New insights into effects of Kaixin Powder on depression via lipid metabolism related adiponectin signaling pathway

IF 4.7 4区 医学 Q1 CHEMISTRY, MEDICINAL Chinese Herbal Medicines Pub Date : 2023-04-01 DOI:10.1016/j.chmed.2022.06.012
Wenshan Yang , Hong Yin , Yichen Wang , Yuanbo Wang , Xia Li , Chaochen Wang , Ping Liu , Yuan Hu
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Abstract

Objective

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.

Methods

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.

Results

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.

Conclusion

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.

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开心散脂质代谢相关脂联素信号通路对抑郁症作用的新认识
目的通过全基因组转录组分析,阐明有助于预防和治疗抑郁症和其他精神疾病的药物开心散抗抑郁的潜在机制。方法对抑郁大鼠海马进行转录组和KEGG通路分析,验证差异表达基因,并用酶法鉴定血清脂质浓度参数。此外,对叙利亚金仓鼠进行了高脂肪饮食诱导的抑郁样行为,以验证从转录组分析中获得的预测分子机制。结果转录组结果显示,慢性轻度应激(CMS)大鼠的24个差异表达基因(DEGs)在KP治疗两周后可以逆转。KP治疗抑郁症的机制首先涉及几个病理模块的调节,包括脂质代谢、突触功能和炎症。KP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,还证实了KP可以改善胆固醇代谢功能障碍,这与AdipoR1 BDNF(脑源性神经营养因子)共调节通路的上调有关。结论总之,我们的研究结果表明,KP不仅通过传统的精神疾病靶点缓解抑郁,而且还可以模拟胆固醇代谢和脂联素信号传导,具有多靶点特征。
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来源期刊
Chinese Herbal Medicines
Chinese Herbal Medicines CHEMISTRY, MEDICINAL-
CiteScore
4.40
自引率
5.30%
发文量
629
审稿时长
10 weeks
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