Wang Yue, Wu Xinyan, Yang Kailin, Liu Qing, Jiang Baoping, Yang Runmei, Xiao Peigen, He Chunnian
Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Science, Peking Union Medical College, Beijing, China.
Front Pharmacol. 2022 Aug 12;13:952876. doi: 10.3389/fphar.2022.952876. eCollection 2022.
(Moutan) is a traditional medicinal plant in China. Its seed coat is rich in resveratrol oligomer, especially suffruticosol B (SB). Previous studies had shown that the seed coat extracts of (PSCE) had good cholinesterase inhibitory activity and neuroprotective effect, but the effective dose range was unknown, and the pharmacodynamic components and molecular mechanism of PSCE had not been discussed. The current study aimed to screen the pharmacodynamic components in PSCE and investigate the improvement effect of PSCE and the selected SB on scopolamine-induced cognitive dysfunction in mice and its mechanism. The results of high-throughput sequencing and bioinformatics analysis showed that suffruticosol B (SB) and -gnetin H (GH) might be the main active components of PSCE; PSCE might improve cognitive dysfunction through p53, HIF-1, MAPK, and PI3K-Akt signaling pathways, while SB and GH might improve cognitive dysfunction through HIF-1 signaling pathway. SB and GH had good molecular docking activity with the target of HIF-1 signaling pathway. The pharmacodynamic activities of PSCE and SB were further verified by behavioral experiments. PSCE and SB could improve the recognition ability of familiar and new objects and shorten the escape latency in the Morris Water Maze test (PSCE 120 mg∙kg-1, < 0.05; SB 60 mg∙kg-1, < 0.01); PSCE and SB could increase Ach and GSH levels, enhance the activities of ChAT, SOD and CAT, decrease the levels of IL-1β, IL-6, and TNF-α, and decrease the activity of AChE. In conclusion, the results indicated that PSCE might exert pharmacodynamic activity through multiple components, targets, and pathways, and SB and GH might be the main active components of PSCE. PSCE and SB might improve cognitive dysfunction by regulating cholinergic, antioxidant, and anti-inflammatory effects. These results indicated that PSCE and SB might be potential anti-AD drug candidates, providing a scientific basis for the development and utilization of Moutan bark.
牡丹是中国的一种传统药用植物。其种皮富含白藜芦醇低聚物，尤其是丹皮酚B（SB）。先前的研究表明，牡丹种皮提取物（PSCE）具有良好的胆碱酯酶抑制活性和神经保护作用，但有效剂量范围未知，且尚未探讨PSCE的药效成分和分子机制。当前的研究旨在筛选PSCE中的药效成分，并研究PSCE和选定的SB对东莨菪碱诱导的小鼠认知功能障碍的改善作用及其机制。高通量测序和生物信息学分析结果表明，丹皮酚B（SB）和去甲二氢愈创木酸（GH）可能是PSCE的主要活性成分；PSCE可能通过p53、HIF-1、MAPK和PI3K-Akt信号通路改善认知功能障碍，而SB和GH可能通过HIF-1信号通路改善认知功能障碍。SB和GH与HIF-1信号通路的靶点具有良好的分子对接活性。行为实验进一步验证了PSCE和SB的药效活性。PSCE和SB可以提高对熟悉和新物体的识别能力，并缩短莫里斯水迷宫试验中的逃避潜伏期（PSCE 120mg∙kg-1，P<0.05；SB 60mg∙kg-1，P<0.01）；PSCE和SB可以增加乙酰胆碱（Ach）和谷胱甘肽（GSH）水平，增强胆碱乙酰转移酶（ChAT）、超氧化物歧化酶（SOD）和过氧化氢酶（CAT）的活性，降低白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）的水平，并降低乙酰胆碱酯酶（AChE）的活性。总之，结果表明PSCE可能通过多种成分、靶点和途径发挥药效活性，SB和GH可能是PSCE的主要活性成分。PSCE和SB可能通过调节胆碱能、抗氧化和抗炎作用来改善认知功能障碍。这些结果表明PSCE和SB可能是潜在的抗阿尔茨海默病药物候选物，为牡丹皮的开发利用提供了科学依据。
