ORIGINAL RESEARCH article
Front. Cardiovasc. Med.
Sec. Cardiovascular Pharmacology and Drug Discovery
Protosappanin A protects against pathological cardiac hypertrophy by inhibiting oxidative stress and NLRP3 inflammasome-mediated pyroptosis via activation of the Nrf2 signaling pathway
Provisionally accepted
- Xijing Hospital, Xi’an, China
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Pathological cardiac hypertrophy is a pivotal pathological process underlying various cardiac diseases, including heart failure (HF). Protosappanin A (PTA), a major biphenyl compound isolated from Caesalpinia sappan, has been shown to confer significant protective effects against multiple cardiovascular insults. However, its precise role in pressure overload-induced pathological cardiac hypertrophy remains elusive. In the present study, a mouse model was established through transverse aortic constriction (TAC) surgery and then intragastrically administered with PTA for 4 weeks. Our results indicate that PTA treatment led to an improvement in cardiac contractile function, a reduction in cardiomyocyte hypertrophy, and an attenuation of myocardial fibrosis in TAC-operated mice. Notably, PTA exerted its anti-hypertrophic actions by mitigating myocardial oxidative stress injury and inhibiting cardiomyocyte pyroptosis. Nevertheless, the above cardioprotective effects of PTA were largely abrogated by the use of the nuclear factor erythroid 2-related factor 2 (Nrf2) specific inhibitor ML385 in TAC-treated mice or Nrf2 siRNA in angiotensin II (Ang II)-treated neonatal mouse cardiomyocytes (NMCMs). In summary, our study demonstrates for the first time that PTA ameliorates cardiac remodeling and dysfunction in mice with pathological cardiac hypertrophy by suppressing oxidative stress and cardiomyocyte pyroptosis through activating of the Nrf2 signaling pathway, highlighting additional therapeutic option for clinical prevention and treatment of HF patients.
Keywords: cardiac hypertrophy, Nrf2 signaling pathway, Oxidative Stress, Protosappanin A, pyroptosis
Received: 09 Aug 2025; Accepted: 18 Dec 2025.
Copyright: © 2025 He, Zheng, Yan, Lv and Yu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Bo Yu
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