Chu Tan-Lu, Guo Ze-Jun, Zhang Wei, Wang Ling-Feng, Lyu Shu-Rui, Guo Wan-Yu, Zhong Xiao-Ming, Qiu Feng-Mei, Huang Zhen
School of Pharmay, Zhejiang Chinese Medical University Hangzhou 310053, China.
Jinhua Academy, Zhejiang Chinese Medical University Jinhua 321000, China.
Zhongguo Zhong Yao Za Zhi. 2025 Jun;50(11):3147-3158. doi: 10.19540/j.cnki.cjcmm.20250313.305.
The antidepressant activity and molecular mechanisms of Yueju Wan volatile oil were investigated. The Yueju Wan volatile oil was extracted by using supercritical CO_2. Gas chromatography-mass spectrometry(GC-MS) combined with network pharmacology identified 28 chemical constituents in Yueju Wan volatile oil, primarily terpenes and lactones. A total of 123 overlapping targets were associated with depression, including core targets of interleukin-1β(IL-1β), signal transducer and activator of transcription 3(STAT3), and caspase-3(CASP3). These targets were mainly involved in the prolactin, advanced glycation end products/receptor(AGE/RAGE), and phosphoinositide 3-kinase/protein kinase B(PI3K/Akt) signaling pathways. A reserpine-induced depression mouse model was established to evaluate the therapeutic effects and mechanisms of Yueju Wan volatile oil. The effects of Yueju Wan volatile oil on depression-like behavior in mice were evaluated by analyzing body mass, body temperature index, tail suspension immobility time, forced swimming immobility time, and sucrose preference. Hematoxylin-eosin(HE) staining revealed neuronal protection of Yueju Wan volatile oil in the brain of mice. Enzyme-linked immunosorbent assay(ELISA) and Western blot were employed to detect the protein expression of AGEs, IL-1β, phosphorylated PI3K(p-PI3K), Akt, phosphorylated Akt(p-Akt), nuclear factor κB(NF-κB), and brain-derived neurotrophic factor(BDNF). Behavioral evaluation showed that Yueju Wan volatile oil could effectively control the decline of body mass and body temperature of depressed mice, reduce tail suspension and swimming immobility time, and enhance their preference for sucrose. Histopathological examination showed that Yueju Wan volatile oil could alleviate the neuronal damage in CA1 and dentate gyrus(DG) of the hippocampus of mice. ELISA and Western blot results showed that Yueju Wan volatile oil could significantly increase the protein expression levels of PI3K, Akt, and BDNF and significantly decrease the protein expression levels of AGEs, IL-1β, p-PI3K, p-Akt, and NF-κB in the hippocampus of mice. Furthermore, the p-PI3K/PI3K and p-Akt/Akt ratios were significantly decreased at medium and high doses. These findings suggest that the aromatherapy of Yueju Wan volatile oil can significantly improve reserpine-induced depression-like behavior in mice, which may be related to reducing the expression of neuronal membrane protein AGEs, reducing the phosphorylation levels of PI3K and Akt, inhibiting NF-κB entry into the nucleus, and alleviating the release of pro-inflammatory factors and nerve injury.
研究了越鞠丸挥发油的抗抑郁活性及分子机制。采用超临界CO₂萃取越鞠丸挥发油。气相色谱-质谱联用（GC-MS）结合网络药理学鉴定出越鞠丸挥发油中的28种化学成分，主要为萜类和内酯类。共有123个重叠靶点与抑郁症相关，包括白细胞介素-1β（IL-1β）、信号转导和转录激活因子3（STAT3）及半胱天冬酶-3（CASP3）等核心靶点。这些靶点主要参与催乳素、晚期糖基化终产物/受体（AGE/RAGE）及磷脂酰肌醇3-激酶/蛋白激酶B（PI3K/Akt）信号通路。建立利血平诱导的抑郁小鼠模型，以评估越鞠丸挥发油的治疗效果及机制。通过分析体重、体温指数、悬尾不动时间、强迫游泳不动时间及蔗糖偏好来评估越鞠丸挥发油对小鼠抑郁样行为的影响。苏木精-伊红（HE）染色显示越鞠丸挥发油对小鼠脑神经元有保护作用。采用酶联免疫吸附测定（ELISA）和蛋白质印迹法检测AGEs、IL-1β、磷酸化PI3K（p-PI3K）、Akt、磷酸化Akt（p-Akt）、核因子κB（NF-κB）及脑源性神经营养因子（BDNF）的蛋白表达。行为学评估表明，越鞠丸挥发油可有效控制抑郁小鼠体重和体温的下降，减少悬尾和游泳不动时间，并增强其对蔗糖的偏好。组织病理学检查显示，越鞠丸挥发油可减轻小鼠海马CA1区和齿状回（DG）的神经元损伤。ELISA和蛋白质印迹结果显示，越鞠丸挥发油可显著提高小鼠海马中PI3K、Akt和BDNF的蛋白表达水平，并显著降低AGEs、IL-1β、p-PI3K、p-Akt和NF-κB的蛋白表达水平。此外，中、高剂量时p-PI3K/PI3K和p-Akt/Akt比值显著降低。这些研究结果表明，越鞠丸挥发油芳香疗法可显著改善利血平诱导的小鼠抑郁样行为，这可能与降低神经元膜蛋白AGEs的表达、降低PI3K和Akt的磷酸化水平、抑制NF-κB入核以及减轻促炎因子释放和神经损伤有关。
