Mechanism of Wendan decoction in preventing obesity by regulating multiple signal pathway networks based on gene promoter methylation

Objective:To investigate the potential mechanism of Wendan decoction in obesity by screening target genes with promoter region methylation changes and constructing a multiple signaling pathways network based on promoter methylation.Methods:The methylation degree of Itgad,Col8a1,Adra2b,Jund,Rab2a,Wnt8b,Fzd9,B4galt7,Pik3cd,Creb1,Stard8,and Mmp1 in the abdominal adipose tissue of obese rats was determined using the Agena MassARRAY system.Western blot was performed to assess protein expression levels.Target genes were identified based on the methylation degree in the promoter region and protein expression.Enrichment analysis of signaling pathways was conducted to identify relevant target genes and obtain a multiple signaling pathway network associated with obesity.Core and terminal effector molecules in the pathway networks were selected as research targets for reverse transcription-polymerase chain reaction(RT-PCR)analysis.Results:Four genes(Adra2b,Creb1,Itgad,and Pik3cd)showed a degree of promoter methylation consistent with their respective protein expression levels.Among them,Adra2b,Creb1,and Pik3cd expression increased,while that of Itgad decreased.Enrichment analysis revealed that Creb1 and Pik3cd were involved in 6 signaling pathways related to obesity:tumor necrosis factor(TNF)signaling pathway,growth hormone synthesis/secretion and action,adenosine 5'-monophosphate-activated protein kinase(AMPK)signaling pathway,relaxin signaling pathway,cyclic nucleotide(cAMP)signaling pathway,and phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)signaling pathway.Subsequently,a multiple signaling pathways network was constructed based on promoter methylation.Key molecules including protein kinase B(AKT),mechanistic target of rapamycin complex 1(mTORC1),and unc-51 like autophagy activating kinase 1(ULK1),as well as terminal effector molecules interleukin-1β(IL-1β),interleukin-6(IL-6),and chemokine(C-X-C motif)ligand 2(CXCL2)were selected as research targets.Wendan decoction decreased the expressions of AKT,mTORC1,IL-1β,IL-6,and CXCL2 while up-regulating ULK1 expression.Conclusion:The mechanism of Wendan decoction in preventing obesity involves the regulation of multiple signaling pathways through the control of Creb1 and Pik3cd gene promoter methylation.However,the associated multi-path gene regulation mechanism in preventing obesity is complex.Thus,further exploration is needed to elucidate the role of methylation changes in this mechanism.

Therapeutic effect of Wendan Decoction combined with mosapride on gastroesophageal reflux disease after esophageal cancer surgery

BACKGROUND Gastroesophageal reflux disease(GERD)is a common complication of esophageal cancer surgery that can affect quality of life and increase the risk of esophageal stricture and anastomotic leakage.Wendan Decoction(WDD)is a traditional Chinese herbal formula used to treat various gastrointestinal disorders,such as gastritis,functional dyspepsia,and irritable bowel syndrome.Mosapride,a prokinetic agent,functions as a selective 5-hydroxytryptamine 4 agonist,enhancing gastrointestinal motility.AIM To evaluate the therapeutic effects of WDD combined with mosapride on GERD after esophageal cancer surgery.METHODS Eighty patients with GERD were randomly divided into treatment(receiving WDD combined with mosapride)and control(receiving mosapride alone)groups.The treatment was conducted from January 2021 to January 2023.The primary outcome was improved GERD symptoms as measured using the reflux disease questionnaire(RDQ).The secondary outcomes were improved esophageal motility(measured using esophageal manometry),gastric emptying(measured using gastric scintigraphy),and quality of life[measured via the Short Form-36(SF-36)Health Survey].RESULTS The treatment group showed a notably reduced RDQ score and improved esophageal motility parameters,such as lower esophageal sphincter pressure,peristaltic amplitude,and peristaltic velocity compared to the control group.The treatment group showed significantly higher gastric emptying rates and SF-36 scores(in both physical and mental domains)compared to the control group.No serious adverse effects were observed in either group.CONCLUSION WDD combined with mosapride is an effective and safe therapy for GERD after esophageal cancer surgery.It can improve GERD symptoms,esophageal motility,gastric emptying,and the quality of life of patients.Further studies with larger sample sizes and longer follow-up periods are required to confirm these findings.

