Deok Jeong1, Young-Su Yi1, Gi-Ho Sung2, Woo Seok Yang1, Jae Gwang Park1, Keejung Yoon1, Deok Hyo Yoon3, Changsik Song4, Yunmi Lee5, Man Hee Rhee6, Tae Woong Kim3, Jong-Hoon Kim7, Jae Youl Cho8. 1. Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea. 2. Department of Herbal Crop Research, National Institutes of Horticultural & Herbal Science, Rural Development Administration, Suwon 441-707, Korea. 3. Department of Biochemistry, Kangwon National University, Chuncehon 200-701, Republic of Korea. 4. Department of Chemistry, Sungkyunkwan University, Suwon 440-746, Republic of Korea. 5. Department of Chemistry, Kwangwoon University, Seoul 139-701, Republic of Korea. 6. College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, Republic of Korea. 7. Department of Veterinary Physiology, College of Veterinary Medicine, Biosafety Research Institute, Chonbuk National University, Jeonju 561-756, Republic of Korea. Electronic address: jhkim1@chonbuk.ac.kr. 8. Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea. Electronic address: jaecho@skku.edu.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia asiatica Nakai (Compositae) is a representative herbal plant used to treat infection and inflammatory diseases. Although Artemisia asiatica is reported to have immunopharmacological activities, the mechanisms of these activities and the effectiveness of Artemisia asiatica preparations in use are not known. MATERIALS AND METHODS: To evaluate the anti-inflammatory activities of Artemisia asiatica ethanol extract (Aa-EE), we assayed nitric oxide (NO), tumor necrosis factor (TNF)-α, and prostaglandin E2 (PGE2) in macrophages and measured the extent of tissue injury in a model of gastric ulcer induced in mice by treatment with HCl in EtOH. Putative enzymatic mediators of Aa-EE activities were identified by nuclear fractionation, reporter gene assay, immunoprecipitation, immunoblotting, and kinase assay. Active compound in Aa-EE was identified using HPLC. RESULTS: Treatment of RAW264.7 cells and peritoneal macrophages with Aa-EE suppressed the production of NO, PGE2, and TNF-α in response to lipopolysaccharide (LPS) and induced heme oxygenase-1 expression. The Aa-EE also ameliorated symptoms of gastric ulcer in HCl/EtOH-treated mice. These effects were associated with the inhibition of nuclear translocation of nuclear factor (NF)-κB and activator protein (AP)-1, implying that the anti-inflammatory action of the Aa-EE occurred through transcriptional inhibition. The upstream regulatory signals Syk and Src for translocation of NF-κB and TRAF6 for AP-1 were identified as targets of this effect. Analysis of Aa-EE by HPLC revealed the presence of luteolin, known to inhibit NO and PGE2 activity. CONCLUSION: The anti-inflammatory activities attributed to Artemisia asiatica Nakai in traditional medicine may be mediated by luteolin through inhibition of Src/Syk/NF-κB and TRAF6/JNK/AP-1 signaling pathways.
ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia asiatica Nakai (Compositae) is a representative herbal plant used to treat infection and inflammatory diseases. Although Artemisia asiatica is reported to have immunopharmacological activities, the mechanisms of these activities and the effectiveness of Artemisia asiatica preparations in use are not known. MATERIALS AND METHODS: To evaluate the anti-inflammatory activities of Artemisia asiatica ethanol extract (Aa-EE), we assayed nitric oxide (NO), tumor necrosis factor (TNF)-α, and prostaglandin E2 (PGE2) in macrophages and measured the extent of tissue injury in a model of gastric ulcer induced in mice by treatment with HCl in EtOH. Putative enzymatic mediators of Aa-EE activities were identified by nuclear fractionation, reporter gene assay, immunoprecipitation, immunoblotting, and kinase assay. Active compound in Aa-EE was identified using HPLC. RESULTS: Treatment of RAW264.7 cells and peritoneal macrophages with Aa-EE suppressed the production of NO, PGE2, and TNF-α in response to lipopolysaccharide (LPS) and induced heme oxygenase-1 expression. The Aa-EE also ameliorated symptoms of gastric ulcer in HCl/EtOH-treated mice. These effects were associated with the inhibition of nuclear translocation of nuclear factor (NF)-κB and activator protein (AP)-1, implying that the anti-inflammatory action of the Aa-EE occurred through transcriptional inhibition. The upstream regulatory signals Syk and Src for translocation of NF-κB and TRAF6 for AP-1 were identified as targets of this effect. Analysis of Aa-EE by HPLC revealed the presence of luteolin, known to inhibit NO and PGE2 activity. CONCLUSION: The anti-inflammatory activities attributed to Artemisia asiatica Nakai in traditional medicine may be mediated by luteolin through inhibition of Src/Syk/NF-κB and TRAF6/JNK/AP-1 signaling pathways.