Biomed Research International
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2022
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IF 3.246
Shisheng Jiang,Chaoming Huang,Shulin Wang,Biyun Huang,Dan Wu,Guodong Zheng,Yi Cai
Objective. Through a network pharmacology method, we screened the main active compounds of Citri Reticulatae Pericarpium (CRP), constructed a drug-ingredient-disease-target network, explored the molecular mechanism of its treatment of myocardial hypertrophy, and validated it by using molecular biology approach. Methods. Traditional Chinese Medicine Systems Pharmacology (TCMSP) and GeneCards were utilised to collect the effective component in CRP and the targets of CRP and myocardial hypertrophy. The STRING database constructed the protein interaction network. The drug-ingredient-disease-target network was outlined by the Cytoscape 3.9.0 software. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted using the Metascape database. Real-time PCR (RT-PCR) and Western blotting were utilised to determine the mRNA and protein level of the critical targets of CRP therapy for myocardial hypertrophy. Results. We found that five practical components of CRP exerted therapeutic effects on myocardial hypertrophy by modulating 41 targets. Further analysis revealed that naringenin was the essential active compound in CRP that regulated myocardial hypertrophy. In addition, we showed that the active compounds of CRP might exert antihypertrophy effects via regulating essential target proteins such as AKT1-, MAPK3-, PPARA-, PPARG-, and ESR1-mediated signaling pathways such as cell proliferation, nuclear receptor activation, and oxidative stress. The molecular biology experiments demonstrated that naringenin inhibited the mRNA level of NPPA and NPPB induced by Ang II and regulated related targets such as AKT1, MAPK3, PPARA, PPARG, and ESR1. Conclusion. CRP could inhibit myocardial hypertrophy through multitarget and multiapproach.
研究领域:
药理学
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分子生物学
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中医药学
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心脏病学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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2022
·Vol. 23
·期 24
·15761
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IF 6.208
Zixuan Zhou,Aijia Zhang,Xinyi Liu,Yang Yang,Ruqian Zhao,Yimin Jia
Excess fat deposition in broilers leads to great economic losses and is harmful to consumers’ health. Chronic stress in the life cycle of chickens could be an important trigger. However, the underlying mechanisms are still unclear. In this study, 30-day-old chickens were subcutaneously injected with 2 mg/kg corticosterone (CORT) twice a day for 14 days to simulate long-term stress. It was shown that chronic CORT exposure significantly increased plasma triglyceride concentrations and enlarged the adipocyte sizes in chickens. Meanwhile, chronic CORT administration significantly enlarged the adipocyte sizes, increased the protein contents of FASN and decreased HSL, ATGL, Beclin1 and PPARA protein levels. Moreover, global m6A methylations were significantly reduced and accompanied by downregulated METTL3 and YTHDF2 protein expression by CORT treatment. Interestingly, the significant differences of site-specific m6A demethylation were observed in exon7 ofPPARAmRNA. Additionally, a mutation of the m6A site in the PPARA gene fused GFP and revealed that demethylated RRACH in PPARA CDS impaired protein translation in vitro. In conclusion, these results indicated that m6A-mediated PPARA translational suppression contributes to CORT-induced visceral fat deposition in chickens, which may provide a new target for the treatment of Cushing’s syndrome.Keywords:adipose tissues;chicken;corticosterone;m6A;PPARA
研究领域:
动物科学
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分子生物学
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内分泌学
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DOI
PubMed
高影响因子
PHYTOMEDICINE
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2023
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IF 7.9
Qian Li,Wen Zhang,Nuo Cheng,Yadi Zhu,Hao Li,Shuijun Zhang,Wenzhi Guo,Guangbo Ge
