2. Academic Validation
  3. Calenduloside E suppresses calcium overload by promoting the interaction between L-type calcium channels and Bcl2-associated athanogene 3 to alleviate myocardial ischemia/reperfusion injury

Calenduloside E suppresses calcium overload by promoting the interaction between L-type calcium channels and Bcl2-associated athanogene 3 to alleviate myocardial ischemia/reperfusion injury

  • J Adv Res. 2020 Oct 31:34:173-186. doi: 10.1016/j.jare.2020.10.005.
Ruiying Wang 1 2 3,  Min Wang 1 2 3,  Jiahui Zhou 1 2 3,  Ziru Dai 1 2 3,  Guibo Sun 1 2 3,  Xiaobo Sun 1 2 3
Affiliations

Affiliations

  • 1 Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China.
  • 2 Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100193, China.
  • 3 Key Laboratory of New Drug Discovery Based on Classic Chinese Medicine Prescription, Chinese Academy of Medical Sciences, Beijing 100193, China.
PMID: 35024189 DOI: 10.1016/j.jare.2020.10.005
Abstract

Introduction: Intracellular calcium overload is an important contributor to myocardial ischemia/reperfusion (MI/R) injury. Total saponins of the traditional Chinese medicinal plant Aralia elata (Miq.) Seem. (AS) are beneficial for treating MI/R injury, and Calenduloside E (CE) is the main active ingredient of AS.

Objectives: This study aimed to investigate the effects of CE on MI/R injury and determine its specific regulatory mechanisms.

Methods: To verify whether CE mediated cardiac protection in vivo and in vitro, we performed MI/R surgery in SD rats and subjected neonatal rat ventricular myocytes (NRVMs) to hypoxia-reoxygenation (HR). CE's cardioprotective against MI/R injury was detected by Evans blue/TTC staining, echocardiography, HE staining, myocardial Enzyme levels. Impedance and field potential recording, and patch-clamp techniques of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were used to detect the function of L-type calcium channels (LTCC). The mechanisms underlying between CE and LTCC was studied through western blot, immunofluorescence, and immunohistochemistry. Drug affinity responsive target stability (DARTS) and co-immunoprecipitation (co-IP) used to further clarify the effect of CE on LTCC and BAG3.

Results: We found that CE protected against MI/R injury by inhibiting calcium overload. Furthermore, CE improved contraction and field potential signals of hiPSC-CMs and restored sarcomere contraction and calcium transient of adult rat ventricular myocytes (ARVMs). Moreover, patch-clamp data showed that CE suppressed increased L-type calcium current (ICA,L) caused by LTCC agonist, proving that CE could regulate calcium homeostasis through LTCC. Importantly, we found that CE promoted the interaction between LTCC and Bcl2-associated athanogene 3 (BAG3) by co-IP and DARTS.

Conclusion: Our results demonstrate that CE enhanced LTCC-BAG3 interaction to reduce MI/R induced-calcium overload, exerting a cardioprotective effect.

Keywords

Bcl2-associated athanogene 3; Calcium overload; Calenduloside E; L-type calcium channels; Myocardial ischemia/reperfusion injury.

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