Network pharmacology study and in vitro experimental validation of Xiaojianzhong decoction against gastric cancer

BACKGROUND Cancer is one of the most serious threats to human health worldwide.Conventional treatments such as surgery and chemotherapy are associated with some drawbacks.In recent years,traditional Chinese medicine treatment has been increasingly advocated by patients and attracted attention from clinicians,and has become an indispensable part of the comprehensive treatment for gastric cancer.AIM To investigate the mechanism of Xiaojianzhong decoction(XJZ)in the treatment of gastric cancer(GC)by utilizing network pharmacology and experimental validation,so as to provide a theoretical basis for later experimental research.METHODS We analyzed the mechanism and targets of XJZ in the treatment of GC through network pharmacology and bioinformatics.Subsequently,we verified the impact of XJZ treatment on the proliferative ability of GC cells through CCK-8,apoptosis,cell cycle,and clone formation assays.Additionally,we performed Western blot analysis and real-time quantitative PCR to assess the protein and mRNA expression of the core proteins.RESULTS XJZ mainly regulates IL6,PTGS2,CCL2,MMP9,MMP2,HMOX1,and other target genes and pathways in cancer to treat GC.The inhibition of cell viability,the increase of apoptosis,the blockage of the cell cycle at the G0/G1 phase,and the inhibition of the ability of cell clone formation were observed in AGS and HGC-27 cells after XJZ treatment.In addition,XJZ induced a decrease in the mRNA expression of IL6,PTGS2,MMP9,MMP2,and CCL2,and an increase in the mRNA expression of HOMX1.XJZ significantly inhibited the expression of IL6,PTGS2,MMP9,MMP2,and CCL2 proteins and promoted the expression of the heme oxygenase-1 protein.CONCLUSION XJZ exerts therapeutic effects against GC through multiple components,multiple targets,and multiple pathways.Our findings provide a new idea and scientific basis for further research on the molecular mechanisms underlying the therapeutic effects of XJZ in the treatment of GC.

Mechanism of pachymic acid in the treatment of gastric cancer based on network pharmacology and experimental verification

BACKGROUND Pachymic acid(PA)is derived from Poria cocos.PA has a variety of pharmacological and inhibitory effects on various tumors.However,the mechanism of action of PA in gastric cancer(GC)remains unclear.AIM To investigate the mechanism of PA in treating GC via the combination of network pharmacology and experimental verification.METHODS The GeneCards and OMIM databases were used to derive the GC targets,while the Pharm Mapper database provided the PA targets.Utilizing the STRING database,a protein-protein interaction network was constructed and core targets were screened.The analyses of Gene Ontology,Kyoto Encyclopedia of Genes and Genomes(KEGG),and gene set enrichment analysis were conducted,and molecular docking and clinical correlation analyses were performed on the core targets.Ultimately,the network pharmacology findings were validated through in vitro cell assays,encompassing assessments of cell viability,apoptosis,cell cycle,cloning,and western blot analysis.RESULTS According to network pharmacology analysis,the core targets were screened,and the PI3K/AKT signaling pathway is likely to be the mechanism by which PA effectively treats GC,according to KEGG enrichment analysis.The experimental findings showed that PA could control PI3K/AKT signaling to prevent GC cell proliferation,induce apoptosis,and pause the cell cycle.CONCLUSION Network pharmacology demonstrated that PA could treat GC by controlling a variety of signaling pathways and acting on a variety of targets.This has also been supported by in vitro cell studies,which serve as benchmarks for further research.

