Depression is a psychological disease with no particularly effective therapy currently available.In the present study,we aimed to examine the antidepressive activity of a pharmaceutical Chinese medicine called TaiZi(T...Depression is a psychological disease with no particularly effective therapy currently available.In the present study,we aimed to examine the antidepressive activity of a pharmaceutical Chinese medicine called TaiZi(TZ)capsule,consisting of total polysaccharides of Radix Pseudostellariae and total flavonoids of both Radix Pueraria and Herba Epimedii.A tail suspension test and forced swimming test were performed to assess the effect of TZ in vivo.A plasmid of TPH2(tryptophan hydroxylase-2)was constructed to determine the exact target of TZ in vitro.In addition,mRNA expression was detected using a real-time PCR assay,and the protein expression was investigated using a Western blotting analysis.The results showed that TZ had an anti-depression effect in mouse and rat models with increased serotonin in the brain,and in the upregulation of mRNA and protein expression of TPH2 in the brain simultaneously by inhibition of NRSF(neuron restrictive silencer factor)expression because NRSF could bind to NRSE(neuron restrictive silencer element)to repress TPH2 transcription during the depression conditions.Icariin could bind to NRSE directly and block NRSF protein toward to NRSE for TPH2 inhibition.Therefore,we concluded that TZ had potential antidepressive effects because it could ameliorat the depression-like behavior in the animals,and the underlying mechanism of the effect was involved in NRSF/NRSE-TPH2 signaling.Icariin was identified as the active component of TZ.This study provided a new perspective for the development of antidepression drugs(Chinese medicines)based on NRSF/NRSE-TPH2 signaling.展开更多
目的探索TPH2基因多态性与抑郁症的关系。方法检索PubMed、Web of SCI、SE、CNKI与万方数据库,全面搜集有关于TPH2基因多态性与抑郁症相关性的文献,截至2019-09-01,最后用STATA15.0进行meta分析。结果此次研究纳入文献20篇,涉及4289例...目的探索TPH2基因多态性与抑郁症的关系。方法检索PubMed、Web of SCI、SE、CNKI与万方数据库,全面搜集有关于TPH2基因多态性与抑郁症相关性的文献,截至2019-09-01,最后用STATA15.0进行meta分析。结果此次研究纳入文献20篇,涉及4289例抑郁症患者和4806例正常对照。提取TPH2基因上的2个SNP位点(rs1386494、rs7305115)的基因型和等位基因数据,并对它们的显性、隐性和等位基因模型分别进行meta分析,结果差异均无统计学意义。然后将这两个位点按亚洲国家与非亚洲国家进行亚组分析,我们发现在rs1386494位点中,结果仍无统计学关联;而在rs7305115位点中,亚洲国家人群中的GG基因型会增加抑郁症患病风险[比值比(odds ratio,OR)=1.181,95%置信区间(confidence interval,CI)(1.024,1.362),P=0.004],G等位基因也会增加抑郁症患病风险[OR=1.097,95%CI(1.006,1.196),P=0.036],在非亚洲国家人群中,结果差异仍无统计学意义(P>0.05)。结论在亚洲国家人群中,TPH2基因上的rs7305115位点的隐性模型和等位基因模型可能与抑郁症患病有关。展开更多
基金The Student Research Training(SRT)Program of Tsinghua University(Grant No.1522T0221)the National Natural Science Foundation of China(Grant No.81374006 and 81073092)。
文摘Depression is a psychological disease with no particularly effective therapy currently available.In the present study,we aimed to examine the antidepressive activity of a pharmaceutical Chinese medicine called TaiZi(TZ)capsule,consisting of total polysaccharides of Radix Pseudostellariae and total flavonoids of both Radix Pueraria and Herba Epimedii.A tail suspension test and forced swimming test were performed to assess the effect of TZ in vivo.A plasmid of TPH2(tryptophan hydroxylase-2)was constructed to determine the exact target of TZ in vitro.In addition,mRNA expression was detected using a real-time PCR assay,and the protein expression was investigated using a Western blotting analysis.The results showed that TZ had an anti-depression effect in mouse and rat models with increased serotonin in the brain,and in the upregulation of mRNA and protein expression of TPH2 in the brain simultaneously by inhibition of NRSF(neuron restrictive silencer factor)expression because NRSF could bind to NRSE(neuron restrictive silencer element)to repress TPH2 transcription during the depression conditions.Icariin could bind to NRSE directly and block NRSF protein toward to NRSE for TPH2 inhibition.Therefore,we concluded that TZ had potential antidepressive effects because it could ameliorat the depression-like behavior in the animals,and the underlying mechanism of the effect was involved in NRSF/NRSE-TPH2 signaling.Icariin was identified as the active component of TZ.This study provided a new perspective for the development of antidepression drugs(Chinese medicines)based on NRSF/NRSE-TPH2 signaling.
文摘目的探索TPH2基因多态性与抑郁症的关系。方法检索PubMed、Web of SCI、SE、CNKI与万方数据库,全面搜集有关于TPH2基因多态性与抑郁症相关性的文献,截至2019-09-01,最后用STATA15.0进行meta分析。结果此次研究纳入文献20篇,涉及4289例抑郁症患者和4806例正常对照。提取TPH2基因上的2个SNP位点(rs1386494、rs7305115)的基因型和等位基因数据,并对它们的显性、隐性和等位基因模型分别进行meta分析,结果差异均无统计学意义。然后将这两个位点按亚洲国家与非亚洲国家进行亚组分析,我们发现在rs1386494位点中,结果仍无统计学关联;而在rs7305115位点中,亚洲国家人群中的GG基因型会增加抑郁症患病风险[比值比(odds ratio,OR)=1.181,95%置信区间(confidence interval,CI)(1.024,1.362),P=0.004],G等位基因也会增加抑郁症患病风险[OR=1.097,95%CI(1.006,1.196),P=0.036],在非亚洲国家人群中,结果差异仍无统计学意义(P>0.05)。结论在亚洲国家人群中,TPH2基因上的rs7305115位点的隐性模型和等位基因模型可能与抑郁症患病有关。
