Integrating UHPLC-MS/MS quantitative analysis and exogenous purine supplementation to elucidate the antidepressant mechanism of Chaigui granules by regulating purine metabolism

Jiajun Chen; Tian Li; Dehua Huang; Wenxia Gong; Junsheng Tian; Xiaoxia Gao; Xuemei Qin; Guanhua Du; Yuzhi Zhou

doi:10.1016/j.jpha.2023.08.008

Volume 13 Issue 12

Dec. 2023

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Article Navigation > Journal of Pharmaceutical Analysis > 2023 > 13(12): 1562-1576

Jiajun Chen, Tian Li, Dehua Huang, Wenxia Gong, Junsheng Tian, Xiaoxia Gao, Xuemei Qin, Guanhua Du, Yuzhi Zhou. Integrating UHPLC-MS/MS quantitative analysis and exogenous purine supplementation to elucidate the antidepressant mechanism of Chaigui granules by regulating purine metabolism[J]. Journal of Pharmaceutical Analysis, 2023, 13(12): 1562-1576. doi: 10.1016/j.jpha.2023.08.008

Citation:

Jiajun Chen, Tian Li, Dehua Huang, Wenxia Gong, Junsheng Tian, Xiaoxia Gao, Xuemei Qin, Guanhua Du, Yuzhi Zhou. Integrating UHPLC-MS/MS quantitative analysis and exogenous purine supplementation to elucidate the antidepressant mechanism of Chaigui granules by regulating purine metabolism[J]. Journal of Pharmaceutical Analysis, 2023, 13(12): 1562-1576. doi: 10.1016/j.jpha.2023.08.008

Citation:

Jiajun Chen, Tian Li, Dehua Huang, Wenxia Gong, Junsheng Tian, Xiaoxia Gao, Xuemei Qin, Guanhua Du, Yuzhi Zhou. Integrating UHPLC-MS/MS quantitative analysis and exogenous purine supplementation to elucidate the antidepressant mechanism of Chaigui granules by regulating purine metabolism[J]. Journal of Pharmaceutical Analysis, 2023, 13(12): 1562-1576. doi: 10.1016/j.jpha.2023.08.008

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Integrating UHPLC-MS/MS quantitative analysis and exogenous purine supplementation to elucidate the antidepressant mechanism of Chaigui granules by regulating purine metabolism

doi: 10.1016/j.jpha.2023.08.008

Jiajun Chen^a,b,c,
Tian Li^a,b,c,
Dehua Huang^a,b,c,
Wenxia Gong^a,b,c,
Junsheng Tian^a,b,c,
Xiaoxia Gao^a,b,c,
Xuemei Qin^a,b,c,
Guanhua Du^a,d,
Yuzhi Zhou^{a,b,c
,
,}

a. Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan, 030006, China;
b. The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, Taiyuan, 030006, China;
c. The Key Laboratory of Effective Substances Research and Utilization in TCM of Shanxi Province, Taiyuan, 030006, China;
d. Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China

Funds:

This work was financially supported by the National Natural Science Foundation of China (Grant Nos.: 82074323 and 81673572), Key Research and Development Program of Shanxi Province (Grant No.: 202102130501010), Innovation Project for Graduate Students in Shanxi Province (Grant No.: 2022Y162), the Major Science and Technology Project for “Significant New Drugs Creation” (Grant No.: 2017ZX09301047), and Research Project Supported by Shanxi Scholarship Council of China (Grant No.: 2020019).

Received Date: Mar. 28, 2023
Accepted Date: Aug. 10, 2023
Rev Recd Date: Jul. 14, 2023
Publish Date: Aug. 17, 2023

Abstract

Abstract

Chaigui granules (CG) are a compound composed of six herbal medicines with significant antidepressant effects. However, the antidepressant mechanism of CG remains unclear. In the present study, we attempted to elucidate the antidepressant mechanism of CG by regulating purine metabolism and purinergic signaling. First, the regulatory effect of CG on purine metabolites in the prefrontal cortex (PFC) of chronic unpredictable mild stress (CUMS) rats was analyzed by ultra high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) targeted quantitative analysis. Meanwhile, purinergic receptors (P2X7 receptor (P2X7R), A₁ receptor (A₁R) and A_2A receptor (A_2AR)) and signaling pathways (nod-like receptor protein 3 (NLRP3) inflammasome pathway and cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) pathway) associated with purine metabolism were analyzed by western blotting and enzyme-linked immunosorbent assay (ELISA). Besides, antidepressant mechanism of CG by modulating purine metabolites to activate purinergic receptors and related signaling pathways was dissected by exogenous supplementation of purine metabolites and antagonism of purinergic receptors in vitro. An in vivo study showed that the decrease in xanthine and the increase in four purine nucleosides were closely related to the antidepressant effects of CG. Additionally, purinergic receptors (P2X7R, A₁R and A_2AR) and related signaling pathways (NLRP3 inflammasome pathway and cAMP-PKA pathway) were also significantly regulated by CG. The results of exogenous supplementation of purine metabolites and antagonism of purinergic receptors showed that excessive accumulation of xanthine led to activation of the P2X7R-NLRP3 inflammasome pathway, and the reduction of adenosine and inosine inhibited the A₁R-cAMP-PKA pathway, which was significantly ameliorated by CG. Overall, CG could promote neuroprotection and ultimately play an antidepressant role by inhibiting the xanthine-P2X7R-NLRP3 inflammasome pathway and activating the adenosine/inosine-A₁R-cAMP-PKA pathway.
- Chaigui granules,
- Traditional Chinese medicine,
- Antidepressant mechanism,
- Purine metabolism,
- Purinergic signaling

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References(38)

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