Immp2l Mutation Induces Mitochondrial Membrane Depolarization and Complex Ⅲ Activity Suppression after Middle Cerebral Artery Occlusion in Mice

Objective We previously reported that mutations in inner mitochondrial membrane peptidase 2-like(Immp2l)increase infarct volume,enhance superoxide production,and suppress mitochondrial respiration after transient cerebral focal ischemia and reperfusion injury.The present study investigated the impact of heterozygous Immp2l mutation on mitochondria function after ischemia and reperfusion injury in mice.Methods Mice were subjected to middle cerebral artery occlusion for 1 h followed by 0,1,5,and 24 h of reperfusion.The effects of Immp2l^(+/−)on mitochondrial membrane potential,mitochondrial respiratory complex III activity,caspase-3,and apoptosis-inducing factor(AIF)translocation were examined.Results Immp2l^(+/−)increased ischemic brain damage and the number of TUNEL-positive cells compared with wild-type mice.Immp2l^(+/−)led to mitochondrial damage,mitochondrial membrane potential depolarization,mitochondrial respiratory complex III activity suppression,caspase-3 activation,and AIF nuclear translocation.Conclusion The adverse impact of Immp2l^(+/−)on the brain after ischemia and reperfusion might be related to mitochondrial damage that involves depolarization of the mitochondrial membrane potential,inhibition of the mitochondrial respiratory complex III,and activation of mitochondria-mediated cell death pathways.These results suggest that patients with stroke carrying Immp2l^(+/−)might have worse and more severe infarcts,followed by a worse prognosis than those without Immp2l mutations.

Clinical Observation on Modified Huan'gan Lipi Decoction Combined with Acupuncture in Treating Spleen Deficiency and Liver Hyperactivity Type Tic Disorders

[Objectives]To observe the clinical efficacy of Modified Huan'gan Lipi Decoction combined with acupuncture in the treatment of spleen deficiency and liver hyperactivity type tic disorders(TD).[Methods]Sixty patients with spleen deficiency and liver hyperactivity type TD were randomly divided into a treatment group of 40 cases and a control group of 20 cases.The treatment group received Modified Huan'gan Lipi Decoction combined with acupuncture,and the control group received Haloperidol Tablets.After 4 weeks of treatment,the Yale Global Tic Severity Scale(YGTSS)score,the total score of TCM syndrome and the clinical efficacy were compared between the two groups before and after treatment.[Results]After treatment,the total effective rate of 87.5%in the treatment group was higher than 80.0%in the control group(P>0.05);the total score of YGTSS and the total score of TCM syndromes in the two groups were compared within groups,P﹤0.01;between groups,P﹤0.01.The recurrence rates of the treatment group and the control group were 11.1%and 71.4%,respectively.The difference between the two groups was statistically significant(P﹤0.01).[Conclusions]Modified Huan'gan Lipi Decoction combined with acupuncture in the treatment of spleen deficiency and liver hyperactivity type TD can significantly improve the patient's tic symptoms,and its long-term efficacy is stable.

Efficacy and safety of Sancai powder in patients with type 2 diabetes mellitus: a randomized controlled trial

OBJECTIVE: To assess the efficacy and safety of Sancai powder in patients with type 2 diabetes mellitus(T2DM) inadequately controlled with single oral metformin in a randomized controlled trial(RCT).METHODS: A total of 132 patients with T2 DM were enrolled in the study, who only took metformin(500-1000 mg/day) for at least three months and with inadequate glycemic control(7.0% ≤ hemoglobin A1 c ≤ 9.0%) in the past three months.The patients stopped taking metformin with lifestyle interventions for three weeks, and 105 patients qualified for the program. They were randomly divided into the Sancai powder group and the metformin group(1500 mg/day). The follow-up period was for 12 weeks. Comparisons of several variables were analyzed.RESULTS: No significant differences were found between the two groups in hemoglobin A1c(Hb A1c),fasting plasma glucose(FPG) and 2 h post-meal glucose(2h PG), although they had decreased significantly(P < 0.01). Homeostasis model assessment of beta cell function index was significantly improved in Sancai powder group(P < 0.01), and there were significant differences in the changes of homeostasis model assessment of insulin resistance and insulin sensitivity index in the two groups(P < 0.05). Sancai powder significantly reduced triglyceride level(P < 0.05), although there was no significant difference in the body weight and body mass index in the two groups.CONCLUSION: In this 12-week study, Sancai powder could significantly reduce hemoglobin A1 c,FPG and 2h PG levels, improved beta-cell function and insulin resistance of the T2 DM inadequately controlled with metformin.