Shugan Jieyu capsule effects on peripheral blood micro-124, micro- 132, and brain-derived neurotrophic factor in patients with mild to moderate depression

BACKGROUND To assess the effectiveness of Shugan Jieyu capsules on peripheral blood miR-124,miR-132,and brain-derived neurotrophic factor(BDNF)levels in patients with mild to moderate depression following coronary artery intervention[percuta-neous coronary intervention(PCI)]for coronary heart disease.Patients with mild-to-moderate depression of the liver-qi stagnation type after PCI for coronary heart disease at the 305th Hospital of the People’s Liberation Army were enrolled from June 2022 to November 2023 and randomly assigned to two groups:Experimental(treated with Shugan Jieyu capsules)and control(tr-eated with escitalopram oxalate tablets).This study compared the antidepressant effects of these treatments using 17-item Hamilton Rating Scale for Depression(HAMD-17)scores,metabolic equivalents,low-density lipoprotein cholesterol,BDNF,high-sensitivity C-reactive protein levels,miR-124 and miR-132 levels,distribution of immune-related lymphocyte subsets,and traditional Chinese me-dicine syndrome scores before and after 6 weeks of treatment.RESULTS No significant difference was observed in any index between the two groups before treatment(P>0.05).After treatment,the total efficacy rates were 93.33%and 90.00%in the experimental and control groups,respectively.Experimental group had significantly lower scores for the main and secondary syndromes compared to the control group(P<0.05).No significant difference was observed in the metabolic equivalents between the two groups be-fore and after treatment(P>0.05).The levels of low-density lipoprotein cholesterol,high-sensitivity C-reactive pro-tein,and miR-132 were significantly lower,whereas those of miR-124,BDNF,CD3+T lymphocytes,CD3+CD4+T helper lymphocytes,and CD3+CD4+/CD3+CD8+cells were significantly higher in the experimental group com-pared to the control group(P<0.05).The incidence of adverse reactions during experimental group was signi-ficantly lower than that in control group(P<0.05).CONCLUSION Shugan Jieyu capsules have good efficacy in patients with mild-to-moderate depression after PCI,and its me-chanism may contribute to the regulation of miR-124,miR-132,BDNF levels,and lymphoid immune cells.

Clinical Efficacy of Chaihu Shugan Powder Classical Formula in Treating Chronic Superficial Gastritis with Liver-Stomach Disharmony

[Objectives] To investigate the clinical efficacy of Chaihu Shugan Powder on chronic superficial gastritis with liver-stomach disharmony syndrome.[Methods] A total of 72 patients diagnosed with chronic superficial gastritis characterized by liver-stomach disharmony syndrome between September 2023 and August 2024 were randomly assigned into two groups. The control group received treatment with western medicine, and the treatment group was administered both western medicine and Chaihu Shugan Powder. The therapeutic effects, TCM syndrome scores, adverse reactions, and recurrence rate were compared between the two groups.[Results] The total effective rate was 88.89% in the treatment group and 80.56% in the control group. The differences between the two groups were statistically significant ( P <0.05), indicating that the improvement observed in the treatment group was significantly greater than that in the control group ( P <0.05). In comparison to pre-treatment levels, the TCM syndrome scores for both patient groups exhibited a reduction following treatment. Notably, the extent of this reduction in the treatment group was significantly greater than that observed in the control group ( P <0.05). Neither group of patients experienced serious adverse reactions during treatment. Furthermore, the recurrence rate among patients in the control group was found to be higher than that in the treatment group.[Conclusions] The clinical efficacy of Chaihu Shugan Powder in the treatment of chronic superficial gastritis with liver-stomach disharmony syndrome is significant, demonstrating a notable reduction in the recurrence rate of the condition.

