Yang Wenshan, Yin Hong, Wang Yichen, Wang Yuanbo, Li Xia, Wang Chaochen, Liu Ping, Hu Yuan
Department of Pharmacy, Medical Supplies Center of PLA General Hospital, Chinese PLA General Hospital, Beijing 100853, China.
Chinese PLA Medical School, Chinese PLA General Hospital, Beijing 100853, China.
Chin Herb Med. 2023 Jan 11;15(2):240-250. doi: 10.1016/j.chmed.2022.06.012. eCollection 2023 Apr.
To clarify the anti-depressive potential mechanisms of Kaixin Powder (KP), a drug that helps to prevent and treat depression and other mentaldiseases, from genome-wide transcriptome profiling.
Transcriptome and KEGG pathway analysis were conducted on the hippocampus of depressed rats, then the differentially expressed genes were validated and serum concentration of lipid parameters were identified by enzymatic assays. Furthermore, high-fat diets induced depression-like behaviors in Syrian golden hamsters were conducted to verify the predicted molecular mechanisms acquired from the transcriptome analysis.
Transcriptome results revealed that the 24 differentially expressed genes (DEGs) in chronic mild stress (CMS) rats could be reversed after two weeks of KP treatment. The mechanisms of KP in treating depression firstly involved the regulation of several pathology modules, including lipid metabolism, synapse function and inflammation. KP could regulate imbalances of lipid homeostasis in high-fat diet induced depressive symptoms. Furthermore, it was validated that cholesterol metabolism dysfunction can be ameliorated by KP, which was correlated with upregulation of the AdipoR1-BDNF (brain-derived neurotrophic factor) co-regulatory pathway.
Taken together, our results demonstrated that KP not only alleviates depression via traditional mental illness targets, but it may also simulates the cholesterol metabolism and adiponectin signaling with multi-target characteristics.
通过全基因组转录组分析，阐明开心散（KP）预防和治疗抑郁症及其他精神疾病的抗抑郁潜在机制。
对抑郁大鼠的海马进行转录组和KEGG通路分析，然后对差异表达基因进行验证，并通过酶法测定血清脂质参数浓度。此外，采用高脂饮食诱导叙利亚金仓鼠出现抑郁样行为，以验证从转录组分析中获得的预测分子机制。
转录组结果显示，慢性轻度应激（CMS）大鼠中的24个差异表达基因（DEGs）在接受两周的开心散治疗后可被逆转。开心散治疗抑郁症的机制首先涉及对几个病理模块的调节，包括脂质代谢、突触功能和炎症。开心散可以调节高脂饮食诱导的抑郁症状中脂质稳态的失衡。此外，还证实开心散可以改善胆固醇代谢功能障碍，这与AdipoR1-脑源性神经营养因子（BDNF）共同调节通路的上调有关。
综上所述，我们的结果表明，开心散不仅通过传统的精神疾病靶点缓解抑郁，还可能通过多靶点特性模拟胆固醇代谢和脂联素信号传导。
