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Mechanism of total glucosides from Chishao(Radix Paeoniae Rubra)on proliferation and apoptosis of hepatocellular carcinoma cells via phosphatase and tensin homolog deleted on chromosome ten/phosphatidylinositol 3-kinase/protein kinase B signaling pathway
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作者 FAN Bingbing LI Tianjiao +3 位作者 MENG Xiansheng WANG Shuai BAO Yongrui WANG Fei 《Journal of Traditional Chinese Medicine》 SCIE CSCD 2021年第5期677-683,共7页
OBJECTIVE:To investigate the possible molecular mechanism of total glycosides of Chishao(Radix Paeoniae Rubra)(TG-RPR)on proliferation and apoptosis of hepatocellular carcinoma cells.METHODS:The proliferation of TG-RP... OBJECTIVE:To investigate the possible molecular mechanism of total glycosides of Chishao(Radix Paeoniae Rubra)(TG-RPR)on proliferation and apoptosis of hepatocellular carcinoma cells.METHODS:The proliferation of TG-RPR on Hep G2 cells was detected using the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)assay.The apoptosis of Hep G2 cells was measured by annexin V-FITC/double staining.The phosphatase and tensin homolog deleted on chromosome ten(PTEN)/phosphatidylinositol 3-kinase(PI3 K)/protein kinase B(Akt)signaling pathway was evaluated by Western Blot and reverse transcription-polymerase chain reaction(RT-PCR).RESULTS:TG-RPR can up-regulation the expression of pro-apoptotic factors such as PTEN and BCL2-Associated X(Bax),down-regulation the expression of anti-apoptotic factors including B-cell lymphoma-2(Bcl-2),PI3 K,and Akt.CONCLUSION:TG-RPR significantly inhibits the proliferation of Hep G2 cells in a dose-dependent manner and promotes apoptosis.These results demonstrated TG-RPR has significant inhibitory effect on Hep G2 cells.These results identify a critical role of TG-RPR in proliferation and apoptosis of Hep G2 cells via modulating PTEN/PI3 K/Akt signaling pathway.TG-RPR may offer a promise as a potential pharmaceutical therapy for hepatocellular carcinoma. 展开更多
关键词 carcinoma hepatocellular GLYCOSIDES PTEN phosphohydrolase phosphatidylinositol 3-kinase proto-oncogene proteins c-akt Chishao(Radix Paeoniae Rubra)
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Efficacy of Ganshuang granules(肝爽颗粒)on non-alcoholic fatty liver and underlying mechanism:a network pharmacology and experimental verification
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作者 ZHI Guoguo SHAO Bingjie +5 位作者 ZHENG Tianyan JI Shaoxiu LI Jingwei DANG Yanni LIU Feng WANG Dong 《Journal of Traditional Chinese Medicine》 SCIE CSCD 2024年第1期122-130,共9页
OBJECTIVE:To investigate the potential pharmacological mechanisms of Ganshuang granules(肝爽颗粒,GSG)in treating non-alcoholic fatty liver(NAFLD).METHODS:All the active components and targets of GSG were retrieved fro... OBJECTIVE:To investigate the potential pharmacological mechanisms of Ganshuang granules(肝爽颗粒,GSG)in treating non-alcoholic fatty liver(NAFLD).METHODS:All the active components and targets of GSG were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform.Protein-Protein interaction network,Kyoto Encyclopedia of Genes and Genomes and Gene Ontology function annotation of common targets were analyzed to predict the mechanisms of action of GSG in the treatment of NAFLD.Then,the mouse models of NAFLD were constructed in a diet-induced manner and treated with GSG.The levels of interleukin 6(IL-6),tumor necrosis factor-alpha(TNF-α)and phosphatidylinositol 3-kinase/protein kinase B(PI3K/AKT)pathway-related proteins in the liver of mice in each group were measured by enzyme linked immunosorbent assay and Western blot,respectively.RESULTS:Network pharmacology revealed a total of 159 potential targets of GSG for the treatment of NAFLD.Functional enrichment analysis indicated that the PI3K/AKT signaling pathway may be involved during GSG treatment of NAFLD.Further experiments showed that the significantly decreased alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase,total cholesterol,triglyceride and low-density lipoprotein cholesterol levels in NAFLD model mice serum after GSG treatment,as well as the expression levels of IL-6 and TNF-αin the liver.Furthermore,drug intervention increased the protein expression levels of phosphorylated-PI3K(P-PI3K)and P-AKT in the liver of the model group mice,and decreased the protein expression level of sterol regulatory element-binding protein 1.CONCLUSION:We found that GSG is effective in treating NAFLD and the potential therapeutic targets may be involved in PI3K/AKT signaling pathway. 展开更多
