Mechanistic of Yueju Wan volatile oil in inhibiting inflammation for antidepressant effects by regulating AGE/PI3K/Akt pathway.
10.19540/j.cnki.cjcmm.20250313.305
- Author:
Tan-Lu CHU
1
;
Ze-Jun GUO
1
;
Wei ZHANG
1
;
Ling-Feng WANG
2
;
Shu-Rui LYU
1
;
Wan-Yu GUO
1
;
Xiao-Ming ZHONG
1
;
Feng-Mei QIU
1
;
Zhen HUANG
1
Author Information
1. School of Pharmay, Zhejiang Chinese Medical University Hangzhou 310053, China.
2. Jinhua Academy, Zhejiang Chinese Medical University Jinhua 321000, China.
- Publication Type:Journal Article
- Keywords:
AGE/PI3K/Akt pathway;
GC-MS;
Yueju Wan volatile oil;
depression;
network pharmacology
- MeSH:
Animals;
Antidepressive Agents/chemistry*;
Mice;
Proto-Oncogene Proteins c-akt/immunology*;
Phosphatidylinositol 3-Kinases/immunology*;
Oils, Volatile/chemistry*;
Male;
Drugs, Chinese Herbal/chemistry*;
Signal Transduction/drug effects*;
Depression/metabolism*;
Glycation End Products, Advanced/immunology*;
Humans
- From:
China Journal of Chinese Materia Medica
2025;50(11):3147-3158
- CountryChina
- Language:Chinese
-
Abstract:
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.
