Areca Thirteen Pill Improves Depression in Rat by Modulation of the Chemokine/Chemokine Receptor Axis

Jing-Jing Bai; Min Ao; An Xing; Li-Jun Yu; Hai-Ying Tong; Wu-Ye Bao; Yu Wang

doi:10.1007/s12035-023-03855-1

Areca Thirteen Pill Improves Depression in Rat by Modulation of the Chemokine/Chemokine Receptor Axis

Mol Neurobiol. 2023 Dec 19. doi: 10.1007/s12035-023-03855-1. Online ahead of print.

Authors

Jing-Jing Bai^#^{1

2}, Min Ao^#³, An Xing^#³, Li-Jun Yu⁴, Hai-Ying Tong³, Wu-Ye Bao⁵, Yu Wang⁶

Affiliations

¹ Key Laboratory of Basic Pharmacology of Ministry of Education, Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou, 563006, People's Republic of China.
² Tongliao Institute of agriculture and animal husbandry, Tongliao, Inner Mongolia, People's Republic of China.
³ Affiliated Hospital of Inner Mongolia Minzu University, Tongliao, Inner Mongolia, People's Republic of China.
⁴ Inner Mongolia Minzu University, Tongliao, Inner Mongolia, People's Republic of China.
⁵ Affiliated Hospital of Inner Mongolia Minzu University, Tongliao, Inner Mongolia, People's Republic of China. 436042593@qq.com.
⁶ Key Laboratory of Basic Pharmacology of Ministry of Education, Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou, 563006, People's Republic of China. shen348@126.com.

^# Contributed equally.

PMID: 38110645
DOI: 10.1007/s12035-023-03855-1

Abstract

Depressive disorder is a severe and complex mental illness. There are a few anti-depressive medications that can reduce depressive symptoms, but with adverse or side effects. GaoYou-13 (GY-13), commonly known as Areca Thirteen Pill, is a traditional medicine for depression treatment with significant clinical impact. However, the molecular mechanism of GY-13 has not been fully elucidated. This study aimed to explore and explain the action and mechanism of GY-13 in treatment for depression. SD male rats were stimulated differently daily for 42 days to construct a depression rat model and divided into six groups: the control, CUMS model, GY-13L, GY-13 M, GY-13H, and FLUO. The body weight of was measured on day 7, 14, 21, 28, 35, and 42 or different days, and the behavioral tests (Open-field test, Sucrose preference test, Morris water maze) were made alongside. After the rats were decapitated, the rat brains were stained with Nissl or H&E dyes. The serums of TNF-α and IL-1β were tested. The protein of p-IKKα, p-IкBα, and p-NFкBp65 was traced. Then nano-LC-MS/MS analysis was made to detect the mechanism of GY-13. The active ingredients, drug targets, and key pathways of GY-13 in treating depression were analyzed through network pharmacology and molecular docking. With immunohistochemistry, quantitative RT-PCR, and western-blot techniques, the therapeutic mechanism of GY-13 was traced and analyzed. This study revealed that GY-13 significantly enhances autonomous and exploratory behavior, sucrose consumption, learning and memory ability, and hippocampal neuronal degeneration, which inhibits inflammation. In addition, omics analysis showed several proteins were altered in the hippocampus of rats following CUMS and GY-13 treatment. Bioinformatics analysis and network pharmacology revealed the antidepressant effects of GY-13 are related to the chemokine/chemokine receptor axis. Immunohistochemistry, western blotting and RT-PCR assay further support the findings of omics analysis. We highlighted the importance of the chemokine/chemokine receptor axis in the treatment of depression, as well as showed GY-13 can be used as a novel targeted therapy for depression treatment.

Keywords: Chemokines; Depression; Neuroinflammation; Proteomics.

Abstract

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