PMID- 30642008 OWN - NLM STAT- MEDLINE DCOM- 20190401 LR - 20200225 IS - 1420-3049 (Electronic) IS - 1420-3049 (Linking) VI - 24 IP - 2 DP - 2019 Jan 11 TI - Anti-Allergic and Anti-Inflammatory Effects of Kuwanon G and Morusin on MC/9 Mast Cells and HaCaT Keratinocytes. LID - 10.3390/molecules24020265 [doi] LID - 265 AB - Atopic dermatitis (AD) is a prevalent chronic inflammatory skin disease. The use of immunomodulatory corticosteroids in AD treatment causes adverse side effects. Therefore, novel natural anti-inflammatory therapeutics are needed. The aim of the present study was to investigate the anti-allergic and anti-inflammatory activities of kuwanon G and morusin. To investigate the effect of kuwanon G and morusin on skin inflammation, enzyme-linked immunosorbent assays (ELISA) to quantitate secreted (RANTES/CCL5), thymus- and activation-regulated chemokine (TARC/CCL17), and macrophage-derived chemokine (MDC/CCL22) were performed, followed by Western blotting to measure the phosphorylation of signal transducer and activator of transcription 1 (STAT1) and nuclear transcription factor-kappaB (NF-kappaB) p65 in tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma)-stimulated HaCaT keratinocytes. In order to evaluate the anti-allergic effects, ELISA to quantify histamine and leukotriene C(4) (LTC(4)) production and Western blotting to measure 5-lipoxygenase (5-LO) activation were performed using PMA and A23187-stimulated MC/9 mast cells. Kuwanon G reduced the release of RANTES/CCL5, TARC/CCL17, and MDC/CCL22 via down-regulation of STAT1 and NF-kappaB p65 signaling in TNF-alpha and IFN-gamma-stimulated HaCaT keratinocytes. Kuwanon G also inhibited histamine production and 5-LO activation in PMA and A23187-stimulated MC/9 mast cells. Morusin inhibited RANTES/CCL5 and TARC/CCL17 secretion via the suppression of STAT1 and NF-kappaB p65 phosphorylation in TNF-alpha and IFN-gamma-stimulated HaCaT keratinocytes, and the release of histamine and LTC(4) by suppressing 5-LO activation in PMA and A23187-stimulated MC/9 mast cells. Kuwanon G and morusin are potential anti-inflammatory mediators for the treatment of allergic and inflammatory skin diseases such as AD. FAU - Jin, Seong Eun AU - Jin SE AD - Herbal Medicine Research Division, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon 34054, Korea. noellajin@kiom.re.kr. FAU - Ha, Hyekyung AU - Ha H AUID- ORCID: 0000-0002-7326-6366 AD - Herbal Medicine Research Division, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon 34054, Korea. hkha@kiom.re.kr. FAU - Shin, Hyeun-Kyoo AU - Shin HK AD - Herbal Medicine Research Division, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon 34054, Korea. hkshin@kiom.re.kr. FAU - Seo, Chang-Seob AU - Seo CS AUID- ORCID: 0000-0002-8156-446X AD - Herbal Medicine Research Division, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon 34054, Korea. csseo0914@kiom.re.kr. LA - eng GR - K17251/Korea Institute of Oriental Medicine/ GR - K18241/Korea Institute of Oriental Medicine/ PT - Journal Article DEP - 20190111 PL - Switzerland TA - Molecules JT - Molecules (Basel, Switzerland) JID - 100964009 RN - 0 (Anti-Allergic Agents) RN - 0 (Anti-Inflammatory Agents) RN - 0 (Biomarkers) RN - 0 (Chemokines) RN - 0 (Flavonoids) RN - 0 (NF-kappa B) RN - 0 (STAT1 Transcription Factor) RN - 0 (STAT1 protein, human) RN - 62596-29-6 (morusin) RN - 75629-19-5 (kuwanon G) SB - IM MH - Anti-Allergic Agents/chemistry/*pharmacology MH - Anti-Inflammatory Agents/chemistry/*pharmacology MH - Biomarkers MH - Cell Line MH - Chemokines/metabolism MH - Chromatography, High Pressure Liquid MH - Flavonoids/chemistry/*pharmacology MH - Humans MH - Keratinocytes/*drug effects/*metabolism MH - Mast Cells/*drug effects/*metabolism MH - Molecular Structure MH - NF-kappa B/metabolism MH - Phosphorylation MH - STAT1 Transcription Factor/metabolism PMC - PMC6359505 OTO - NOTNLM OT - Kuwanon G OT - anti-allergy OT - anti-skin inflammation OT - morusin COIS- The authors declare no conflict of interest. EDAT- 2019/01/16 06:00 MHDA- 2019/04/02 06:00 PMCR- 2019/01/11 CRDT- 2019/01/16 06:00 PHST- 2018/11/22 00:00 [received] PHST- 2018/12/24 00:00 [revised] PHST- 2019/01/09 00:00 [accepted] PHST- 2019/01/16 06:00 [entrez] PHST- 2019/01/16 06:00 [pubmed] PHST- 2019/04/02 06:00 [medline] PHST- 2019/01/11 00:00 [pmc-release] AID - molecules24020265 [pii] AID - molecules-24-00265 [pii] AID - 10.3390/molecules24020265 [doi] PST - epublish SO - Molecules. 2019 Jan 11;24(2):265. doi: 10.3390/molecules24020265.