal medicine, exhibits anti-inflammatory, analgesic, immunomodulatory, and neuroprotective effects. Evidence suggests that VO regulates lipid metabolism; however, its role in AS remains unclear. In the present study, an integrated network pharmacology approach, molecular docking, and molecular dynamics simulation (MDS) were applied to examine the mechanism of VO against AS. Analysis revealed 209 potential targets for the 11 main ingredients in VO. Further, 2698 mechanistic targets for AS were identified, including 147 intersection targets between VO and AS. Quercetin, luteolin, and kaempferol were considered key ingredients for the treatment of AS based on a potential ingredient target–AS target network. GO analysis revealed that biological processes were primarily associated with responses to xenobiotic stimuli, cellular responses to lipids, and responses to hormones. Cell components were predominantly focused on the membrane microdomain, membrane raft, and caveola nucleus. Molecular functions were mainly focused on DNA-binding transcription factor binding, RNA polymerase II-specific DNA-binding transcription factor binding, and transcription factor binding. KEGG pathway enrichment analysis identified pathways in cancer, fluid shear stress, and atherosclerosis, with lipid and atherosclerosis being the most significantly enriched pathways. Molecular docking revealed that three key ingredients in VO (i.e., quercetin, luteolin, and kaempferol) strongly interacted with three potential targets (i.e., AKT1, IL-6, and TNF-α). Further, MDS revealed that quercetin had a stronger binding affinity for AKT1. These findings suggest that VO has beneficial effects on AS via these potential targets that are closely related to the lipid and atherosclerosis pathways. Our study utilized a new computer-aided drug design to identify key ingredients, potential targets, various biological processes, and multiple pathways associated with the clinical roles of VO in AS, which provides a comprehensive and systemic pharmacological explanation for the anti-atherosclerotic activity of VO.

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“…Based on the characteristics of clinical manifestations, DKD can be classified into the categories of traditional Chinese medicine (TCM) “edema”, “deficiency”, and “Guange” [ 18 ]. It is mainly caused by spleen and kidney deficiency, dampness, and blood stasis block and is treated by invigorating the spleen and kidney and eliminating the turbid by purgation [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

Ginsenoside Rg3 induces mesangial cells proliferation and attenuates apoptosis by miR-216a-5p/MAPK pathway in diabetic kidney disease

Chen,

Peng,

et al. 2024

Aging

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Background: Ginsenoside Rg3 is an active saponin isolated from ginseng, which can reduce renal inflammation. However, the role and mechanism of Rg3 in diabetic kidney disease (DKD) are far from being studied. Methods: The effects of Rg3 and miR-216a-5p on the proliferation, apoptosis, and MAPK pathway in high glucose (HG)-induced SV40 MES 13 were monitored by CCK-8, TUNEL staining, and western blot. Results: Rg3 treatment could accelerate proliferation and suppress apoptosis in HG-induced SV40 MES. Moreover, miR-216a-5p inhibition also could alleviate renal injury, prevent apoptosis, and activate the MAPK pathway in kidney tissues of diabetic model mice. Conclusion: Rg3 could attenuate DKD progression by downregulating miR-216a-5p, suggesting Rg3 and miR-216a-5p might be the potential drug and molecular targets for DKD therapy.

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Prediction of the Potential Mechanism of Triptolide in Improving Diabetic Nephropathy by Utilizing A Network Pharmacology and Molecular Docking Approach

Cited by 7 publications

References 0 publications

Colquhounia Root Tablet Promotes Autophagy and Inhibits Apoptosis in Diabetic Nephropathy by Suppressing CD36 Expression In Vivo and In Vitro

Colquhounia Root Tablet Promotes Autophagy and Inhibits Apoptosis in Diabetic Nephropathy by Suppressing CD36 Expression In Vivo and In Vitro

Key ingredients in Verbena officinalis and determination of their anti-atherosclerotic effect using a computer-aided drug design approach

Ginsenoside Rg3 induces mesangial cells proliferation and attenuates apoptosis by miR-216a-5p/MAPK pathway in diabetic kidney disease

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