Jung Hyo Won, Yoon Cheol-Ho, Park Kwon Moo, Han Hyung Soo, Park Yong-Ki
Department of Herbology, College of Oriental Medicine, Dongguk University, Seok-Jang Dong, Gyeongju 780-714, Republic of Korea.
Food Chem Toxicol. 2009 Jun;47(6):1190-7. doi: 10.1016/j.fct.2009.02.012. Epub 2009 Feb 20.
Excessive production of inflammatory mediators such as nitric oxide (NO), prostaglandin E(2) (PGE2), and proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) from activated microglia contributes to uncontrolled inflammation in neurodegenerative diseases. It seems possible that treatment with anti-inflammatory agents, including plants used in Oriental medicine, might delay the progression of neurodegeneration through the inhibition of microglial activation. The present study is focused on the inhibitory effect of the rhizome hexane fraction extract of Zingiber officinale Roscoe (ginger hexan extract; GHE) on the production of inflammatory mediators such as NO, PGE(2), and proinflammatory cytokines in lipopolysaccharide (LPS)-stimulated BV-2 cells, a mouse microglial cell line. GHE significantly inhibited the excessive production of NO, PGE(2), TNF-alpha, and IL-1beta in LPS-stimulated BV2 cells. In addition, GHE attenuated the mRNA expressions and protein levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and proinflammatory cytokines. The molecular mechanisms that underlie GHE-mediated attenuation are related to the inhibition of the phosphorylation of three mitogen-activated protein kinases (MAPKs), extracellular signal-regulated kinases 1 and 2 (ERK1/2), p38 MAPK, and c-Jun N-terminal kinase (JNK), and the activation of nuclear factor-kappaB (NF-kappaB). Our results indicate that GHE exhibits anti-inflammatory properties by suppressing the transcription of inflammatory mediator genes through the MAPK and NF-kappaB signaling pathways. The anti-inflammatory properties of GHE may make it useful as a therapeutic candidate for the treatment of human neurodegenerative diseases.
活化的小胶质细胞过度产生炎性介质，如一氧化氮（NO）、前列腺素E2（PGE2）以及促炎细胞因子，包括肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β），会导致神经退行性疾病中炎症失控。使用包括东方医学中使用的植物在内的抗炎药物进行治疗，似乎有可能通过抑制小胶质细胞活化来延缓神经退行性变的进展。本研究聚焦于姜（Zingiber officinale Roscoe）根茎己烷提取物（姜己烷提取物；GHE）对脂多糖（LPS）刺激的BV-2细胞（一种小鼠小胶质细胞系）中NO、PGE2和促炎细胞因子等炎性介质产生的抑制作用。GHE显著抑制了LPS刺激的BV2细胞中NO、PGE2、TNF-α和IL-1β的过度产生。此外，GHE减弱了诱导型一氧化氮合酶（iNOS）、环氧化酶-2（COX-2）和促炎细胞因子的mRNA表达和蛋白水平。GHE介导的减弱作用的分子机制与三种丝裂原活化蛋白激酶（MAPK），即细胞外信号调节激酶1和2（ERK1/2）、p38 MAPK和c-Jun N端激酶（JNK）的磷酸化抑制以及核因子-κB（NF-κB）的激活有关。我们的结果表明，GHE通过MAPK和NF-κB信号通路抑制炎性介质基因的转录，从而表现出抗炎特性。GHE的抗炎特性可能使其成为治疗人类神经退行性疾病的有用候选药物。
