Sun Jing, Zhang Kai, Yin Yihui, Qi Yunpeng, Li Siyuan, Sun Haonan, Luo Min, Sun Yixuan, Yu Zhiying, Yang Jie, Wu Jingjing, Chen Lijuan, Xu Wenjuan, Dong Ling
School of Life Sciences, Beijing University of Chinese Medicine, Beijing 102488, China.
School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China.
Toxics. 2023 Dec 4;11(12):984. doi: 10.3390/toxics11120984.
Arecoline is a pyridine alkaloid derived from areca nut in the Arecaceae family. It has extensive medicinal activity, such as analgesic, anti-inflammatory, and anti-allergic. However, the toxicity of Arecoline limits its application. Most current studies on its toxicity mainly focus on immunotoxicity, carcinogenesis, and cancer promotion. However, there are few systematic studies on its hepatotoxicity and mechanisms. Therefore, this research explored the mechanism of hepatotoxicity induced by Arecoline in rats and analyzed endogenous metabolite changes in rat plasma by combining network toxicology with metabolomics. The differential metabolites after Arecoline exposure, such as D-Lysine, N4-Acetylaminobutanal, and L-Arginine, were obtained by metabolomics study, and these differential metabolites were involved in the regulation of lipid metabolism, amino acid metabolism, and vitamin metabolism. Based on the strategy of network toxicology, Arecoline can affect the HIF-1 signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway, and other concerning pathways by regulating critical targets, such as ALB, CASP3, EGFR, and MMP9. Integration of metabolomics and network toxicology results were further analyzed, and it was concluded that Arecoline may induce hepatotoxicity by mediating oxidative stress, inflammatory response, energy and lipid metabolism, and cell apoptosis.
槟榔碱是一种吡啶生物碱，源自棕榈科植物槟榔的种子。它具有广泛的药用活性，如镇痛、抗炎和抗过敏。然而，槟榔碱的毒性限制了其应用。目前关于其毒性的大多数研究主要集中在免疫毒性、致癌作用和癌症促进方面。然而，关于其肝毒性及其机制的系统研究较少。因此，本研究通过将网络毒理学与代谢组学相结合，探讨了槟榔碱诱导大鼠肝毒性的机制，并分析了大鼠血浆中的内源性代谢物变化。通过代谢组学研究获得了槟榔碱暴露后的差异代谢物，如D-赖氨酸、N4-乙酰氨基丁醛和L-精氨酸，这些差异代谢物参与了脂质代谢、氨基酸代谢和维生素代谢的调节。基于网络毒理学策略，槟榔碱可通过调节关键靶点如ALB、CASP3、EGFR和MMP9来影响HIF-1信号通路、MAPK信号通路、PI3K-Akt信号通路等相关通路。进一步分析代谢组学和网络毒理学结果的整合情况，得出槟榔碱可能通过介导氧化应激、炎症反应、能量和脂质代谢以及细胞凋亡来诱导肝毒性的结论。
