Neurochemical Research ( IF 3.7 ) Pub Date : 2022-10-28 , DOI: 10.1007/s11064-022-03779-7 Girdhari Lal Gupta 1, 2 , Lalit Sharma 2, 3 , Manu Sharma 2, 4
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Evidence shows that inflammatory responses may encompass the onset of severe depressive illness. Traditionally used licorice contains 18β-glycyrrhetinic acid (18βGA), which has been demonstrated to reduce inflammation and oxidative stress. This study investigates the antidepressant effects of 18βGA and the underlying mechanism in rats exposed to chronic unpredictable mild stress (CUMS). Wistar rats were exposed to CUMS for 36 consecutive days to establish depression. 18βGA (10, 20, and 50 mg/kg) or fluoxetine was given once daily (from day 30 to day 36). Thereafter, behavior parameters (sucrose preference test, forced-swimming test, open-field test, body weight), pro-inflammatory cytokines, neurotransmitters, adrenocorticotropic hormone (ACTH), corticosterone (CORT), and liver biomarkers were studied. Immunohistochemistry and western blot analyses were conducted to investigate the protein’s expression. 18βGA (20 and 50 mg/kg) treatment increased sucrose intake, locomotion in the open-field test, decreased immobility time in the forced swim test, and improved body weight in CUMS-exposed rats. The therapy of 18βGA dramatically declined cytokines, ACTH and CORT and improved 5HT and norepinephrine in CUMS rats. Furthermore, BDNF and TrkB proteins were down-regulated in CUMS group, which was increased to varying degrees by 18βGA at doses of 20 and 50 mg/kg. Therefore, 18βGA ameliorates depressive-like behavior persuaded by chronic unpredictable mild stress, decreases neuroinflammation, liver biomarkers, stress hormones, and improves body weight, brain neurotransmitter concentration via activating on BDNF/TrkB signaling pathway in both PFC and hippocampus in rats.
Graphical Abstract
中文翻译：
18β-甘草次酸通过触发大鼠 BDNF/TrkB 信号通路改善由慢性不可预测的轻度应激引起的神经炎症相关的抑郁行为
证据表明炎症反应可能包括严重抑郁症的发作。传统上使用的甘草含有 18β-甘草次酸 (18βGA)，已被证明可以减少炎症和氧化应激。本研究调查了 18βGA 的抗抑郁作用及其在暴露于慢性不可预测轻度应激 (CUMS) 大鼠中的潜在机制。Wistar 大鼠连续 36 天暴露于 CUMS 以建立抑郁症。18βGA（10、20 和 50 mg/kg）或氟西汀每天给药一次（从第 30 天到第 36 天）。此后，研究了行为参数（蔗糖偏好测试、强迫游泳测试、开放场地测试、体重）、促炎细胞因子、神经递质、促肾上腺皮质激素（ACTH）、皮质酮（CORT）和肝脏生物标志物。进行免疫组织化学和蛋白质印迹分析以研究蛋白质的表达。18βGA（20 和 50 mg/kg）处理增加了蔗糖摄入量，增加了开放场地试验中的运动能力，减少了强迫游泳试验中的不动时间，并改善了暴露于 CUMS 的大鼠的体重。18βGA 治疗显着降低了 CUMS 大鼠的细胞因子、ACTH 和 CORT，并改善了 5HT 和去甲肾上腺素。此外，BDNF 和 TrkB 蛋白在 CUMS 组中下调，18βGA 在 20 和 50 mg/kg 剂量下不同程度地增加。因此，18βGA 可改善由慢性不可预测的轻度压力引起的抑郁样行为，减少神经炎症、肝脏生物标志物、应激激素，并改善体重，
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