Study on the Efficacy of Shugan Jieyu Capsules Combined with Trazodone in Patients with Post-Stroke Depression and Insomnia

Objective:To analyze the effectiveness of applying ShuGan JieYu Capsules(SGJYC)combined with trazodone in patients with post-stroke depression(PSD)with insomnia.Methods:60 cases of PSD with insomnia patients admitted to the hospital from May 2022 to May 2023 were selected and randomly divided into a reference group(trazodone)and a research group(SGJYC combined with trazodone)of 30 cases each.Statistics were analyzed using the Hamilton Depression Rating Scale(HAM-D),Pittsburgh Sleep Quality Index(PSQI),and Activities of Daily Living(ADL)scale before treatment and 4,8,and 12 weeks after treatment.Results:Before treatment,The results of HAM-D,PSQI,and ADL scale studies in the two groups before treatment were not statistically significant(P>0.05);4,8,and 12 weeks after treatment,the results of HAM-D and PSQI studies in the research group were lower than that of the reference group,and the results of ADL scale studies were higher than that of the reference group.There was a significant difference between the groups(P<0.05).The total adverse reaction rate of the research group was lower than that of the reference group,and there was a significant difference between the groups(P<0.05).Conclusion:The combination of SGJYC and trazodone reduced depression in post-stroke patients,corrected insomnia,improved sleep quality,was safe,and had a low rate of adverse reactions.

疏肝滋肾汤治疗膝骨关节炎临床研究

目的:研究疏肝滋肾汤治疗膝骨关节炎的临床疗效。方法:80例患者随机分为2组,治疗组40例患者予疏肝滋肾汤,每次300 m L,早晚各1次;对照组40例给予非甾体抗炎药(NSAIDS)美洛昔康口服,1粒/次,1次/日,连服2月,应用WOMAC积分表、膝关节X线评价,对比治疗前后、随访6月指标变化。结果:治疗组与对照组总有效率分别为90.0%、77.5%(P<0.05);2组WOMAC评价积分均下降,但治疗组效果明显优于对照组;2组膝关节X线评分均下降,治疗组优于对照组,差异有显著性。结论:疏肝滋肾汤治疗膝骨关节炎疗效确切,能有效缓解膝骨关节炎症状,且副作用少,安全可靠。

Alterations in serotonin, transient receptor potential channels and protease-activated receptors in rats with irritable bowel syndrome attenuated by Shugan decoction

AIM:To determine the molecular mechanisms of Shugan decoction(SGD) in the regulation of colonic motility and visceral hyperalgesia(VHL) in irritable bowel syndrome(IBS).METHODS:The chemical compounds contained in SGD were measured by high-performance liquid chromatography.A rat model of IBS was induced by chronic water avoidance stress(WAS).The number of fecal pellets was counted after WAS and the pain pressure threshold was measured by colorectal distension.Morphological changes in colonic mucosa were detected by hematoxylin-eosin staining.The contents of tumor necrosis factor(TNF)-αin colonic tissue and calcitonin-gene-related peptide(CGRP)in serum were measured by ELISA.The protein expression of serotonin[5-hydroxytryptamide(5-HT)],serotonin transporter(SERT),chromogranin A(Cg A)and CGRP incolon tissue was measured by immunohistochemistry.RESULTS:SGD inhibited colonic motility dysfunction and VHL in rats with IBS.Blockers of transient receptor potential(TRP)vanilloid 1(TRPV1)(Ruthenium Red)and TRP ankyrin-1(TRPA1)(HC-030031)and activator of protease-activated receptor(PAR)4 increased the pain pressure threshold,whereas activators of PAR2and TRPV4 decreased the pain pressure threshold in rats with IBS.The effect of SGD on pain pressure threshold in these rats was abolished by activators of TRPV1(capsaicin),TRPV4(RN1747),TRPA1(Polygodial)and PAR2(AC55541).In addition,CGRP levels in serum and colonic tissue were both increased in these rats.TNF-αlevel in colonic tissue was also significantly upregulated.However,the levels of 5-HT,SERT and Cg A in colonic tissue were decreased.All these pathological changes in rats with IBS were attenuated by SGD.CONCLUSION:SGD alleviated VHL and attenuated colon motility in IBS,partly by regulating TRPV1,TRPV4,TRPA1,PAR2,5-HT,Cg A and SERT,and reducing CGRP and TNF-αlevel.

