Efficacy and safety of Jiawei Simiao powder combined with celecoxib for acute gouty arthritis:A meta-analysis

Objective:To evaluate the efficacy and safety of Jiawei Simiao powder(JWSMP)combined with celecoxib for the treatment of acute gouty arthritis by conducting a meta-analysis of randomized controlled trials(RCTs).Methods: The Chinese National Knowledge Infrastructure Databases,Chinese Scientific Journal Database,Wanfang,Cochrane Library,EMBASE,PubMed,and Web of Science databases were searched from inception until December 2023.Continuous variables were analyzed using the mean difference(MD)for analysis,and dichotomous variables were used as risk ratios.Data with similar characteristics were pooled for meta-analysis,and heterogeneity was assessed using I2.The Cochrane Handbook was used to assess the risk of bias and quality.RevMan 5.3 software was used to perform the meta-analysis.Results: Thirteen RCTs involving 1007 patients were included in the study.The quality of the included studies was low(unclear randomization processes and insufficient blinding reporting).The group receiving JWSMP combined with celecoxib showed significantly lower levels of serum uric acid(SUA,MD=−66.32,95%confidence interval(CI):−80.97 to−51.67,P<.001),erythrocyte sedimentation rate(ESR,MD=−6.05,95%CI:−8.29 to−3.82,P<.001),C-reactive protein(CRP,MD=−7.39,95%CI:−11.15,−3.63,P<.001),and joint pain score(VAS score,MD=−2.14,95%CI:−2.4 to−1.88,P<.001)compared to celecoxib alone.Additionally,the JWSMP combined group had a higher total effective rate(risk ratio=1.22,95%CI:1.14 to 1.29,P<.001)and fewer adverse compared to celecoxib alone.Conclusions: JWSMP combined with celecoxib is more effective than celecoxib alone in improving the total efficacy rate,alleviating joint pain,and improving SUA,ESR,and CRP levels.JWSMP also reduced the occurrence of adverse events caused by celecoxib.However,the quality of the included studies was low,highlighting the need for further high-quality research with larger sample sizes and robust methodologies,such as double-blind randomization,to confirm these findings.

Effects of Jiawei Wendan decoction on hippocampal p-CREB protein expression in a rat model of depression

BACKGROUND： Jiawei W＇endan decoction can elevate hippocampal brain-derived neurotrophic factor （BDNF） protein expression in rats with depression. It has been hypothesized that Jiawei Wendan decoction can exhibit antidepressant effects through the hippocampal signal transduction pathway of cyclic adenosine monophosphate response element binding protein （CREB）-BDNF. OBJECTIVE： Using phosphorylated-CREB （p-CREB） as an entry point, the present study was designed to observe intervention effects ofJiawei Wendan decoction compared with fluoxetine. DESIGN, TIME AND SETTING： A randomized, controlled, cellular biology experiment was performed at the Central Laboratory of Guangxi University of Traditional Chinese Medicine, MATERIALS： A total of 40 healthy, male, Sprague-Dawley rats were included in the present study. Rhizoma Acori Talarinowii （Shichangpu）, Flos Albiziae （Hehuanhua）, Rhizoma Pinelliae （Banxia）, Caulis Bambusae in Taeniam （Zhuru）, Fructus Aurantii Immaturus （Zhishi）, Poria （Fuling）, and Radix Bupleuri （Chaihu）, the primary ingredients ofJiawei Wendan decoction, were purchased from First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine. The raw drug was decocted at a concentration of 1.5 g/mL. Fluoxetine capsules were purchased from Shanghai Zhongxi Pharmaceutical Co., Ltd., China. METHODS： Following behavioral testing, 36 rats were selected from the initial 40 rats according to similar behavioral scores, and were randomly divided into 4 groups： model （n = 8）, Jiawei Wendan decoction-treated （n = I 0）, fluoxetine-treated （~ = 10）, and normal control （n = 8）. All rats, except for those in the normal control group, were separately raised in a chronic and unpredictable, mild-stimulation environment for 2 l days to establish a depression model. The Jiawei Wendan decoction-treated and fluoxetine-treated groups were intragastrically administered Jiawei Wendan decoction （12 g/kg/d） and fluoxetine （1.8 mg/kg/d）, respectively. The model and normal control groups received double-distilled water （2 mL/kg/d） once a day for a total of 21 days. MAIN OUTCOME MEASURES： Prior to depression induction and subsequent to administration, memory and degree of depression were measured by open field and tail suspension tests, respectively. At 24 hours after administration, p-CREB expression in the hippocampat CA3 region was analyzed by the immunohistochemical SABC method. RESULTS： Two rats from the Jiawei Wendan decoction-treated group, and one from the fluoxetine-treated group, died of unknown causes. The remaining rats in each group, except for one rat that was randomly selected from the fluoxetine-treated group, were included in the final analysis. Following administration, the model group exhibited significantly decreased numbers of hippocampal p-CREB-positive cells, horizontal and vertical movements, and significantly prolonged duration of immobility in tail-suspension test, compared with the normal control group （P 〈 0.01）. The numbers of p-CREB-positive cells, as well as horizontal and vertical movements, were significantly greater, and the duration of immobility was significantly shorter, in the Jiawei Wendan decoction and fluoxetine groups, compared with the model group （P 〈 0.05-0.01）. There was no significant difference in the above-mentioned three indices between the Jiawei Wendan decoction and fluoxetine groups （P 〉 0.05）. CONCLUSION： Jiawei Wendan decoction increased hippocampal p-CREB expression by influencing the rat hippocampal signal transduction pathway of CREB-BDNF. Jiawei Wendan decoction exhibited antidepressant effects equivalent to fluoxetine.

