Kim Ho-Gyoung, Yoon Deok-Hyo, Kim Chun-Hoi, Shrestha Bhushan, Chang Woo-Chul, Lim So-Yeon, Lee Won-Ho, Han Sang-Guk, Lee Je-O, Lim Mi-Hee, Kim Geun-Young, Choi Sunga, Song Won O, Sung Jae-Mo, Hwang Ki-Chul, Kim Tae-Woong
Department of Biochemistry and Research Institute of Life Sciences, Kangwon National University, Republic of Korea.
J Med Food. 2007 Mar;10(1):80-9. doi: 10.1089/jmf.2006.156.
Inonotus obliquus (Pers.:Fr.) Pil. is a white rot fungus that belongs to the family Hymenochaetaceae of Basidiomycetes. Extracts and fractions of this fungus have been known to have biological activities, including antimutagenic, anticancer, antioxidative, and immunostimulating effects. Recently, there have been reports that the anti-inflammatory and antinociceptive properties of the methanol extract of I. obliquus may be due to the inhibition of inducible nitric oxide (NO) synthase (iNOS) and cyclooxygenase-2 (COX-2) expression via the down-regulation of nuclear factor kappaB (NF-kappaB) binding activity. However, the effects of I. obliquus on Akt and mitogen-activated protein kinase (MAPK) activation of inflammatory mediator production have not yet been elucidated. In the present study, a 70% ethanol extract of I. obliquus (IOE70) showed antioxidative effects. We also tested the ability of the I. obliquus extract to inhibit the inflammatory cascades in lipopolysaccharide (LPS)-induced RAW 264.7 macrophage cells. The NO inhibition of IOE70 was better than that of other ethanol extracts from I. obliquus. To investigate the mechanism by which IOE 70 inhibits NO production and iNOS and COX-2 expression, we examined the activations of IkappaBalpha, Akt, and c-Jun NH(2) -terminal kinase (JNK) in LPS-activated macrophages. IOE70 markedly inhibited the phosphorylation of IkappaBalpha, Akt, and MAPKs in dose-dependent manners in LPS-activated macrophages. Taken together, these experiments demonstrated that IOE70 inhibition of LPS-induced expression of iNOS and COX-2 protein is mediated by Akt and JNK. Based on our findings, the most likely mechanism that can account for this biological effect of IOE70 involves the inhibition of NF-kappaB through the phosphatidylinositol 3-kinase/Akt/IkappaB pathway and the inhibition of JNK activation. Thus, IOE70 might have useful clinical applications in the management of inflammatory diseases and may also be useful as a medicinal food.
桦褐孔菌（Inonotus obliquus (Pers.:Fr.) Pil.）是一种属于担子菌纲多孔菌科的白腐真菌。已知该真菌的提取物和馏分具有生物活性，包括抗诱变、抗癌、抗氧化和免疫刺激作用。最近，有报道称桦褐孔菌甲醇提取物的抗炎和镇痛特性可能归因于通过下调核因子κB（NF-κB）结合活性来抑制诱导型一氧化氮（NO）合酶（iNOS）和环氧化酶-2（COX-2）的表达。然而，桦褐孔菌对炎症介质产生过程中Akt和丝裂原活化蛋白激酶（MAPK）激活的影响尚未阐明。在本研究中，桦褐孔菌70%乙醇提取物（IOE70）显示出抗氧化作用。我们还测试了桦褐孔菌提取物抑制脂多糖（LPS）诱导的RAW 264.7巨噬细胞炎症级联反应的能力。IOE70对NO的抑制作用优于桦褐孔菌的其他乙醇提取物。为了研究IOE 70抑制NO产生以及iNOS和COX-2表达的机制，我们检测了LPS激活的巨噬细胞中IκBα、Akt和c-Jun氨基末端激酶（JNK）的激活情况。IOE70在LPS激活的巨噬细胞中以剂量依赖方式显著抑制IκBα、Akt和MAPK的磷酸化。综上所述，这些实验表明IOE70对LPS诱导的iNOS和COX-2蛋白表达的抑制作用是由Akt和JNK介导的。基于我们的研究结果，最有可能解释IOE70这种生物学效应的机制涉及通过磷脂酰肌醇3激酶/Akt/IκB途径抑制NF-κB以及抑制JNK激活。因此，IOE70在炎症性疾病的治疗中可能具有有用的临床应用价值，也可能作为一种药用食品发挥作用。
