Liu Xiaoxin, Liu Chao
Department of Physiology, School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing 210009, PR China.
Department of Pharmaceutical, Nanjing First Hospital, China Pharmaceutical University, Nanjing 210000, PR China.
Int Immunopharmacol. 2017 Jul;48:30-34. doi: 10.1016/j.intimp.2017.04.019. Epub 2017 May 3.
Abnormal activation of nucleotide-binding domain, leucine-rich repeat, pyrin domain containing protein 3 (NLRP3) inflammasome could induce inflammation in the central nervous system and result in the hyperactivity of HPA axis, which were involved in the pathophysiology of depression. Baicalin, a major polyphenol compound extracts from Scutellaria radix roots, has been previously confirmed to normalize the hyperactivity of HPA axis in rats received chronic mild stress. However, its antidepressant effects and mechanisms are remains unclear in chronic unpredictable mild stress (CUMS) model of depression. In this study, CUMS treated rats showed a notable depressive-like behavior (decreased sucrose intake and locomotor activity, and increased immobility time), and significant increase in the activation of NLRP3 inflammasome and the levels of pro-inflammatory cytokines (IL-1β and IL-6) in rat prefrontal cortex. Treatment with baicalin (20, 40mg/kg) significantly reversed these changes. The present study confirmed that baicalin has antidepressant effect and its mechanisms likely related to the inhibition of NLRP3 inflammasome activation in rat prefrontal cortex.
核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)炎性小体的异常激活可诱发中枢神经系统炎症,并导致下丘脑-垂体-肾上腺(HPA)轴功能亢进,这参与了抑郁症的病理生理过程。黄芩苷是从黄芩根中提取的一种主要多酚化合物,先前已证实其可使接受慢性轻度应激的大鼠的HPA轴功能亢进恢复正常。然而,在慢性不可预测性轻度应激(CUMS)抑郁症模型中,其抗抑郁作用及机制仍不清楚。在本研究中,经CUMS处理的大鼠表现出明显的抑郁样行为(蔗糖摄入量和运动活性降低,不动时间增加),且大鼠前额叶皮质中NLRP3炎性小体的激活及促炎细胞因子(IL-1β和IL-6)水平显著升高。黄芩苷(20、40mg/kg)治疗可显著逆转这些变化。本研究证实黄芩苷具有抗抑郁作用,其机制可能与抑制大鼠前额叶皮质中NLRP3炎性小体的激活有关。