Combination Effect of Titrated Extract ofCentella asiaticaand Astaxanthin in a Mouse Model of Phthalic Anhydride-Induced Atopic Dermatitis

Abstract

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 μg/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)-κB activity. We also measured the concentrations of tumor necrosis factor (TNF)-α, 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-κB activity; and the release of TNF-α, 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-κB signaling.

Pharmacological Effects of Centella asiatica on Skin Diseases: Evidence and Possible Mechanisms

“…Topical treatment with C. asiatica phytosome inhibited the expression of iNOS and COX-2, the activity of NF- κ B, and the release of TNF- α , IL-1 β , and IgE, leading to the suppression of inflammatory cell infiltration [ 41 ]. Furthermore, TECA mixed with astaxanthin augmented the inhibitory effect of TECA on PA-induced morphological changes in skin and ear thickness [ 42 ]. Interestingly, both topical and oral administration of C. asiatica ethanol extract decreased mast cell infiltration in the ear tissue and reduced the expression of various proinflammatory cytokines such as TNF- α , IL-4, IL-5, IL-6, IL-10, and IL-17 [ 43 ].…”

“…Titrated extract of C. asiatica (TECA) treatment suppressed NF- κ B activity and subsequently inhibited the expression of TNF- α , IL-1 β , and IL-6 in a phthalic anhydride (PA)-induced atopic dermatitis (AD) animal model [ 40 ]. Furthermore, the addition of astaxanthin to TECA augmented the NF- κ B-mediated anti-inflammatory activity of TECA [ 42 ]. Another similar report supports the therapeutic effect of C. asiatica on AD via NF- κ B signaling.…”

Anti-Inflammatory and Anticancer Effects of Microalgal Carotenoids

“…As regards skin diseases, it has been reported that this carotenoid administered topically on the ear or back skin of mice alleviated hyperkeratosis and inflammatory response in a model of phthalic anhydride-induced atopic dermatitis. These actions were related to a down-regulation of NF-κB and its proinflammatory target genes iNOS and COX-2 [260,261]. In the same model, ATX-loaded liposomes were more effective than free ATX in alleviating skin inflammation due to inhibition of oxidative stress and STAT3 and NF-κB signaling pathways as well as a reduction of IgE, a marker of allergic inflammation [262].…”

Peran Stres Oksidatif dan Antioksidan pada Dermatitis Atopik

“…Hasilnya terdapat perbaikan klinis signifikan (morfologi dan ketebalan kulit di belakang telinga tikus) setelah aplikasi topikal TECA + AST dibandingkan TECA atau AST tunggal. 22 Pada pemeriksaan imunohistokimia didapatkan penurunan signifikan produksi NO setelah aplikasi topikal TECA + AST dibandingkan TECA atau AST tunggal. 22 Beberapa hasil penelitian dan systematic review pemberian antioksidan sistemik dan topikal pada kasus DA dalam rentang 10 tahun terakhir dirangkum dalam Tabel (Lampiran).…”