School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China.
Jiangsu Engineering Research Center for Efficient Delivery System of TCM, Nanjing, China.
Commun Biol. 2024 Sep 11;7(1):1118. doi: 10.1038/s42003-024-06801-6.
Aconiti Lateralis Radix Praeparata (Fuzi in Chinese) is widely used in the clinical treatment of tumors. This study aims to explore the active fractions and underlying mechanisms of Fuzi in the treatment of non-small cell lung cancer (NSCLC). Fuzi alkaloids (FZA) is prepared and found to inhibit the growth of NSCLC both in vitro and in vivo significantly. A total of 53 alkaloids are identified in FZA by UPLC-Q-TOF-MS. Proteomics experiment show that 238 differentially expressed proteins regulated by FZA are involved in amino acid anabolism, pyrimidine metabolism and PI3K/Akt-mTOR signaling pathway. Metabolomics analyses identify 32 significant differential metabolites which are mainly involved in amino acid metabolism, TCA cycle and other pathways. Multi-omics research combined with molecular biological assays suggest that FZA might regulate glycolysis through PI3K/Akt-mTOR pathway to treat NSCLC. The study lays a foundation for the anti-cancer investigation of Fuzi and provides a possible scientific basis for its clinical application.
制川乌（附子）在肿瘤的临床治疗中被广泛应用。本研究旨在探索附子治疗非小细胞肺癌（NSCLC）的活性部位及作用机制。制川乌总生物碱（FZA）被制备出来，并被发现能显著抑制 NSCLC 的体外和体内生长。通过 UPLC-Q-TOF-MS 共鉴定出 FZA 中的 53 种生物碱。蛋白质组学实验表明，FZA 调节的 238 种差异表达蛋白参与了氨基酸合成代谢、嘧啶代谢和 PI3K/Akt-mTOR 信号通路。代谢组学分析鉴定出 32 种显著差异的代谢物，主要涉及氨基酸代谢、三羧酸循环和其他途径。多组学研究结合分子生物学实验表明，FZA 可能通过 PI3K/Akt-mTOR 通路调节糖酵解来治疗 NSCLC。该研究为附子的抗癌研究奠定了基础，并为其临床应用提供了可能的科学依据。
