Wei Yicong, Hu Yonghong, Qi Keming, Li Ye, Chen Jianxiong, Wang Ruiguo
College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China.
Behav Brain Res. 2022 Apr 9;423:113775. doi: 10.1016/j.bbr.2022.113775. Epub 2022 Jan 29.
The NLRP3 inflammasome activation and neuroinflammation play a crucial role in nerve damage, which can lead to sickness and depressive-like behavior. Dihydromyricetin (DMY) is an important flavanone extracted from Ampelopsis grossedentata. It has been shown to have a significant anti-inflammatory effect in multiple disease models. However, its protective effects on sickness and depressive-like behavior caused by neuroinflammation and its underlying mechanism are still unclear. In this study, we investigated the effects and mechanism of DMY on lipopolysaccharide (LPS)-treated mice with sickness behavior and BV2 cells in Vitro. The effects of LPS treatment and DMY administration on behavioral changes were determined by using behavioral tests including an open field test, tail suspension test and a sucrose preference test. The anti-inflammatory effects of DMY in conditions of neuroinflammatory injury in Vitro and in Vivo were analyzed by using real-time PCR analysis and western blot. The results indicated that DMY improved sickness and depressive-like behaviors in mice induced by LPS. DMY suppressed the expression of microglia markers CD11b, accompanied by reduced expression of pro-inflammatory cytokines, such as TNFα, IL-6, IL-1β, COX-2, and iNOS in a dose-dependent manner. Interestingly, DMY dramatically inhibited the expression of TLR4/Akt/HIF1a/NLRP3 signaling pathway-related proteins both in Vitro and in Vivo, including TLR4, CD14, PDPk1, p-Akt, p-NF-κB p65, p-GSK-3β, HIF1a, NLRP3, ASC, and caspase-1. The above results suggested that DMY suppressed the activation of the TLR4/Akt/HIF1a/NLRP3 pathway, which may contribute to its anti-depressive effects.
NLRP3炎性小体激活和神经炎症在神经损伤中起关键作用，可导致疾病行为和抑郁样行为。二氢杨梅素（DMY）是从显齿蛇葡萄中提取的一种重要黄酮类化合物。在多种疾病模型中已显示其具有显著的抗炎作用。然而，其对神经炎症引起的疾病行为和抑郁样行为的保护作用及其潜在机制仍不清楚。在本研究中，我们研究了DMY对脂多糖（LPS）处理的疾病行为小鼠和体外BV2细胞的影响及机制。通过旷场试验、尾悬试验和蔗糖偏好试验等行为测试来确定LPS处理和DMY给药对行为变化的影响。利用实时PCR分析和蛋白质免疫印迹法分析DMY在体外和体内神经炎症损伤条件下的抗炎作用。结果表明，DMY改善了LPS诱导的小鼠疾病行为和抑郁样行为。DMY抑制了小胶质细胞标志物CD11b的表达，同时以剂量依赖的方式降低了促炎细胞因子如TNFα、IL-6、IL-1β、COX-2和iNOS的表达。有趣的是，DMY在体外和体内均显著抑制了TLR4/Akt/HIF1a/NLRP3信号通路相关蛋白的表达，包括TLR4、CD14、PDPk1、p-Akt、p-NF-κB p65、p-GSK-3β、HIF1a、NLRP3、ASC和caspase-1。上述结果表明，DMY抑制了TLR4/Akt/HIF1a/NLRP3通路的激活，这可能有助于其抗抑郁作用。
