ABSTRACT
Depression is a common psychiatric disease that seriously affects the physical and mental health and quality of life of patients， and has become one of the major global disease burdens. The etiology of depression is intricate， and despite extensive research， its pathogenesis remains inconclusive， resulting in various hypotheses of its onset mechanisms. Presently， the primary approach for clinically treating depression involves the utilization of selective inhibitors targeting the reuptake of monoamine neurotransmitters within the central nervous system. However， these drugs are generally characterized by delayed onset of action， limited efficacy and obvious resistance. Recently， researchers have gradually turned their attention to the development of antidepressant drugs with novel mechanisms. Notably， as a category of abundantly available active ingredients in Chinese medicine， numerous pharmacological studies have demonstrated that oligosaccharides and polysaccharides possess promising antidepressant properties， such as Morindae Officinalis Radix oligosaccharides， Polygalae Radix oligosaccharide esters， Poria polysaccharides and Astragali Radix polysaccharides. Their pharmacological mechanisms are various， including enhancing the levels of monoamine neurotransmitters in the brain， inhibiting the hyperactivation of the hypothalamic-pituitary-adrenal axis（HPA axis）， increasing the expression of neurotrophic factors（NTF）， regulating immune-inflammatory responses and modulating the microbiota-gut-brain axis. Therefore， oligosaccharides and polysaccharides from Chinese medicine have become a vital source of safe and effective novel antidepressant candidates due to the potential to improve depression through integrated regulatory effects. This article aims to provide a comprehensive and systematic review of recent progress to contribute to the elucidation of the mechanisms underlying the antidepressant effects of oligosaccharides and polysaccharides derived from Chinese medicine.
ABSTRACT
Objective:To investigate the effect of salvianolic acid on depressive behavior in depression model rats induced by chronic mild stress (CMS) and its mechanism.Methods:Fifty healthy male clean grade Sprague-Dawley(SD) rats were divided into five groups according to a random number table with 10 in each group: control group (nCMS+ Nal group), CMS+ normal saline group (CMS+ Nal group), CMS+ fluoxetine group (CMS+ Flu group), CMS+ salvia acid group (CMS+ Sal group), CMS+ fluoxetine+ Salvia acid group (CMS+ Flu+ Sal group). Except the control group, the rats in the other four groups were all received CMS modeling for 21 days. Twenty-one days after CMS modeling, rats were intraperitoneally injected with 0.9% normal saline (10 mg·kg -1·d -1), fluoxetine (20 mg·kg -1·d -1), salvia acid(40 mg·kg -1·d -1), fluoxetine(20 mg·kg -1·d -1)+ salvia acid(40 mg·kg -1·d -1)for 21 days. During the administration period, rats in the other four groups continued to receive CMS intervention for 21 days. Forced swimming test and sucrose preference test were conducted at baseline (day 0), after modeling (day 21) and after intervention (day 42) so as to evaluate depression like behavior. Then the rats were sacrificed and the hippocampus and prefrontal cortex were taken. The mRNA levels of Toll like receptor 4 (TLR4) and myeloid differentiation primary response 88 (MyD88) were detected by RT-qPCR. The cytokines including interleukin-1β(IL-1β), interleukin-2(IL-2), interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) were detected by Luminex technique.SPSS 21.0 was used for statistical analysis.Repeated measurement ANOVA was used for behavioral data analysis, one-way ANOVA was used for molecular index data analysis, and Spearman was used for correlation analysis. Results:The results of repeated measurement ANOVA showed that the interaction effects between group and time of body mass, sucrose preference, forced swimming immobility time were significant at baseline, after modeling and after intervention ( F=18.238, 6.921, 7.591, all P<0.05). After modeling, compared with nCMS+ Nal group, the rats in CMS+ Flu group, CMS+ Sal group, CMS+ Flu+ Sal group and CMS+ Nal group had lower body weight, lower sucrose preference rate and longer forced swimming immobility time (all P<0.05). After intervention, compared with CMS+ Nal group(body weight (350.15±41.65)g, sucrose preference(52.95±11.13)%, static time(91.40±15.22)s), the body weight((378.21±30.78)g, (385.12±43.19)g, (391.41±31.21)g, (402.33±18.67)g, all P<0.05) and sucrose preference((69.30±15.56)%, (68.12±10.99)%, (71.18±9.51)%, (75.47±11.55)%, all P<0.05) of CMS+ Flu group, CMS+ Sal group, CMS+ Flu+ Sal group and nCMS+ Nal group were all increased, while the forced swimming immobility time ((68.81±21.74)s, (66.10±25.51)s, (63.53±22.32)s, (71.21±21.41)s, all P<0.05) were shorter (all P<0.05). After intervention, among the body weight, sucrose preference and the immobility time of CMS+ Flu group、CMS+ Sal group and CMS+ Flu+ Sal group, there were no differences between each two groups(all P>0.05). After intervention, the levels of TLR4 mRNA and MyD88 mRNA in prefrontal cortex and hippocampus of CMS+ Flu group, CMS+ Sal group, CMS+ Flu+ Sal group and nCMS+ Nal group were all lower than those in CMS+ Nal group (all P<0.05). In prefrontal cortex, the levels of TLR4 mRNA (0.715±0.358) and MyD88 mRNA (0.739±0.233) in CMS+ Flu+ Sal group were lower than those in CMS+ Sal group (1.943±0.606, 1.815±0.897) (both P<0.05). The level of TLR4 mRNA in prefrontal cortex and hippocampus of rats were positively correlated with the level of MyD88 mRNA and TNF-α level and forced swimming immobility time and negatively correlated with sucrose preference rate (prefrontal cortex r=0.915, 0.041, 0.027, -0.178, all P<0.05; hippocampus r=0.810, 0.070, 0.011, -0.153, all P<0.05). Conclusion:The antidepressant effect of salvianolic acid is presumedly achieved by inhibiting the immunoinflammatory response mediated by the TLR4/Myd88 signaling pathway in CMS rats.
ABSTRACT
Objective:To explore the effects of Shenwei Ningyu pills （SNP）， a new Chinese medicine for depression， on the immunoinflammatory response mediated by Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88） signaling pathway in the hippocampus of rats exposed to chronic restraint stress （CRS）. Method:Forty-four male Sprague Dawley rats were randomly enrolled into a normal group， a model group， an escitalopram group， and an SNP group. Except for the rats in the normal group， all rats were exposed to CRS and isolated rearing for 21 days continuously. Rats in the escitalopram group and the SNP group were administered with escitalopram （30 mg·kg<sup>-1</sup>） and SNP （18 mg·kg<sup>-1</sup>） one hour prior to CRS， respectively. The changes in body weight， sucrose preference index， horizontal movement scores， and vertical movement scores were observed by body weight assessment， sucrose preference test， and open field test. The expression of hippocampal TLR4 and MyD88 was detected by Western blot. The content of serum interleukin-1<italic>β</italic> （IL-1<italic>β</italic>）， IL-10， and tumor necrosis factor-<italic>α</italic> （TNF-<italic>α</italic>） was detected by enzyme-linked immunosorbent assay （ELISA）. Result:The results of the behavioral assessment showed that there was no significant difference in the changes of behavioral baselines among the groups before intervention. However， significant differences were found among the groups following different interventions. The body weight， sugar preference index， horizontal movement score， and vertical movement score of rats in the model group decreased after CRS for 21 days as compared with those in the normal group （<italic>P</italic><0.01）. The above indicators in the SNP<italic> </italic>group and the escitalopram group were higher than those in the model group （<italic>P</italic><0.01）， which indicated that SNP<italic> </italic>exerted an obvious antidepressant effect. The results of Western blot and ELISA showed that compared with the normal group， the model group showed elevated levels of hippocampal TLR4 and MyD88 and serum IL-1<italic>β</italic> and TNF-<italic>α </italic>（<italic>P</italic>˂0.01） and dwindled serum IL-10 （<italic>P</italic>˂0.01）， while SNP<italic> </italic>and escitalopram reversed the conditions in the model group （<italic>P</italic>˂0.01） except for TNF-<italic>α</italic>. Conclusion:The present study indicated that the antidepressant effect of SNP was presumedly achieved by inhibiting the immunoinflammatory response mediated by the TLR4/Myd88 signaling pathway in CRS rats.
ABSTRACT
Objective To investigate the myocardium protective effect of immunoinflammatory response induced by preinfarction angina. Methods Eighty-eight patients of acute myocardial infarction were divided into preinfarction angina group (48 subjects) and sudden onset group (40 subjects). The incidence of severe arrhythmia,heart failure,cardiac shock and in-hospital mortality were assessed in the two groups. The myocardial infarction size,ventricular function,coronary angiography were compared between the two groups. Some immunoinflammatory markers levels were detected. Results In preinfarction angina group,the incidences of severe arrhythmia,heart failure,and in-hospital mortality were lower (P