Comparative Study of the Effect of Shugan Shuru Granule (疏肝舒乳颗粒) on Pathology and p53 Gene Expression in Patients with Hyperplastic Disease of Breast

Objective: To study the effect of Shugan Shuru Granule (疏肝舒乳颗粒,SSG) on the p53 gene expression in patients with hyperplastic disease of breast (HDB) to indirectly explore the mechanism of SSG’s effect on HDB on the molecular pathological level. Methods: Sixty-six patients with HDB were allocated in the treated group and the control group,with the former treated with SSG and the latter not. All patients underwent breast operation and their diseased mammary tissues were cut out, sectioned, and observed under microscopy with HE staining and immunohistochemical staining, with ABC method adopted to estimate the degree of hyperplasia and p53 gene expression. The severity of HDB was classified into normal, mild, moderate and severe grades (marked as 0 to Ⅲ), according to the degree of hyperplasia in the mammary gland. Results: Hyperplasia in the control group mostly belonged to grade Ⅰ-Ⅲ before treatment, showing overgrowth of gland and proliferation of glandular epithelial cells, which were high columnar shaped, more stratified, with papillary or substantive dysplasia. While in the treated group, most belonged to grade 0-Ⅰ after SSG treatment, with proliferated gland and dysplasia recovered to normal or disappeared. The positive rate of p53 gene expression in the treated group was 9.09%, and in the control group 39.39%, comparison between the two groups showing significant difference (P<0.01), the intensity in the former was significantly weaker than that in the latter.Conclusion: SSG could not only inhibit the proliferation of mammary duct epithelia and lobuli, but also inhibit the over-expression of P53. Therefore, it could be regarded as an effective remedy for treatment of HDB and prevention of mammary cancer genesis.

Efficacy of Shugan Hewei Therapy for Chronic Atrophic Gastritis:A Systematic Review and Meta-Analysis

Objective:Shugan Hewei therapy(SHT)acts to soothe the liver and harmonize the stomach.It is a classical traditional Chinese medicine method widely used in China to treat chronic atrophic gastritis(CAG)due to liver qi invading the stomach.However,the clinical effects of SHT remain unclear.We aimed to evaluate the overall clinical effective rate and safety of SHT in treating CAG.Methods:We used the Jadad scale and Cochrane Collaboration risk of bias tool to evaluate the methodological quality of studies investigating SHT.Eight medical databases were searched to identify relevant studies.After data extraction and quality evaluation,27 randomized controlled trials,including 2,441 patients,were considered eligible for analysis.No serious heterogeneity or publication bias was observed across the included studies.We used Revman 5.3 statistical software to evaluate the general clinical effective rate and safety of SHT.Results:The results showed that SHT was more effective(RR=1.25;95%CI[1.20,1.29];P<0.01)and safer(MD=0.24,95%CI[0.08,0.75];P<0.01)than control interventions comprising western medicine,Chinese patent medicine,and/or western medicine+Chinese patent medicine.Compared with the control interventions,SHT resulted in greater improvements in the symptom scores for stomach distension and stomachache,serum gastrin level,histopathologic changes,Helicobacter pylori(HP)inhibition rate,and gastric mucosal inflammation.Conclusion:SHT was more effective and safer than control interventions for CAG.

Treatment of Patients with Erectile Dysfunction by Shugan Yiyang Capsule(疏肝益阳胶囊)A Multi-Centered Randomized Controlled Trial

