Network pharmacology-based study on the mechanism of ShenKang injection in diabetic kidney disease through Keap1/Nrf2/Ho-1 signaling pathway

Liu, Yunhua; Wang, Sitong; Ge, Jian; Gao, Kun; Wang, Shuyue; Zhang, Xinjiang; Zhou, Kaidong; Cai, Yanmo; Zhou, Xin; Zhao, Zhonghua

doi:10.1016/j.phymed.2023.154915

Cited by 20 publications

(4 citation statements)

References 35 publications

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“…Simultaneously, a disease target library for Cd-induced AKI was established by integrating data from CTD (The Comparative Toxicogenomics Database; ctdbase.org; accessed on 25 January 2023), DisGeNET (a database of gene-disease associations; accessed on 25 January 2023), NCBI’s National Center for Biotechnology Information ( accessed on 25 January 2023); GeneCard (GeneCards—Human Genes|Gene Database|Gene Search);accessed on 25 January 2023), and OMIM. The intersection of drug targets and disease targets was determined using a Venny2.1.0 analysis as previously described [ 73 ].…”

Section: Methodsmentioning

confidence: 99%

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A Tripeptide (Ser-Arg-Pro, SRP) from Sipunculus nudus L. Improves Cadmium-Induced Acute Kidney Injury by Targeting the MAPK, Inflammatory, and Apoptosis Pathways in Mice

Pan,

Peng,

Fang

et al. 2024

Marine Drugs

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Cadmium (Cd) is a toxic heavy metal that causes nephrosis, including acute kidney injury. To prevent and treat acute kidney injury (AKI) following Cd exposure, a tripeptide, Ser-Arg-Pro (SRP), from Sipunculus nudus L. was employed, and its potential efficacy in AKI was assessed. Oral administration of SRP significantly alleviated Cd-induced kidney damage, leading to improved renal function and the attenuation of structural abnormalities. A network pharmacology analysis revealed the potential of SRP in renal protection by targeting various pathways, including mitogen-activated protein kinase (MAPK) signaling, inflammatory response, and apoptosis pathways. Mechanistic studies indicated that SRP achieves renal protection by inhibiting the activation of MAPK pathways (phosphorylation of p38, p56, ERK, and JNK) in the oxidative stress cascade, suppressing inflammatory responses (iNOS, Arg1, Cox2, TNF-α, IL-1β, and IL-6), and restoring altered apoptosis factors (caspase-9, caspase-3, Bax, and Bcl-2). Hence, SRP has the potential to be used as a therapeutic agent for the treatment of Cd-induced nephrotoxicity.

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Section: Methodsmentioning

confidence: 99%

“…nlm.nih.gov/ accessed on 25 January 2023); GeneCard (GeneCards-Human Genes|Gene Database|Gene Search);accessed on 25 January 2023), and OMIM. The intersection of drug targets and disease targets was determined using a Venny2.1.0 analysis as previously described [73].…”

Section: Target Prediction Using Network Pharmacologymentioning

confidence: 99%

A Tripeptide (Ser-Arg-Pro, SRP) from Sipunculus nudus L. Improves Cadmium-Induced Acute Kidney Injury by Targeting the MAPK, Inflammatory, and Apoptosis Pathways in Mice

Pan,

Peng,

Fang

et al. 2024

Marine Drugs

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“…Oral bioavailability (OB) is one of the most commonly used parameters for screening candidate ingredients with further pharmaceutical potential (Liu et al, 2023b). SMILES number of chemical ingredients (Mean ratio of peak area ≥0.1%) identified by UPLC-QE-Orbitrap-HRMS was input into the ADMETLab 2.0 platform, and ingredients meeting OB > 20% were screened as potential active ingredients (Xiong et al, 2021).…”

Section: Potential Therapeutic Targets Of Xlgb Against MImentioning

confidence: 99%

Targeting the PANoptosis signaling pathway for myocardial protection: therapeutic potential of Xian Ling Gu Bao capsule

Wu,

Wei,

Zhang

et al. 2024

Front. Pharmacol.

