Li Xiaohan, Wang Qi, Liu Ling, Shi Yang, Hong Yang, Xu Wanqing, Xu Henghui, Feng Jing, Xie Minzhen, Li Yang, Yang Baofeng, Zhang Yong
Department of Pharmacology, College of Pharmacy, Harbin Medical University, Harbin 150081, China.
Department of Medicinal Chemistry and Natural Medicinal Chemistry, College of Pharmacy, Harbin Medical University, Harbin 150081, China.
Pharmaceuticals (Basel). 2024 Apr 19;17(4):524. doi: 10.3390/ph17040524.
(Roxb.) DC. () is a traditional Chinese medicinal plant that is indigenous to the southern regions of China. Previous research has provided evidence of the significant anti-inflammatory, antibacterial, and anticancer properties exhibited by . The potential therapeutic effects and cardiac toxicity of remain uncertain. The aim of this research was to investigate the potential therapeutic properties of the four main compounds of in cardiovascular diseases, their impact on the electrical activity of cardiomyocytes, and the underlying mechanism of their anti-inflammatory effects. We selected the four compounds from with a high concentration and specific biological activity: nitidine chloride (NC), chelerythrine chloride (CHE), magnoflorine chloride (MAG), and hesperidin (HE). A proteomic analysis was conducted on the myocardial tissues of beagle dogs following the administration of NC to investigate the role of NC in vivo and the associated biological processes. A bioinformatic analysis was used to predict the in vivo biological processes that MAG, CHE, and HE were involved in. Molecular docking was used to simulate the binding between compounds and their targets. The effect of the compounds on ion channels in cardiomyocytes was evaluated through a patch clamp experiment. Organ-on-a-chip (OOC) technology was developed to mimic the physiological conditions of the heart in vivo. Proteomic and bioinformatic analyses demonstrated that the four compounds of are extensively involved in various cardiovascular-related biological pathways. The findings from the patch clamp experiments indicate that NC, CHE, MAG, and HE elicit a distinct activation or inhibition of the I and I in cardiomyocytes. Finally, the anti-inflammatory effects of the compounds on cardiomyocytes were verified using OOC technology. NC, CHE, MAG, and HE demonstrate anti-inflammatory effects through their specific interactions with prostaglandin-endoperoxide synthase 2 (PTGS2) and significantly influence ion channels in cardiomyocytes. Our study provides a foundation for utilizing NC, CHE, MAG, and HE in the treatment of cardiovascular diseases.
（Roxb.）DC.（）是一种原产于中国南方地区的传统中药材。先前的研究已证实（）具有显著的抗炎、抗菌和抗癌特性。（）的潜在治疗效果和心脏毒性仍不确定。本研究的目的是探究（）的四种主要化合物在心血管疾病中的潜在治疗特性、它们对心肌细胞电活动的影响以及其抗炎作用的潜在机制。我们从（）中选择了四种具有高浓度和特定生物活性的化合物：氯化两面针碱（NC）、氯化白屈菜红碱（CHE）、氯化黄连碱（MAG）和橙皮苷（HE）。对给予NC后的比格犬心肌组织进行蛋白质组学分析，以研究NC在体内的作用及相关生物学过程。使用生物信息学分析来预测MAG、CHE和HE所参与的体内生物学过程。采用分子对接来模拟化合物与其靶点之间的结合。通过膜片钳实验评估化合物对心肌细胞离子通道的影响。开发了芯片器官（OOC）技术以模拟体内心脏的生理条件。蛋白质组学和生物信息学分析表明，（）的四种化合物广泛参与各种与心血管相关的生物学途径。膜片钳实验的结果表明，NC、CHE、MAG和HE对心肌细胞中的I和I产生明显的激活或抑制作用。最后，使用OOC技术验证了化合物对心肌细胞的抗炎作用。NC、CHE、MAG和HE通过与前列腺素内过氧化物合酶2（PTGS2）的特异性相互作用发挥抗炎作用，并显著影响心肌细胞中的离子通道。我们的研究为利用NC、CHE、MAG和HE治疗心血管疾病提供了基础。
