ABSTRACT
Objective:To observe the effect of Sinisan on the brain-derived neurotrophic factor （BDNF）/tyrosine kinase receptor B （TrKB）， 5-hydroxytryptamine （5-HT）/5-HT1A receptor （5-HT1AR）， and hypothalamus-pituitary-adrenal （HPA） axis in depressed rats， and explore the antidepressant mechanism of Sinisan based on BDNF/TrKB， 5-HT/5-HT1AR， and HPA axis. Method:A total of 120 male Wistar rats were randomly divided into a normal group， a model group， a fluoxetine （0.01 g·kg<sup>-1</sup>） group， and low- （1.25 g·kg<sup>-1</sup>）， medium- （2.5 g·kg<sup>-1</sup>）， and high-dose （5 g·kg<sup>-1</sup>） Sinisan groups， with 20 rats in each group. The depression model was induced by isolation combined with chronic unpredictable mild stimulation（CUMS） in rats except for those in the normal group for 21 days. Rats were then treated correspondingly once a day for 21 days by gavage. Those in the normal group and the model group received an equal volume of normal saline. During the intervention， the model rats were stimulated continuously. The depressive state of CUMS model rats was evaluated by sucrose preference test and open field test. Enzyme-linked immunosorbent assay （ELISA） was used to determine the levels of corticotropin-releasing hormone （CRH）， adrenocorticotropic hormone （ACTH）， and corticosterone （CORT） in the plasma and BDNF and 5-HT levels in the hippocampal homogenate. The mRNA expression of hippocampal TrKB， 5-HT1AR， glucocorticoid receptor （GR）， and mineralocorticoid receptor （MR） was detected by real-time fluorescence-based quantitative polymerase chain reaction （Real-time PCR）. The protein expression of hippocampal TrKB， 5-HT1AR， GR， and MR was detected by Western blot. The histomorphological changes of the hippocampus were observed by hematoxylin-eosin （HE） staining. Result:Compared with the normal group， the model group showed decreased sucrose preference rate （<italic>P</italic><0.01）， reduced horizontal and vertical scores in the open field test （<italic>P</italic><0.01）， increased plasma content of CRH， ACTH， and CORT （<italic>P</italic><0.01）， declining content of BDNF and 5-HT in the hippocampus （<italic>P</italic><0.01）， dwindled mRNA and protein expression levels of TrKB， 5-HT1AR， and GR （<italic>P</italic><0.01）， elevated mRNA and protein expression of MR （<italic>P</italic><0.01）， and damaged hippocampal neurons revealed by HE staining. Compared with the model group， the groups with drug intervention showed increased sucrose preference rate （<italic>P</italic><0.01） and horizontal and vertical scores in the open field test （<italic>P</italic><0.05， <italic>P</italic><0.01）， decreased content of plasma CRH， ACTH， and CORT （<italic>P</italic><0.05， <italic>P</italic><0.01）， elevated content of hippocampal BDNF and 5-HT （<italic>P</italic><0.05， <italic>P</italic><0.01）， elevated mRNA and protein expression levels of hippocampal TrKB， 5-HT1AR， and GR （<italic>P</italic><0.05， <italic>P</italic><0.01）， reduced mRNA and protein expression levels of hippocampal MR （<italic>P</italic><0.05， <italic>P</italic><0.01）， and recovered hippocampal neurons as revealed by HE staining. Conclusion:Sinisan can exert a significant antidepressant effect by increasing hippocampal BDNF and 5-HT content， up-regulating TrKB， 5-HT1AR， and GR mRNA and protein expression， down-regulating MR mRNA and protein expression， inhibiting HPA axis hypertrophy， and enhancing the regeneration and repair of hippocampal neurons.
ABSTRACT
OBJECTIVE@#To provide evidence on the efficacy and safety of Chinese herbal medicine (CHM) as interventions for systemic lupus erythematosus (SLE).@*METHODS@#Seven electronic databases, including the Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP), Chinese Biomedical Literature Service System (SinoMed), Wanfang, Embase, and PubMed, were comprehensively searched, from their inception to August 16, 2020, for all randomized controlled trials (RCTs) that focused on CHM used alone or in combination with conventional medicine for SLE. Outcomes were SLE activity index (SLEDAI), traditional Chinese medicine symptom/syndrome score (TCMSS), dosage of glucocorticoids, main serological testing, and incidence of adverse events. Data were extracted and pooled using Review Manager 5.3 software.@*RESULTS@#A total of 13 RCTs enrolling 856 participants met our inclusion criteria. Meta-analyses showed that, compared to placebo, CHM had statistically significant effect on reducing SLEDAI score (MD=-1.74, 95% CI: -2.29 to -1.18), diminishing TCMSS (SMD=-0.89, 95% CI: -1.16 to -0.62), decreasing dosage of glucocorticoids (MD=-2.41 mg/d, 95% CI: -3.34 to -1.48), lowering erythrocyte sedimentation rate (MD=-4.78 mm/h, 95% CI: -8.86 to -0.71), and increasing serum complement C4 level (MD=0.03 mg/dL, 95% CI: 0.00 to 0.06). No significant difference was found between CHM and placebo on adverse events.@*CONCLUSIONS@#CHM provided significant beneficial effect on controlling disease activity and reducing dose of glucocorticoids used among SLE patients. Future advanced designed RCTs for CHM treating moderate to severe SLE with multicenter and longer follow-up are urgently needed.