Mechanism of Wenyang jieyu granules regulating NLRP3/ASC/Caspase-1 pathway on antidepressant effect in rats
- VernacularTitle:温阳解郁颗粒调控NLRP3/ASC/Caspase-1通路对大鼠的抗抑郁作用机制研究
- Author:
Shuang MENG
1
;
Jie ZHAO
1
;
Xinxin WANG
1
;
Dandan TAN
2
;
Xiaorong ZHOU
1
;
Huimin SUN
1
;
Xiaojuan MA
1
;
Zhenyu FENG
3
Author Information
1. Central Laboratory，Shanxi Hospital of Integrated Traditional Chinese and Western Medicine，Taiyuan 030013，China;Shanxi Key Laboratory of Fuyang with Classical Prescriptions，Taiyuan 030013，China
2. Dept. of Spleen and Stomach Diseases，Ningyuan County Hospital of Traditional Chinese Medicine，Hunan Yongzhou 425699，China
3. Central Laboratory，Shanxi Hospital of Integrated Traditional Chinese and Western Medicine，Taiyuan 030013，China
- Publication Type:Journal Article
- Keywords:
Wenyang jieyu granules;
depression;
NLRP3 inflammasome;
ASC;
Caspase-1;
neuroinflammation;
neurons
- From:
China Pharmacy
2026;37(11):1440-1446
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To explore the antidepressant mechanism of Wenyang jieyu granules （WYJYG） via the NOD-like receptor thermal protein domain associated protein 3 （NLRP3）/apoptosis-associated speck-like protein containing a CARD （ASC）/Caspase-1 pathway. METHODS A rat model of depression was established by chronic unpredictable mild stress combined with single-housing for 42 consecutive days.The experiment set up blank group， model group， MCC950 （NLRP3 inflammasome inhibitor） group （10 mg/kg）， fluoxetine group （positive control，2.08 mg/kg），low-dose WYJYG（3.78 g/kg） and high-dose WYJYG group （7.56 g/kg），with 10 rats in each group. From the 22nd day of the experiment， rats in the fluoxetine group， low-dose and high-dose WYJYG groups were intragastrically administered with the corresponding drugs and intraperitoneally injected with an equal volume of normal saline. Rats in the MCC950 group were intraperitoneally injected with MCC950 at the corresponding concentration and intragastrically administered with an equal volume of distilled water. Rats in the blank group and model group were given an equal volume of distilled water by gavage and an equal volume of normal saline by intraperitoneal injection. All interventions were performed once a day for 21 consecutive days. Behavioral tests were conducted once a week. After the last administration， the contents of ASC， ionized calcium binding adaptor molecule 1 （Iba1）， interleukin-1β （IL-1β）， and IL-18 in hippocampal tissues were detected. The protein expressions of NLRP3， cluster of differentiation 68 （CD68）， Caspase-1， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein were determined， and neuronal apoptosis was observed. RESULTS After the last administration， compared with the model group， the open-field activity time was significantly prolonged （ P ＜0.05）， and the latency to feed in a novel environment was significantly shortened （ P ＜0.05） in rats of the high-dose WYJYG group. In hippocampal tissue， the contents of ASC， Iba1， IL-1β， and IL-18， as well as the protein expression levels of NLRP3， Caspase-1， and CD68， and the positive rate of neuronal apoptosis were all significantly decreased/downregulated （ P ＜0.05）. Bcl-2 protein expression was significantly upregulated （ P ＜0.05）， and the density of neuronal apoptosis-positive cells was significantly reduced （ P ＜0.05）. CONCLUSIONS WYJYG play on antidepressant role by inhibiting the NLRP3/ASC/Caspase-1 pathway， reducing microglia-mediated neuroinflammation， and inhibiting hippocampal neurons apoptosis.
