Journal of Translational Medicine
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2023
·Vol. 21
·期 1
·1-14
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IF 7.4
Chen Shengnan,Li Bo,Chen Lei,Jiang Hongli
Background Diabetic kidney disease (DKD) has been the leading cause of chronic kidney disease in developed countries. Evidence of the benefits of resveratrol (RES) for the treatment of DKD is accumulating. However, comprehensive therapeutic targets and underlying mechanisms through which RES exerts its effects against DKD are limited.Methods Drug targets of RES were obtained from Drugbank and SwissTargetPrediction Databases. Disease targets of DKD were obtained from DisGeNET, Genecards, and Therapeutic Target Database. Therapeutic targets for RES against DKD were identified by intersecting the drug targets and disease targets. GO functional enrichment analysis, KEGG pathway analysis, and disease association analysis were performed using the DAVID database and visualized by Cytoscape software. Molecular docking validation of the binding capacity between RES and targets was performed by UCSF Chimera software and SwissDock webserver. The high glucose (HG)-induced podocyte injury model, RT-qPCR, and western blot were used to verify the reliability of the effects of RES on target proteins.Results After the intersection of the 86 drug targets and 566 disease targets, 25 therapeutic targets for RES against DKD were obtained. And the target proteins were classified into 6 functional categories. A total of 11 cellular components terms and 27 diseases, and the top 20 enriched biological processes, molecular functions, and KEGG pathways potentially involved in the RES action against DKD were recorded. Molecular docking studies showed that RES had a strong binding affinity toward PPARA, ESR1, SLC2A1, SHBG, AR, AKR1B1, PPARG, IGF1R, RELA, PIK3CA, MMP9, AKT1, INSR, MMP2, TTR, and CYP2C9 domains. The HG-induced podocyte injury model was successfully constructed and validated by RT-qPCR and western blot. RES treatment was able to reverse the abnormal gene expression of PPARA, SHBG, AKR1B1, PPARG, IGF1R, MMP9, AKT1, and INSR.Conclusion sRES may target PPARA, SHBG, AKR1B1, PPARG, IGF1R, MMP9, AKT1, and INSR domains to act as a therapeutic agent for DKD. These findings comprehensively reveal the potential therapeutic targets for RES against DKD and provide theoretical bases for the clinical application of RES in the treatment of DKD.
研究领域:
药理学
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分子生物学
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糖尿病
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肾病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2023
·
IF 5.6
Peijun Liu,Weihua Tang,Dong Zhao,Pan Zhou,Ke Hu
Background: Notopterygium incisum K.C. Ting ex H.T. Chang, a synonym of Hansenia weberbaueriana (Fedde ex H. Wolff) Pimenov & Kljuykov, is an anti-inflammatory medicinal plant. Although abrnotopterol has been reported to be its primary active metabolite, the other metabolites and their mechanisms of action remain unclear. This study aims to investigate the potential mechanisms by which its active metabolites treat Obstructive Sleep Apnea Syndrome (OSAS) through network analysis and experimental assessment. Methods: The metabolites and potential targets of Notopterygium incisum were extracted from public databases. We searched for OSAS-related genes in the Genecards, OMIM, PharmGkb, TTD, and DrugBank databases. Cytoscape 3.9.0 was used to construct the drug-target-disease network and screen for hub genes. Human bronchial epithelial (HBE) cells were cultivated in normoxia and chronic intermittent hypoxia (CIH) medium for 24 h. Interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and prostaglandin E2 (PGE2) were quantified using enzyme-linked immunosorbent assay (ELISA). Prostaglandin-endoperoxide synthase 2(PTGS2) mRNA was detected using RT-qPCR, while PTGS2 and nuclear factor-kappa B (NF-κB) proteins were identified using Western blot analysis. Co-Immunoprecipitation (CoIP) and Western blotting were utilized to evaluate the ubiquitination of PTGS2 in HBE cells. Results: Pterostilbene and notopterol, isolated from Notopterygium incisum , had potential therapeutic effects on OSAS. The PTGS2 and estrogen receptor alpha (ESR1) hub genes were associated with OSAS. The pathway enrichment analysis focuses on the NF-κB, apoptosis, and HIF-1A pathways. In response to CIH, pterostilbene and notopterol decreased IL-6, TNF-α, and PGE2 levels. The NF-κB pathway was activated by an increase in PTGS2 levels. Pterostilbene promoted proteasome-mediated ubiquitination of PTGS2 protein and reduced PTGS2 levels, inhibiting the NF-κB pathway. Conclusion: This study reveals the active metabolites of Notopterygium incisum and hub genes involved in treating OSAS, which provide a basis for the follow-up development and exploitation of the botanical drug.
