Li Dongmei, Zheng Ji, Wang Mingyang, Feng Lu, Liu Yanyong, Yang Nan, Zuo Pingping
Department of Pharmacology, Institute of Basic Medical Sciences, Neuroscience Center, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, Beijing 100005, China.
Department of Pharmacology, Institute of Basic Medical Sciences, Neuroscience Center, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, Beijing 100005, China.
J Ethnopharmacol. 2016 Jun 20;186:181-188. doi: 10.1016/j.jep.2016.03.065. Epub 2016 Apr 5.
Wuling powder (trade name: Wuling capsule), a traditional Chinese medicine (TCM), was extracted from mycelia of precious Xylaria Nigripes (Kl.) Sacc by modern fermentation technology, and has been claimed to be fully potent in improving the signs of insomnia and cognitive deficits. Moreover, Wuling capsule was effective in treating post-stroke and orther co-cormbid depression both in clinical and in basic research. In order to clarify the molecular mechanisms of the antidepressant effect of Wuling powder, we established learned helplessness (LH) depression animal model and focused on 18kDa translocator protein (TSPO) mediated-mitophagy pathway.
Mice were exposed to the inescapable e-shock (IS) once a day for three consecutive days to establish the LH model. Then mice were orally administered Wuling powder for 2 weeks. For the behavioral assessment, Shuttle box test, novelty suppressed feeding test (NSF) and forced swimming test (FST) were performed. Following the behavioral assessment, we assessed the protein expression level that were related to TSPO-mediated mitophagy signaling pathway by Western blotting analysis. Finally, immunohistochemistry method was used to assess the neuroprotective effects of Wuling powder.
Compared with mice that were subjected to inescapable e-shock, Wuling powder exhibited antidepressant effect in the multiple behavioral tests. In addition, Wuling powder altered the expression level of multiple proteins related to TSPO-mediated mitophagy signaling pathway.
Our results suggested that Wuling powder exhibited an obvious antidepressant effect, which could be due to the improvement of TSPO-mediated mitophagy signaling pathway.
五灵散（商品名：五灵胶囊）是一种中药，通过现代发酵技术从珍贵的黑柄炭角菌（Xylaria Nigripes (Kl.) Sacc）菌丝体中提取，据称在改善失眠症状和认知缺陷方面具有充分的效力。此外，在临床和基础研究中，五灵胶囊对治疗中风后及其他共病性抑郁症均有效。为了阐明五灵散抗抑郁作用的分子机制，我们建立了习得性无助（LH）抑郁动物模型，并聚焦于18 kDa转位蛋白（TSPO）介导的线粒体自噬途径。
小鼠连续三天每天接受一次不可逃避的电击（IS）以建立LH模型。然后小鼠口服五灵散2周。进行行为评估时，进行穿梭箱试验、新奇抑制摄食试验（NSF）和强迫游泳试验（FST）。行为评估后，通过蛋白质免疫印迹分析评估与TSPO介导的线粒体自噬信号通路相关的蛋白质表达水平。最后，采用免疫组织化学方法评估五灵散的神经保护作用。
与接受不可逃避电击的小鼠相比，五灵散在多项行为测试中表现出抗抑郁作用。此外，五灵散改变了与TSPO介导的线粒体自噬信号通路相关的多种蛋白质的表达水平。
我们的结果表明，五灵散表现出明显的抗抑郁作用，这可能是由于TSPO介导的线粒体自噬信号通路得到改善。
