Plasma metabolomics and network pharmacology identified glutamate, glutamine, and arginine as biomarkers of depression under Shuganjieyu capsule treatment.

Depression is a psychiatric disorder and confers an enormous burden on society. Mild to moderate forms of depression (MMD) are particularly common. Our previous studies showed that the Shuganjieyu (SGJY) capsule might improve depressive and cognitive symptoms in patients with MMD. However, biomarkers evaluating the efficacy of SGJY and the underlying mechanism remains unclear. The aim of the present study was to discover efficacy biomarkers and explore the underlying mechanisms of SGJY as antidepression treatment. Twenty-three patients with MMD were recruited and administered with SGJY for 8 weeks. Results showed that the content of 19 metabolites changed significantly in the plasma of patients with MMD, among which 8 metabolites improved significantly after SGJY treatment. Network pharmacology analysis showed that 19 active compounds, 102 potential targets, and 73 enzymes were related to the mechanistic action of SGJY. Through a comprehensive analysis, we identified four hub enzymes (GLS2, GLS, GLUL, and ADC), three key differential metabolites (glutamine, glutamate, and arginine), and two shared pathways (alanine, aspartate, and glutamate metabolism; and arginine biosynthesis). Receiver operating characteristic curve (ROC) analysis showed that the three metabolites had a high diagnostic ability. The expression of hub enzymes was validated using RT-qPCR in animal models. Overall, glutamate, glutamine, and arginine may be potential biomarkers for evaluating the efficacy of SGJY. The present study provides a new strategy for pharmacodynamic evaluation and mechanistic study of SGJY, and offers new information for clinical practice and treatment research.

Combined fractional anisotropy and subcortical volumetric deficits in patients with mild-to-moderate depression: Evidence from the treatment of antidepressant traditional Chinese medicine.

Numerous neuroimaging studies have demonstrated that diverse brain structural plasticity could occur in a human brain during a depressive episode. However, there is a lack of knowledge regarding the underlying mechanisms of mild-to-moderate depression (MMD), especially the changes of brain structural characteristics after treatment with the Shuganjieyu capsule (SG), a kind of traditional Chinese medicine that has been recommended for the specialized treatment of MMD. In this study, we investigated the structural brain plasticity in MMD that have been undergoing 8 weeks of SG treatment compared with age- and sex-matched healthy controls (HCs) and assessed the relationship between these brain structural alternations and clinical symptoms in MMD. At the baseline, we found that: (1) fractional anisotropy (FA) values in patients with MMD were found to be significantly increased in the regions of anterior limb of internal capsule (ALIC) [MNI coordinates: Peak (x/y/z) = 102, 126, 77; MMD FA peak (Mean ± SD) = 0.621 ± 0.043; HCs FA peak (Mean ± SD) = 0.524 ± 0.052; MMD > HCs, t = 9.625, p < 0.001] and posterior limb of internal capsule (PLIC) [MNI coordinates: Peak (x/y/z) = 109, 117, 87; MMD FA peak (Mean ± SD) = 0.694 ± 0.042; HCs FA peak (Mean ± SD) = 0.581 ± 0.041; MMD > HCs, t = 12.90, p < 0.001], and FA values were significantly positively correlated with HAMD scores in patients with MMD. (2) Patients with MMD showed smaller gray matter volume (GMV) of the dorsolateral prefrontal cortex (DLPFC), frontal cortex, occipital cortex, and precuneus, and the GMV of DLPFC was negatively correlated with HAMD scores. After SG treatment, we found that (1) the HAMD scores decreased; (2) FA values were significantly decreased in the regions of the ALIC and PLIC compared to those at baseline and TBSS revealed no significant differences in FA values between patients with MMD and HCs. (3) The structural characteristics of DLPFC in patients with MMD obtained at the 8th week were improved, e.g., no significant differences in GMV of DLPFC between the two groups. Taken together, our results provided neuroimaging evidence suggesting that SG is an effective treatment for patients with MMD. Moreover, alterations of GMV after 8 weeks of SG treatment indicated a potential modulation mechanism in brain structural plasticity within the DLPFC in patients with MMD.

