Metformin and depression: A protocol for systematic review and meta-analysis

Introduction:Metformin(MET)has been shown in animal models and diabetic patients with depression to have antidepressant effects.MET is gaining attraction as a treatment for depression;nevertheless,a comprehensive review and evaluation are essential.The primary objective of this review article is to evaluate metformin's effectiveness and safety in the treatment of depression.Methods and analysis:From inception,a wide-ranging survey of the literature will be conducted to categorize possibly suitable studies from online databanks such as the Wan-Fang Database,Chinese Scientific Journal Database(VIP database),Chinese Biomedical Literature Database(CBM),China National Knowledge Infrastructure(CNKI),Traditional Chinese Medicine databases,the Web of Science,EMBASE,PubMed,and the Cochrane Central Register of Controlled Trials(CENTRAL).For this search,no linguistic constraints will be applied.Only randomized controlled trials will be considered,and each study's bias risk will be assessed using the Cochrane Risk of Bias tool.The primary outcome measures will be self-rating scales or clinician-rated scales.Depression remission and quality-of-life indices will be secondary outcomes.The evidence quality for each study will be assessed by grading the review process,development,and recommendations.Ethics and dissemination:The primary data will not be collected in this review;therefore,no ethical consent is required.The results of this methodical review will be available in a peer-reviewed scientific publication and will be made freely accessible.PROSPERO registration number CRD42021286394 Strengths and limitations of this study:This protocol will ensures that the methodologies and processes employed are transparent,allows for peer review,and avoids the risk of bias and duplication.Meta-analyses will not be used as a method of quantitative synthesis.This review study will map the literature on randomized controlled trials of metformin for depression treatment,assess the scope and significance of future systematic reviews on the topic,and identify research gaps and limitations of this study.

Combination of Geniposide and Eleutheroside B Exerts Antidepressant-like Effect on Lipopolysaccharide-Induced Depression Mice Model

Objective To study the antidepressant-like effect and action mechanism of geniposide and eleutheroside B combination treatment on the lipopolysaccharide(LPS)-induced depression mice model.Methods Depression mice model was established by lipopolysaccharide(LPS)injection.Totally 48 mice were randomly divided into 6 groups(8 rats per group)according to a random number table,including normal,model,fluoxetine(20 mg/kg),geniposide(100 mg/kg)+eleutheroside B(100 mg/kg),geniposide+eleutheroside B+WAY 100635(0.03 mg/kg),geniposide+eleutheroside B+N-methyl-D-aspartic acid receptor(NMDA,75 mg/kg)groups,respectively.After continuous administration for 10 days,autonomic activity tests after 30 min of administration were performed on the 10th day.On the 11th day,except for the normal group,the mice in the other groups were intraperitoneally injected with LPS(1 mg/kg),and the behavioral tests were performed 4 h later.Enzyme linked immunosorbent assay was used to detect tumor necrosis factor alpha(TNF-α)and interleukin-1β(IL-1β)levels in mice serum.The mRNA expression of indoleamine 2,3-dioxygenase(IDO)and nuclear transcription factor(NF-κB)were detected by real-time quantitative polymerase chain reaction.Western-blot analysis was used to detect IDO and NF-κB protein expressions in hippocampus tissue.Results Compared with the normal group,a single administration of LPS increased the immobility time in the forced swimming test(FST)and tail suspension test(TST,P<0.01),without affecting autonomous activity.Compared with the model group,fluoxetine and geniposide+eleutheroside B administration significantly improved the immobility time of depressed mice in the FST and TST,decreased serum IL-1βcontent,inhibited the expression levels of NF-κB gene and protein in hippocampus tissues(P<0.05 or P<0.01).Compared with the model group,geniposide+eleutheroside B treatment significantly reduced serum TNF-αcontent and inhibited IDO mRNA and protein expressions in hippocampus(P<0.05 or P<0.01).In addition,NMDA partly prevented the inhibition of IDO mRNA expression by geniposide+eleutheroside B;NMDA and WAY-100635 also partly prevented the reduction of IL-1ßcontent induced by geniposide+eleutheroside B treatment(P<0.05 or P<0.01).Conclusions The combination of geniposide and eleutheroside B showed a certain antidepression-like effect.Its main mechanism of action may be contributed to inhibiting the activation of NF-κB,decreasing the proinflammatory cytokines such as TNF-α,IL-1β,and inhibiting in the neuroinflammatory reaction.Additionally,it also affects tryptophan metabolism,reduces the expression of a key enzyme of tryptophan metabolism,IDO.And this antidepressant-like effect may be mediated by 5-hydroxytryptamine and glutamate systems.

The antibacterial activity of Berberis heteropoda Schrenk and its effect on irritable bowel syndrome in rats

The dried roots of Berberis heteropoda Schrenk have traditionally been used to treat acute gastroenteritis and dysentery. The aim of this study was to confirm the antibacterial activity of an extract of Berberis heteropoda Schrenk root in vitro and its therapeutic effects on rats with diarrhea-predominant irritable bowel syndrome(D-IBS) in vivo, as well as to identify the related signaling pathways. A water extract of Berberis heteropoda Schrenk root(BHS) inhibited the growth of S. aureus, E. coli, P. aeruginosa and S. faecalis. BHS potentially damaged the structure of the bacterial cell membrane and decreased the activity of some membranous enzymes, eventually killing the S. aureus, E. coli, P. aeruginosa and S. faecalis bacteria. Oral administration of BHS(low, middle and high dose group, L, M and H) significantly alleviated the abdominal pain, diarrhea, and depression-like symptoms of D-IBS rats, and the efficacy index ranged from 30% to 60%, indicating that the BHS treatment was effective. BHS(L, M and H) alleviated the abnormal pathological changes in the brain, as evidenced by HE staining. The expression of CHAT, 5-HT, C-FOS and CGRP was reduced by the BHS treatment(L, M and H). Our findings provide novel insights into the use of the natural product BHS to inhibit pathogenic bacteria by destroying the bacterial structure, indicating that BHS possesses certain biological activities. Furthermore, BHS has the potential to alleviate diarrhea, abdominal pain and depression-like behaviors in D-IBS rats by regulating the brain-gut peptide levels.