Initial steps on the analysis of the underlying pharmacological mechanisms of Wendan decoction on sudden deafness using network pharmacology and molecular docking

Background:Despite its widespread therapeutic use and effectiveness,the underlying pharmacologic mechanisms of Wendan decoction(WDD)and how it works to treat sudden deafness(SD)remain unclear.In this study,the pharmacological mechanisms of WDD underlying SD were analyzed using network pharmacology and molecular docking.Methods:The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)was employed to identify the active compounds and target genes of WDD,and genes associated with SD were screened on five databases.RGUI conducted Gene Ontology(GO)functional and the Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses.A compound-target network was established using Cytoscape,and the STRING database created a protein-protein interaction(PPI)network to identify the key compounds and targets.Subsequently,a network of crucial compound-target was generated for further molecular docking analysis.For molecular docking simulations of the macromolecular target proteins and their matching ligand molecules,AutoDock Vina and AutoDockTool were utilized.Results:TCMSP identified 162 active target genes and 36 active compounds for WDD.The active target genes were compared with the 2271 genes associated with SD to identify 70 intersecting active target genes linked to 34 active compounds.The GO functional enrichment and KEGG pathway enrichment analyses were undertaken,and compound–target,and PPI networks were built.The key compounds and protein targets were identified and integrated to form a key compound–target network.Eventually,molecular docking was performed to investigate the interactions of the protein targets with their respective compounds.Conclusion:This study highlights the mechanisms of multi-compounds,targets,and pathways of WDD acting on SD and provides further evidence of crucial compounds and their matching target proteins of WDD acting on SD.

Bibliometric analysis of Wendan decoction research based on the Web of Science database

Objective:With the development of Wendan decoction(WDD)and more literature on the research of WDD,we aimed to present an insight into WDD research using bibliometric analysis.Methods:We retrieved data from the Web of Science database from 2008 to 2022.Publication trends were examined using data from journals,authors,institutions,international collaborations,citations,and keywords from the online analytical platform Bibliometric(http://bibliometric.com).Results:Over the years,an increase in the use of keywords,including depression,insomnia,Alzheimer’s disease,schizophrenia,hippocampus,and insomnia,was observed.The outcomes of the analysis revealed that topics related to WDD have become increasingly prevalent in the last five years,and the internationally recognized application of WDD is mainly neuropsychiatric diseases.Conclusion:We exhibited WDD research progress by identifying and evaluating WDD-focused articles.Our analysis revealed the trend of the topics from 2008 to 2022,which can assist scholars in identifying future trends.

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.

Wendan decoction improves learning and memory deficits in a rat model of schizophrenia

An experimental model of schizophrenia was established using dizocilpine （MK-801）. Rats were intragastrically administered with Wendan decoction or clozapine for 21 days prior to establishing the model. The results revealed that the latency of schizophrenia model rats to escape from the hidden platform in the Morris water maze was significantly shortened after administration of Wendan decoction or clozapine. In addition, the treated rats crossed the platform significantly more times than the untreated model rats. Moreover, the rate of successful long-term potentiation induction in the Wendan decoction group and clozapine group were also obviously increased compared with the model group, and the population spike peak latency was significantly shortened. These experimental findings suggest that Wendan decoction can improve the learning and memory ability of schizophrenic rats to the same extent as clozapine treatment.

Meta-analysis of the efficacy and safety of Huanglian Wendan Decoction alone or combined with western medicine in treating insomnia caused by phlegm-heat internal disturbance

