Fan Li, Peng Ying, Chen Xiaonan, Ma Ping, Li Xiaobo
School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, P. R. China.
Food Funct. 2022 Aug 15;13(16):8542-8557. doi: 10.1039/d2fo01357f.
(CH), as a nutritional and functional supplement used in food and health care products for centuries, consists of the stems of and . Our previous studies confirmed that the stems of exerted advantageous antidepressant effect. However, whether the difference in the phytochemical compositions between the stems of and would lead to diverse bioavailability and accompanying antidepressant effects remain unclear, as well as their specific bioactive compounds and underlying mechanism. In this study, a series of comparative studies showed that the antidepressant activity of extract (CTE) was stronger than that of the extract (CDE), which was accompanied with the discovery of 10 differential markers from 52 identified compounds between CTE and CDE, and different pharmacokinetic behaviors of 9 prototype and 4 metabolites belonging to the glycosides between the CTE-treated and CDE-treated group in normal and depressive rats were simultaneously found by a validated UPLC-QTRAP-MS/MS method. Subsequently, network pharmacology prediction, and experiment verification from these differential markers further revealed that 7 compounds were confirmed to contribute to the antidepressant action of CH by inhibiting neuronal apoptosis mediated by mitochondrial function and activation of the AKT/GSK3β signaling pathway, synchronously indicating most of those, with higher bioavailability after CTE administration, that were responsible for the stronger antidepressant effect of CTE over CDE. Hence, the integrated analysis of phytochemical composition, pharmacokinetics, and network pharmacology provide new insights into the applications of CH from different botanical origins against depression.
几个世纪以来，（某物质，文中未明确写出具体名称，暂用CH代替）作为一种用于食品和保健品的营养及功能性补充剂，由（两种植物，文中未明确写出具体名称，暂用和代替）的茎组成。我们之前的研究证实，（某植物，文中未明确写出具体名称，暂用代替）的茎具有有益的抗抑郁作用。然而，（某植物，文中未明确写出具体名称，暂用代替）和（某植物，文中未明确写出具体名称，暂用代替）茎中植物化学成分的差异是否会导致不同的生物利用度以及随之而来的抗抑郁作用尚不清楚，其具体的生物活性化合物和潜在机制也不明确。在本研究中，一系列比较研究表明，（某植物，文中未明确写出具体名称，暂用代替）提取物（CTE）的抗抑郁活性强于（某植物，文中未明确写出具体名称，暂用代替）提取物（CDE），同时在CTE和CDE之间从52种已鉴定化合物中发现了10种差异标志物，并且通过经过验证的超高效液相色谱-四极杆飞行时间串联质谱法（UPLC-QTRAP-MS/MS）同时发现了正常和抑郁大鼠中CTE处理组和CDE处理组之间属于糖苷类的9种原型化合物和4种代谢物的不同药代动力学行为。随后，基于这些差异标志物的网络药理学预测以及（两种实验，文中未明确写出具体名称，暂用和代替）实验验证进一步表明，7种化合物通过抑制线粒体功能介导的神经元凋亡和激活AKT/GSK3β信号通路被证实有助于CH的抗抑郁作用，同时表明其中大多数在CTE给药后具有较高的生物利用度，这是CTE比CDE具有更强抗抑郁作用的原因。因此，对植物化学成分、药代动力学和网络药理学的综合分析为不同植物来源的CH在抗抑郁方面的应用提供了新的见解。