Clinical Study of Jiawei Huangqi Guizhi Wuwu Decoction (加味黄芪桂枝五物汤) in Preventing and Treating Peripheral Neuro-sensory Toxicity Caused by Oxaliplatin

Objective： To evaluate the efficacy of Jiawei Huangqi Guizhi Wuwu Decoction （加味黄芪桂枝五物汤, JHGWD） in treating neuro-sensory toxicity induced by oxaliplatin. Methods： A randomized controlled self-crossover trial was performed. Thirty-one patients were randomly divided into AB and BA groups. Patients in A cycle belonged to the treated group, who were treated with chemotherapy combined with oxaliplatin plus JHGWD. Patients in B cycle belonged to the control group and were treated with chemotherapy alone. The peripheral neuro-sensory toxicity was observed and analyzed. Results： The main neurotoxicity was cold-induced paresthesia after the use of oxaliplatin, which included hyperaesthesia, chill, anaesthesia in the extremities, electrified sensation, formication, foreign body sensation and pain that might be exacerbated by exposure to cold. Twenty patients （64.5 % ） suffered from neuro-sensory toxicity in the treated group and 27 cases （87.1% ） in the control group. Symptoms were more serious and lasted longer in the control group than those in the treated group （P〈0.01）. Conclusion： JHGWD could prevent and reduce the occurence and intensity of acute peripheral neuro-sensory toxicity caused by oxaliplatin.

Clinical Observation of Jiawei Buzhong Yiqi Decoction in the Treatment of Obese Polycystic Ovarian Syndrome

[Objectives] To observe the clinical efficacy of Jiawei Buzhong Yiqi Decoction in the treatment of polycystic ovarian syndrome(PCOS).[Methods]Obese patients with PCOS were recruited for the study in September 2014-December 2016 from Chinese medicine gynecological clinic in the affiliated hospital of Hubei University of Medicine.All these patients were given one dose of Jiawei Buzhong Yiqi Decoction one time a day for three months.Body mass index(BMI) was measured before and after treatment.Sex hormone levels and ovulation were measured,and the improvement of clinical symptoms was compared before and after treatment.[Results] After treatment,the levels of BMI and serum luteinizing hormone(LH),testosterone(T) were significantly decreased,and the level of serum estradiol(E2) was significantly higher than that before treatment.Ovarian enlargement and polycystic changes,menstrual cycle,menstrual flow and menstrual period were improved in varying degrees.[Conclusions] Jiawei Buzhong Yiqi Decoction has a good clinical effect in the treatment of obese PCOS.

Effects of Jiawei Buzhong Yiqi Decoction on the Endometrial Receptivity of Rats with Polycystic Ovary Syndrome