Objective: To evaluate the efficacy and safety of Shugan Yiyang Capsule (SGYY,疏肝益阳胶囊 ) in treating psychogenic and mild arteriogenic erectile dysfunction (ED) of Gan stagnation and Shen deficiency Syndrome type with or without blood stasis. Methods: A multi-centered, randomized, double-blinded, placebo-controlled trial in 304 patients was conducted by dividing them into 3 groups, who received respectively SGYY (n = 102), placebo (n = 101) and Suoyang Bushen capsule (锁阳补肾胶囊, SYBS, n = 101), 1.0g taken three times a day for 4 weeks. Besides, 205 patients were arranged in an open-label study and treated with SGYY 1.0 g taken three times a day for 4 weeks. The total effective rate, total remarkably effective rate, erection recovery rate tested by penis hardness test ring, time taken for improving erection a-mong groups, as well as therapeutic effect between psychogenic ED group and mild arteriogenic ED group were compared. Adverse reactions related to SGYY were recorded. And a 3-month follow-up study was conducted on 105 cured patients. Results: The trial was completed in 500 patients. The total effective rate and total remarkably effective rate in the SGYY treated double-blinded group were 88. 0% and 64. 0% respectively, and those in the open-label group 90. 5% and 65. 0% , respectively, all significantly higher than those in the placebo (21.0%, 6. 0% ) and SYBS groups (60. 0% , 29.0%), P<0.01. At the same time, the e-rection recovery rate and improving time in SGYY group were significantly better than those in other groups ( P<0. 01). No adverse reactions related to SGYY were found. The successful rate of potency to have intercourse within 3 months was over 80% (100 patients out of the 105 cured patients). Conclusion: SGYY was an effective and safe treatment for patients with psychogenic and mild arteriogenic ED of Gan stagnation and Shen deficiency Syndrome type with or without blood stasis, especially for psychogenic ED patients.

Exploring the molecular biological mechanism of Shugan Jianpi Decoction in the treatment of depression-related breast cancer based on network pharmacology

Objective:To explore the molecular biological mechanism of Shugan Jianpi Decoction in treating depression-related breast cancer based on network pharmacology.Methods:The active compounds of Shugan Jianpi Decoction were explored to obtain their drug targets,and the venny network,"TCM-component-target"network,PPI network,"pathway-gene"network,GO and KEGG enrichment results were constructed using relevant softwares.Results:A total of 121 active ingredients,250 genes,2357 GO functions and 184 KEGG pathways were obtained.Conclusion:The active ingredients of Shugan Jianpi Decoction are quercetinll、kaempferol、luteolin、naringenin.The key targets are MAPK1,MAPK3,RELA,and AKT1.GO functions include cellular response to hormone stimulus、cellular response to lipid、cellular response to oxidative stress and so on.KEGG mainly involves PI3K-Akt,microRNAs,and FoxO signaling pathways.This study preliminarily explores the molecular biological mechanism of Shugan Jianpi Decoction in the treatment of depression-related breast cancer,and speculates that it mainly acts by arresting the cell cycle,inhibiting cancer cell proliferation,mediating cancer cell apoptosis,and preventing its recurrence and metastasis,which provides new evidence and new direction for subsequent clinical application and experimental research.

Mechanism of Shugan Lidan decoction in treating chronic calculous cholecystitis

Chronic calculous cholecystitis is a common clinical medical disease,which is classified as"hypochondriac pain"in traditional Chinese medicine(TCM).It is caused by liver failure and stagnation of liver qi.Therefore,the method of Soothing the liver and promoting bile flow is often used for regulating and harmonizing qi and blood.This paper discusses its mechanism of action,and points out that Shugan Lidan decoction has great effect on the treatment of chronic calculous cholecystitis,especially in the early treatment of the disease and delaying the progress of the disease,which provides help for the clinical treatment of chronic calculous cholecystitis.

Potential mechanism of Shugan Jieyu capsule in the treatment of hepatitis B based on network pharmacology

Objective:In this study,the effective components and related targets of Shugan Jieyu Capsule(SGJY)in the treatment of hepatitis B were determined to explore the mechanism of SGJY in the treatment of hepatitis B.Methods:In this study,the effective components and targets of SGJY,and the related targets of hepatitis B were searched,and obtained the targets of SGJY in the treatment of hepatitis B according to the principle of Venn diagram.To build a protein-protein interaction network,String database was used,Cytoscape(3.7.2)software was used for topology analysis,R(4.0.5)software was used for go analysis,KEGG pathway enrichment analysis,and study of putative signaling pathways to determine how they could work.Results:SZJY was used to predict a total of 11 Chinese herbal components and 85 associated targets for the treatment of hepatitis B.34 important targets were examined,including AKT1,EGFR,and 10 important pathways were examined,including proteoglycans in cancer and the PI3K/Akt signaling pathway.Conclusion:SGJY in the treatment of hepatitis B mainly inhibits the secretion of HBsAg and HBeAg by affecting PI3K-Akt and proteoglycans in cancer,and inhibits the progression of liver cancer.

