Cyanidin-related antidepressant-like efficacy requires PI3K/AKT/FoxG1/FGF-2 pathway modulated enhancement of neuronal differentiation and dendritic maturation

Xin Shan; Jing Chen; Shilin Dai; Jie Wang; Zhiheng Huang; Zhiyang Lv; Qian Wang; Qinan Wu

doi:10.1016/j.phymed.2020.153269

Cyanidin-related antidepressant-like efficacy requires PI3K/AKT/FoxG1/FGF-2 pathway modulated enhancement of neuronal differentiation and dendritic maturation

Phytomedicine. 2020 Jun 20:76:153269. doi: 10.1016/j.phymed.2020.153269. Online ahead of print.

Authors

Xin Shan¹, Jing Chen², Shilin Dai³, Jie Wang², Zhiheng Huang³, Zhiyang Lv², Qian Wang³, Qinan Wu⁴

Affiliations

¹ Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, Jiangsu, 210023, China; Hanlin College, Nanjing University of Chinese Medicine, Taizhou 225300, China.
² Hanlin College, Nanjing University of Chinese Medicine, Taizhou 225300, China.
³ Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, Jiangsu, 210023, China.
⁴ Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, Jiangsu, 210023, China. Electronic address: qnwyjs@126.com.

PMID: 32593103
DOI: 10.1016/j.phymed.2020.153269

Abstract

Background: Cyanidin (CY) is one of the most abundant anthocyanidins found in red-purple diet sources such as grapes, blueberries and purple corns. CY has been proven to exhibit a wide range of biological functions including antioxidant, antiviral, anticarcinogenic and anti-inflammatory properties.

Purpose: This study investigated the anti-depressive activity of CY and its related mechanism.

Methods: In the behavioral tests, CY-related effects on depressive symptoms were evaluated. Then the changes in PI3K/AKT/FOXG1/FGF-2 signaling and adult neurogenesis including doublecortin (DCX+) cell number, dendritic length, secondary and third dendrites number in the hippocampus were investigated by Immunofluorescence and Western blot analyses. PI3K antagonist LY 294,002 was used to verify the unique impact of PI3K/AKT/FoxG1/FGF-2 signaling on CY-related antidepressant efficacy.

Results: CY grossly reversed CUMS-induced behavioral defects, The DCX+ cell number and protein levels increased in CUMS mice receiving CY administration. LY 294,002 successfully blocked CY-induced improvements in depressive behaviors, neurogenesis, and protein levels in CUMS mice.

Conclusion: The findings demonstrated that CY was efficacious in alleviating depression-like symptoms, which was dependent on PI3K/AKT/FoxG1/FGF-2 signaling-modulated neurogenesis enhancement.

Keywords: Adult neurogenesis; Cyanidin; Depression; PI3K/AKT/FoxG1/FGF-2.