Euphorbia neriifolia L. extract attenuates heart failure by modulating the Nrf2/ROS/HIF-1α signaling pathway

Abstract

Heart failure (HF) remains a major global health challenge with limited therapeutic options, thus prompting the search for novel cardioprotective agents among traditional Chinese medicines. In this study, screening of 828 herbal extracts in an oxygen glucose deprivation injury H9c2 cardiomyocyte model led to the identification of Euphorbia neriifolia L. extract (JM04) as a promising candidate. JM04 significantly increased cell viability while decreasing lactate dehydrogenase release and reactive oxygen species (ROS) accumulation in both H9c2 and primary cardiomyocytes. In vivo, JM04 ameliorated cardiac function and attenuated myocardial fibrosis in isoproterenol-induced HF mice, as evidenced by echocardiography and histological analysis. Network pharmacology and mechanistic studies revealed that JM04 modulated the Nrf2/ROS/HIF-1α axis by exerting free radical scavenging activity, activating the Nrf2 antioxidant pathway, restoring mTOR phosphorylation, and enhancing HIF-1α expression, thereby protecting against cardiomyocyte apoptosis. Furthermore, UPLC-MS/MS identified six active components consistent with network pharmacology predictions, thus highlighting its multicomponent and multitarget nature. Collectively, these findings demonstrated that JM04 exerts potent cardioprotective effects through integrated antioxidant and signaling modulation, and support its further development as a candidate botanical drug for HF intervention.

Keywords

Euphorbia neriifolia L. / Heart failure / Network pharmacology / Nrf2/ROS/HIF-1α pathway

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