PMID- 31172723 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20201001 IS - 2092-7355 (Print) IS - 2092-7363 (Electronic) IS - 2092-7355 (Linking) VI - 11 IP - 4 DP - 2019 Jul TI - Combination Effect of Titrated Extract of Centella asiatica and Astaxanthin in a Mouse Model of Phthalic Anhydride-Induced Atopic Dermatitis. PG - 548-559 LID - 10.4168/aair.2019.11.4.548 [doi] AB - PURPOSE: In our previous study, we demonstrated that both titrated extract of Centella asiatica (TECA) and astaxanthin (AST) have anti-inflammatory effects in a 5% phthalic anhydride (PA) mouse model of atopic dermatitis (AD). The increasing prevalence of AD demands new therapeutic approaches for treating the disease. We investigated the therapeutic efficacy of the ointment form of TECA, AST and a TECA + AST combination in a mouse model of AD to see whether a combination of the reduced doses of 2 compounds could have a synergistic effect. METHODS: An AD-like lesion was induced by the topical application of 5% PA to the dorsal ear and back skin of an Hos:HR-1 mouse. After AD induction, TECA (0.5%), AST (0.5%) and the TECA (0.25%) + AST (0.25%) combination ointment (20 mug/cm(2)) were spread on the dorsum of the ear or back skin 3 times a week for 4 weeks. We evaluated dermatitis severity, histopathological changes and changes in protein expression by Western blotting for inducible nitric oxide synthase (iNOS), cyclocxygenase (COX)-2, and nuclear factor (NF)-kappaB activity. We also measured the concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6 and immunoglobulin E (IgE) in the blood of AD mice by enzyme-linked immunosorbent assay (ELISA). RESULTS: PA-induced skin morphological changes and ear thickness were significantly reduced by TECA, AST and TECA + AST treatments, but these inhibiting effects were more pronounced in the TECA + AST treatment. TECA, AST and the TECA+AST reatments inhibited the expression of iNOS and COX-2; NF-kappaB activity; and the release of TNF-alpha, IL-6 and IgE. However, the TECA+AST treatment showed additive or synergistic effects on AD. CONCLUSIONS: Our results demonstrate that the combination of TECA and AST could be a promising therapeutic agent for AD by inhibiting NF-kappaB signaling. CI - Copyright (c) 2019 The Korean Academy of Asthma, Allergy and Clinical Immunology . The Korean Academy of Pediatric Allergy and Respiratory Disease. FAU - Park, Ju Ho AU - Park JH AD - College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju, Korea. FAU - Yeo, In Jun AU - Yeo IJ AUID- ORCID: 0000-0002-6799-667X AD - College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju, Korea. FAU - Jang, Jun Sung AU - Jang JS AD - College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju, Korea. FAU - Kim, Ki Cheon AU - Kim KC AD - College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju, Korea. FAU - Park, Mi Hee AU - Park MH AD - College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju, Korea. FAU - Lee, Hee Pom AU - Lee HP AD - College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju, Korea. FAU - Han, Sang Bae AU - Han SB AD - College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju, Korea. FAU - Hong, Jin Tae AU - Hong JT AUID- ORCID: 0000-0002-6534-9575 AD - College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju, Korea. jinthong@chungbuk.ac.kr. LA - eng GR - 2017R1A5A2015541/NRF/National Research Foundation of Korea/Korea GR - 1415139249/MOTIE/Ministry of Trade, Industry and Energy/Korea PT - Journal Article PL - Korea (South) TA - Allergy Asthma Immunol Res JT - Allergy, asthma & immunology research JID - 101518382 PMC - PMC6557773 OTO - NOTNLM OT - Astaxanthin OT - NF-kappaB OT - atopic dermatitis OT - inflammation OT - titrated extract of Centella asiatica COIS- There are no financial or other issues that might lead to conflict of interest. EDAT- 2019/06/07 06:00 MHDA- 2019/06/07 06:01 PMCR- 2019/07/01 CRDT- 2019/06/08 06:00 PHST- 2018/05/10 00:00 [received] PHST- 2019/01/02 00:00 [revised] PHST- 2019/01/08 00:00 [accepted] PHST- 2019/06/08 06:00 [entrez] PHST- 2019/06/07 06:00 [pubmed] PHST- 2019/06/07 06:01 [medline] PHST- 2019/07/01 00:00 [pmc-release] AID - 11.548 [pii] AID - 10.4168/aair.2019.11.4.548 [doi] PST - ppublish SO - Allergy Asthma Immunol Res. 2019 Jul;11(4):548-559. doi: 10.4168/aair.2019.11.4.548.