PMID- 28159725 OWN - NLM STAT- MEDLINE DCOM- 20170714 LR - 20170714 IS - 1872-7573 (Electronic) IS - 0378-8741 (Linking) VI - 199 DP - 2017 Mar 6 TI - Topical treatments of Saussurea costus root and Thuja orientalis L. synergistically alleviate atopic dermatitis-like skin lesions by inhibiting protease-activated receptor-2 and NF-kappaB signaling in HaCaT cells and Nc/Nga mice. PG - 97-105 LID - S0378-8741(17)30401-4 [pii] LID - 10.1016/j.jep.2017.01.055 [doi] AB - ETHNOPHARMACOLOGICAL RELEVANCE: The root of Saussurea costus (Aucklandia lappa Decne, Aucklandiae Radix, SC) and Thuja orientalis L. (TOL) have been traditionally used as anti-inflammatory agents in Korea. However, they have not been studied for the efficacy of atopic dermatitis (AD) treatment, a chronic inflammatory skin disease. We investigated the efficacy of topical applications with 1,3-butyleneglycol extracts of SC and TOL to alleviate the symptoms of AD. MATERIALS AND METHODS: HaCaT cells and the dorsal skin of Nc/Nga mice had a local exposure of house mite extracts and 2,4-dinitrochlorobenzene (DNCB), respectively. After lesions developed, we topically applied 1,3-butylen glycol (vehicle; control), SC (30%), TOL (30%), or SC (15%)+TOL (15%) to the skin lesions for 5 weeks. The normal-control was not exposed to DNCB. The skin thickness, mast cell infiltration, serum immunoglobulin E (IgE) and IgG1 and gene expressions of interleukin (IL)-4, IL-13, and IFN-gamma in the dorsal skin and HaCaT cells were measured. RESULTS: Chlorogenic acid (129.6+/-10.2mug/g) for SC and catechin and apigenin (93.4+/-13.2 and 16.9+/-1.3mug/g, respectively) for TOL were used as indicator compounds for the strength of the extracts. SC+TOL decreased the expression of protease-activated receptor-2 and ICAM-1 and the release of TNF-alpha and IL-6 in HaCaT cells activated by 3mug/mL house mite extracts in comparison to either of SC or TOL alone. In Nc/Nga mice challenged with DNCB, SC+TOL synergistically attenuated clinical symptoms of AD such as erythema, hemorrhage, edema, excoriation and dryness in the dorsal skin better than either SC or TOL alone. Histological analysis of the dorsal skin also showed that SC+TOL treatment significantly and additively decreased the inflammatory cellular infiltrate, including mast cells and eosinophils in comparison to either of SC or TOL. SC+TOL also decreased serum IgE and IgG1 levels and the expression of IFN-gamma, IL-4, and IL-13 mRNA in dorsal skin in DNCB-treated Nc/Nga mice. CONCLUSION: SC+TOL relieved the symptoms of AD by reducing pro-inflammatory activity and over-activated immune responses. These data suggest that SC+TOL may be an effective alternative intervention for the management of AD. CI - Copyright (c) 2017 Elsevier Ireland Ltd. All rights reserved. FAU - Yang, Hye Jeong AU - Yang HJ AD - Division of Strategic Food Industry Research, Korea Food Research Institute, South Korea; Department of Food Science and Nutrition, Yong In University, South Korea. Electronic address: yhj@kfri.re.kr. FAU - Kim, Min Jung AU - Kim MJ AD - Division of Nutrition and Metabolism Research, Korea Food Research Institute, South Korea; Department of Food Science and Nutrition, Yong In University, South Korea. Electronic address: kmj@kfri.re.kr. FAU - Kang, Suna AU - Kang S AD - Department of Food and Nutrition, Obesity/Diabetes Center, Hoseo University, Asan, South Korea. Electronic address: roypower003@naver.com. FAU - Moon, Na Rang AU - Moon NR AD - Department of Food and Nutrition, Obesity/Diabetes Center, Hoseo University, Asan, South Korea. Electronic address: a213900@hanmail.net. FAU - Kim, Da Sol AU - Kim DS AD - Department of Food and Nutrition, Obesity/Diabetes Center, Hoseo University, Asan, South Korea. Electronic address: tpfptm14@daum.net. FAU - Lee, Na Ra AU - Lee NR AD - Department of Nanobiomechatronics, Hoseo University, Asan, South Korea. Electronic address: zzzz8238@naver.com. FAU - Kim, Kang Sung AU - Kim KS AD - Department of Food Science and Nutrition, Yong In University, South Korea. Electronic address: kss@yongin.ac.kr. FAU - Park, Sunmin AU - Park S AD - Department of Food and Nutrition, Obesity/Diabetes Center, Hoseo University, Asan, South Korea. Electronic address: smpark@hoseo.edu. LA - eng PT - Journal Article DEP - 20170201 PL - Ireland TA - J Ethnopharmacol JT - Journal of ethnopharmacology JID - 7903310 RN - 0 (Anti-Inflammatory Agents) RN - 0 (NF-kappa B) RN - 0 (Plant Extracts) RN - 0 (Receptor, PAR-2) SB - IM MH - Administration, Topical MH - Animals MH - Anti-Inflammatory Agents/isolation & purification/pharmacology/therapeutic use MH - Cell Line, Transformed MH - Dermatitis, Atopic/drug therapy/*metabolism MH - Drug Synergism MH - Humans MH - Male MH - Mice MH - NF-kappa B/antagonists & inhibitors/*metabolism MH - Plant Extracts/isolation & purification/pharmacology/*therapeutic use MH - Random Allocation MH - Receptor, PAR-2/antagonists & inhibitors/*metabolism MH - *Saussurea MH - Signal Transduction/drug effects/physiology MH - *Thuja OTO - NOTNLM OT - Atopic dermatitis OT - Aucklandiae radix OT - IL-4 OT - Ig E OT - Mast cells OT - Saussurea costus root OT - Thuja orientalis L EDAT- 2017/02/06 06:00 MHDA- 2017/07/15 06:00 CRDT- 2017/02/05 06:00 PHST- 2016/05/21 00:00 [received] PHST- 2016/11/24 00:00 [revised] PHST- 2017/01/30 00:00 [accepted] PHST- 2017/02/06 06:00 [pubmed] PHST- 2017/07/15 06:00 [medline] PHST- 2017/02/05 06:00 [entrez] AID - S0378-8741(17)30401-4 [pii] AID - 10.1016/j.jep.2017.01.055 [doi] PST - ppublish SO - J Ethnopharmacol. 2017 Mar 6;199:97-105. doi: 10.1016/j.jep.2017.01.055. Epub 2017 Feb 1.