Discussion on the anti-depression mechanism of Zishui Qinggan Decoction based on PINK1/Parkin and cGAS/STING signaling pathways
10.3760/cma.j.cn115398-20231126-00306
- VernacularTitle:基于PINK1/Parkin及cGAS/STING通路探讨滋水清肝饮的抗抑郁机制
- Author:
Wen ZHU
1
;
Wen ZHANG
;
Min CAI
;
Feng YANG
;
Yijin XIANG
;
Xiangting LI
;
Yunke YANG
;
Dingfang CAI
;
Jun XIANG
Author Information
1. 复旦大学附属中山医院中医-中西医结合科 复旦大学中西医结合研究院内科研究所 国家中医药管理局中医药科研实验室（三级）-神经生理病理实验室，上海 200032
- Keywords:
Depression;
Zishui Qinggan Decoction;
PTEN-induced putative kinase protein 1;
Parkin;
cGAS/STING signaling pathway;
Rats
- From:
International Journal of Traditional Chinese Medicine
2024;46(6):724-730
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the effects of Zishui Qinggan Decoction on the PTEN-induced putative kinase protein 1 (PINK1)/Parkin and cyclic GMP-AMP (cGAS)/ stimulator of interferon genes (STING) signaling pathways; To reveal the anti-inflammatory mechanism of Zishui Qinggan Decoction in treating depression.Methods:Totally 60 rats were randomly divided into control group, model group, and Zishui Qinggan Decoction low-, medium-, and high-dosage groups using a random number table method ( n=12 in each group) . All rats except for the rats in control group were prepared with CUMS induced depression models. The rats in the Zishui Qinggan Decoction low-, medium-, and high-dosage groups were orally administered with 12, 24, and 48 g/kg of Zishui Qinggan Decoction for gavage, respectively. The control group and model group were orally administered with distilled water of equal volume for gavage, once a day for 4 weeks. Forced swimming test (FST), the open field test (OFT) and the sucrose preference test (SPT) were used to detect behavioral changes in rats in each group. Hematoxylin eosin (HE) staining was used to observe the cell structure of the medial prefrontal cortex. The levels of IL-1 β, IL-6, TNF-α and Interferon-γ (IFN-γ) were detected using ELISA. Western blot was used to detect the expressions of Pink1, Parkin, cGAS and STING. Results:Behavioral testing results showed that, compared with the model group, the incubation period for rats in Zishui Qinggan Decoction low-, medium-, and high-dosage groups to enter the first immobility state in FST was significantly prolonged ( P<0.05), and the immobility time was significantly shortened ( P<0.05); the time spent in the central area was significantly increased ( P<0.05), and the incubation period for entering the central area was significantly shortened in ( P<0.05); the percentage of sugar water consumption significantly increased in ( P<0.05). HE staining revealed that the aggregation of prefrontal cortex nuclei decreased, the number of neurons increased, and the distribution of neurons was uniform in Zishui Qinggan Decoction low-, medium-, and high-dosage groups. Compared with the model group, the levels of IL-1β, IL-6, TNF-α and IFN-γ in the Zishui Qinggan Decoction groups significantly decreased ( P<0.05). The protein expressions of PINK1 and Parkin in the prefrontal cortex in Zishui Qinggan Decoction groups significantly increased ( P<0.05), while the protein expression levels of cGAS and STING significantly decreased ( P<0.05). Conclusion:Zishui Qinggan Decoction can significantly improve the depressive behavior, neuronal damage, and neuroinflammatory response in CUMS rats. Its mechanism may be related to up-regulating the PINK1/Parkin signaling pathway and inhibiting the cGAS/STING signaling pathway.