Study on the pharmacological mechanism of chaihu shugan powder in the treatment of hepatocellular carcinoma

Liver depression and qi stagnation type liver cancer accounts for a high proportion of primary liver cancer,western medicine has no special treatment for this type of liver cancer in addition to routine treatment,while patients with this type of liver cancer often show pain in the right flank,mass under the right side,chest depression and other clinical symptoms seriously affect the quality of life of patients with liver cancer and bring great trouble to patients and their families.Chaihu Shugan San,which originated from the General order of Medicine in the Ming Dynasty,has a serious impact on the quality of life of patients with liver cancer and brings great trouble to patients and their families.It is the representative prescription of soothing the liver and regulating qi in traditional Chinese medicine.in recent years,its clinical application and pharmacological action in liver cancer have been studied more and more deeply,but the anti-tumor pharmacological research and effective components of Chaihu Shugan Powder are still lack of systematic summary.Based on the relevant studies at home and abroad,this paper summarizes the anti-tumor mechanism and possible effective components of Chaihu Shugan Powder,so as to provide further pharmacodynamic material basis and mechanism reference for the further clinical application of primary liver cancer.

Rapid Antidepressant-Like Potential of Chaihu Shugan San Depends on Suppressing Glutamate Neurotransmission and Activating Synaptic Proteins in Hippocampus of Female Mice

Objective To explore the rapid antidepressant potential and the underlying mechanism of Chaihu Shugan San(CSS)in female mice.Methods Liquid chromatography mass spectrometry(LC-MS)/MS was used to determine the content of main components in CSS to determine its stability.Female C57BL/6J mice were randomly divided into 4 groups,including control(saline),vehicle(saline),CSS(4 g/kg)and ketamine(30 mg/kg)groups.Mice were subjected to irregular stress stimulation for 4 weeks to establish the chronic mild stress(CMS)model,then received a single administration of drugs.Two hours later,the behavioral tests were performed,including open field test,tail suspension test(TST),forced swimming test(FST),novelty suppression feeding test(NSF),and sucrose preference test(SPT).Western blot analysis was used to detect the expression levels of N-methyl-D-aspartate receptor(NMDA)subtypes[N-methyl-D-aspartate receptor 1(NR1),NR2A,NR2B],synaptic proteins[synapsin1 and post synaptic density protein 95(PSD95)],and brain-derived neurotrophic factor(BDNF).Moreover,the rapid antidepressant effect of CSS was tested by pharmacological technologies and optogenetic interventions that activated glutamate receptors,NMDA.Results Compared with the vehicle group,a single administration of CSS(4 g/kg)reversed all behavioral defects in TST,FST,SPT and NSF caused by CMS(P<0.05 or P<0.01).CSS also significantly decreased the expressions of NMDA subtypes(NR1,NR2A,NR2B)at 2 h in hippocampus of mice(all P<0.01).In addition,similar to ketamine,CSS increased levels of synaptic proteins and BDNF(P<0.05 or P<0.01).Furthermore,the rapid antidepressant effects of CSS were blocked by transient activation of NMDA receptors in the hippocampus(all P<0.01).Conclusion Rapid antidepressant effects of CSS by improving behavioral deficits in female CMS mice depended on rapid suppression of NMDA receptors and activation of synaptic proteins.

The clinical effect and safety evaluation of Shugan Quzhi capsule in the treatment of adult simple obesity

