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基于PI3K/Akt/mTOR通路的植物药代谢产物对肿瘤和心血管疾病的潜在双向调节作用。

Potential bidirectional regulatory effects of botanical drug metabolites on tumors and cardiovascular diseases based on the PI3K/Akt/mTOR pathway.

作者信息

Ma Su-Ya, Liu Yong-Mei, Wang Jie

机构信息

Guang'anmen Hospital, China Academy of Chinese Medicine Sciences, Beijing, China.

出版信息

Front Pharmacol. 2025 Mar 24;16:1467894. doi: 10.3389/fphar.2025.1467894. eCollection 2025.

Abstract

Pharmacological interventions targeting the phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway are predominantly employed as anticancer therapies, yet they are frequently associated with significant cardiac toxicity. Additionally, the PI3K/Akt/mTOR pathway plays a crucial role in the treatment of cardiovascular diseases, highlighting its dual significance in both oncology and cardiology. Therefore, the PI3K/Akt/mTOR pathway has become an ideal signaling pathway for studying cardioprotection, anticancer effects, and their associated cardiac toxicity. Botanical drugs have emerged as a significant source for developing therapeutic agents with anticancer and cardioprotective effects, often exhibiting bidirectional protective properties. Consequently, this study investigates the bidirectional regulatory influence of botanical drug metabolites in oncology and cardiology via the PI3K/Akt/mTOR pathway. The research indicated that the PI3K/Akt/mTOR signaling pathway plays a critical regulatory role in the pathogenesis of both tumors and cardiovascular diseases. The botanical drug metabolites Ruscogenin, Sulforaphane, Naringenin, Kaempferol, Poncirin, and Puerarin can improve cancer by inhibiting the phosphorylation levels within the PI3K/Akt/mTOR signaling cascade. Moreover, they also provide cardioprotective effects in cardiac injury conditions by activating the phosphorylation levels of the PI3K/Akt/mTOR pathway. Therefore, the phosphorylation dynamics of key components in the PI3K/Akt/mTOR pathway, particularly the phosphorylation of Akt, along with the functional implications of different phosphorylation sites, may offer new therapeutic strategies and insights for cancer treatment and the mitigation of cardiotoxicity associated with cancer therapies.

摘要

针对磷脂酰肌醇-3-激酶/蛋白激酶B/雷帕霉素哺乳动物靶点(PI3K/Akt/mTOR)信号通路的药物干预主要用作抗癌疗法,但其常常与显著的心脏毒性相关。此外,PI3K/Akt/mTOR通路在心血管疾病治疗中发挥关键作用,凸显了其在肿瘤学和心脏病学中的双重重要性。因此,PI3K/Akt/mTOR通路已成为研究心脏保护、抗癌作用及其相关心脏毒性的理想信号通路。植物药已成为开发具有抗癌和心脏保护作用治疗药物的重要来源,通常表现出双向保护特性。因此,本研究通过PI3K/Akt/mTOR通路探讨植物药代谢产物在肿瘤学和心脏病学中的双向调节影响。研究表明,PI3K/Akt/mTOR信号通路在肿瘤和心血管疾病的发病机制中发挥关键调节作用。植物药代谢产物鲁斯可皂苷元、萝卜硫素、柚皮素、山奈酚、枳属苷和葛根素可通过抑制PI3K/Akt/mTOR信号级联反应中的磷酸化水平来改善癌症。此外,它们还通过激活PI3K/Akt/mTOR通路的磷酸化水平在心脏损伤情况下提供心脏保护作用。因此,PI3K/Akt/mTOR通路关键成分的磷酸化动态变化,尤其是Akt的磷酸化,以及不同磷酸化位点的功能意义,可能为癌症治疗以及减轻癌症治疗相关的心脏毒性提供新的治疗策略和见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/072d/11973345/9925aa84bc40/fphar-16-1467894-g001.jpg

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