Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Ginsenosides Decrease β-Amyloid Production via Potentiating Capacitative Calcium Entry

  • Yoon Young Cho (Department of Physiology, Sungkyunkwan University School of Medicine) ;
  • Jeong Hill Park (Research Institute of Pharmaceutical Sciences, Seoul National University, College of Pharmacy) ;
  • Jung Hee Lee (Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Sungkwon Chung (Department of Physiology, Sungkyunkwan University School of Medicine)
  • Received : 2023.09.26
  • Accepted : 2024.03.15
  • Published : 2024.05.01
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Abstract

Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disorder characterized by extracellular amyloid plaques composed of amyloid β-peptide (Aβ). Studies have indicated that Ca2+ dysregulation is involved in AD pathology. It is reported that decreased capacitative Ca2+ entry (CCE), a refilling mechanism of intracellular Ca2+, resulting in increased Aβ production. In contrast, constitutive activation of CCE could decrease Aβ production. Panax ginseng Meyer is known to enhance memory and cognitive functions in healthy human subjects. We have previously reported that some ginsenosides decrease Aβ levels in cultured primary neurons and AD mouse model brains. However, mechanisms involved in the Aβ-lowering effect of ginsenosides remain unclear. In this study, we investigated the relationship between CCE and Aβ production by examining the effects of various ginsenosides on CCE levels. Aβ-lowering ginsenosides such as Rk1, Rg5, and Rg3 potentiated CCE. In contrast, ginsenosides without Aβ-lowering effects (Re and Rb2) failed to potentiate CCE. The potentiating effect of ginsenosides on CCE was inhibited by the presence of 2-aminoethoxydiphenyl borate (2APB), an inhibitor of CCE. 2APB alone increased Aβ42 production. Furthermore, the presence of 2APB prevented the effects of ginsenosides on Aβ42 production. Our results indicate that ginsenosides decrease Aβ production via potentiating CCE levels, confirming a close relationship between CCE levels and Aβ production. Since CCE levels are closely related to Aβ production, modulating CCE could be a novel target for AD therapeutics.

Keywords

Acknowledgement

This work was supported by grants to S.C. (2022R1A2C1007252) and (2021R1I1A1A01056365) to Y.Y.C. of the Basic Science Research Program through the National Research Foundation funded by the Ministry of Education, Science and Technology, Republic of Korea. It was also supported by a grant (2016R1A2A1A05004952) to J.H.L. of the National Research Foundation, Republic of Korea.

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