Liensinine prevents ischemic injury following myocardial infarction via inhibition of Wnt/β‑catenin signaling activation

莲心碱通过抑制 Wnt/β‑catenin 信号激活预防心肌梗死后的缺血性损伤

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作者:Fang Shen, Celiang Wu, Xiaomei Zhong, En Ma, Jun Peng, Weidong Zhu, Da Wo, Dan-Ni Ren

Background

Myocardial infarction (MI) is the leading cause of deaths worldwide, triggering widespread and irreversible damage to the heart. Currently, there are no drugs that can reverse ischemic damage to the myocardium and hence, finding novel therapeutic agents that can limit the extent of myocardial damage following MI is crucial. Liensinine (LSN) is a naturally derived bisbenzylisoquinoline alkaloid that is known to exhibit numerous antioxidative and cardiovascular beneficial effects. However, the role of LSN in MI-induced injury and its underlying mechanisms remain unexplored.

Conclusions

Our findings reveal for the first time a novel cardioprotective role of LSN during myocardial infarction and most notably, its ability to protect cardiomyocytes against oxidative stress-induced damage via inhibiting Wnt/β-catenin signaling. Our study therefore suggests new therapeutic potential of LSN or plants that contain the natural alkaloid LSN in ischemic heart diseases.

Methods

We constructed murine models of MI in order to examine the potential cardioprotective effects and mechanisms of LSN in protecting against myocardial ischemic damage both in vivo and in vitro.

Purpose

Our study aims to evaluate the cardioprotective effects of LSN following MI and its underlying molecular mechanisms.

Results

Administration with LSN strongly protected against cardiac injuries following MI by decreasing the extent of ischemic damage and improving cardiac function. Additionally, LSN was found to be a potent inhibitor of Wnt/β‑catenin signaling pathway. Hence, the beneficial effects of LSN in preventing oxidative and DNA damage following ischemia was due to its ability to inhibit aberrant activation of Wnt/β‑catenin signaling. Conclusions: Our findings reveal for the first time a novel cardioprotective role of LSN during myocardial infarction and most notably, its ability to protect cardiomyocytes against oxidative stress-induced damage via inhibiting Wnt/β-catenin signaling. Our study therefore suggests new therapeutic potential of LSN or plants that contain the natural alkaloid LSN in ischemic heart diseases.

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