Chen Jia-Wei, Liu Mao-Hui, Yang Zhi-Da, Zhu Jiu-Shuang, Wang Jie-Xin, Yang Kun, Gao Jing-Xin, Gan Rong, Wen Ling-Miao, Zhang Li, Guo Ze-Yi, Yang You-Jun, Gong Yan-Ju, Xia Xiu-Wen, Ding Wei-Jun
Department of Fundamental Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, Sichuan, PR China.
College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, Sichuan, PR China.
J Ethnopharmacol. 2025 Aug 29;352:120218. doi: 10.1016/j.jep.2025.120218. Epub 2025 Jul 3.
Erchen decoction (ECD) is a traditional Chinese medicine composed of six herbs that are historically recognized for their therapeutic effects on obesity, lipid metabolic disorders and systemic inflammation. However, the role and underlying mechanisms of ECD in alleviating anxiety and depression-like behaviors (ADBs) associated with obesity remain unclear.
This study aimed to investigate the role and mechanisms by which ECD improves ADBs in obese mice, with a focus on the adipose-brain axis.
An obesity model was established by feeding a high-fat diet (HFD) and then administering ECD by gavage. ADBs were evaluated via the open-field test and elevated plus maze test. Biochemical assays, histopathological observation, real-time PCR, immunofluorescence staining, untargeted metabolomics, and network pharmacology analysis were performed to investigate the potential mechanisms underlying the effects of ECD. Furthermore, the active components of ECD were qualitatively and quantitatively identified through extensive targeted mass spectrometry.
ECD treatment not only improved HFD-induced adipose deposition and liver steatosis but also reduced neuroinflammation and inguinal white adipose tissue (iWAT) inflammation. Additionally, ECD inhibited the activation of microglia in the brain (p < 0.001), enhanced astrocyte activation (p < 0.001), and upregulated brain-derived neurotrophic factor (BDNF) expression (p < 0.05, p < 0.01). Furthermore, ECD intervention significantly alleviated HFD-induced ADBs.
ECD alleviated HFD-induced ADBs by ameliorating inflammation in both iWAT and the brain, indicating that ECD is a potential therapy for ADBs. In addition, this is a preclinical mouse study to temper its applicability to human populations.
二陈汤（ECD）是一种中药方剂，由六味草药组成，历史上因其对肥胖、脂质代谢紊乱和全身炎症的治疗作用而闻名。然而，ECD在减轻与肥胖相关的焦虑和抑郁样行为（ADB）中的作用及潜在机制仍不清楚。
本研究旨在探讨ECD改善肥胖小鼠ADB的作用及机制，重点关注脂肪-脑轴。
通过高脂饮食（HFD）建立肥胖模型，然后通过灌胃给予ECD。通过旷场试验和高架十字迷宫试验评估ADB。进行生化分析、组织病理学观察、实时PCR、免疫荧光染色、非靶向代谢组学和网络药理学分析，以研究ECD作用的潜在机制。此外，通过广泛的靶向质谱对ECD的活性成分进行定性和定量鉴定。
ECD治疗不仅改善了HFD诱导的脂肪沉积和肝脏脂肪变性，还减少了神经炎症和腹股沟白色脂肪组织（iWAT）炎症。此外，ECD抑制了脑中小胶质细胞的激活（p < 0.001），增强了星形胶质细胞的激活（p < 0.001），并上调了脑源性神经营养因子（BDNF）的表达（p < 0.05，p < 0.01）。此外，ECD干预显著减轻了HFD诱导的ADB。
ECD通过改善iWAT和脑中的炎症来减轻HFD诱导的ADB，表明ECD是ADB的一种潜在治疗方法。此外，这是一项临床前小鼠研究，其对人群的适用性有待进一步验证。
