Genipin inhibits the inflammatory response of rat brain microglial cells = 흰쥐 뇌 소교세포에서 genipin의 염증반응 억제에 관한 연구

다국어 초록 (Multilingual Abstract)

Microglia are the prime effectors in immune and inflammatory responses of the central nervous system (CNS). Under pathological conditions, the activation of these cells helps restore CNS homeostasis. However, chronic microglial activation endangers neuronal survival through the release of various proinflammatory and neurotoxic factors. Thus, negative regulators of microglial activation have been considered as potential therapeutic candidates to target neurodegeneration, such as that in Alzheimer’s and Parkinson’s diseases. Genipin, the aglycon of geniposide found in gardenia fruit has long been considered for treatment of various disorders in traditional oriental medicine. Genipin has recently been reported to have diverse pharmacological functions, such as antimicrobial, antitumor, and anti-inflammatory effects. The specific aim of this study was to examine whether genipin represses brain microglial activation. Genipin was effective at inhibiting LPS-induced nitric oxide (NO) release from cultured rat brain microglial cells. Genipin reduced the LPS-stimulated production of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), prostaglandin E2 (PGE2), and intracellular reactive oxygen species. In addition, genipin reduced NO release from microglia stimulated with interferon-γ(IFN-γ) and amyloid-β(Aβ). Both pretreatment and post-treatment of genipin to LPS-stimulated microglia were effective at decreasing NO release. These results suggest that genipin provide neuroprotection by reducing the production of various neurotoxic molecules from activated microglia.

국문 초록 (Abstract)

소교세포(microglia)는 중추신경계에서 면역과 염증 반응에 중요한 작용을 하는 인자로, 병적 상태에서는 소교세포가 활성화되어 중추신경의 항상성을 복구시킨다. 그러나 만성적인 소교세포의 활성은 다양한 염증전구물질과 신경독성 인자를 방출하여 신경세포의 생존을 위협하게 된다. 따라서 소교세포의 만성적 활성을 억제하는 것은 알쯔하이머나 파킨슨병과 같은 퇴행성 신경질환에 대한 치료 작용으로 간주되고 있다. Genipin은 치자열매의 활성물질로 항균작용, 항암작용, 항염증작용에 대한 약리작용이 있는 것으로 보고되고 있다. 이 논문은 특히 genipin이 뇌소교세포 활성을 억제 할 수 있는지에 초점을 두었다.
실험 결과에 의하면 genipin은 배양된 쥐의 뇌소교세포에서 lipopolysaccharide (LPS)에 의해 유발된 nitric oxide (NO)를 억제하는데 효과적이었다. 또한 LPS에 의해 유발된 tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), prostaglandin E2 (PGE2), 그리고 세포내 활성산소를 감소시켰고, interferon-γ(IFN-γ), amyloid-β(Aβ)에 의해 자극된 소교세포로부터 방출된 NO를 감소시켰다. LPS에 자극된 소교세포에 genipin을 전처리 한 것과 후처리한 것 모두 NO방출을 감소시키는데 효과적이었다. 따라서 이 연구 결과 genipin은 활성화된 소교세포에서 방출된 다양한 신경독성 분자들의 생성을 감소시킴으로써 신경 보호 작용이 있음을 알 수 있었다.

목차 (Table of Contents)

• I. Introduction 1
• II. Materials and methods 3
• 1. Materials and reagents 3
• 2. Cell culture and treatment 3
• 3. Nitrite assay 4
• 4. Cell viability assay 4
• 5. Cytokine assay 4
• 6. Measurement of intracellular ROS (DCFH-DA assay) 5
• 7. Statistical analysis 5
• III. Results 6
• 1. Suppression of LPS-induced NO production 6
• 2. Suppression of LPS-induced secretion of proinflammatory cytokines 6
• 3. Suppression of LPS-induced ROS production 9
• 4. Effects of post-treatment of genipin on LPS-stimulated inflammatory response 9
• 5. Suppression of IFN-γ and Aβ-induced NO production 11
• IV. Discussion 12
• V. Conclusions 15
• VI. References 16
• Abstract 20
• 국문초록 21