[Objectives]The study aims to discuss the effects of Jiawei Buzhong Yiqi Decoction on the endometrial receptivity of rats with polycystic ovarian syndrome(PCOS).[Methods]Adult female SD rats were selected and randomly divided into the model group and control group.In the model group,the PCOS model was established by using the method of Poretsky L.Rats in the control group were given physiological saline intervention at the same time.The successfully modeled rats were randomly divided into the PCOS group and traditional Chinese medicine group.Among them,rats in the Chinese medicine group were given Jiawei Buzhong Yiqi Decoction by gavage;rats in the model group and the control group were given normal saline for 14 d.All rats were killed by anesthesia after the last administration,and serum and uterine specimens were collected.Serum sex hormones(including T,E_(2),and P),glucose and insulin levels were detected;the equivalent diameter and area of endometrial gland and gland cavity,and the endometrial thickness of rats were measured;the expression of endometrial leukemia inhibitory factor(LIF),integrinαvβ3 protein and mRNA was detected by using Elisa and RT-PCR methods.[Results]The serum T,glucose,and insulin levels of rats in the PCOS group were significantly higher than those of the control group and the traditional Chinese medicine group,and there was no significant difference in the above indicators between the control group and the traditional Chinese medicine group;there was no significant difference in the E_(2) and P levels between the three groups.The equivalent diameter and area of endometrial gland and gland cavity,and the endometrial thickness of rats in the PCOS group were lower than those of the control group and the traditional Chinese medicine group;there was no significant difference in the above indicators between the traditional Chinese medicine group and the control group.The expression of LIF,integrinαvβ3 protein and mRNA in the endometrium of rats in various groups was basically the same.The expression of LIF and integrinαvβ3 in the endometrium of rats in the PCOS group was significantly lower than that of the control group and the traditional Chinese medicine group;there was no significant difference in the above indicators between the control group and the traditional Chinese medicine group.[Conclusions]The endometrial receptivity of PCOS rats was decreased;Jiawei Buzhong Yiqi Decoction can improve the endometrial receptivity of PCOS rats by increasing the expression of LIF and integrinαvβ3 in the endometrium.

The therapeutic effect of Jiawei Danshen Decoction on myocardial ischemia-reperfusion injury by inhibiting H_(2)S-mediated autophagy signaling pathway

Objective To investigate the protective effects of Jiawei Danshen Decoction(加味丹参饮,JWDSD)on myocardial ischemia-reperfusion injury(MIRI)via the regulation of serum Hydrogen sulfide(H2S)and cardiac Beclin1,light Chain 3 A/B(LC3 A/B),p62,and autophagy protein5(ATG5).Methods Seventy specific pathogen free(SPF)Sprague-Dawley(SD)rats were randomly assigned to seven groups(n=10 in each group),including normal control,sham operation,MIRI model(model),ischemic preconditioning,Na HS,JWDSD,and JWDSD+CSE inhibitor(JWDSD+PPG)groups,and orally administered the indicated drugs for 14 d.Two hours after the last administration,the left anterior decreased branch of the coronary artery of each rat in model,Na HS,JWDSD,and JWDSD+PPG groups was ligated for 30 min and subsequently reperfused for 90 min to establish the MIRI model,and the rats in the sham operation group were only exposed to the thorax after surgery without coronary ligation.Blood samples were collected to detect H2S levels using an enzyme-linked immunosorbent assay(ELISA).Heart tissues were harvested for histopathological and immunohistochemical examination and quantitative reverse transcription polymerase chain reaction analysis of Beclin1 and ATG5 m RNA expression and Western blot analysis of Beclin1,LC3 A/B,and p62 protein expression.Results(1)The serum H2S content in model group rats was significantly reduced(P<0.01),JWDSD significantly increased the serum H2S content of model group rats(P<0.01),and the CSE inhibitor(PPG)significantly reduced H2S levels in the JWDSD group rats(P<0.01).(2)Compared with the normal control group,the myocardial tissue necrosis and cell destruction occurred in the MIRI model group,and JWDSD could alleviate the myocardial tissue necrosis of model rats,but the ameliorative effect of JWDSD could be reversed by PPG.(3)Beclin1,LC3 A/B,and p62 expression levels in the heart tissues of the model group were significantly increased(P<0.001),whereas decreased by JWDSD(P<0.05,P<0.01,and P<0.001,respectively),and the inhibitory effects of JWDSD on Beclin1,LC3 A/B,and p62 expression were partially reversed by PPG(P<0.01,P<0.05,and P<0.01,respectively).(4)The expression levels of autophagy-related genes Beclin1 and ATG5 were significantly increased in the model group(P<0.001).JWDSD clearly downregulated the expression levels of Beclin1 and ATG5(P<0.05 and P<0.001,respectively),which were reversed by PPG(P<0.001).Conclusion Our experimental data show that JWDSD can exhibit an anti-MIRI role by increasing endogenous H2S generation,and downregulating the expression of Beclin1,LC3 A/B,p62 and ATG5,which are related to inhibiting autophagy signaling.

