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LuQi formula attenuates Cardiomyocyte ferroptosis via activating Nrf2/GPX4 signaling axis in heart failure.
Cheng, Peipei; Wang, Xinting; Liu, Qian; Yang, Tianshu; Dai, Enrui; Sha, Wanjing; Qu, Huiyan; Zhou, Hua.
Afiliación
  • Cheng P; Institute of Cardiovascular Disease of Integrated Traditional Chinese and Western Medicine, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Branch of National Clinical Research Center for Chinese Medicine Cardiology, Shuguang Hospital Affi
  • Wang X; Institute of Cardiovascular Disease of Integrated Traditional Chinese and Western Medicine, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Branch of National Clinical Research Center for Chinese Medicine Cardiology, Shuguang Hospital Affi
  • Liu Q; Institute of Cardiovascular Disease of Integrated Traditional Chinese and Western Medicine, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Branch of National Clinical Research Center for Chinese Medicine Cardiology, Shuguang Hospital Affi
  • Yang T; Department of Cardiology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai 200071, China.
  • Dai E; Department of Cardiology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
  • Sha W; Department of Cardiology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
  • Qu H; Branch of National Clinical Research Center for Chinese Medicine Cardiology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Department of Cardiology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Sha
  • Zhou H; Institute of Cardiovascular Disease of Integrated Traditional Chinese and Western Medicine, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Branch of National Clinical Research Center for Chinese Medicine Cardiology, Shuguang Hospital Affi
Phytomedicine ; 125: 155357, 2024 Mar.
Article en En | MEDLINE | ID: mdl-38295662
ABSTRACT

BACKGROUND:

The terminal stage of all cardiovascular diseases typically culminates in heart failure (HF), with no effective intervention available to halt its progression. LuQi formula (LQF) has been employed in clinical for numerous years to significantly ameliorate cardiac function in HF patients. Nevertheless, the underlying mechanism of LQF's efficacy remains inadequately comprehended. Cardiomyocyte ferroptosis has served as a pathogenic mechanism in HF. The goal of the current experiment was to ascertain whether LQF ameliorates HF by preventing cardiomyocyte ferroptosis and to elucidate the intrinsic mechanism involved.

PURPOSE:

This research objective is to investigate the impact and underlying mechanism of LQF attenuating cardiomyocyte ferroptosis in heart failure.

METHODS:

Transverse aortic constriction (TAC) was performed to construct the HF mouse model. Neonatal rat cardiomyocytes (NRCMs) were subjected to in vitro experiments. High-performance liquid chromatography (HPLC) identified the bioactive compounds in LQF. Transcriptomic and quantitative proteomic analyses revealed the potential targets of LQF anti-HF. Specifically, histological staining evaluated cardiac hypertrophy and fibrosis. Transmission electron microscopy (TEM) observed mitochondrial morphology. The content of Fe2+, ROS, MDA, GSH, and GSSH was detected using kits. Molecular docking evaluated the binding activities between essential active ingredients of LQF and critical proteins of cardiomyocyte ferroptosis. Mechanistically, the expression levels of Nrf2, Keap1, HO-1, SLC7A11, and GPX4 were evaluated using qPCR, Western blot (WB), or immunohistochemical staining.

RESULTS:

The primary nine active ingredients in LQF were detected. Transcriptomic and proteomic analyses demonstrated that LQF may ameliorate HF by preventing cardiomyocyte ferroptosis. Histomorphometric analyses revealed that LQF attenuates myocardial hypertrophy and fibrosis. TEM revealed that LQF diminished mitochondrial shrinkage and increased membrane density in myocardial tissue. Additionally, LQF diminished reactive oxygen species (ROS) generation in cardiomyocytes and suppressed cardiomyocyte ferroptosis. Furthermore, the molecular docking technique revealed that the primary active ingredients of LQF had suitable binding activities with Nrf2, GPX4, and SLC7A11. Western analysis further verified that LQF activated the Nrf2/GPX4 signaling axis. decreased SLC7A11 and HO-1 expression.

CONCLUSIONS:

These results demonstrated that LQF prevents cardiomyocyte ferroptosis via activating Nrf2/GPX4 signaling axis and suppressing SLC7A11 and HO-1 expression. Concurrently, it contributed to elucidating the intrinsic mechanism of LQF and provided a scientific rationale for its development as a novel cardiovascular therapeutic drug.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fármacos Cardiovasculares / Ferroptosis / Insuficiencia Cardíaca Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Phytomedicine Asunto de la revista: TERAPIAS COMPLEMENTARES Año: 2024 Tipo del documento: Article

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fármacos Cardiovasculares / Ferroptosis / Insuficiencia Cardíaca Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Phytomedicine Asunto de la revista: TERAPIAS COMPLEMENTARES Año: 2024 Tipo del documento: Article
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