Zhang Li, Lu Ren-Rui, Xu Rui-Hao, Wang Hui-Hui, Feng Wei-Sheng, Zheng Xiao-Ke
School of Pharmacy, Henan University of Chinese Medicine, Zhengzhou 450046, China.
Co-construction Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan & Education Ministry of PR China, Zhengzhou 450046, China.
Heliyon. 2023 Apr 20;9(5):e15618. doi: 10.1016/j.heliyon.2023.e15618. eCollection 2023 May.
Depression is a common kind of mental illness, and it becomes the main health burden in the world.
The aim of this study was to investigate the antidepressant effects of naringin and apigenin isolated from Ramatis.
Firstly, 20 mg/kg corticosterone (CORT) was injected into mice to establish an 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 model of depression, and lipopolysaccharide (LPS) (1 μg ml) induced N9 microglia cells was used as an model of neuroinflammation in N9 microglia cells, to investigate the neuroprotective mechanisms of naringenin and apigenin.
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.
These results suggested that naringenin and apigenin may improve depressive behaviors through promoting BDNF and inhibiting neuroinflammation and neuronal apoptosis.
抑郁症是一种常见的精神疾病，已成为全球主要的健康负担。
本研究旨在探讨从 Ramatis 中分离出的柚皮苷和芹菜素的抗抑郁作用。
首先，给小鼠注射20mg/kg皮质酮（CORT）以建立抑郁症模型。用不同剂量的柚皮苷和芹菜素处理3周后，对小鼠进行一系列行为实验。之后，处死所有小鼠并进行生化分析。随后，将CORT（500μM）诱导的PC12细胞用作抑郁症模型，将脂多糖（LPS）（1μg/ml）诱导的N9小胶质细胞用作N9小胶质细胞神经炎症模型，以研究柚皮苷和芹菜素的神经保护机制。
结果表明，柚皮苷和芹菜素处理可改善CORT诱导的蔗糖偏好降低和不动时间增加，提高5-羟色胺（5-HT）、多巴胺（DA）和去甲肾上腺素（NE）水平，并增强海马中cAMP反应元件结合蛋白（CREB）和脑源性神经营养因子（BDNF）蛋白表达。结果表明，柚皮苷和芹菜素处理通过降低CORT诱导的凋亡率提高了PC-12细胞活力。此外，柚皮苷和芹菜素能够抑制LPS诱导后N9细胞的活化，并使小胶质细胞从促炎M1小胶质细胞向抗炎M2小胶质细胞转变，M1型小胶质细胞标志物CD86与M2型小胶质细胞标志物CD206的比例降低证明了这一点。
这些结果表明，柚皮苷和芹菜素可能通过促进BDNF和抑制神经炎症及神经元凋亡来改善抑郁行为。
