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Effects of 18β-glycyrrhetinic acid on pro-inflammatory cytokines and neuronal apoptosis in the hippocampus of lipopolysaccharide-treated mice

18β-Glycyrrhetinic acid가 lipopolysaccharide에 의한 생쥐 뇌조직의 염증성 사이토카인과 해마신경세포 자연사에 미치는 영향

  • Lee, Ji-Seung (Department of Oriental Medical Science, Graduate School of East-West Medical Science, Kyung Hee University) ;
  • Kwon, Man-Jae (Department of Oriental Medical Science, Graduate School of East-West Medical Science, Kyung Hee University) ;
  • Kweon, Su-Hyeon (Department of Oriental Medical Science, Graduate School of East-West Medical Science, Kyung Hee University) ;
  • Kim, Jeeho (Department of Oriental Medical Science, Graduate School of East-West Medical Science, Kyung Hee University) ;
  • Moon, Ji-Young (Department of Oriental Medical Science, Graduate School of East-West Medical Science, Kyung Hee University) ;
  • Cho, Yoon-Cheong (Department of Oriental Medical Science, Graduate School of East-West Medical Science, Kyung Hee University) ;
  • Shin, Jung-Won (Department of Oriental Medical Science, Graduate School of East-West Medical Science, Kyung Hee University) ;
  • Lee, Jong-Soo (Department of Rehabilitation Medicine, College of Korean Medicine, Kyung Hee University) ;
  • Sohn, Nak-Won (Department of Oriental Medical Science, Graduate School of East-West Medical Science, Kyung Hee University)
  • 이지승 (경희대학교 동서의학대학원 한의과학전공) ;
  • 권만재 (경희대학교 동서의학대학원 한의과학전공) ;
  • 권수현 (경희대학교 동서의학대학원 한의과학전공) ;
  • 김지호 (경희대학교 동서의학대학원 한의과학전공) ;
  • 문지영 (경희대학교 동서의학대학원 한의과학전공) ;
  • 조윤정 (경희대학교 동서의학대학원 한의과학전공) ;
  • 신정원 (경희대학교 동서의학대학원 한의과학전공) ;
  • 이종수 (경희대학교 한의과대학 한방재활의학과) ;
  • 손낙원 (경희대학교 동서의학대학원 한의과학전공)
  • Received : 2016.10.10
  • Accepted : 2016.11.16
  • Published : 2016.11.30

Abstract

Objectives : $18{\beta}$-Glycyrrhetinic acid (18betaGA) is an metabolite of glycyrrhizin in Glycyrrhiza (licorice). The present study investigated anti-inflammatory and anti-apoptosis effect of 18betaGA on the brain tissue of lipopolysaccharide (LPS)-treated C57BL/6 mice. Methods : 18betaGA was administered orally with low (30 mg/kg) and high (100 mg/kg) doses for 3 days prior to LPS (3 mg/kg) injection. Pro-inflammatory cytokines mRNA including tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin (IL)-$1{\beta}$, IL-6, and inflammatory enzyme cyclooxygenase-2 (COX-2) mRNA were measured in the cerebral cortex, hippocampus, and hypothalamus tissue using real-time polymerase chain reaction at 24 h after the LPS injection. Histological changes of Cornu ammonis area 1 (CA1) neurons, Bax, Bcl-2, and caspase-3 expression in the hippocampus was also evaluated by immunohistochemistry and Western blotting method. Results : 18betaGA significantly attenuated the up-regulation of TNF-${\alpha}$, IL-$1{\beta}$, IL-6 mRNA, and COX-2 mRNA expression in the brain tissues induced by the LPS injection. 18betaGA also significantly attenuated the reductions of the thickness of CA1 and the number of CA1 neurons. The up-regulation of Bax protein expression in the hippocampal tissue by the LPS injection was significantly attenuated, while the ratio of Bcl-2/Bax expression was increased by 18betaGA treatment. 18betaGA also significantly attenuated the up-regulation of Bax and caspase-3 expression in the CA1 of the hippocampus. Conclusion : This results indicate that 18betaGA has anti-inflammatory and anti-apoptosis effect under neuroinflammation induced by the LPS injection and suggest that 18betaGA may be a beneficial drug for various brain diseases accompanied with the brain tissue inflammation.

Keywords

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