Shugan Quzhi capsule is a hospital preparation of Xinhua Hospital affiliated to School of Medicine, Shanghai Jiaotong University. It has been used to treat adult patients with fatty liver caused by obesity, high cholesterol and other factors. In the present study, we investigated the clinical efficacy and safety of Shugan Quzhi capsule in adult simple obesity. The patients were randomly divided into the treatment group and control group. The whole treatment lasted 2 months under the same nutritional condition and diet intervention. Body weight, body mass index, total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, creatinine, urine and blood routine examination were recorded before and after treatment. Our data showed that the total effective rate of treatment group was 66.67%, and body weight and body mass index after treatment the body were significantly decreased （P〈0.01）. The levels of total cholesterol, triglyceride, high-density lipoprotein and low-density lipoprotein after treatment were lower than before treatment, but there was no statistical difference （P〉0.05）. The total effective rate of control group was 39.13%, and the body weight and body mass index atter treatment were also significantly lower than before （P〈0.01）. There was no significant difference between the treatment group and control group （P〉0.05）. There were no significant changes in liver function, renal function, urine routine and blood routine examination data after treatment. The results suggested that Shugan Quzhi capsule had certain therapeutic efficacy and safety in adult simple obesity.

Simultaneous determination of four saponins in Shugan Quzhi Capsule by UHPLC-MS/MS

Shugan Quzhi capsule is a hospital preparation of Xinhua Hospital affiliated to School of Medicine, Shanghai Jiaotong University. It has been used for the treatment of adult patients with fatty liver caused by obesity, high cholesterol and other factors. In the present study, we established an ultra-high pressure liquid chromatography-tandem mass spectrometry （UHPLC-MS/MS） method to simultaneously determine 4 saponin ingredients including Notoginsenoside R1, Ginsenoside Rbl, Ginsenoside Re and Ginsenoside Rgl present in Shugan Quzhi capsule. The chromatographic separation was conducted on ZORBAX SB-C18 （2.1 mm×50 mm, 1.8 μm）. The mobile phase was composed of acetonitrile and aqueous solution consisted of 0.05% formic acid and 5 mM ammonium acetate. Gradient elution rate was 0.3 mL/min, the column temperature was 40 ℃ MS was conducted using electrospray ionisation （ESI） and multiple reaction monitoring （MRM） coupled with positive and negative scanning switch. With which, Ginsenoside Re and Ginsenoside Rgl were detected using negative ion mode detection while Notoginsenoside R1, Ginsenoside Rbl and internal standard （Ginsenoside F1） were detected using positive ion mode detection. The limits of quantification （LOQ） for Notoginsenoside R1, Ginsenoside Rbl, Ginsenoside Re and Ginsenoside Rgl were 6.54× 10-4, 2.57×104, 0.11 and 6.91 × 10-3 ng/mL, respectively. The limits of detection （LOD） for these compounds were 1.96×10-4, 7.70×10-5, 3.45× 10-2, and 2.07× 10-3 ng/mL, respectively. All calibration curves showed a good linearity （r2〉0.9633） within the test range. The intra- and inter-day precisions （relative standard deviation, RSD） were lower than 5% and the average recoveries were in the range of 80%-120%. With this method, four kinds of saponins were separated and detected in 6 min. This method is simple, rapid and shows high sensitivity and accuracy.

Mechanism of Chaihu Shugan Powder(柴胡疏肝散) for Treating Depression Based on Network Pharmacology

Objective:To analyze the effective components of Chinese medicine(CM)contained in Chaihu Shugan Powder(柴胡疏肝散,CSP)in the treatment of depressive disorders and to predict its anti-depressant mechanism by network pharmacology.Methods:Absorption,distribution,metabolism,excretion,and toxicity calculation method was used to screen the active components of CSP.Traditional Chinese Medicine System Pharmacological Database Analysis Platform and text mining tool(GoPuMed database)were used to predict and screen the active ingredients of CSP and anti-depressive targets.Through Genetic Association Database,Therapeutic Target Database,and PharmGkb database targets for depression were obtained.Cytoscape3.2.1 software was used to establish a network map of the active ingredients-targets of CSP,and to analyze gene function and metabolic pathways through Database for Annotation,Visualization and Integrated Discovery and the Omicshare database.Results:The 121 active ingredients and 15 depression-related targets which were screened from the database can exert antidepressant effects by improving the neural plasticity,growth,transfer condition and gene expression of neuronal cell,and the raise of the expression of gap junction protein.The 15 targets passed 14 metabolic pathways,mainly involved in the regulation of neurotransmitters(5-hydroxytryptamine,dopamine and epinephrine),inflammatory mediator regulation of TRP channels,calcium signaling pathway,cyclic adenosine monophosphate signaling pathway and neuroactive ligand-receptor interaction and other signal channels to exert anti-depressant effects.Conclusion:This article reveals the possible mechanism of CSP in the treatment of depression through network pharmacology research,and lays a foundation for further target studies.