Evaluation of therapeutic markers and mechanism of Shuganjieyu capsule in treatment of depression / 中华行为医学与脑科学杂志

Objective:To compare the expression levels of candidate genes before and after Shuganjieyu capsule treatment, to analyze their correlation with depression symptoms and cognitive function, and to find and clarify the biomarkers related to the efficacy of Shuganjieyu capsule.Methods:Among 27 patients with mild to moderate depression (MMD), 24 items Hamilton depression rating scale (HAMD-24) was used to assess the severity of depression, Chinese revised Wechsler adult intelligence scale(WAIS-RC) and Chinese revised Wechsler memory scale(WMS) were used to assess cognitive function, and qRT-PCR was used to detect the expression levels of candidate genes in peripheral blood of patients with depression before and after treatment with Shuganjieyu capsule.SPSS 25.0 software was used for statistical analysis, paired t-test, non-parametric test, Spearman correlation analysis and receiver operating characteristic curve were used for data statistics. Results:The symptoms of MMD patients were relieved after Shuganjieyu capsule treatment(HAMD scores: baseline 14.00(9.75, 18.25), 8-week 4.00(2.00, 7.25), Z=-4.462, P<0.01), and the verbal intelligence quotient(VIQ) of WMS was puomoved (VIQ scores: baseline (123.00±10.24), 8-week (128.00±6.77), t=4.372, P<0.01). The level of gene expression brain derived neurotrophic factor(BDNF) (baseline 1.68(0.92, 2.63), 8-week 2.30(1.47, 4.34), Z=-2.781, P=0.005), glial cell derived neurotrophic factor(GDNF) (baseline 0.74(0.31, 1.15), 8-week 0.97(0.50, 1.71), Z=-2.159, P=0.031), 5-hydroxytryptamine receptor 2A(HTR2A) (baseline 0.60(0.39, 1.60), 8-week 0.98(0.44, 2.29), Z=-1.994, P=0.046) and glutamate ionotropic receptor AMPA type subunit 1(GRIA1) (baseline 1.19(0.66, 2.40), 8-week 1.76(0.86, 4.13), Z=-2.756, P=0.006) was up-regulated after treatment.The change rate of BDNF expression were correlated with the score of HAMD-24 ( r=-0.35, P=0.038) and performance intelligence quotient of WMS ( r=0.40, P=0.022). Conclusions:BDNF may be used as a therapeutic marker of Shuganjieyu capsule in the treatment of clinical symptoms and cognitive function of MMD patients, which is used to evaluate the efficacy of antidepressants.

Shuganjieyu capsule alone or in combination with other antidepressants for post-stroke depression:a Meta-analysis / 中国脑血管病杂志

Objective To study the efficacy and safety of Shuganjieyu capsule alone or in combination with other antidepressants for the treatment of post-stroke depression (PSD).Methods Wanfang database,China National Knowledge Infrastructure (CNKI),Chinese VIP journals database,PubMed,EMbase,Cochrane Library,and Chinese dissertations full text database were retrieved by computers.The randomized controlled trials (RCTs) on Shuganjieyu capsule for the treatment of PSD from January 1995 to September 2017 were collected.After literature screening,data extraction,and methodological quality evaluation,RevMan 5.1 software was used to conduct a Meta-analysis.The bias was evaluated with the Stata 12.0 software using Begg's rank correlation and Egger's linear regression.Results A total of 19 RCTs were included,including 1 814 participants.The Meta-analysis results showed that compared with other antidepressants,there were no significant differences in the effective rate and cure rate of Shuganjieyu capsule (combinedeffects:RR=1.04 [95％ CI0.97-1.11],Z=0.99,P=0.32 and RR =1.06 [95％ CI 0.85-1.32];Z =0.52,P =0.60).Compared with other antidepressants,there were significant differences in the effective rate and cure rate of Shuganjieyu capsule in combination with other antidepressants (combined effects:RR =1.19 [95％ CI 1.13-1.26];Z =6.43,P ＜0.01 and RR =1.54 [95％ CI 1.26-1.88];Z =4.17,P ＜0.01).The incidence of adverse events of Shuganjieyu capsule alone was less than that of other antidepressants (combined effect:RR =0.39 [95％ CI 0.27-0.55];Z =5.30,P ＜ 0.01).The incidence of adverse events of Shuganjieyu capsule in combination with other antidepressants was the same as other antidepressants (combined effect:RR =0.99 [95％ CI 0.77-1.26];Z =0.10,P =0.92).Conclusions Shuganjieyu capsule is effective for post-stroke depression.The efficacy of Shuganjieyu capsule alone is as effective as other antidepressants,however,Shuganjieyu capsule in combination with other antidepressants is superior to other antidepressants,and the safety is better than other antidepressants.

[Effect analysis on Deanxit combined with Shuganjieyu capsule in the treatment of refractory gastroesophageal reflux disease].

