Eun-Hye Song1, Kyung-Sook Chung2, Yun-Mi Kang1, Jong-Hyun Lee3, Minho Lee4, Hyo-Jin An5. 1. Department of Pharmacology, College of Korean Medicine, Sangji University, 83 Sangjidae-gil, Wonju-si, Gangwon-do 220-702, Republic of Korea. 2. Catholic Precision Medicine Research Center, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea. 3. Department of Pharmacy, College of Pharmacy, Dongduk Women's University, Seoul 136-714, Republic of Korea. 4. Catholic Precision Medicine Research Center, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea. Electronic address: MinhoLee@catholic.ac.kr. 5. Department of Pharmacology, College of Korean Medicine, Sangji University, 83 Sangjidae-gil, Wonju-si, Gangwon-do 220-702, Republic of Korea. Electronic address: hjan@sj.ac.kr.
Abstract
INTRODUCTION: Eupatilin, a pharmacologically active ingredient found in Artemisia asiatica, has been reported to have anti-oxidative, anti-inflammatory, and anti-apoptotic activities. However, molecular mechanisms underlying its anti-allergic properties are not yet clear. In this study, we investigated the effects of eupatilin on allergic inflammation in phorbol 12-myristate 13-acetate plus calcium ionophore A23187 (PMACI)-stimulated human mast cells and a compound 48/80-induced anaphylactic shock model. METHODS: Cytokine assays, histamine assays, quantitative real-time polymerase chain reaction analysis, western blot analysis and compound 48/80-induced anaphylactic shock model were used in this study. RESULTS: Eupatilin significantly suppresses the expression and production of pro-inflammatory cytokines, such as interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and IL-6 in vitro and in vivo. In addition, eupatilin inhibits nuclear factor kappa B (NF-κB) activation by regulating the phosphorylation and degradation of IκBα via the Akt/IKK(α/β) pathway. Eupatilin treatment also attenuates the phosphorylation of p38, ERK, and JNK MAPKs. Furthermore, eupatilin blocked anaphylactic shock and decreased the release of histamine. CONCLUSIONS: Anti-allergic inflammation may involve the expression and production of regulating pro-inflammatory cytokines via Akt/IKK(α/β) and MAPK activation of NF-κB. On the basis of these data, eupatilin is a potential candidate for the treatment of allergic diseases.
INTRODUCTION:Eupatilin, a pharmacologically active ingredient found in Artemisia asiatica, has been reported to have anti-oxidative, anti-inflammatory, and anti-apoptotic activities. However, molecular mechanisms underlying its anti-allergic properties are not yet clear. In this study, we investigated the effects of eupatilin on allergic inflammation in phorbol 12-myristate 13-acetate plus calcium ionophore A23187 (PMACI)-stimulated human mast cells and a compound 48/80-induced anaphylactic shock model. METHODS: Cytokine assays, histamine assays, quantitative real-time polymerase chain reaction analysis, western blot analysis and compound 48/80-induced anaphylactic shock model were used in this study. RESULTS:Eupatilin significantly suppresses the expression and production of pro-inflammatory cytokines, such as interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and IL-6 in vitro and in vivo. In addition, eupatilin inhibits nuclear factor kappa B (NF-κB) activation by regulating the phosphorylation and degradation of IκBα via the Akt/IKK(α/β) pathway. Eupatilin treatment also attenuates the phosphorylation of p38, ERK, and JNK MAPKs. Furthermore, eupatilin blocked anaphylactic shock and decreased the release of histamine. CONCLUSIONS: Anti-allergic inflammation may involve the expression and production of regulating pro-inflammatory cytokines via Akt/IKK(α/β) and MAPK activation of NF-κB. On the basis of these data, eupatilin is a potential candidate for the treatment of allergic diseases.