Objective To evaluate the efficacy and safety of Huanglian Wendan Decoction(黄连温胆汤,HLWDD)alone or combined with western medicine in treating insomnia caused by phlegm-heat internal disturbance in recent 10 years.Methods The randomized controlled trials of HLWDD alone or combined with western medicine in treating insomnia caused by phlegm-heat internal disturbance from January 1,2012 to April 1,2022 were searched in China National Knowledge Infrastructure(CNKI),China Science and Technology Journal Database(VIP),Wanfang Database,China BioMedical Literature Database(CBM),PubMed,Web of Science,Embase,and Cochrane Library databases.After being screening,the included literature was analyzed to evaluate the effective rate,Pittsburgh Sleep Quality Index(PSQI)score,traditional Chinese medicine(TCM)syndrome score,and adverse reactions of HLWDD on insomnia caused by phlegm-heat internal disturbance.The subgroup analyzed the effect of HLWDD after different treatment courses,and compared the therapeutic effects of HLWDD alone and HLWDD combined with western medicine.Results Twenty-seven randomized controlled trials were finally included,with a total of 2395 patients.The results of the meta-analysis showed that the curative effect of HLWDD alone or combined with the western medicine group was better than that of the western medicine group[RR=1.14,95%CI(1.06,1.22),P=0.000].The PSQI score[SMD=-0.31,95%CI(-0.42,-0.20),P=0.000],TCM syndrome score[SMD=-0.40,95%CI(-0.67,-0.12),P=0.005],and adverse reaction rate[RR=0.21,95%CI(0.15,0.29),P=0.000]of HLWDD alone or combined with western medicine group were significantly reduced compared with the western medicine group.The subgroup’s analysis showed that the curative effect of HLWDD alone or combined with western medicine group of 4 weeks treatment course was better than that of the western medicine group[RR=1.14,95%CI(1.03,1.26),P<0.05].The TCM syndrome score of HLWDD alone or combined with the western medicine group of 4 weeks treatment course decreased more obviously than that of the western medicine group[SMD=-0.60,95%CI(-0.96,-0.25),P<0.05].There were no significant differences between HLWDD alone or combined with western medicine group and western medicine group with different treatment courses based on PSQI score and adverse reaction rate.Based on the effective rate,the comparison between the HLWDD alone group and the western medicine group[RR=1.09,95%CI(1.00,-1.20)P<0.05],and between the HLWDD combined with western medicine group and the western medicine group[RR=1.15,95%CI(1.03,1.29),P<0.05]was the same.PSQI score[SMD=-0.44,95%CI(-0.59,-0.30),P<0.05]and TCM syndrome score[SMD=-1.10,95%CI(-1.59,-0.61),P<0.05]of HLWDD combined with western medicine group were significantly lower than those of the western medicine group.There were no significant differences of adverse reaction rate between HLWDD alone group[RR=0.08,95%CI(0.04,0.17),P<0.05]and HLWDD combined with western medicine group[RR=0.36,95%CI(0.24,0.53),P<0.05].Conclusion HLWDD alone or combined with western medicine is an effective treatment for insomnia caused by phlegm-heat internal disturbance,which has a high effective rate,significantly reduced PSQI score and TCM syndrome score,and favorable safety.The best course of treatment is 4 weeks.

Efficacy of Wendan Decoction series for coronary heart disease with anxiety and depression:A systematic review and meta-analysis

Objective:To systematically evaluate the clinical efficacy of Wendan Decoction series combined with conventional western medicine in the treatment of coronary heart disease complicated with anxiety and depression.Methods:We searched four Chinese databases including CNKI,WanFang,VIP,SinoMed,and five English databases of PubMed,Cochrane Library,Web of Science,EMBASE,Springer Link for clinical randomized controlled trials of using Wendan Decoction series in the treatment of coronary heart disease complicated with anxiety and depression.Time range for searching was from the establishment of these databases to January 2022.Then we screened the retrieved literature according to the inclusion and exclusion criteria,and conducted data extraction and quality evaluation of the selected literature.Meta analysis was conducted using RevMan 5.3 software.Results:A total of 13 RCT studies and 1007 patients with coronary heart disease complicated with anxiety and depression were included.Meta-analysis showed that Wendan Decoction series combined with conventional western medicine treatment showed better effects in the improvement rate of clinical anxiety[RR=1.21,95%CI=(1.12,1.31),P<0.00001],the improvement rate of depression[RR=1.30,95%CI=(1.10,1.53),P=0.002],the improvement rate of angina pectoris[RR=1.28,95%CI=(1.13,1.44),P<0.0001],increasing the ECG improvement rate[RR=1.29,95%CI=(1.07,1.55),P=0.008],increasing the rate of reducing nitroglycerin usage[RR=1.68,95%CI=(1.25,2.25,P=0.0006],as well as increasing the improvement rate of TCM symptoms[RR=1.15,95%CI=(1.04,1.26),P=0.004].It also showed better effects in reducing clinical anxiety and depression scores(SAS,SDS,HAMA,HAMD),SAQ scores and TCM symptom scores.The differences were statistically significant.Conclusion:Wendan Decoction series combined with conventional western medicine shows advantages in treating coronary heart disease patients complicated with anxiety and depression in reducing the angina pectoris score,anxiety and depression score,as well as improving the clinical TCM symptoms.