Metabolomics and network pharmacology reveal the mechanism of the Jiawei Yangshen pill in treatment of cyclophosphamide-induced dyszoospermia in mice

Background:The Jiawei Yangshen pill enhances sperm abundance.However,the pharmacological mechanism of action of the Jiawei Yangshen pill remains unclear.This study aimed to explore the therapeutic effect of the Jiawei Yangshen pill in the treatment of dyszoospermia and study the underlying mechanism.Methods:A dyszoospermia model was established by injecting mice with cyclophosphamide(50 mg/kg)consecutively for 7 days.Physiological and pathological indicators of the testis and hormone levels were examined after 4 weeks of treatment.Untargeted metabolomics using high-performance liquid chromatograph-mass spectrometry was performed on testis specimens.Network pharmacology analysis was used to construct an“ingredient-target-disease”interactive network,followed by metabolic pathway enrichment analysis.Western blotting was performed to examine the levels of the related proteins.Results:The Jiawei Yangshen pill significantly increased the testis index,epididymal index,sperm count,and testosterone level,while concurrently decreasing sperm mortality and luteinizing hormone levels.The spermatogenic cells in the Jiawei Yangshen pill-treated mice were well arranged with an increased number.Significantly different metabolites were identified.Western blotting showed that the expression levels of p-anti-adenosine monophosphate-activated protein kinase/anti-adenosine monophosphate-activated protein kinase and p-protein kinase B/protein kinase B were significantly increased after the Jiawei Yangshen pill treatment,whereas the expression levels of transforming growth factor-β1 and nuclear factor kappa B(p65)were remarkably decreased.Conclusion:The Jiawei Yangshen pill significantly improved testicular microcirculatory injury and overall metabolic levels in mice with dyszoospermia.

Molecular targets and mechanisms of Jiawei Jiaotai Pill on diabetic cardiomyopathy based on network pharmacology

BACKGROUND Jiawei Jiaotai Pill is commonly used in clinical practice to reduce apoptosis,increase insulin secretion,and improve blood glucose tolerance.However,its mechanism of action in the treatment of diabetic cardiomyopathy(DCM)remains unclear,hindering research efforts aimed at developing drugs specifically for the treatment of DCM.AIM To explore the pharmacodynamic basis and molecular mechanism of Jiawei Jiaotai Pill in DCM treatment.METHODS We explored various databases and software,including the Traditional Chinese Medicine Systems Pharmacology Database,Uniport,PubChem,GenCards,String,and Cytoscape,to identify the active components and targets of Jiawei Jiaotai Pill,and the disease targets in DCM.Protein-protein interaction network,gene ontology,and Kyoto Encyclopedia of Genes and Genomes analyses were used to determine the mechanism of action of Jiawei Jiaotai Pill in treating DCM.Molecular docking of key active components and core targets was verified using AutoDock software.RESULTS Total 42 active ingredients and 142 potential targets of Jiawei Jiaotai Pill were identified.There were 100 common targets between the DCM and Jiawei Jiaotai Pills.Through this screening process,TNF,IL6,TP53,EGFR,INS,and other important targets were identified.These targets are mainly involved in the positive regulation of the mitogen-activated protein kinase(MAPK)MAPK cascade,response to xenobiotic stimuli,response to hypoxia,positive regulation of gene expression,positive regulation of cell proliferation,negative regulation of the apoptotic process,and other biological processes.It was mainly enriched in the AGE-RAGE signaling pathway in diabetic complications,DCM,PI3K-Akt,interleukin-17,and MAPK signaling pathways.Molecular docking results showed that Jiawei Jiaotai Pill's active ingredients had good docking activity with DCM's core target.CONCLUSION The active components of Jiawei Jiaotai Pill may play a role in the treatment of DCM by reducing oxidative stress,cardiomyocyte apoptosis and fibrosis,and maintaining metabolic homeostasis.

Effects of Jiawei Danggui Buxuetang on miRNA-155 and SOCS1 in renal tissue of DKD rats

Objective:To observe the effect of Jiawei Danggui Buxuetang on the expression of microRNA-155(miR-155)and cytokine signal transduction inhibitor 1(SOCS1)in renal tissue of rats with diabetic nephropathy(DKD),and to explore the mechanism of Jiawei Danggui Buxuetang in the treatment of DKD.Methods:Firty 6-week-old SPF male SD rats were randomly divided into normal group(CON)and model group.The model group was fed with high-sugar and high-fat diet for 6 weeks,and the DKD rat model was established by intraperitoneal injection of streptozotocin(STZ)(35 mg/kg).Then the rats were randomly divided into model group(MOD),low dose group(DBTL),medium dose group(DBTM),high dose group(DBTH)and irbesartan group(IRB).Each group was given intragastric administration for 20 weeks,during which CON group and MOD group were given the same amount of normal saline.Urine samples were collected after administration,and the ratio of urinary Microalbumin to urinary creatinine(UACR)was analyzed by automatic analyzer.The renal changes in each group were observed by hematoxylin-eosin(HE)staining,Masson pine(Masson)trichromatic staining and PASM staining.The expression of miR-155 and SOCS1mRNA in renal tissue of DKD rats was detected by Real-time PCR,and the expression of SOCS1 was detected by Western blotting.Results:By comparison with CON group,UACR value,MIR-155 mRNA expression and SOCS1 mRNA expression in MOD group increased significantly,while SOCS1 mRNA expression decreased significantly compared with MOD group,UACR decreased significantly in IRB group and DBT group,SOCS1 expression increased significantly in DBTM group,DBTH group and IRB group.The expression of MIR-155 decreased significantly in all treatment groups(P<0.05),and the expression of SOCS1 in DBTM group,DBTH group and IRB group increased significantly(P<0.05).Conclusion:Jiawei Danggui Buxuetang can reduce the expression of miR-155 in high glucose and increase the expression of SOCS1 in renal tissue,so as to significantly reduce renal damage and play a role in renal protection.

