Ginsenoside Rg1 alleviates corticosterone-induced dysfunction of gap junctions in astrocytes
Ginsenoside Rg1 alleviates corticosterone-induced dysfunction of gap junctions in astrocytes
复制标题
人参皂苷 Rg1 减轻皮质酮诱导的星形胶质细胞间隙连接功能障碍
DOI：
10.1016/j.jep.2017.06.031
复制
发表时间：
2017
影响因子：
5.4
通讯作者：
Chen Nai-Hong
中科院分区：
文献类型：
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作者：
Xia Cong-Yuan;Chu Shi-Feng;Zhang Shuai;Gao Yan;Ren Qian;Lou Yu-Xia;Luo Piao;Tian Man-Tong;Wang Zhi-Qi;Du Guo-Hua;Tomioka Yoshihisa;Yamakuni Tohru;Zhang Yi;Wang Zhen-Zhen;Chen Nai-Hong
人参皂苷Rg1（Ginsenoside Rg1，Rg1）是人参（Panax ginseng C.）A. Mey在抑郁症动物模型中具有神经保护作用，但其作用机制尚不清楚。因此，我们调查是否Rg1的抗抑郁样作用与GJIC.Materials和MethodsPrimary大鼠前额叶皮层和海马星形胶质细胞培养物用50 μM CORT处理24 h诱导间隙连接损伤。在CORT治疗前1 h加入Rg1（0.1、1或10 μM）或氟西汀（1 μM）。进行刮片加载和染料转移测定以鉴定间隙连接的功能能力。Western blot检测缝隙连接蛋白43（connexin43，Cx43）的表达和磷酸化，Cx43是缝隙连接的主要组成部分。结果CORT处理星形胶质细胞24 h，可抑制GJIC，降低Cx43的总表达，并以剂量依赖方式增加Cx43在丝氨酸368位的磷酸化。1 μM和10 μM Rg1预处理显著改善皮质激素处理的前额叶皮层和海马星形胶质细胞的GJIC，并伴有Cx43表达上调和Cx43磷酸化下调。结论Rg1可减轻皮质激素诱导的缝隙连接功能障碍，对抑郁症的治疗可能具有临床意义。
Ethnopharmacological relevanceGinsenoside Rg1 (Rg1), one of the major bioactive ingredients ofPanax ginsengC. A. Mey, has neuroprotective effects in animal models of depression, but the mechanism underlying these effects is still largely unknownAim of the studyGap junction intercellular communication (GJIC) dysfunction is a potentially novel pathogenic mechanism for depression. Thus, we investigated that whether antidepressant-like effects of Rg1 were related to GJIC.Materials and methodsPrimary rat prefrontal cortical and hippocampal astrocytes cultures were treated with 50 μM CORT for 24 h to induce gap junction damage. Rg1 (0.1, 1, or 10 μM) or fluoxetine (1 μM) was added 1 h prior to CORT treatment. A scrape loading and dye transfer assay was performed to identify the functional capacity of gap junctions. Western blot was used to detect the expression and phosphorylation of connexin43 (Cx43), the major component of gap junctions.ResultsTreatment of primary astrocytes with CORT for 24 h inhibited GJIC, decreased total Cx43 expression, and increased the phosphorylation of Cx43 at serine368 in a dose-dependent manner. Pre-treatment with 1 μM and 10 μM Rg1 significantly improved GJIC in CORT-treated astrocytes from the prefrontal cortex and hippocampus, respectively, and this was accompanied by upregulation of Cx43 expression and downregulation of Cx43 phosphorylation.ConclusionThese findings provide the first evidence indicating that Rg1 can alleviate CORT-induced gap junction dysfunction, which may have clinical significance in the treatment of depression.