School of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China.
Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China.
Toxins (Basel). 2023 Jan 13;15(1):73. doi: 10.3390/toxins15010073.
Houttuynia cordata (H. cordata) is the most common herb as a food and traditional Chinese medicine. Currently, studies on its toxicity have mainly focused on hepatotoxicity. However, its potential embryotoxicity by long-term exposure is often overlooked. Objective: To investigate the effects of H. cordata on embryonic development and its toxicity mechanism by combining network pharmacology, molecular docking, and in vitro experimental methods. Methods: The effects of H. cordata on embryos were evaluated. Zebrafish embryos and embryoid bodies were administered to observe the effects of H. cordata on embryonic development. Based on network pharmacological analysis, it was found that the main active agents producing toxicity in H. cordata were oleanolic acid, lignan, and aristolactam AII. H. cordata can affect PI3K-Akt, MAPK, and Ras signaling pathways by regulating targets, such as AKT1, EGFR, CASP3, and IGF-1. RT-PCR and immunohistochemistry results showed that the expression of AKT1 and PI3K in the embryoid body was significantly reduced after drug administration (p < 0.05). Conclusions: The results of network pharmacology and in vitro experiments suggest that H. cordata may affect embryonic development by influencing the PI3K-Akt signaling pathway.
鱼腥草(H. cordata)是一种常见的药食同源植物。目前,关于其毒性的研究主要集中在肝毒性上,但长期暴露于鱼腥草可能具有潜在的胚胎毒性,这一点往往被忽视。目的:通过网络药理学、分子对接和体外实验相结合的方法,研究鱼腥草对胚胎发育的影响及其毒性机制。方法:评估鱼腥草对胚胎的影响。用斑马鱼胚胎和类胚胎体进行给药,观察鱼腥草对胚胎发育的影响。基于网络药理学分析,发现鱼腥草产生毒性的主要活性物质为齐墩果酸、木脂素和山麦冬 AII。鱼腥草可通过调节 AKT1、EGFR、CASP3 和 IGF-1 等靶点,影响 PI3K-Akt、MAPK 和 Ras 信号通路。RT-PCR 和免疫组织化学结果显示,药物处理后类胚胎体中 AKT1 和 PI3K 的表达明显降低(p<0.05)。结论:网络药理学和体外实验结果提示,鱼腥草可能通过影响 PI3K-Akt 信号通路影响胚胎发育。