关键词 fatty liver ALCOHOLIC network pharmacology models ANIMAL phosphatidylinositol 3-kinase proto-oncogene proteins c-akt signal transduction Ganshuang granules
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Effects of electroacupuncture at Taichong(LR 3) and Baihui(DU 20)on cardiac hypertrophy in rats with spontaneous hypertension 被引量:9
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作者 Ji Zhi Zhang Yue +4 位作者 Liang Jingrong Wu Jiaojuan Jia Wenrui Wang Zhaoyang Liu Qingguo 《Journal of Traditional Chinese Medicine》 SCIE CAS CSCD 2019年第4期502-508,共7页
OBJECTIVE: To investigate the effects of electroacupuncture(EA) at Taichong(LR 3) and Baihui(DU 20)on myocardial hypertrophy in spontaneously hypertensive rats(SHRs).METHODS: Thirty-six SHRs were randomly assigned to ... OBJECTIVE: To investigate the effects of electroacupuncture(EA) at Taichong(LR 3) and Baihui(DU 20)on myocardial hypertrophy in spontaneously hypertensive rats(SHRs).METHODS: Thirty-six SHRs were randomly assigned to model, EA, and Losartan groups, with twelve rats per group. Twelve Wistar Kyoto rats were selected as the normal control group. Systolic blood pressure(SBP) and cardiac function were measured in all rats.Expression levels of factors associated with the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/Akt/mTOR) pathway were evaluated by Western blotting and real-time PCR.Pathological changes of the heart tissue were observed by hematoxylin-eosin staining.RESULTS: After treatment, enhanced SBP was significantly decreased in the EA and Losartan groups compared with the model group(P < 0.01). Echocardiographic and morphological analyses revealed that enhanced end-diastolic interventricular septal thickness and left ventricular posterior wall thickness, as well as ratio of left ventricular weight to body weight were markedly diminished in the EA and Losartan groups(P < 0.01 or P < 0.05), while reduced left ventricular end-diastolic dimension and left ventricular ejection fraction were significantly ameliorated(P < 0.01). Real-time PCR and western blotting analyses showed that the expression levels of PI3K,Akt, and mT OR in SHRs were significantly up-regulated by EA and Losartan(P < 0.01), while the expression levels of PTEN and ANP were down-regulated(P < 0.01).CONCLUSION: EA at Taichong(LR 3) and Baihui(DU20) inhibited the development of cardiac hypertrophy and improved the cardiac function in SHRs, possibly through regulation of the PI3K/Akt/mTOR signalling pathway. 展开更多
关键词 ELECTROACUPUNCTURE Rats inbred SHR Hypertrophy PHOSPHATIDYLINOSITOL 3-kinases PROTO-ONCOGENE proteins c-akt Mammalian target of rapamycin
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Spleen-kidney supplementing formula alleviates insulin resistance via regulating AKT/glycogen synthase kinase 3β pathway in rats with type 2 diabetic induced by high-fat diet 被引量:3
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作者 Tian Chunyu Wang Ya +2 位作者 La Xiaojin Li Ji'an Zhang Biwei 《Journal of Traditional Chinese Medicine》 SCIE CAS CSCD 2019年第2期199-206,共8页