研究领域:
药理学
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分子生物学
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网络分析
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实验生物学
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睡眠障碍
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产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2024
·Vol. 29
·期 10
·2345
·
IF 4.2
Lingna Xie,Congwei Ma,Xinyu Li,Huixiong Chen,Ping Han,Li Lin,Weiqiang Huang,Menglu Xu,Hailiang Lu,Zhiyun Du
Glycyrrhetinic acid (GA) is a saponin compound, isolated from licorice (Glycyrrhiza glabra), which has been wildly explored for its intriguing pharmacological and medicinal effects. GA is a triterpenoid glycoside displaying an array of pharmacological and biological activities, including anti-inflammatory, anti-bacterial, antiviral and antioxidative properties. In this study, we investigated the underlying mechanisms of GA on acne vulgaris through network pharmacology and proteomics. After the intersection of the 154 drug targets and 581 disease targets, 37 therapeutic targets for GA against acne were obtained. A protein–protein interaction (PPI) network analysis highlighted TNF, IL1B, IL6, ESR1, PPARG, NFKB1, STAT3 and TLR4 as key targets of GA against acne, which is further verified by molecular docking. The experimental results showed that GA inhibited lipid synthesis in vitro and in vivo, improved the histopathological damage of skin, prevented mast cell infiltration and decreased the level of pro-inflammatory cytokines, including TNF-α, IL-1β and IL-6. This study indicates that GA may regulate multiple pathways to improve acne symptoms, and the beneficial effects of GA against acne vulgaris might be through the regulation of sebogenesis and inflammatory responses.
研究领域:
药理学
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皮肤科
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分子生物学
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生物信息学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2022
·
IF 5.988
Chunlan Tang,Zhiling Fang,Donghui Chu,Lulu Zhang,Yuqing Tang,Jinyue Zhou,Rui Fang,Jiaming Ying,Fang Wang,Yuping Zhou,Chunshuang Xu,Qinwen Wang
Alzheimer’s disease (AD) is a common and serious neurodegenerative disease in the elderly; however, the treatment of AD is still lacking of rational drugs. In this paper, the active constituents and targets of the self-developed Chinese medicine Formula 9002A in the treatment of AD were investigated from three aspects: pharmacodynamics based on cell and animal experiments, network pharmacology analysis, and pharmacokinetic analysis. A total of 124 compounds were screened in Formula 9002A, and four constituents including salidroside, gastrodin, niacinamide, and umbelliferone were screened as potential active components for the treatment of AD by network pharmacology. Among them, salidroside and gastrodin showed higher relevance with AD targets, such as ESR1 and AR. The pharmacokinetic study showed that they could be absorbed and identified in plasma; the half-life and mean residence times of salidroside and gastrodin in plasma were nearly increased 2-fold by the administration of Formula 9002A compared with those by the administration of a monomer, indicating the extended action time of active compounds in vivo . Formula 9002A exerted the efficacy in the treatment of AD mainly by regulating APP, GSK3β, ESR1, and AR targets based on the anti-β-amyloid protein deposition, anti-oxidation and anti-apoptosis pathways. Two genes enriched in Alzheimer’s disease pathway, APP and GSK3β, were further validated. The experiments also demonstrated that Formula 9002A could downregulate APP and GSK3β protein expression in the model mice brain and improved their cognitive ability. In summary, Formula 9002A has the characteristics of multiple targets and multiple pathways in the treatment of AD, and salidroside and gastrodin might be the main active constituents, which could provide a foundation for further research and application.
研究领域:
神经学
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药理学
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中医药
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网络药理学
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药代动力学
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产品关联
DOI
PubMed
高影响因子
Food Bioscience
·
2025
·
IF 5.9
Ruoxin Chen,Jiahao Ren,Zhenlong Zhou,Wenjun Zhang,Jianyu Su
Gentiana rigescens Franch. extract have demonstrated various important bioactivities, however, their potential against photoaging has yet to be evaluated. This study explored the anti-photoaging effects of Gentiana rigescens Franch. root extract (GRFR) and stem (GRFS), along with their underlying mechanisms and bioactive components, using the UVB-induced zebrafish model. GRFS demonstrated superior anti-photoaging efficacy compared to GRFR. GRFS significantly alleviated UVB-induced tail fin damage, increasing the relative tail fin area from 31.23% to 80.92% (at 1mg/mL), and reducing ROS levels from 244.80% to 150.95%. It also inhibited lipid peroxidation, lowering malondialdehyde (MDA) levels from 202.87 nmol/g to 142.83 nmol/g. Furthermore, GRFS enhanced antioxidant enzyme activities, increasing superoxide dismutase (SOD) from 80.94 U/g to 104.06 U/g. Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) indicated substantial distinctions in the composition and content of major constituents between GRFR and GFRS, which may explain the differences in their anti-photoaging activities. And then network pharmacology was used to investigate possible mechanisms of GFRS, which identified five potential targets including CTNNB1, ESR1, AKT1, JUN and EGFR, as well as three key active compounds including aspartyl-phenylalanine (Asp-Phe), N-acetyl-L-phenylalanine (N-Acetyl-L-Phe), and phenylalanyl-tyrosine (Phe-Tyr). Finally, the molecular docking revealed that Phe-Tyr exhibited the strongest binding affinity for AKT1 (-8.86 kcal/mol), indicating that it may be the most potent anti-photoaging compound in GFRS. These findings suggest that G . rigescens , with its potent anti-photoaging properties, offers superior protection against UVB-induced photoaging and holds promise as a natural therapeutic agent.
研究领域:
药理学
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植物学
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皮肤科学
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生物化学
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计算生物学
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天然产物研究
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生物技术
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）