A meta-analysis of Wendan decoction in the treatment of diabetic gastroparesis

Objective To evaluate the clinical efficacy and safety of Wendan decoction in the treatment of diabetic gastroparesis (DGP). Methods PubMed, MEDLINE, The Cochrane Library, Embase, China Biology Medicine (CBM), Chinese National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP) and Wanfang databases were searched and eligible randomized controlled clinical trials (RCTs) were included. The quality of the RCTs was evaluated by the Cochrane risk of bias assessment tool, and data analysis were performed with Review Manager 5.3. Results A total of 7 studies were included, including 533 patients. Meta analysis results showed that the effective rate of Wendan decoction in the treatment of diabetic gastroparesis was better than that of the control group [RR=1.30, 95%CI (1.20, 1.40), P<0.001], and the improvement of fasting blood glucose (FBG) was better than that of western medicine [MD =-0.43, 95%CI (-0.91,-0.01), P=0.05]. The recurrence rate in the TCM treatment group was lower than that in the western medicine group[RR = 0.29, 95%CI (0.13, 0.62), P=0.002]. Conclusion Compared with western medicine, Wendan decoction has better curative effect on DGP and can reduce its recurrence rate. However, due to the low quality of the included literatures and the possibility of bias, large-scale and high-quality RCTs are still needed for further confirmation.

The Mechanism of Regulating Leptin Resistance in Obesity and the Influence of Adjusting Methylation of OB-R,POMC Gene Promoter of Wendan Decoction (温胆汤)

Objective:To explore the mechanism of Wendan Decoction(温胆汤)regulating leptin resistance in obesity by analyzing the level of leptin in peripheral blood,the expression of leptin receptor and signal pathway molecule POMC in hypothalamus.To analyze the methylation status of the gene promoters of leptin receptor and POMC in obese rats fed with high fat diet,and the influence of adjusting methylation of OB-R,POMC gene promoter about Wendan decoction.Methods:Model rats were randomly divided into model control group and drug observation group,additional normal rats with 8 rats in each group.The models were established by high fat diet.The observation group was treated with Wendan Decoction(温胆汤)and the other two groups were treated with sterilized drinking water once a day for 6 weeks.Body weight was recorded every week during the intervention.Peripheral blood and hypothalamus were collected at the end of the experiment.The serum leptin level was measured by ELISA method,and the expression of OB-R and POMC in hypothalamus was detected by RT-qPCR method.Methylation level of OB-R and POMC promoter detected by methylation specific PCR.Results:Our results revealed that Wendan Decoction(温胆汤)could effectively reduce body weight,the body weight in the drug observation group was significantly lower than that in the model control group,and the difference between the two groups was statistically significant.The level of leptin in peripheral blood and the expression of OB-R in hypothalamus were consistent with the trend of body weight.The heavier the weight,the higher the level of leptin and OB-R.Wendan Decoction(温胆汤)could reduce the level of leptin and OB-R in peripheral blood while reducing body weight.Compared with the model control group,the difference was statistically significant.The heavier the weight,the lower the level of POMC expression.Wendan Decoction(温胆汤)could increase the expression of POMC while reducing body weight,which had statistical significance compared with the model control group.The methylation status of OB-R and POMC promoter in hypothalamus was not significantly associated with obesity induced by high fat diet,and Wendan Decoction(温胆汤)had no effect on methylation status.Conclusions:Wendan Decoction(温胆汤)could inhibit obesity by affecting the expression of leptin receptor and POMC mRNA in hypothalamus to a large degree.There was no obvious change about the methylation status of the gene promoters of leptin receptor and POMC in obese rats fed with high fat diet.And it was not related to the change of methylation status of gene promoter about the mechanism of Wendan Decoction(温胆汤).

