Biomolecules & Therapeutics

  • 제30권5호
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  • Pages.455-464
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  • 2022
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  • 1976-9148(pISSN)
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  • 2005-4483(eISSN)
한국응용약물학회 (The Korean Society of Applied Pharmacology)
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Efonidipine Inhibits JNK and NF-κB Pathway to Attenuate Inflammation and Cell Migration Induced by Lipopolysaccharide in Microglial Cells

  • Nguyen, Ngoc Minh (College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University-Seoul) ;
  • Duong, Men Thi Hoai (College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University-Seoul) ;
  • Nguyen, Phuong Linh (College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University-Seoul) ;
  • Bui, Bich Phuong (College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University-Seoul) ;
  • Ahn, Hee-Chul (College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University-Seoul) ;
  • Cho, Jungsook (College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University-Seoul)
  • 투고 : 2022.06.02
  • 심사 : 2022.06.20
  • 발행 : 2022.09.01
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초록

Efonidipine, a calcium channel blocker, is widely used for the treatment of hypertension and cardiovascular diseases. In our preliminary study using structure-based virtual screening, efonidipine was identified as a potential inhibitor of c-Jun N-terminal kinase 3 (JNK3). Although its antihypertensive effect is widely known, the role of efonidipine in the central nervous system has remained elusive. The present study investigated the effects of efonidipine on the inflammation and cell migration induced by lipopolysaccharide (LPS) using murine BV2 and human HMC3 microglial cell lines and elucidated signaling molecules mediating its effects. We found that the phosphorylations of JNK and its downstream molecule c-Jun in LPS-treated BV2 cells were declined by efonidipine, confirming the finding from virtual screening. In addition, efonidipine inhibited the LPS-induced production of pro-inflammatory factors, including interleukin-1β (IL-1β) and nitric oxide. Similarly, the IL-1β production in LPS-treated HMC3 cells was also inhibited by efonidipine. Efonidipine markedly impeded cell migration stimulated by LPS in both cells. Furthermore, it inhibited the phosphorylation of inhibitor kappa B, thereby suppressing nuclear translocation of nuclear factor-κB (NF-κB) in LPS-treated BV2 cells. Taken together, efonidipine exerts anti-inflammatory and anti-migratory effects in LPS-treated microglial cells through inhibition of the JNK/NF-κB pathway. These findings imply that efonidipine may be a potential candidate for drug repositioning, with beneficial impacts on brain disorders associated with neuroinflammation.

키워드

과제정보

This work was supported by the National Research Foundation of Korea (NRF) grants funded by the Korean government (MSIT) (NRF-2018R1A5A2023127 and 2020R1F1A1075835 to J.C. and NRF-2018R1D1A1B07050975 and 2021R1F1A1063558 to H.-C.A.), Korea.

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