A network pharmacology analysis on Jiawei Buhuanjin Zhengqi powder against COVID-19 in children

Background:To clarify the effectiveness and potential mechanism of Jiawei Buhuanjin Zhengqi powder(JBZP)for the prevention and treatment of coronavirus disease 2019(COVID-19)in children based on network pharmacology.Methods:The active ingredients and action targets of Jiawei Buhuanjin Zhengqi powder formulas were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform.Genes related to COVID-19 were found on the GeneCards database.The active ingredients-target network map was constructed by Cytoscape.The action mechanisms of these genes were predicted using a Gene Ontology-based functional enrichment and annotation tool and the Kyoto Encyclopedia of Genes and Genomes.Results:Through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,187 eligible compounds and 12,921 targets of Jiawei Buhuanjin Zhengqi powder were identified.A total of 257 genes related to Jiawei Buhuanjin Zhengqi powder and 401 genes related to COVID-19 in children were screened and 59 common target genes were obtained.The network analysis showed that the predicted seven main active components were Quercetin,Luteolin,Wogonin,Kaempferol,Irisolidone,Nobiletin and Licochalcone a.Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that key targets were associated with regulating immunological function or glycosylation through the biological processes.Conclusion:The potential mechanisms of Jiawei Buhuanjin Zhengqi powder on COVID-19 in children might be related to anti-inflammatory,virus infection,and immunomodulatory signaling pathway.

Therapeutic Effect of Shaoyao Jiawei Gancao Decoction(芍药加味甘草汤)with Acupoint Application on Chronic Lumbar Muscle Strain and the Recovery of Lumbar Strength

Objective:To study the therapeutic effect of Shaoyao Jiawei Gancao Decoction(芍药加味甘草汤)with acupoint application on chronic lumbar muscle strain and the recovery of lumbar strength.Methods:From August 2018 to August 2019,100 patients with chronic lumbar muscle strain admitted to our hospital were selected and randomly divided into an acupoint application group and a combined group of 50 cases each.The acupoint application group was treated by acupoint application,and the combined group was treated with Shaoyao Jiawei Gancao Decoction(芍药加味甘草汤)based on acupoint application.The indexes scores,VAS scores,ADL scores,ODI scores,lumbar endurance,TCM syndrome scores and the treatment effects of the two groups before and after treatment were statistically analyzed,and TNF-αand TXB2 levels were detected.Results:After treatment,the scores of indexes,VAS,ODI,TCM syndrome,TNF-αand TXB2 in the combined group were lower than those in the acupoint application group,and the ADL score,lumbar endurance and treatment efficiency were higher than those in the acupoint application group,with a statistical difference(P<0.05).Conclusion:Shaoyao Jiawei Gancao Decoction(芍药加味甘草汤)with acupoint application can effectively reduce pain,improve lumbar function,restore lumbar strength,effectively relieve inflammation,with significant effects.

Effectiveness and safety of Jiawei Xiaoyao pill(加味逍遥丸)in the treatment of premenstrual syndrome(liver depression,spleen deficiency,and blood-heat syndrome):a multi-center,randomized,placebo-controlled trial

