Zhang Yin, Luo Yusha, Zhang Dongqi, Pang Bo, Wen Jun, Zhou Tingting
School of Pharmacy, Second Military Medical University, Shanghai, China.
Shanghai Key Laboratory for Pharmaceutical Metabolite Research, School of Pharmacy, Second Military Medical University, Shanghai, China.
Front Pharmacol. 2021 Jan 25;11:625108. doi: 10.3389/fphar.2020.625108. eCollection 2020.
Zhi-zi-chi Decoction (ZZCD), composed of (Zhizi in Chinese, ZZ in brief) and (Dandouchi in Chinese, DDC in brief), has been used as a drug therapy for depression for thousands of years in China. However, the antidepressant mechanism of ZZCD still remains unknown. This study was aimed at exploring antidepressant effects of ZZCD from the aspect of neuroprotection based on herb compatibility. Glutamate-treated PC12 cells and chronic unpredictable mild stress (CUMS)-induced rats were established as models of depression and respectively. Cell viability, lactate dehydrogenase (LDH), apoptosis rate, reactive oxygen species (ROS), glutathione reductase (GR) and superoxide dismutase (SOD), and the expressions of Bax, Bcl-2 and cyclic adenosine monophosphate-response element binding protein (CREB) were measured to compare neuroprotection among single herbs and the formula . Behavior tests were conducted to validate antidepressant effects of ZZCD . Results showed that the compatibility of ZZ and DDC increased cell viability and activities of GR and SOD, and decreased the levels of LDH, apoptosis cells and ROS. Besides, the expressions of Bcl-2 and CREB were up-regulated while that of Bax was down-regulated by ZZCD. Furthermore, the compatibility of ZZ and DDC reversed abnormal behaviors in CUMS-induced rats and displayed higher efficacy than any of the single herbs. This study revealed that the antidepressant effects of ZZCD were closely associated with neuroprotection and elucidated synergistic effects of the compatibility of ZZ and DDC based on it.
栀子豉汤（ZZCD）由栀子（中文名为“Zhizi”，简称“ZZ”）和淡豆豉（中文名为“Dandouchi”，简称“DDC”）组成，在中国已被用作治疗抑郁症的药物数千年。然而，栀子豉汤的抗抑郁机制仍不清楚。本研究旨在从基于中药配伍的神经保护方面探讨栀子豉汤的抗抑郁作用。分别建立谷氨酸处理的PC12细胞和慢性不可预测轻度应激（CUMS）诱导的大鼠作为抑郁症模型。测量细胞活力、乳酸脱氢酶（LDH）、凋亡率、活性氧（ROS）、谷胱甘肽还原酶（GR）和超氧化物歧化酶（SOD），以及Bax、Bcl-2和环磷腺苷反应元件结合蛋白（CREB）的表达，以比较单味药和方剂之间的神经保护作用。进行行为测试以验证栀子豉汤的抗抑郁作用。结果表明，栀子和淡豆豉的配伍提高了细胞活力以及GR和SOD的活性，降低了LDH水平、凋亡细胞数量和ROS水平。此外，栀子豉汤上调了Bcl-2和CREB的表达，下调了Bax的表达。此外，栀子和淡豆豉的配伍逆转了CUMS诱导大鼠的异常行为，且比任何单味药都具有更高的疗效。本研究表明，栀子豉汤的抗抑郁作用与神经保护密切相关，并在此基础上阐明了栀子和淡豆豉配伍的协同作用。