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Introduction: Myocardial infarction (MI), the most prevalent ischemic heart disease, constitutes a primary cause of global cardiovascular disease with incidence and mortality. The pathogenesis of MI is exceedingly intricate, with PANoptosis playing a pivotal role in its pathological process. Xian Ling Gu Bao capsule (XLGB) contains various active components, including flavonoids, terpenes, and phenylpropanoids, and exhibits a wide range of pharmacological activities. However, it remains unclear whether XLGB can protect the myocardium from damage after MI. This study aimed to investigate the impact of XLGB on isoprenaline (ISO)-induced MI in mice and its potential mechanisms.Methods: This study assessed the protective effects of XLGB against ISO-induced MI through techniques such as echocardiography, HE staining, Masson staining, and enzyme-linked immunosorbent assay (ELISA). Furthermore, the potential mechanisms of XLGB's protective effects on MI were explored using bioinformatics, molecular docking, and molecular dynamics simulations. These mechanisms were further validated through immunofluorescence staining and Western blotting.Results: The results demonstrated that various doses of XLGB exhibited a significant reduction in myocardial injury induced by myocardial infarction. Intriguingly, higher dosages of XLGB displayed superior therapeutic efficacy compared to the positive control metoprolol. This protective effect is primarily achieved through the inhibition of oxidative stress and the inflammatory processes. Furthermore, we have elucidated that XLGB protected the myocardium from MI-induced damage by suppressing PANoptosis, with a critical role played by the NLRP3/Caspase3/RIP1 signaling pathway. Of particular note, the primary compounds of XLGB were found to directly interact with NLRP3/Caspase3/RIP1, a discovery further validated through molecular docking and molecular dynamics simulations. This suggests that NLRP3/Caspase3/RIP1 may be a therapeutic target for XLGB-induced myocardial protection.Conclusion: In summary, our findings reveal a novel property of XLGB: reverses myocardial damage following MI by inhibiting the NLRP3/Caspase3/RIP1-mediated PANoptosis pathway.

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“…Additionally, molecular docking, a method that simulates the binding mode and affinity of molecular interactions between receptors and drug molecules, has been utilized in conjunction with network pharmacology as a supplementary tool in drug research. [ 10 ]…”

Section: Introductionmentioning

confidence: 99%

Mechanism of Huaiqihuang in treatment of diabetic kidney disease based on network pharmacology, molecular docking and in vitro experiment

Wang,

Ma,

Zhang

et al. 2023

Medicine

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Background: This study aimed to investigate the active components, key targets, and potential molecular mechanisms Huaiqihuang (HQH) in the treatment of diabetic kidney disease (DKD) through network pharmacology, molecular docking, and in vitro experiments. Methods: The active components and potential targets of HQH were obtained from the TCMSP and HERB databases. The potential targets of DKD were obtained from the GeneCards, OMIM, DrugBank, and TTD databases. Protein interaction relationships were obtained from the STRING database, and a protein interaction network was constructed using Cytoscape software. Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis was performed using the Metascape database. Molecular docking was performed using AutoDock software to verify the binding between key compounds and core target genes. In vitro experiments were conducted using human renal proximal tubular epithelial cells and various methods, such as CCK8, RT-PCR, immunofluorescence, and western blot, to evaluate the effects of HQH on inflammatory factors, key targets, and pathways. Results: A total of 48 active ingredients, 168 potential targets of HQH, and 1073 potential targets of DKD were obtained. A total of 118 potential targets, 438 biological processes, and 187 signal pathways were identified for the treatment of DKD. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis indicated that HQH may exert its therapeutic effects on DKD by regulating the expression of inflammatory factors through the nuclear factor kappa B (NF-κB) signaling pathway. The molecular docking results showed that β-sitosterol and baicalein had the highest binding affinity with key targets such as AKT1, IL6, TNF, PTGS2, IL1B, and CASP3, suggesting that they may be the most effective active ingredients of HQH in the treatment of DKD. In vitro experimental results demonstrated that HQH could enhance the viability of human renal proximal tubular epithelial cells inhibited by high glucose, decrease the levels of AKT1, TNF, IL6, PTGS2, IL1B, and CASP3, reduce the expression of NF-κB-P65 (P < .01), inhibit NF-κB-p65 nuclear translocation, and decrease chemokine expression (P < .01). Conclusion: HQH may exert its therapeutic effects on DKD by inhibiting the NF-κB signaling pathway, reducing the level of pro-inflammatory cytokines, and alleviating the high glucose-induced injury of renal tubular epithelial cells.

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Network pharmacology-based study on the mechanism of ShenKang injection in diabetic kidney disease through Keap1/Nrf2/Ho-1 signaling pathway

Cited by 20 publications

References 35 publications

A Tripeptide (Ser-Arg-Pro, SRP) from Sipunculus nudus L. Improves Cadmium-Induced Acute Kidney Injury by Targeting the MAPK, Inflammatory, and Apoptosis Pathways in Mice

A Tripeptide (Ser-Arg-Pro, SRP) from Sipunculus nudus L. Improves Cadmium-Induced Acute Kidney Injury by Targeting the MAPK, Inflammatory, and Apoptosis Pathways in Mice

Targeting the PANoptosis signaling pathway for myocardial protection: therapeutic potential of Xian Ling Gu Bao capsule

Mechanism of Huaiqihuang in treatment of diabetic kidney disease based on network pharmacology, molecular docking and in vitro experiment

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