Antidepressant-Like Effects of Chaihu Shugan Powder(柴胡疏肝散)on Rats Exposed to Chronic Unpredictable Mild Stress through Inhibition of Endoplasmic Reticulum Stress-Induced Apoptosis

Objective:To investigate the antidepressant-like effects of Chaihu Shugan Powder(CSP,柴胡疏肝散)and to explore its underlying mechanisms.Methods:Thirty-two Sprague-Dawley rats were randomly divided into control(CON),chronic unpredictable mild stress(CUMS),fluoxetine(FLU),and CSP groups,8 rats in each group.All of the rats except for those in the control group were subjected to 3 consecutive weeks of CUMS to establish the depression model.The open field test(OFT),forced swimming test(FST),and sucrose preference test were used to assess the anti-anxiety and antidepressant effects of CSP.Terminal deoxynucleotidyl transferase(Td T)d UTP nick-end labeling was used to determine the apoptosis rate in the hippocampal tissues.The m RNA and protein levels of glucose-regulated protein(GRP)78,spliced X-box-binding protein(XBP)-1,CCAAT/enhancerbinding protein homologous protein(CHOP),caspase-12,and c-Jun N-terminal kinase(JNK)in the hippocampus of rats were evaluated by real-time PCR and Western blot analysis,respectively.Results:Administration of CSP alleviated anxiety and depression-like behavior in CUMS rats,as revealed by enhanced time and distance in the center of the OFT(P<0.05),an increased preference for sucrose,and longer swimming time and shorter immobility time during the FST(all P<0.05).In addition,CSP treatment significantly reduced the rate of apoptosis in rat hippocampal neurons(P<0.05).The m RNA and protein expression levels of GRP78,spliced XBP-1,and CHOP were down-regulated along with the expression of caspase-12 and cleaved caspase-12 proteins(all P<0.05),whereas total and phosphorylated JNK1 protein levels did not differ significantly between control and CSP-treated rats.Conclusion:CSP can improve depression-like behavior in rats exposed to CUMS,possibly by suppressing CHOP and caspase-12 mediated apoptosis in the rat hippocampus.

Effects of Shugan Jianpi Formula(疏肝健脾方)on Myeloid-Derived Suppression Cells-Mediated Depression Breast Cancer Mice

Objective： To observe the intervention effect of Shugan Jianpi Formula （疏肝健脾方,SGJPF） on a breast cancer mouse model with depression and investigate the underlying mechanism of SGJPF in preventing the development of breast cancer. Metkods： The breast cancer model was induced by inoculation of breast cancer cells, the depression model was induced by chronic stress stimuli, and the depression cancer model was established by combining the two factors. The mice were divided into 7 groups： normal control, depression model, tumor model, depression tumor model, SGJPF, chemotherapy, and SGJPF＋chemotherapy groups. The last 3 groups were depression breast cancer mice and treated respectively with SGJPF, chemotherapy drug gemcitabine （GEM）, and SGJPF alongside GEM. The condition of the mice was evaluated by the expression of 5-hydroxytryptamine in hippocampus after the sucrose water test and open field test, weight change, and survival time. Tumor growth was monitored with in vivo imaging. Flow cytometry was used to analyze the level of myeloid-derived suppression cell （MDSC） in the mouse spleen, T cell subsets, and the early apoptosis of CD8~ T cells, Results： The SGJPF＋GEM group had the highest inhibition rate and the longest survival time （P〈0.01）. The MDSC level and the apoptosis rate of CD8＊ T cells was the highest in the SGJPF＋GEM group （P〈0.05）. Conclusions： Depressive disorders and tumor growth could suppress the immune function of mice to different degrees, and the microenvironment in late 4T1 inflammatory breast cancer may play an important role in the pathological process. SGJYF could regulate the immune microenvironment by reducing CD8＊ T lymphocyte apoptosis and tumor cell activity, increasing immune surveillance capability, and inhibiting MDSC proliferation, thus prolonging the survival time of tumor-bearing mice.

