Exploration of the antidepressant machanism of Shugan hewei tang based on metabolomics of PFC-NAc-VTA neural circuit
- VernacularTitle:基于PFC-NAc-VTA神经环路代谢组学探讨疏肝和胃汤的抗抑郁作用机制
- Author:
Xinyue QU
1
;
Junjie HU
1
;
Juan LI
1
;
Min ZHANG
1
;
Xian ZHOU
2
;
Songlin LIU
2
;
Xin CHEN
1
Author Information
1. Hubei Key Laboratory of Resources and Chemistry of Chinese Medicine，Hubei University of Chinese Medicine，Wuhan 430065，China
2. Clinical College of Chinese Medicine，Hubei University of Chinese Medicine，Wuhan 430060，China
- Publication Type:Journal Article
- Keywords:
Shugan hewei tang;
depression;
non-targeted metabolomics;
PFC-NAc-VTA neural circuit;
NMDAR1/Akt/mTOR
- From:
China Pharmacy
2025;36(10):1172-1178
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To investigate the antidepressant mechanism of Shugan hewei tang （SGHWT） based on the metabolomics of prefrontal cortex （PFC）-nucleus accumbens （NAc）-ventral tegmental area （VTA） neural circuit. METHODS Male SD rats were randomly divided into blank group， model group， SGHWT low-， medium- and high-dose groups [3.67， 7.34， 14.68 g/（kg·d）， by raw material]， and fluoxetine group [1.58 mg/（kg·d）， positive control]， with 12 rats in each group. Except for the blank group， the depression model was established by chronic unpredictable mild stress combined with individual cage housing in the remaining groups， and the corresponding drug solution or normal saline was administered via gavage during modeling， once a day， for 6 consecutive weeks. After the last administration， the body weight， sucrose preference rate， total moving distance， frequency into the center and immobility time of rats in each group were detected. Samples of PFC， NAc and VTA areas of rats in the blank group， model group， SGHWT medium-dose group and fluoxetine positive control groups were collected，and their histomorphological features were observed， and non-targeted metabolomics analysis （except for fluoxetine group）were performed and validated. RESULTS Compared with model group， the cytolysis， structural damage and other pathological damages in three brain regions of rats were significantly alleviated in each drug group， while their body weight， sucrose preference rate， total moving distance and frequency into the center were all significantly higher or longer （P＜0.05）， and immobility time was significantly shorter （P＜0.05）. The results of non-targeted metabolomics showed that a total of 78 endogenous differential metabolites were identified， with 40， 35 and 24 in the PFC， NAc and VTA regions respectively， mainly involved in amino acid， lipid and sphingolipid metabolism. The results of metabolic pathway enrichment analysis showed that SGHWT affected the neural circuits of depressed rats by regulating sphingolipid metabolism， alanine， aspartic acid and glutamic acid metabolism， saturated fatty acid biosynthesis， among which alanine， aspartic acid and glutamic acid metabolism was predominantly involved. Validation experiments showed that SGHWT significantly increased the phosphorylation levels of protein kinase B （Akt） and mammalian target of rapamycin （mTOR）， and decreased the protein expression of N-methyl-D-aspartic acid receptor 1 （NMDAR1） in the NAc region of rats. CONCLUSIONS SGHWT significantly improves the depression-like behavior and attenuates pathological damage of PFC-NAc-VTA neural circuit of model rats， the mechanism of which is associated with inhibiting NMDAR1 expression and activating the Akt/mTOR signaling pathway.
