Research Institute for Marine Drugs and Nutrition, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang, Guangdong, China.
Stem Cell Research and Cellular Therapy Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.
J Psychopharmacol. 2021 Oct;35(10):1285-1299. doi: 10.1177/02698811211032473. Epub 2021 Jul 19.
Microglia activation-induced neuroinflammation may contribute to the etiology of depression. containing high concentration of isoginkgetin could effectively treat mental diseases in ancient times. However, the therapeutic role, peculiarly in the brain-immune modulation in depression is still unclear. This study aimed to determine effects of isoginkgetin on lipopolysaccharide (LPS)-induced depression-like changes. Furthermore, its modulation on the p38/nuclear factor-kappa B (NF-κB) pathway in LPS-activated microglia was evaluated.
Adult Kunming mice were intraperitoneally injected vehicle or isoginkgetin (4 mg/kg) daily for 14 days before saline or LPS (0.83 mg/kg) administration. Depression-like behavior, neurotransmitter levels, and markers of neuroinflammation were determined. Isoginkgetin effect on LPS-induced microglial activation was then assessed in BV2 cells. Finally, conditioned medium (CM) derived from isoginkgetin-treated BV2 cells was co-cultured with SH-SY5Y cells for 24 h. Cell viability and apoptosis were evaluated.
LPS significantly induced helplessness and anxiety, which were associated with decreased 5-HT, noradrenaline, and dopamine concentrations. Meanwhile, LPS increased microglia M1 hallmark Iba1 expression and serum interleukin (IL)-1β concentration. These changes were attenuated by isoginkgetin treatment. In vitro, isoginkgetin markedly suppressed the production of IL-1β, IL-6, tumor necrosis factor-alpha, cyclooxygenase-2, inducible nitric oxide, and reactive oxygen species, which are released from LPS-stimulated BV2 cells. More interestingly, CM from isoginkgetin-treated BV2 cells significantly alleviated SH-SY5Y cell apoptosis and restored cell viability compared to LPS-treated group through the inhibition of p38/NF-κB signaling pathway.
These data demonstrate that isoginkgetin is an effective therapeutic agent for depression-like behaviors and neuropathological changes via potent anti-inflammatory property.
小胶质细胞激活诱导的神经炎症可能导致抑郁症的发生。自古以来，含有高浓度异银杏素的药物就能有效治疗精神疾病。然而，其在抑郁症中的治疗作用，特别是在大脑免疫调节方面的作用尚不清楚。本研究旨在确定异银杏素对脂多糖（LPS）诱导的抑郁样变化的治疗作用。此外，还评估了其对 LPS 激活的小胶质细胞中 p38/核因子-κB（NF-κB）通路的调节作用。
成年昆明小鼠连续 14 天每天腹腔注射溶剂或异银杏素（4mg/kg），然后给予生理盐水或 LPS（0.83mg/kg）。测定抑郁样行为、神经递质水平和神经炎症标志物。然后在 BV2 细胞中评估异银杏素对 LPS 诱导的小胶质细胞激活的影响。最后，将异银杏素处理的 BV2 细胞的条件培养基（CM）与 SH-SY5Y 细胞共培养 24 小时。评估细胞活力和细胞凋亡。
LPS 显著诱导无助和焦虑，这与 5-HT、去甲肾上腺素和多巴胺浓度降低有关。同时，LPS 增加了小胶质细胞 M1 标志物 Iba1 的表达和血清白细胞介素（IL）-1β浓度。这些变化通过异银杏素治疗得到缓解。体外，异银杏素显著抑制 LPS 刺激的 BV2 细胞释放的白细胞介素（IL）-1β、IL-6、肿瘤坏死因子-α、环氧化酶-2、诱导型一氧化氮合酶和活性氧。更有趣的是，与 LPS 处理组相比，异银杏素处理的 BV2 细胞的 CM 显著减轻了 SH-SY5Y 细胞的凋亡，并通过抑制 p38/NF-κB 信号通路恢复了细胞活力。
这些数据表明，异银杏素通过其强大的抗炎特性，成为一种有效的治疗抑郁样行为和神经病理变化的药物。
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