Mechanism underlying efficacy of Shugan Sanjie decoction(疏肝散结汤) on plasma cell mastitis,based on network pharmacology and experimental verification

OBJECTIVE:To investigate the mechanism underpinning the effeicay of Shugan Sanjie decoction(疏肝散结汤,SGSJD)on plasma cell mastitis(PCM)based on network pharmacology,and to verify it through in vitro.METHODS:Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and Bioinformatics Analysis Tool for Molecular mechanism of Traditional Chinese Medicine were used to screen effective compounds and drug targets;Online Mendelian Inheritance in Man and Gene Cards were used to search for PCM targets.The potential targets of SGSJD in treating PCM were obtained after the drug targets and disease targets were crossed.Cytoscape software was used to establish and analyze the network of Chinese medicines-active compounds-targets-disease;STRING database platform was used to analyze Protein Protein Interaction network;Bioconductor software package was used to perform Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment for potential targets.Western blot analysis was used to verify the janus kinase/signal transducer and activator of transcription(JAK-STAT)pathway in vitro.RESULTS:(a)47 potential pharmacological components of SGSJD treatment of PCM were screened including quercetin,luteolin,kaempferol and others;20 common targets were obtained,including interleukin-6(IL-6),epidermal growth factor receptor,estrogen receptor 1,nitric oxide synthase 3 and others;a number of signal pathways were available,of which advanced glycation end product/receptor for advanced glycation end products signaling pathway in diabetic complications,hypoxia-inducible factor 1 signaling pathway and janus tyrosine kinase-signal transducer and transcription activator(JAK-STAT)signaling pathway were the main signal pathways related to PCM.(b)Compared with the Blank group,the expressions of p-JAK2/JAK2,pSTAT3/STAT3 and IL-6 protein in the Model group were significantly increased(P<0.01);Compared with the Model group,the expression of p-JAK2/JAK2,p-STAT3/STAT3,and IL-6 protein in the treatment group were significantly reduced in a dose-dependent manner(P<0.05).Compared with the Model group,the dexamethasone significantly reduced the expression of p-JAK2/JAK2,p-STAT3/STAT3,and IL-6(P<0.01).CONCLUSIONS:The SGSJD may regulate the JAKSTAT signaling pathway to achieve the effect of treating PCM by reducing the expression of p-JAK2/JAK2,p-STAT3/STAT3 and IL-6 in a dose-dependent manner.

Mechanism underlying effect of Chaihu Shugan San(柴胡疏肝散)on major depressive disorder:a network pharmacology-based study

OBJECTIVE:To investigate the mechanism underpinning the effect of Chaihu Shugan San(柴胡疏肝散,CHSGS)on major depressive disorder(MDD).METHODS:We searched the compound components of from seven herbal ingredients of CHSGS from TCMSP,SymMap,ETCM,NPASS databases,and the chemical structure of the compound from PubChem,and collected the compound targets from TCMSP and TargetNet databases,and MDD-related targets from DiseaseGene Network.We established protein-protein interaction in the STRING database.Through gene mapping,topology analysis and enrichment analysis,the core targets and pathways of CHSGS for MDD,and the involved biological processes(BP),cell components(CC),and molecular functions(MF)were predicted.RESULTS:We collected a total of 1135 CHSGS compounds.After screening by ADME standards and the five rules of Ribinski,we obtained 99 different chemical components with different chemical structures,and related targets of 183 different CHSGS compounds.In the DiseaseGene Network,a total of 740 relevant targets for MDD were collected.Through gene mapping and topological analysis,62 related targets of CHSGS for MDD,24 targets with topological Chinese herbal medicine were obtained.Through enrichment analysis,10 relevant pathways and 3 core pathways were obtained with the involvement of 127 BP,27 CC,and 43 MF.CONCLUSION:There are multiple targets and signaling pathways are involved in the action of CHSGS in the treatment of MDD.