远志提取物通过促进自噬和抑制神经炎症发挥抗行为绝望小鼠和慢性束缚应激诱导大鼠的作用。
Radix Polygalae extract exerts antidepressant effects in behavioral despair mice and chronic restraint stress-induced rats probably by promoting autophagy and inhibiting neuroinflammation.
机构信息
Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100193, China.
Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100193, China; The State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, 100094, China.
出版信息
J Ethnopharmacol. 2021 Jan 30;265:113317. doi: 10.1016/j.jep.2020.113317. Epub 2020 Aug 28.
ETHNOPHARMACOLOGICAL RELEVANCE
Radix Polygalae (RP) has been traditionally used for the treatment of various psychiatric disorders in East Asia.
AIM OF THE STUDY
Depression is a severe mental disease with high prevalence in people, and neurobiology changes of depression are not fully clarified yet. The present study aimed to investigate the antidepressant effect and underlying mechanism of RP in behavioral despair mice and chronic restraint stress (CRS)-induced rats.
MATERIALS AND METHODS
ICR mice were treated with various doses of RP (0.13-1.0 g/kg) for 14 days and then subjected to forced swimming test (FST). Wistar rats were exposed to 6-hour restraint stress daily for 28 days, and RP (0.5 and 1 g/kg) was administered by gavage 1 h prior to CRS procedure. Subsequently, behavioral tests were performed and brains were collected for biochemical analysis.
RESULTS
RP reduced immobility time of mice in FST and reversed abnormal behaviors of rats induced by CRS in sucrose preference test, novelty-suppressed feeding test, open field test and FST. Moreover, RP could enhance the expression of LC3-II and beclin1 and decrease the level of p62 both in cortex of mice and prefrontal cortex (PFC) of rats, and regulate the dysfunction of AMPK-mTOR pathway in PFC of CRS rats. Activated microglia, impaired astrocyte, elevated protein expression of NLRP3, ASC and caspase-1, and increased mRNA levels of proinflammatory cytokines were observed in PFC of CRS rats, all of which were corrected by RP treatment.
CONCLUSION
RP exerted remarkable antidepressant activity in behavioral despair mice and CRS-induced rats, probably by promoting autophagy and inhibiting neuroinflammation.
民族药理学相关性
远志(RP)在东亚传统上被用于治疗各种精神疾病。
研究目的
抑郁症是一种严重的精神疾病,在人群中的发病率很高,其神经生物学变化尚未完全阐明。本研究旨在探讨 RP 对行为绝望小鼠和慢性束缚应激(CRS)诱导大鼠的抗抑郁作用及其潜在机制。
材料和方法
ICR 小鼠用不同剂量的 RP(0.13-1.0 g/kg)处理 14 天,然后进行强迫游泳试验(FST)。Wistar 大鼠每天接受 6 小时束缚应激 28 天,在 CRS 前 1 小时通过灌胃给予 RP(0.5 和 1 g/kg)。随后进行行为测试并采集大脑进行生化分析。
结果
RP 减少了 FST 中小鼠的不动时间,并逆转了 CRS 诱导的大鼠蔗糖偏好试验、新异抑制性摄食试验、旷场试验和 FST 中的异常行为。此外,RP 可以增强 LC3-II 和 beclin1 的表达,降低皮质和前额叶皮质(PFC)中 p62 的水平,并调节 CRS 大鼠 PFC 中 AMPK-mTOR 通路的功能障碍。在 CRS 大鼠的 PFC 中观察到激活的小胶质细胞、受损的星形胶质细胞、NLRP3、ASC 和半胱天冬酶-1 的蛋白表达升高,以及促炎细胞因子的 mRNA 水平升高,这些都被 RP 治疗纠正。
结论
RP 在行为绝望小鼠和 CRS 诱导大鼠中表现出显著的抗抑郁活性,可能通过促进自噬和抑制神经炎症。