OBJECTIVE:To investigate the effectiveness and safety of Jiawei Xiaoyao pill(加味逍遥丸,JXP)in the treatment of symptoms associated with premenstrual syndrome(PMS).METHODS:A total of 144 regularly menstruating women with PMS were recruited at 8 sites in China from August 2017 to December 2018,and randomized to receive either a JXP or a matching placebo(12 g/d,6 g twice a day)for 3 menstrual cycles.The primary indicator was the reduced Daily Record of Severity of Problems(DRSP)scores in the luteal phase after 3 months of treatment.The safety outcomes included clinical adverse events(AEs),adverse reactions(ARs),changes in vital signs,and laboratory tests.RESULTS:JXP surpassed the placebo in reducing DRSP scores(psychological/somatic dysfunction)in the luteal phase over 3 menstrual cycles of treatment(PFAS=0.002,PPPS=0.001).Additionally,there were no significant differences in the incidence of AEs,severe AEs,withdrawal due to AEs and ARs between the two groups(all P>0.05),and no clinically significant adverse medical events related to the test drug observed.CONCLUSIONS:JXP was superior to the placebo in relieving the symptoms associated with PMS,which signified that JXP may be effective,safe,and welltolerated as an alternative therapy.

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

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.

加味逍遥散通过外泌体miRNA途径发挥抗肝癌作用

背景:在课题组先前研究中发现加味逍遥散具有明显的抗肝癌作用,但具体作用机制不明。目的:基于高通量测序结合生物信息学,探讨加味逍遥散对二乙基亚硝胺慢性诱导的原发性肝癌模型大鼠血浆外泌体miRNA水平的调节作用。方法:将SD大鼠随机分为空白对照组、肝癌模型组、加味逍遥散组。以二乙基亚硝胺持续给药12周诱导肝癌模型,从第17周开始,加味逍遥散组大鼠给予加味逍遥散灌服,每日1次,直至第20周末停药,空白对照组和肝癌模型组大鼠给予等量生理盐水灌胃,通过检测大鼠肝组织的形态结构、肝癌标志物Glypican-3蛋白和血清甲胎蛋白表达验证抗肝癌效应。使用超速离心法分离提取各组大鼠血浆外泌体,利用高通量测序技术筛选出大鼠血浆外泌体中差异表达的miRNA,生物信息学预测加味逍遥散通过肝癌血浆来源外泌体miRNA发挥抗肝癌作用的潜在生物标志物,并进行功能分析。结果与结论:①加味逍遥散对肝癌模型大鼠肝组织的形态结构有显著改善作用,与肝癌模型组相比,加味逍遥散组肝癌标志物Glypican-3蛋白和血清甲胎蛋白的表达均显著降低;②生物信息学分析显示,加味逍遥散组对肝癌模型组上调的miR-223-3p与基因E2F1、NCOA1存在靶向结合位点,并且与肝癌生存率及预后密切相关。由此可见,加味逍遥散对肝癌有治疗作用,可能是通过肝癌血浆来源外泌体miR-223-3p靶向负调控NCOA1/E2F1进而发挥抗肝癌效应。

Effect of Jiawei Shenfu decoction on tumor necrosis factor-alpha and nuclear factor-kappa B in patients who have chronic heart failure with syndromes of deficiency of heart Yang

OBJECTIVE:To examine the clinical efficacy of Jiawei Shenfu decoction on tumor necrosis factor-alpha (TNF-cα) and nuclear factor-kappa B (NF-KB) levels in patients who have chronic heart failure with syndromes of deficiency of heart Yang.METHODS:A total of 63 patients with syndromes of deficiency of heart Yang (chronic heart failure)were enrolled.Patients were randomly divided into the control group and Jiawei Shenfu group.All patients received standard medications for treatment of chronic heart failure.Patients in the Jiawei Shenfu group were additionally provided Jiawei Shenfu decoction one dose daily.Treatments continued for 4 consecutive weeks.The primary endpoint was the change in plasma B-type natriuretic peptide (BNP),NF-KB,and TNF-cα levels during 4 weeks of treatment.RESULTS:At the 4-week follow-up,a significant reduction in BNP levels compared with baseline was observed in both groups,but the Jiawei Shenfu decoction group showed a significantly greater reduction than did the control group.The Jiawei Shenfu group also showed superior performance regarding the Minnesota Living with Heart Failure Questionnaire score,the Chinese medicine syndrome score,heart rate,left ventricular ejection fraction,and 6-min walking distance compared with the control group.The degree of changes in NF-KB and TNF-α levels in the Jiawei Shenfu group was more significant than that in the control group.CONCLUSION:Routine medicine combined with Jiawei Shenfu decoction for patients with heart Yang deficiency syndrome in chronic heart failure can improve the left ventricular ejection fraction and cardiac function,and reduce BNP levels.The mechanism may be related to inhibition of pro-inflammatory cytokines and the NF-KB-induced kinase pathway,leading to amelioration of the inflammatory response.