OBJECTIVE: To explore the molecular mechanism underpinning the action by investigating its effect on glycogen content and AKT(also known as protein kinase B)/glycogen synthase kinase 3β(GSK-3β) pathway in the liver ... OBJECTIVE: To explore the molecular mechanism underpinning the action by investigating its effect on glycogen content and AKT(also known as protein kinase B)/glycogen synthase kinase 3β(GSK-3β) pathway in the liver of rats with type 2 diabetic induced by high-fat diet.METHODS: The rat model of type 2 diabetes was induced by high-fat diet and multiple low-dose streptozotocin injection. Diabetic rats were divided into five groups: the model control group, the Metformin group, spleen-kidney supplementing formula groups of low, medium and high doses. Fasting blood glucose(FBG) levels were measured before treatment and every two weeks during treatment.After the treatment, oral glucose tolerance test was performed, and hemoglobin A1c (HbA1c) and C-peptide were measured to assess the formula's effect on glucose metabolism and insulin resistance. The protein expression levels of AKT, GSK-3βand their phosphorylated forms in the liver were also measured to study the formula's role in insulin signaling pathway.RESULTS: Spleen-kidney supplementing formula significantly relieved the symptoms of polydipsia,polyuria and weight loss in type 2 diabetic rats, reduced FBG and HbA1c levels, increased glycogen content, and improved insulin sensitivity. The anti-diabetic effects of spleen-kidney supplementing formula are dose dependent. It also increased the total AKT protein level and the GSK-3β phosphorylation in the liver of type 2 diabetic rats.CONCLUSION: Spleen-kidney supplementing formula has hypoglycemic effect and relieves insulin resistance by enhancing AKT/GSK-3β signaling pathway in the liver of type 2 diabetic rats. 展开更多
关键词 Spleen-kidney supplementing FORMULA Insulin resistance PROTO-ONCOGENE proteins c-akt Glycogen Phosphorylation
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Network pharmacology and molecular docking study on the effect of Kaempferol in treatment of metabolic associated fatty liver disease 被引量:3
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作者 ZHOU Kaixuan ZHANG Dong +1 位作者 BAO Huiwei LI Lijing 《Journal of Traditional Chinese Medicine》 SCIE CSCD 2022年第5期788-794,共7页
OBJECTIVE: To study therapeutic effect of kaempferol on metabolic associated fatty liver disease(MAFLD) by network pharmacology and molecular docking combined with cell experiments. METHODS: First, use the Swiss Targe... OBJECTIVE: To study therapeutic effect of kaempferol on metabolic associated fatty liver disease(MAFLD) by network pharmacology and molecular docking combined with cell experiments. METHODS: First, use the Swiss Target Prediction database to predict the targets of kaempferol, and collect the targets of MAFLD through the Disgenet database and the Gene Cards database. Then, the common target of kaempferol and MAFLD was enriched and analyzed by the Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes, and the protein-protein interaction(PPI) network was constructed through the string database to obtain the key targets, and carry out molecular docking of key targets with kaempferol;In cell experiment, oleic acid induced steatosis in Hep G2 cells, which was intervened by kaempferol, the level of triglyceride(TG) was detected, the lipid deposition was observed by oil red O staining, and the protein expression was detected by Western blot. RESULTS: The results showed that there are 33 common targets for kaempferol and MAFLD. The biological process of GO is related to the regulation of protein kinase B, cell apoptosis, inflammatory factors, lipoxygenase, etc. Its action pathway is related to the phosphatidylinositol-3-kinase and protein kinase B(PI3K-AKT) signaling pathway, hypoxia-inducible factor 1 signaling pathway, forkhead box protein O signaling pathway, AMP-activated protein kinase signaling pathway, tumor necrosis factor signaling pathway, etc., the key targets are protein kinase B(AKT1), prostaglandin G/H synthase 2, matrix metalloproteinase-9, epidermal growth factor receptor, and the molecular docking of kaempferol with the four key targets shows good binding properties. Cell experiments show that kaempferol can reduce cell TG levels, reduce lipid deposition, increase the expression of PI3K, AKT, and beclin-1, and reduce the expression of caspase-3 and nuclear factor-kappa B. Kaempferol can treat MAFLD by regulating the PI3K-AKT signaling pathway to regulate cell autophagy, apoptosis, and inflammation. CONCLUSIONS: This study shows that kaempferol can regulate lipid metabolism, reduce apoptosis, regulate inflammation and autophagy in the fatty liver cell model. It reveals the therapeutic mechanism of kaempferol on MAFLD and provides a natural product candidate for the treatment of MAFLD. 展开更多
