Department of Pharmacology, School of Pharmacy & Technology Management, SVKM'S Narsee Monjee Institute of Management Studies (NMIMS), Shirpur, Maharashtra, 425 405, India.
Department of Biotechnology, Bioinformatics, and Pharmacy, Jaypee University of Information Technology, Waknaghat, Solan, Himachal Pradesh, 173 234, India.
Neurochem Res. 2023 Feb;48(2):551-569. doi: 10.1007/s11064-022-03779-7. Epub 2022 Oct 28.
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.
证据表明，炎症反应可能包含严重抑郁疾病的发作。传统使用的甘草含有 18β-甘草次酸（18βGA），已证明其具有抗炎和抗氧化应激作用。本研究探讨了 18βGA 在慢性不可预测轻度应激（CUMS）暴露大鼠中的抗抑郁作用及其潜在机制。Wistar 大鼠连续 36 天暴露于 CUMS 中以建立抑郁。18βGA（10、20 和 50mg/kg）或氟西汀每天一次（从第 30 天到第 36 天）给药。此后，研究了行为参数（蔗糖偏好试验、强迫游泳试验、旷场试验、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）和肝生物标志物。进行免疫组织化学和 Western blot 分析以研究蛋白质的表达。18βGA（20 和 50mg/kg）治疗可增加蔗糖摄入、旷场试验中的运动、减少强迫游泳试验中的不动时间，并改善 CUMS 暴露大鼠的体重。18βGA 治疗可显著降低 CUMS 大鼠的细胞因子、ACTH 和 CORT，并改善 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 50mg/kg 剂量下可不同程度地增加其表达。因此，18βGA 通过激活 PFC 和海马中的 BDNF/TrkB 信号通路，改善了慢性不可预测轻度应激诱导的抑郁样行为，降低了神经炎症、肝生物标志物、应激激素，并改善了体重、脑神经递质浓度。