Jiawei Xiaoyao capsule treatment for mild to moderate major depression with anxiety symptoms: a randomized, double-blind, double-dummy, controlled, multicenter, parallel-treatment trial

OBJECTIVE:To assess the efficacy and safety of Jiawei Xiaoyao (JWXY) capsules on mild to moderate depression with anxiety symptoms,a randomized,double-blind,double-dummy controlled,multicenter,parallel-treatment trial was carried out among 210 outpatients with mild to moderate depression and anxiety symptoms from three hospitals in Beijing China.METHODS:Participants were randomized into the JWXY group or the sertraline group.Each group received JWXY treatment and sertraline placebo,or sertraline and JWXY placebo for 8 weeks.Main outcomes were measured using the Hamilton Depression Rating Scale (HAMD),Hamilton Anxiety Rating Scale (HAMA) and the Clinical Global Impression Scale.RESULTS:JWXY and sertraline had the equivalent effect on HAMD at every interview point.JWXY was more effective at reducing the HAMA scores at the 2nd and 12th week,HAMD sleep disturbance subscale scores at the 8th and 12th week,and HAMA somatic anxiety subscale scores at the 12th week.The rate of adverse events in the two groups was the same.CONCLUSION:For mild to moderate depression with anxiety symptoms,JWXY could be as effective as sertraline in alleviating depressive symptoms.For anxiety symptoms,JWXY may be effective more quickly and with longer lasting effects than sertraline.In particular,it may also improve quality of sleep and somatic anxiety symptoms.JWXY is safe and cheaper than conventional antidepressants,and may be the first alternative choice for depression with anxiety symptoms.

Jiawei Erzhiwan improves menopausal metabolic syndrome by enhancing insulin secretion in pancreatic β cells

Menopausal metabolic syndrome(MMS) is a series of syndrome caused by ovarian function decline and hormone insufficiency, and is a high risk factor for cardiovascular diseases(CVD) and type II diabetes mellitus(T2DM). Erzhiwan(EZW),composed of Herba Ecliptae and Fructus Ligustri Lucidi, is a traditional Chinese herbal formula that has been used to treat menopausal syndrome for many years. We added Herba Epimedii, Radix Rehmanniae, and Fructus Corni into EZW, to prepare a new formula, termed Jiawei Erzhiwan(JE). The present study was designed to determine the anti-MMS effects of JE using ovariectomized(OVX) adult female rats that were treated with JE for 4 weeks, and β-tc-6 cells and INS cells were used to detected the protect effectiveness of JE. Our results showed JE could increase insulin sensitivity and ameliorated hyperlipidemia. Metabolomics analysis showed that the serum levels of branched and aromatic amino acids were down-regulated in serum by JE administration. Moreover, JE enhanced the function of islet βcells INS-1 and β-tc-6, through increasing the glucose stimulated insulin secretion(GSIS), which was abolished by estrogen receptor(ER)antagonist, indicating that JE functions were mediated by ER signaling. Additionally, JE did not induce tumorigenesis in rat mammary tissue or promoted proliferation of MCF-7 and Hela cells. In conclusion, our work demonstrated that JE ameliorated OVX-induced glucose and lipid metabolism disorder through activating estrogen receptor pathway and promoting GSIS in islet β cells, thus indicating that JE could be a safe and effective medication for MMS therapy.

Effects and mechanism of Chinese medicine Jiawei Yupingfeng in a mouse model of allergic rhinitis

Objective: Chinese medicine has the potential to modulate allergic rhinitis(AR). There have been studies investigating the treatment efficacy of Yupingfeng San, alone or in combination with other ingredients, in AR, though few have studied the potential mechanisms of these drugs. In the present study, we measured the effects of Jiawei Yupingfeng(JWYPF), a traditional Chinese medicine formula, on mice with ovalbumin-induced AR and explored its underlying mechanism of action.Methods: Forty BALB/c mice were randomly divided into normal control, allergy control and two treatment groups of ten mice each. In the normal control group, mice were sensitized and challenged with saline. The mice in the allergy control and treatment groups were sensitized and challenged with ovalbumin and aluminum hydroxide gel. The treatments of JWYPF and Nasonex were administered intranasally in the AR mice for one week. Several signs of allergic inflammation, such as nasal eosinophils and inflammatory cytokines, were measured to determine the underlying mechanisms.Results: Mice in the JWYPF and Nasonex groups had significantly lower AR symptom scores than those in the allergy control group(the mean differences between JWYPF and the allergy control, and Nasonex and the allergy control were -2.00 ± 0.35 and -2.40 ± 0.32). After treatment with JWYPF and Nasonex, the levels of ovalbumin-specific Ig E and histamine were significantly reduced, as were the levels of interlukin-4 and transforming growth factor-b, while interferon-c levels were increased(all P < 0.0001,vs. allergy control). These two treatments also significantly inhibited eosinophil and mast cell infiltration into the nasal cavity but were not statistically different from one-another.Conclusion: JWYPF has a potential therapeutic effect on AR via adjusting the rebalance of T helper 1 and T helper 2.