Effect of the modified wendan decoction on hippocampal astrocyte neurotrophy by regulating the TRP-KYN metabolic pathway in depression-model rats

Objective:To observe the effect of the modified Wendan decoction on the neurotrophic function of hippocampal astrocytes by regulating the tryptophan-kynurenine(TRP-KYN)neuroprotective metabolic pathway in depression-model rats.Methods:A total of 96 Sprague Dawley(SD)rats were randomly divided into the blank group,model group,sham surgery group,neurotoxicity blocker group(blocker 1 for short)group,decoction group,fluoxetine group,blocker 1 plus decoction group,and blocker 1 plus fluoxetine group.Depression in rats of all groups,except for the blank group,was generated by isolation combined with chronic unpredictable mild stress.After corresponding treatments of the rats in each group,the sucrose preference test was performed to evaluate the depressive behaviors of the rats.Serum levels of tryptophan(TRP),kynurenine(KYN),and kynurenic acid(KYNA)were detected via enzyme-linked immunosorbent assay(ELISA);the mRNA/protein expression of hippocampal astrocyte markers,glial fibrillary acidic protein(GFAP)and S100β,was detected via reverse transcription-polymerase chain reaction(RT-PCR)and immunohistochemistry.ELISA and RT-PCR were carried out to detect the levels/mRNA expressions of brain-derived neurotrophic factor(BDNF)and glial-cell-line-derived neurotrophic factor(GDNF),the nutrient secretions of hippocampal astrocytes in rats.Results:Compared to the blank group,the number of activities of rats was significantly reduced,and the GFAP expression in the hippocampus was significantly increased while the BDNF and GDNF expressions were significantly decreased in the model group.With the intervention of the modified Wendan decoction,the depression of rats was significantly improved,and the BDNF and GDNF expressions in the hippocampus were increased while the GFAP expression was decreased significantly in the model group.Conclusion:The modified Wendan decoction may improve the neurotrophic function of rats’hippocampal astrocytes by enhancing the neuroprotective function of the TRP-KYN pathway,thereby exerting an antidepressant effect.

Protective effects of modified Wendan decoction on hippocampal neurons in a rat model of depression

Objective:To study the effects of modified Wendan decoction on hippocampal neuron plasticity in a rat model of depression.Methods:Thirty-two rats were randomly divided into a blank control group,model group,traditional Chinese medicine(modified Wendan decoction)group,and Western medicine(fluoxetine)group.Isolation in conjunction with the chronic unpredictable mild stress(CUMS)method was used to replicate depression in rats from the experimental groups.The rats were treated for 28d following successful modeling.After treatment,transmission electron microscopy(TEM)was used to observe the ultrastructure of hippocampal dentate gyrus(DG)region in the rats.Enzyme-linked immunosorbent assay(ELISA)was performed to measure the levels of brain-derived neurotrophic factor(BDNF)and glial cell line-derived neurotrophic factor(GDNF)in hippocampal tissue.Additionally,RT-PCR was used to measure hippocampal BDNF and GDNF mRNA expression levels.Results:Compared to the control group,there was significant swelling,disordered cell arrangement,pyknosis,deepening of cytoplasmic staining in the hippocampal neurons,and severe hippocampal injury in the model group.Following treatment with the traditional Chinese medicine intervention,hippocampal neuronal injury was significantly alleviated,hippocampus structure was normal,and brain injury was significantly reduced in the depression rat model.Compared to the control group,hippocampal BDNF and GDNF mRNA levels in the model group were reduced(P<0.05).Compared to the model group,hippocampal BDNF and GDNF mRNA levels in the traditional Chinese medicine group increased(P<0.05).Conclusion:Modified Wendan decoction can increase hippocampal neurotrophic function and repair hippocampal neuronal injury,thereby preventing depression.

On the Modern Clinical Application of Wendan Decoction

Wendan Decoction is one of the commonly used prescriptions in clinical practice.it has a wide range of applications.On the basis of traditional Chinese medicine(TCM)syndrome differentiation,as long as it can be added or subdivided flexibly,it can be used to conquer various difficult and miscellaneous diseases seen in daily life.