Objective: To investigate the curative effect of Deanxit combined with Shuganjieyu capsule on the treatment of refractory gastroesophageal reflux disease. Methods: A total of 125 patients with refractory gastroesophageal reflux disease who had failed in standard lansolazole capsule treatment in the Department of Gastroenterology, First People's Hospital of Neijiang were selected. According to the symptom scores and mood scores of gastroesophageal reflux disease, patients were randomly and double-blindly divided into five groups. Group A(Lansoprazole Capsules + Mosapride Citrate + Deanxit), B(Lansoprazole Capsules + Mosapride Citrate + Shuganjieyu capsule), C(Lansoprazole Capsules + Mosapride Citrate+ Deanxit + Shuganjieyu capsule) and D(Deanxit) groups are study groups, the other was control group (Lansoprazole Capsules + Mosapride Citrate). The scores of symptoms and mood were compared after 4 weeks and 8 weeks of treatment. Results: The clinical symptoms score, HAMA and HAMD scores were significantly lower in the all study groups in comparison to the control group after 4 weeks and 8 weeks therapy. The clinical symptoms score, HAMA and HAMD scores in group C were significantly lower than those in group A and B (P<0.05), while the difference between group A and B was not statistically significant(P>0.05). The HAMA and HAMD scores of group D were significantly higher than those of group A, B, C and control group, and the differences were statistically significant (P<0.05). The total effective rate of study groups were significantly higher than those of the control group, and the difference was statistically significant (P<0.05). The total effective rate of group C was significantly higher than that of group A and B (χ(2)=6.47, P<0.05). The total effective rate of group A at the end of the 8th week was significantly higher than that of group B (χ(2)=6.52, P<0.05). The total effective rate of group D at the end of the 4th and 8th week was significantly lower than those of the group A, B, C and control group, the difference was statistically significant (χ(2)=5.85, P<0.05). Conclusions: Deanxit combined with Shuganjieyu capsule is significantly effective in treatment of refractory gastroesophageal reflux disease, which can effectively improve the total treatment efficiency, reduce the symptom scores and mood scores of gastroesophageal reflux disease patients.

Effects of Shuganjieyu capsule of plasma glucose and lipid metabolism and sleep and body weight in depression / 中国生化药物杂志

Objective To study effects of shuganjieyu capsule of plasma glucose and lipid metabolism and sleep and body weight in patients with depression.Methods 90 patients of depression who received therapy from July 2013 to July 2016 in our hospital were selected.According to random number table, those patients were divided into the observation group ( n =45 ) and the control group ( n =45 ) .The control group was treated with citalopram, while the observation group was treated with shuganjieyu capsule, then glucose and lipid metabolism, sleep, weight and clinical curative effect were compared.Results After treatment, the fasting blood glucose (FBG), postprandial 2h blood glucose (2 hPG), triacylglycerol (TG), total cholesterol (TC) in the observation group were lower than the control group(all P<0.05), the sleep state self rating scale (SRSS) and the Pittsburgh sleep quality index ( PSQI) in the observation group were lower than the control group ( all P <0.05 ) .The body weight and body mass index in the observation group were lower than the control group (all P<0.05).The total effective rate in the observation group 95.56% (43/45)was higher than the control group 77.78% (35/45) (P<0.05); the incidence of adverse reactions in observation group 20.00% (9/45) was lower the control group 46.67% (21/45) ( P <0.05).Conclusion Shuganjieyu capsule is well for depression, which can conducive to maintaining glucose and lipid metabolism, weight stability, and improve sleep quality and clinical symptoms, and high security,it's worthy of application and promotion.

Efficacy and safety of double doses of SHUGANJIEYU capsules in treating moderate depressive disor-der:a multicenter, random, double-blind, and parallel-controlled trial / 中国神经精神疾病杂志

Objective To explore the efficacy and safety of double dosage of SHUGANJIEYU capsule on mod?erate depression. Methods The study was conducted by a multicenter, random, double-blind and parallel-controlled trial. Trial group received SHUGANJIEYU capsules 4# twice a day. Control group got two SHUGANJIEYU capsules and two simulated ones twice a day. The study lasted 56 days (8 weeks) for both groups. Primary efficacies were evalu? ated by the total score and score changed rate of Hamilton depression scale-17 (HAMD-17)and Hamilton anxiety scale (HAMA) as well safety by reported adverse events and laboratory tests for patients. Results One hundred twenty patients were recruited in trial group and 120 patients in control group. After a 8-week treatment, the remission ratio was 84.2% and 63.3% for the trial group and the control group, respectively according to the HAMD-17. The differ?ence in the remission ratio was significant (P0.05). Conclusion SHUGANJIEYU capsule ex?hibits a good therapeutic effect on the depressive symptoms and anxiety symptoms in patients with moderate depres?sion. Double doses of SHUGANJIEYU capsule can increase the effect of SHUGANJIEYU and accelerates SHUGAN?JIEYU-induced improvement of depression symptoms with an acceptable safety.