Jiawei Xiaoyao San in treatment of anxiety disorder and anxiety:A review

Jiawei Xiaoyao San(JWXYS)has shown excellent clinical efficacy in anxiety disorder,but has not yet attracted widespread attention.The animal experiments,clinical trials and mechanism studies of JWXYS were reviewed in this article,which may provide a reference for developing new anxiolytic drugs based on this prescription.The literature was searched in PubMed and CNKI and the documents written in English or with English abstracts were selected.JWXYS could reduce the anxiety symptoms of patients alone and reduce the adverse reactions when it is used in combination with other drugs in the clinic.In preclinical studies,JWXYS also showed therapeutic effects in reducing anxiety-like behavior.The mechanisms may include improving the hypothalamic–pituitaryadrenal(HPA)axis and hormone disorders,increasing neurotransmitter content,neurogenesis,and regulating the synthesis of related enzymes.This article shows that JWXYS could effectively treat anxiety disorders by regulating the central nervous system.In the future,with the participation of more researchers,it is expected to develop innovative drugs for the treatment of anxiety disorders based on JWXYS.

加味春泽汤调控内质网应激凋亡治疗脊髓损伤大鼠的尿潴留

背景:前期临床观察发现加味春泽汤是临床治疗脊髓损伤后尿潴留的有效方剂。动物实验发现磷脂酰肌醇3激酶/蛋白激酶B(PI3K/Akt)信号通路与膀胱功能障碍程度密切相关。目的:进一步验证加味春泽汤对脊髓损伤后尿潴留大鼠膀胱功能及PI3K/Akt通路的影响。方法:将60只SD雌性大鼠随机分为假手术组、模型组、加味春泽汤低剂量组、加味春泽汤高剂量组、激动剂组。假手术组大鼠暴露脊髓但不切断,其余各组大鼠采用改良后的Hassan Shaker脊髓横断法建立骶髓损伤大鼠模型。造模24 h后,假手术组和模型组大鼠给予等体积生理盐水灌胃,加味春泽汤低、高剂量组大鼠分别给予含有14.4 g/kg和28.8 g/kg的加味春泽汤颗粒剂,等体积灌胃4周,激动剂组大鼠给予PI3K/Akt信号通路激动剂740Y-P腹腔注射0.02 mg/kg治疗。治疗4周后采用尿流动力学检测各组大鼠膀胱最大容量、漏尿点压力、膀胱顺应性,膀胱离体逼尿肌条收缩性检测各组大鼠膀胱最小收缩张力、收缩频率,苏木精-伊红染色观察各组大鼠膀胱病理学改变,ELISA法检测各组大鼠血清中GRP78、CHOP、Caspase-12水平,RT-PCR、Western blot法检测大鼠膀胱组织PI3K、Akt、GRP78、CHOP、Caspase-12 mRNA及蛋白的表达。结果与结论:①与假手术组相比,模型组大鼠膀胱最大容量、膀胱顺应性、最小收缩张力升高(P<0.05),漏尿点压力、膀胱收缩频率降低(P<0.05);血清中GRP78、CHOP、Caspase-12水平升高(P<0.05);膀胱上皮细胞排列紊乱,细胞间存在单核细胞浸润,组织水肿,逼尿肌束萎缩;膀胱组织PI3K、Akt mRNA和蛋白表达降低,GRP78、CHOP、Caspase-12 mRNA和蛋白表达升高(P<0.05)。②与模型组相比,加味春泽汤低、高剂量组及激动剂组干预4周后,大鼠膀胱最大容量、膀胱顺应性、最小收缩张力降低(P<0.05),漏尿点压力、膀胱收缩频率升高(P<0.05);血清中GRP78、CHOP、Caspase-12水平降低(P<0.05);膀胱上皮细胞分布较均匀,排列较整齐,炎细胞浸润较少,逼尿肌束较饱满;膀胱组织PI3K、Akt mRNA和蛋白表达增加,GRP78、CHOP、Caspase-12 mRNA和蛋白表达降低(P<0.05)。加味春泽汤高剂量组优于低剂量组,与激动剂组结果相似。③结果说明,加味春泽汤可以改善脊髓损伤后尿潴留大鼠膀胱功能,其作用机制可能与通过PI3K/Akt信号通路减轻膀胱组织内质网应激的发生,进而减轻凋亡有关。