Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
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The purified extract of steamed Panax ginseng protects cardiomyocyte from ischemic injury via caveolin-1 phosphorylation-mediating calcium influx

  • Hai-Xia Li (School of Pharmaceutical Sciences, Zhengzhou University) ;
  • Yan Ma (School of Pharmaceutical Sciences, Zhengzhou University) ;
  • Yu-Xiao Yan (School of Pharmaceutical Sciences, Zhengzhou University) ;
  • Xin-Ke Zhai (School of Pharmaceutical Sciences, Zhengzhou University) ;
  • Meng-Yu Xin (School of Pharmaceutical Sciences, Zhengzhou University) ;
  • Tian Wang (School of Pharmaceutical Sciences, Zhengzhou University) ;
  • Dong-Cao Xu (School of Pharmaceutical Sciences, Zhengzhou University) ;
  • Yu-Tong Song (School of Pharmaceutical Sciences, Zhengzhou University) ;
  • Chun-Dong Song (The First Affiliated Hospital of Henan University of Traditional Chinese Medicine) ;
  • Cheng-Xue Pan (School of Pharmaceutical Sciences, Zhengzhou University)
  • Received : 2022.09.01
  • Accepted : 2023.07.07
  • Published : 2023.11.01
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Abstract

Background: Caveolin-1, the scaffolding protein of cholesterol-rich invaginations, plays an important role in store-operated Ca2+ influx and its phosphorylation at Tyr14 (p-caveolin-1) is vital to mobilize protection against myocardial ischemia (MI) injury. SOCE, comprising STIM1, ORAI1 and TRPC1, contributes to intracellular Ca2+ ([Ca2+]i) accumulation in cardiomyocytes. The purified extract of steamed Panax ginseng (EPG) attenuated [Ca2+]i overload against MI injury. Thus, the aim of this study was to investigate the possibility of EPG affecting p-caveolin-1 to further mediate SOCE/[Ca2+]i against MI injury in neonatal rat cardiomyocytes and a rat model. Methods: PP2, an inhibitor of p-caveolin-1, was used. Cell viability, [Ca2+]i concentration were analyzed in cardiomyocytes. In rats, myocardial infarct size, pathological damages, apoptosis and cardiac fibrosis were evaluated, p-caveolin-1 and STIM1 were detected by immunofluorescence, and the levels of caveolin-1, STIM1, ORAI1 and TRPC1 were determined by RT-PCR and Western blot. And, release of LDH, cTnI and BNP was measured. Results: EPG, ginsenosides accounting for 57.96%, suppressed release of LDH, cTnI and BNP, and protected cardiomyocytes by inhibiting Ca2+ influx. And, EPG significantly relieved myocardial infarct size, cardiac apoptosis, fibrosis, and ultrastructure abnormality. Moreover, EPG negatively regulated SOCE via increasing p-caveolin-1 protein, decreasing ORAI1 mRNA and protein levels of ORAI1, TRPC1 and STIM1. More importantly, inhibition of the p-caveolin-1 significantly suppressed all of the above cardioprotection of EPG. Conclusions: Caveolin-1 phosphorylation is involved in the protective effects of EPG against MI injury via increasing p-caveolin-1 to negatively regulate SOCE/[Ca2+]i.

Keywords

Acknowledgement

This work was supported by the National Natural Science Foundation of China (Grant No. 81973727 & 82074493), the Programs of Innovation and Entrepreneurship for Undergraduates of Henan Province (Grant No. S202110459059).

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