Yu-Lu Wang, Meng L U, Yue-Yue Wang, Ru Jia, Yan Chen, Shu-Ling Zhang, Yu Lin
College of Pharmacy, Fujian University of Traditional Chinese Medicine Fuzhou 350122, China.
College of Pharmacy, Henan University of Traditional Chinese Medicine Zhengzhou 450046, China.
Zhongguo Zhong Yao Za Zhi. 2020 Oct;45(20):4971-4977. doi: 10.19540/j.cnki.cjcmm.20200603.402.
This study aimed to investigate the antidepressant effects of Puyu Capsules and its potential mechanism. The antidepressant activity of Puyu Capsules was evaluated by forced swimming test(FST) and tail suspension test(TST) after subchronic administration in mice. Next, the mice were subjected to a chronic unpredictable stress(CUS) protocol for a period of 28 d to induce depressive-like behaviors. Then, a sucrose preference test, open-field test and novelty-suppressed feeding test were performed to evaluate the antidepressant effect of Puyu Capsules. After the behavioral test, the adrenal index was calculated; the levels of serum corticosterone(CORT) and adrenocorticotropic hormone(ACTH) were detected by enzyme-linked immunosorbent assay(ELISA); the levels of glucocorticoid receptor(GR), protein expression of brain-derived neurotrophic factor(BDNF), and the ratio of phosphorylated cAMP response element binding protein(CREB) to total CREB were detected by Western blot to explore the antidepressant function and mechanism of Puyu Capsules. The results suggested that Puyu Capsules had significant antidepressant effects on both the depression model and CUS model. At the same time, the drug could prevent the change of adrenal index induced by CUS and reverse the abnormal activation of CORT and ACTH in the serum of depressed mice. Finally, Puyu Capsules could also reverse the lower expression of pCREB, BDNF and GR in the hippocampus of CUS mice. In conclusion, Puyu Capsules produced significant antidepressant effects, and the mechanism was closely related to hypothalamic pituitary adrenal(HPA) axis activity, GR and CREB-BDNF pathway expression.
本研究旨在探讨朴郁胶囊的抗抑郁作用及其潜在机制。在小鼠亚慢性给药后，通过强迫游泳试验（FST）和悬尾试验（TST）评估朴郁胶囊的抗抑郁活性。接下来，对小鼠进行为期28天的慢性不可预测应激（CUS）方案以诱导抑郁样行为。然后，进行蔗糖偏好试验、旷场试验和新奇抑制摄食试验以评估朴郁胶囊的抗抑郁效果。行为试验后，计算肾上腺指数；采用酶联免疫吸附测定（ELISA）检测血清皮质酮（CORT）和促肾上腺皮质激素（ACTH）水平；通过蛋白质免疫印迹法检测糖皮质激素受体（GR）水平、脑源性神经营养因子（BDNF）蛋白表达以及磷酸化环磷酸腺苷反应元件结合蛋白（CREB）与总CREB的比值，以探讨朴郁胶囊的抗抑郁作用及机制。结果表明，朴郁胶囊对抑郁模型和CUS模型均具有显著的抗抑郁作用。同时，该药物可防止CUS诱导的肾上腺指数变化，并逆转抑郁小鼠血清中CORT和ACTH的异常激活。最后，朴郁胶囊还可逆转CUS小鼠海马中pCREB、BDNF和GR的低表达。综上所述，朴郁胶囊具有显著的抗抑郁作用，其机制与下丘脑-垂体-肾上腺（HPA）轴活性、GR和CREB-BDNF通路表达密切相关。
