Naringenin and apigenin ameliorates corticosterone-induced depressive behaviors

Li Zhang; Ren-Rui Lu; Rui-Hao Xu; Hui-Hui Wang; Wei-Sheng Feng; Xiao-Ke Zheng

doi:10.1016/j.heliyon.2023.e15618

Naringenin and apigenin ameliorates corticosterone-induced depressive behaviors

Heliyon. 2023 Apr 20;9(5):e15618. doi: 10.1016/j.heliyon.2023.e15618. eCollection 2023 May.

Authors

Li Zhang^{1

2}, Ren-Rui Lu¹, Rui-Hao Xu¹, Hui-Hui Wang¹, Wei-Sheng Feng^{1

2}, Xiao-Ke Zheng^{1

2}

Affiliations

¹ School of Pharmacy, Henan University of Chinese Medicine, Zhengzhou 450046, China.
² Co-construction Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan & Education Ministry of PR China, Zhengzhou 450046, China.

Abstract

Background: Depression is a common kind of mental illness, and it becomes the main health burden in the world.

Purpose: The aim of this study was to investigate the antidepressant effects of naringin and apigenin isolated from Chrysanthemum morifolium Ramatis.

Methods: Firstly, 20 mg/kg corticosterone (CORT) was injected into mice to establish an in vivo model of depression. After treated with different dosages of naringenin and apigenin for 3 weeks, the mice underwent a series of behavioral experiments. Following this, all mice were sacrificed and biochemical analyses were performed. Subsequently, CORT (500 μM) induced PC12 cells was used as an in vitro model of depression, and lipopolysaccharide (LPS) (1 μg ml^-1) induced N9 microglia cells was used as an in vitro model of neuroinflammation in N9 microglia cells, to investigate the neuroprotective mechanisms of naringenin and apigenin.

Results: Results showed that the naringenin and apigenin treatment ameliorated CORT-induced sucrose preference decrease and immobility time increase, elevated the 5-hydroxytryptamine(5-HT), dopamine (DA) and norepinephrine (NE) levels, and enhanced the cAMP-response element binding protein (CREB) and brain derived neurotrophic factor (BDNF) protein expressions in the hippocampus. The results showed that the naringenin and apigenin treatment improved the PC-12 cell viability through reducing apoptosis rate induced by CORT. Furthermore, naringenin and apigenin were able to inhibit the activation of N9 cells after LPS induction, and shift microglia from proinflammatory M1 microglia toward anti-inflammatory M2 microglia, as evidenced by the decreased ratio of M1 type microglia marker CD86 and M2 type microglia marker CD86.

Conclusion: These results suggested that naringenin and apigenin may improve depressive behaviors through promoting BDNF and inhibiting neuroinflammation and neuronal apoptosis.

Keywords: Apigenin; CORT; Depression; Naringenin; Neuroinflammation; Neuronal apoptosis; cAMP-CREB-BDNF.