关键词 Metabolic associated fatty liver disease KAEMPFEROL network pharmacology molecular docking simulation protein kinase B protoonco-gene proteins c-akt signaling transduction
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Network-based pharmacology and experimental validation to explore the mechanism of action of the Jiawei Pentongling formula(加味盆痛灵方)for the treatment of endometriosis-related pain
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作者 YU Siyun ZHANG Shiwen +3 位作者 XIA Yu LIU Xiaoqing LIU Yajie FU Jinrong 《Journal of Traditional Chinese Medicine》 SCIE 2024年第5期991-999,共9页
OBJECTIVE:To investigate the effects and mechanisms of the Jiawei Pentongling formula(加味盆痛灵方,JWPTL)in treating endometriosis-related pain using network pharmacology study and experimental validation.METHODS:Acti... OBJECTIVE:To investigate the effects and mechanisms of the Jiawei Pentongling formula(加味盆痛灵方,JWPTL)in treating endometriosis-related pain using network pharmacology study and experimental validation.METHODS:Active ingredients and relevant targets of JWPTL,as well as genes for endometriosis-related pain,were collected from public databases.Prediction of core targets and pathways of JWPTL against pain associated with endometriosis by protein-protein interaction(PPI)network work,gene ontology(GO),and Kyoto Encyclopedia of Genes and Genomes(KEGG)functional enrichment analysis.The Sprague-Dawley rat endometriosis model was constructed using the autologous endosomal transplantation method,and the successfully modeled rats were randomly divided into the model group and the JWPTL group,with 8 rats in each group.Another 8 rats were set up in the sham group.Rats in the JWPTL group used the rectal delivery method with the addition of JWPTL(7.77 g·kg^(-1)·d^(-1))once a day for 28 d.Rats in the model and sham-operated groups were given equal amounts of saline using the same administration method.The 50%paw withdrawal threshold(PWT)of the rats was measured at different time points.After the intervention,the expression of phosphatidylinositol 3-kinase(PI3K)and protein kinase B(Akt)proteins and mRNA in endometriotic tissues was detected by immuneohistochemistry and reverse transcription-polymerase chain reaction.RESULTS:From GeneCards,Online Mendelian Inheritance in Man and other databases,a total of 964 endometriosis(EMs)-related pain targets were screened,142 active ingredients of JWPTL,605 targets,and 221 potential targets were obtained by intersection of Venn diagram;44 core targets were identified by constructing PPI network.KEGG enrichment analysis showed that JWPTL mainly involves the PI3K-Akt signaling pathway,estrogen signaling pathway,hypoxia inducible factor-1 signaling pathway,tumour necrotizing factor signaling pathway,and other signaling pathways in the treatment of EMs-related pain.Animal experiments showed that JWPTL could up-regulate the mechanical pain threshold and reduce the expression of PI3K and Akt proteins and mRNA in ectopic endometrial tissues of model rats.CONCLUSIONS:The present study preliminarily analyzed the pharmacological mechanism of the formula,and molecular docking and animal experiments showed the feasibility of this study,suggesting that the formula may inhibit the release of inflammatory factors and reverse the pain associated with EMs by downregulating the PI3K/Akt signaling pathway. 展开更多
关键词 Endometriosis-related pain phosphatidylinositol 3-kinase proto-oncogene proteins c-akt Signal Transduction Jiawei Pentongling formula network pharmacology
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