Effect of modified Wendan Decoction on enteric glia cells in depression model rats

Background:To explore the effect of modified Wendan Decoction on expression of enteric glial cells in depression model rats.Methods:Eighteen rats were randomly divided into the Blank group,Model group,and modified Wendan Decoction group(Decoction group).Depression was induced by isolation combined with chronic unpredictable mild stress in rats of all groups except for the Blank group.Changes of protein and mRNA expressions of the specific markers of enteric glial cells,glial fibrillary acidic protein,and S100 calcium-binding proteinβsubunit(S100β)in the stomach and colon tissues of rats in each group were detected respectively using immunohistochemistry and reverse transcription-polymerase chain reaction(RT-PCR).Results:Compared with the Blank group,the percentage of positive cells and the mRNA expression of GFAP and S100βwere increased in the Model group,and the difference was statistically significant(P<0.05);compared with the Model group,the percentage of positive cells and the mRNA expression of GFAP and S100βin gastrointestinal tissues of rats were decreased in the Decoction group,and the difference was statistically significant(P<0.05).Conclusion:The depression model rats developed hyperplasia,and enteric glial cells(EGCs)was activated.The mechanism of action of the Wendan Decoction on improving depression and promoting gastrointestinal motility may be achieved by inhibiting the hyperplasia and activation of EGCs in rats with depression.

Protective effects of Huanglian Wendan Decoction aganist cognitive deficits and neuronal damages in rats with diabetic encephalopathy by inhibiting the release of inflammatory cytokines and repairing insulin signaling pathway in hippocampus

Huanglian Wendan decoction(HLWDD) has been used for the treatment of symptom of "Re", one of major causes in diabetes and metabolic disorders, according to the theory of traditional Chinese medicine. The present study aimed at investigating the cerebral protective effects of HLWDD on diabetic encephalopathy(DE), one of the major diabetic complications. The effects of HLWDD and metformin were analyzed in the streptozocin(STZ) + high-glucose-fat(HGF) diet-induced DE rats by gastric intubation. In the present study, the effects of HLWDD on cognition deficits were investigated after 30-day intervention at two daily dose levels(3 and 6 g·kg^(-1)). To explore the potential mechanisms underlying the effects of HLWDD, we detected the alterations of neuronal damages, inflammatory cytokines, and impaired insulin signaling pathway in hippocampus of the DE rats. Based on our results from the present study, we concluded that the protective effects of HLWDD against the cognitive deficits and neuronal damages through inhibiting the release of inflammatory cytokines and repairing insulin signaling pathway in hippocampus of the DE rats.

Wendan Decoction(温胆汤) for Treatment of Schizophrenia: A Systematic Review of Randomized Controlled Trials

Objective： To assess the beneficial and adverse effects of Wendan Decoction （温胆汤, WDD） for the treatment of schizophrenia. Methods： Five electronic databases were searched until May 2014, including the Chinese National Knowledge Infrastructure, the Chinese Biomedical Literature Database, the Chinese Scientist Journal Database, PubMed, and the Cochrane Central Register of Controlled Trials in the Cochrane Library. The randomized controlled trials （RCTs） testing WDD against placebo, antipsychotic drugs, or WDD combined with antipsychotic drugs against antipsychotic drugs alone were included. Study selection, data extraction, quality assessment, and data analyses were conducted according to the Cochrane standards. Results： Thirteen RCTs （involving 1,174 patients） were included and the methodological quality was evaluated as generally low. The pooled results showed that WDD combined with antipsychotic drugs were more effective in clinical comprehensive effect, Positive and Negative Syndrome Scale （PANSS） scores and Brief Psychiatric Rating Scale scores compared with antipsychotic drugs alone. However, WDD had less effectiveness compared with antipsychotics in clinical comprehensive effect; and WDD was not different from antipsychotic drugs for PANSS scores. The side effects were significantly reduced in the intervention group compared with the control group. Conclusions： WDD appears to be effective on improving symptoms in patients with schizophrenia. However, due to poor methodological quality in the majority of the included trials, the potential benefit from WDD needs to be confirmed in rigorous trials and the design and reporting of trials should follow the international standards.

