Xu Qiyao, Liu Xuan, Chen Zhaoyang, Guo Can, Lu Pengyu, Zhang Sujie, Wang Xindong, Shen Jianping
Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.
Graduate School, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.
Front Pharmacol. 2024 Dec 16;15:1447546. doi: 10.3389/fphar.2024.1447546. eCollection 2024.
Astragalus mongholicus (AM) and Salvia miltiorrhiza (SM) are commonly used in traditional Chinese medicine to treat heart failure (HF). Ferroptosis has been studied as a key factor in the occurrence of HF. It remains unclear whether the combined use of AM and SM can effectively improve HF and the underlying mechanisms.
This study aims to explore whether the combined use of AM and SM can improve HF by inhibiting ferroptosis. It also examines the roles and interactions of the pathways associated with GPX4, FSP1, and DHODH.
experiments used angiotensin II-induced (4 μM for 48 h) hypertrophic H9c2 cells, while studies employed a rat model of transverse aortic constriction-induced (to 1 mm for 8 weeks) HF. Interventions included decoctions of AM and SM (for animal experiments) and medicated serum (for cell experiments), along with specific pathway inhibitors such as erastin, FSP1 inhibitor and brequinar. Subsequently, various molecular biology methods were used to measure the protein levels of GPX4, FSP1, and DHODH, as well as each sample group's ferroptosis-related and HF-related indicators, to elucidate the underlying mechanisms.
The combined use of AM and SM can effectively restore the levels of GPX4, FSP1, and DHODH that are reduced after HF, as well as improve indicators related to ferroptosis and HF. When GPX4, FSP1, or DHODH is inhibited, the ferroptosis-inhibiting effect and the ability of AM and SM to improve HF are both weakened. When two of the three proteins are inhibited, the protective effect of HDC is strongest when GPX4 is retained, followed by FSP1, and weakest when DHODH is retained.
This study confirms that the combined use of AM and SM inhibits ferroptosis and alleviates HF by increasing GPX4, FSP1, and DHODH levels. It shows that the protective effect is strongest through GPX4, followed by FSP1, and weakest through DHODH. These findings provide new insights into the therapeutic mechanisms of this combination of botanical drugs.
黄芪和丹参常用于中医治疗心力衰竭（HF）。铁死亡已被研究为HF发生的关键因素。黄芪和丹参联合使用是否能有效改善HF及其潜在机制仍不清楚。
本研究旨在探讨黄芪和丹参联合使用是否能通过抑制铁死亡来改善HF。同时研究与谷胱甘肽过氧化物酶4（GPX4）、铁死亡抑制蛋白1（FSP1）和二氢乳清酸脱氢酶（DHODH）相关途径的作用及相互作用。
实验采用血管紧张素II诱导（4 μM，作用48小时）的肥大H9c2细胞，而研究采用横断主动脉缩窄诱导（缩窄至1 mm，持续8周）的HF大鼠模型。干预措施包括黄芪和丹参水煎剂（用于动物实验）和含药血清（用于细胞实验），以及特异性途径抑制剂，如厄拉司丁、FSP1抑制剂和布喹那。随后，采用各种分子生物学方法检测GPX4、FSP1和DHODH的蛋白水平，以及各样本组的铁死亡相关指标和HF相关指标，以阐明其潜在机制。
黄芪和丹参联合使用可有效恢复HF后降低的GPX4、FSP1和DHODH水平，同时改善与铁死亡和HF相关的指标。当GPX4、FSP1或DHODH受到抑制时，铁死亡抑制作用以及黄芪和丹参改善HF的能力均减弱。当这三种蛋白中的两种受到抑制时，保留GPX4时，黄芪和丹参联合用药的保护作用最强，其次是保留FSP1，保留DHODH时保护作用最弱。
本研究证实，黄芪和丹参联合使用通过提高GPX4、FSP1和DHODH水平抑制铁死亡并减轻HF。结果表明，通过GPX4的保护作用最强，其次是FSP1，通过DHODH的保护作用最弱。这些发现为这种植物药组合的治疗机制提供了新的见解。