Background Cirsii Japonici Herba Carbonisata (Dajitan in Chinese) has been used to treat liver disorders in Asian countries. Pectolinarigenin (PEC), an abundant constituent in Dajitan, has been found to possess a wide range of biological benefits, including hepatoprotective effects. However, the effects of PEC on acetaminophen (APAP)-induced liver injury (AILI) and the underlying mechanisms have not been studied. Purposes To explore the role and mechanisms of PEC in protecting against AILI. Study design and methods The hepatoprotective benefits of PEC were studied using a mouse model and HepG2 cells. PEC was tested for its effects by injecting it intraperitoneally before APAP administration. To assess liver damage, histological and biochemical tests were performed. The levels of inflammatory factors in the liver were measured using RT-PCR and ELISA . Western blotting was used to measure the expression of a panel of key proteins involved in APAP metabolism, as well as Nrf2 and PPARα. PEC mechanisms on AILI were investigated using HepG2 cells, while the Nrf2 inhibitor (ML385) and PPARα inhibitor (GW6471) were used to validate the importance of either Nrf2 and PPARα in the hepatoprotective effects of PEC. Results PEC treatment decreased serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) levels in the liver. PEC pretreatment increased the activity of superoxide dismutase (SOD) and glutathione (GSH) while decreasing malondialdehyde production (MDA). PEC could also up-regulate two important APAP detoxification enzymes (UGT1A1 and SULT1A1). Further research revealed that PEC reduced hepatic oxidative damage and inflammation, and up-regulated APAP detoxification enzymes in hepatocytes by activating the Nrf2 and PPARα signaling pathways . Conclusions PEC ameliorates AILI by decreasing hepatic oxidative stress and inflammation while increasing phase Ⅱ detoxification enzymes related to APAP harmless metabolism through activation of Nrf2 and PPARα signaling. Hence, PEC may serve as a promising therapeutic drug against AILI.
研究领域:
药理学
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肝病学
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分子生物学
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毒理学
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DOI
PubMed
高影响因子
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
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2023
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IF 5.4
Jiaqi Xie,Yihong Li,Yulu Liang,Hongqian Kui,Can Wang,Jianmei Huang
Ethnopharmacological relevance Platycladi Semen was recorded in Shen Nong's Herbal Classic and was considered a herbal medicine with low toxicity after long-term medication. Multiple traditional Chinese medicine prescriptions containing Platycladi Semen have been used to treat insomnia. Modern clinical practitioners commonly use Platycladi Semen to treat anxiety disorders, but there are few studies on its composition and anxiolytic mechanisms. Aim of the study To describe the main components of Platycladi Semen and investigate its anxiolytic effects and mechanisms. Materials and methods The main components of Platycladi Semen were characterized by liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS). The anxiolytic effects of oral Platycladi Semen were evaluated in chronic unpredictable mild stress (CUMS) induced mice. To explore the anxiolytic mechanisms of Platycladi Semen , serum non-targeted metabolomics combined with network pharmacology and molecular docking was performed. Results Fourteen compounds were identified in the 50% methanol extract and 11 fatty acid derivatives were identified in the methyl-esterified fatty oil of Platycladi Semen . In CUMS mice, both the aqueous extract and fatty oil of Platycladi Semen had anxiolytic effects, which were shown by the increase in the time and frequency of mice entering the open arm in the elevated plus maze (EPM) experiment. Through serum non-targeted metabolomics, 34 differential metabolites were identified, and lipid metabolic pathways such as sphingolipid metabolism, steroidogenesis, alpha-linoleic acid, and linoleic acid metabolism were enriched. Through network pharmacology, 109 targets of the main components in Platycladi Semen were identified, and the ‘neuroactive ligand-receptor interaction’ and ‘lipid metabolism’ were enriched. The molecular docking results showed that the main components in Platycladi Semen could bind to the key targets such as peroxisome proliferator-activated receptor delta (PPARD), peroxisome proliferator-activated receptor alpha (PPARA), fatty acid binding protein 5 (FABP5), fatty acid binding protein 3 (FABP3), peroxisome proliferator-activated receptor gamma (PPARG), arachidonate 5-lipoxygenase (ALOX5) and fatty acid amide hydrolase (FAAH). Conclusion This study indicated that Platycladi Semen has anxiolytic effects, and the anxiolytic mechanisms may be the regulation of lipid metabolism and the neuroactive ligand-receptor interaction.
研究领域:
药理学
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代谢组学
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中药学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
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