ATF-2/CREB/IRF-3-targeted anti-inflammatory activity of Korean red ginseng water extract

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• 作者：Yanyan Yang^a ; ¹ ; Woo Seok Yang^a ; ¹ ; Tao Yu^a ; ¹ ; Gi-Ho Sung^b ; Kye Won Park^c ; Keejung Yoon^a ; Young-Jin Son^d ; Hyunsik Hwang^a ; Yi-Seong Kwak^e ; Chang-Muk Lee^f ; Man Hee Rhee^g ; Jong-Hoon Kim^h ; ^{jhkim1@chonbuk.ac.kr" class="auth_mail} ; Jae Youl Cho^a ; ^{jaecho@skku.edu" class="auth_mail} ; ^{jaecho67@gmail.com" class="auth_mail}
• 关键词：PG ; prostaglandin ; NO ; nitric oxide ; COX ; cyclooxygenase ; iNOS ; inducible NO synthase ; TNF 伪 ; tumor necrosis factor-伪 ; TLR ; toll-like receptors ; NF-魏B ; nuclear factor-魏B ; MTT ; 3-4 ; 5-dimethylthiazol-2-yl)-2 ; 5-diphenyltetrazolium bromide ; PI3K ; phosphoinositide 3-kinase ; LPS ; lipopolysaccharide ; PCR ; polymerase chain reaction ; I魏Ba ; inhibitor of kappa B alpha ; I魏魏 ; I魏B kinase ; CMC ; sodium carboxymethylcellulose ; ATF-2 ; activating transcription factor-2 ; CREB ; cAMP response element-binding protein
• 刊名：Journal of Ethnopharmacology
• 出版年：28 May 2014
• 年：2014
• 卷：154
• 期：1
• 页码：218-228
• 全文大小：952 K

文摘

Korean Red Ginseng (KRG) is one of the representative traditional herbal medicines prepared from Panax ginseng Meyer (Araliaceae) in Korea. It has been reported that KRG exhibits a lot of different biological actions such as anti-aging, anti-fatigue, anti-stress, anti-atherosclerosis, anti-diabetic, anti-cancer, and anti-inflammatory activities. Although systematic studies have investigated how KRG is able to ameliorate various inflammatory diseases, its molecular inhibitory mechanisms had not been carried out prior to this study.

Materials and methods

In order to investigate these mechanisms, we evaluated the effects of a water extract of Korean Red Ginseng (KRG-WE) on the in vitro inflammatory responses of activated RAW264.7 cells, and on in vivo gastritis and peritonitis models by analyzing the activation events of inflammation-inducing transcription factors and their upstream kinases.

Results

KRG-WE reduced the production of nitric oxide (NO), protected cells against NO-induced apoptosis, suppressed mRNA levels of inducible NO synthase (iNOS), cyclooxygenase (COX)-2, and interferon (IFN)-尾, ameliorated EtOH/HCl-induced gastritis, and downregulated peritoneal exudate-derived NO production from lipopolysaccharide (LPS)-injected mice. The inhibition of these inflammatory responses by KRG-WE was regulated through the suppression of p38, c-Jun N-terminal kinase (JNK), and TANK-binding kinase 1 (TBK1) and by subsequent inhibition of activating transcription factor (ATF)-2, cAMP response element-binding protein (CREB), and IRF-3 activation. Of ginsensides included in this extract, interestingly, G-Rc showed the highest inhibitory potency on IRF-3-mediated luciferase activity.

Conclusion

These results strongly suggest that the anti-inflammatory activities of KRG-WE could be due to its inhibition of the p38/JNK/TBK1 activation pathway.