Exploring the mechanism of wendan decoction in the treatment of ischemic stroke using bioinformatics and network pharmacology

We investigated the pharmacological mechanism of WendanDecoction(WDD)in treating ischemicstroke(IS)using network pharmacology and molecular docking methods.The Gene Expression Omnibusdatabase was searched with“stroke”as akeyword,species as“Homosapiens,”andGeneChip data was usedto identify,screen,and analyze thedifferentially expressed genesof IS.The potential active components and related WDDtarget proteins were screened from the Traditional Chinese medicine systems pharmacology database.Cytoscape(3.8.2)was used to construct the drug-disease-target regulatory network,and Bisogenet and the CytoNCA plug-in were used to construct the protein-protein interaction(PPI).Gene Ontology and the Kyoto Encyclopedia of Genes and Genomesenrichment analyses were performed and AutoDock was used for molecular docking verification.A total of 2497 targets were obtained from 181 active compounds in WDD with8relatedIS targets.PPI network showed thatJUN,NFKBIA,FOS,and CDKN1A have high gene node degree values,withJUN exhibitingthe largest value.This suggestedthat JUN maybe amajor potential target for WDD treatment of IS.Enrichment analysis showed that WDD core targets were involved in the IL-17 and TNF signaling pathway,lipid and atherosclerosis,NF kappa B,toll-like receiver,and nod-like receiver signaling pathways.Network topology analysis showed that the key components of WDDwere luteolin,naringin,ligustrazine,beta sitosterol,quercetin,and stigmasterol;eachplayed a key role and may serve ascore compoundsfor treatingIS.Molecular docking results showed that the active components in WDDbind well with key targets.Our results suggest that various active components of WDD play a therapeutic role in IS by regulating multiple targets such as JUN,NFKBIA,FOS,and CDKN1A in multiple channels such as inflammation,immunity,and lipid metabolism.

Antidepressant mechanism of Jieyu No.1 decoction in a rat model of depression

Rats were subjected to unpredictable chronic stress and isolation-induced depression, and were then intragastrically perfused with Jieyu No.1 decoction or amitriptyline water solution for 21 consecutive days. Open-field test showed that Jieyu No.1 decoction and amitriptyline water solution significantly improved the abnormal behaviors of the depressed rats; it reduced plasma surfactant protein, corticosterone, and corticotropin releasing hormone levels, increased neuropeptide Y and somatostatin levels, and upregulated interleukin-ll3, -2, -6 protein expression in the hippocampal CA3 region. Somatostatin and interleukin-l[3 protein expression were negatively correlated with corticosterone level, and interleukin-113 protein expression was negatively correlated with corticotropin releasing hormone level. Results demonstrated that Jieyu No.1 decoction improved abnormal behaviors of depressed animals by regulating the function of the neuroimmunoendocrine system.

New Clinical Application of Chaihu Decoction

The classified prescriptions from Chaihu decoction have been widely used in ancient and modern times.In spite of many previous research studies,the extensiveness and diversity of their applications have not been systematically studied.The author applied Chaihu Wendan decoction to treat phlegm and qi stagnation in the middle energizer,applied Chaihu Guizhi decoction to treat simultaneous disease of Shaoyang and Taiyang,applied Chaihu Xiexin decoction to treat simultaneous disease of the spleen,stomach,liver,and gallbladder,applied Chaihu Ermiao powder to treat simultaneous disease of hand Shaoyang and foot Taiyin,applied Chaihu Erchen decoction to treat simultaneous disease of Shaoyang and Taiyin,applied Chailing decoction to treat simultaneous disease of hand Shaoyin and foot Taiyang,applied Chaihu Guizhi Ganjiang decoction to treat Shaoyang and Taiyin cold fluid retention and heat stagnation syndrome of Shaoyang complicated with Taiyin,applied Chaihu Xingren decoction to treat simultaneous disease of hand Shaoyang and hand Taiyin,applied Chaihu Sanren decoction to treat the disease caused by damp-heat stagnation in the hand Shaoyang and the foot Taiyin,and applied Chaihu Ganlu Xiaodu pellet to treat the diseases of hand Shaoyang and foot Yangming.The effects were all remarkable.