Shuganjieyu capsule increases neurotrophic factor expression in a rat model of depression.

Shuganjieyu capsule has been approved for clinical treatment by the State Food and Drug Ad-ministration of China since 2008. In the clinic, Shuganjieyu capsule is often used to treat mild to moderate depression. In the rat model of depression established in this study, Shuganjieyu capsule was administered intragastrically daily before stress. Behavioral results confirmed that depressive symptoms lessened after treatment with high-dose (150 mg/kg) Shuganjieyu capsule. Immunohistochemistry results showed that high-dose Shuganjieyu capsule significantly increased phosphorylation levels of phosphorylation cyclic adenosine monophosphate response element binding protein and brain-derived neurotrophic factor expression in the medial prefrontal cortex and hippocampal CA3 area. Overall, our results suggest that in rats, Shuganjieyu capsule effec-tively reverses depressive-like behaviors by increasing expression levels of neurotrophic factors in the brain.

Shuganjieyu capsule for major depressive disorder (MDD) in adults: a systematic review.

OBJECTIVES: Shuganjieyu capsule is a pure herbal pharmaceutical product for depression. Our objective was to explore the effectiveness and safety of Shuganjieyu capsule for the treatment of major depressive disorder in adults. METHOD: Eight computerized databases were searched. In addition, randomized controlled trials (RCTs) on Shuganjieyu capsule were hand-searched on seven key Chinese journals. Data were extracted and evaluated by two reviewers independently. Analysis was performed by intention-to-treat where possible. Prespecified subgroup analyses were different-dose regimens, patient spectrum, publication status, and treatment duration. RESULTS: Seven RCTs with 595 participants were included. Shuganjieyu capsule was superior than placebo in terms of response rate (RR = 2.42, 95% CI: 1.55-3.79; P = 0.0001), remission rate (RR = 4.29, 95% CI: 1.61-11.45; P = 0.004), the scores of the mean change from baseline of the HAM-D17 (MD = -4.17, 95% CI: -5.61 to -2.73; P < 0.00001) and from baseline of traditional Chinese medicine (TCM) syndrome score scale scores (MD = -6.00, 95% CI: -8.25 to -3.75; P < 0.00001). In addition, Shuganjieyu plus venlafaxine had a significantly higher response rate (RR = 1.56, 95% CI: 1.29-1.88; P < 0.00001) and was superior in terms of the scores of the mean change from baseline of the treatment emergent symptoms scale scores (MD = -0.74, 95% CI:-1.12 to -0.35; P = 0.0002) than venlafaxine alone. CONCLUSION: Shuganjieyu capsule is superior to placebo in terms of overall treatment effectiveness and safety. Both response rate and remission rate among patients treated with the combination of Shuganjieyu plus venlafaxine were significantly higher than those treated with venlafaxine alone. Due to the considerable risk of bias in majority of trials, recommendations for practice should be cautious, and additional, well-designed RCTs are needed in next step.

Effect of venlafaxine sustained-release tablet combined with Shuganjieyu capsule in the treatment of post-stroke depression / 中国基层医药

Objective To compare the effect and safety of venlafaxine sustained-release tablet combined with Shuganjieyu capsule and venlafaxine sustained-release tablet used singlely in the treatment of moderate to severe poststroke depression.Methods 70 patients suffered from moderate to severe post-stroke depression were randomly divided into two groups,35 cases in each group.The patients in the control group were only treated with venlafaxine sustained-release tablet,and the patients in the study group were treated by venlafaxine sustained-release tablet combined with Shuganjieyu capsule.The treatment lasted 6 weeks.The therapeutic effect and safety were evaluated by the positive and negative syndrome scale of HAMD (17 items),and treatment emergent symptom scale of TESS.Results After treatment for 6 weeks,the total effective rate of the study group was 88.57％,which was significantly higher than 65.71％ of the control group (x2 =5.19,P ＜ 0.05).The HAM D score of the study group w.as (16.42 ± 6.07) points,and the HAMD score of the control group was(10.54 ± 5.23) points after 6 weeks.The difference was statistically significant between the two groups (t =4.34,P ＜ 0.01).The difference of TESS score between two groups was not significant(t =0.18,P ＞ 0.05).Conclusion Venlafaxine sustained-release tablet combined with Shuganjieyu capsule is effective and safe in the treatment of moderate to severe post-stroke depression.