Impressic Acid Ameliorates Atopic Dermatitis-Like Skin Lesions by Inhibiting ERK1/2-Mediated Phosphorylation of NF-κB and STAT1.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, [2000-

Dermatitis, Atopic/*drug therapy ; MAP Kinase Signaling System/*drug effects ; NF-kappa B/*metabolism ; STAT1 Transcription Factor/*metabolism ; Triterpenes/*therapeutic use; Animals ; Cell Line ; Cytokines/metabolism ; Dermatitis, Atopic/metabolism ; Dermatitis, Atopic/pathology ; Humans ; Male ; Mice ; Mice, Inbred BALB C ; Phosphorylation/drug effects ; Skin/drug effects ; Skin/metabolism ; Skin/pathology

Impressic acid (IPA), a lupane-type triterpenoid from Acanthopanax koreanum , has many pharmacological activities, including the attenuation of vascular endothelium dysfunction, cartilage destruction, and inflammatory diseases, but its influence on atopic dermatitis (AD)-like skin lesions is unknown. Therefore, we investigated the suppressive effect of IPA on 2,4-dinitrochlorobenzene (DNCB)-induced AD-like skin symptoms in mice and the underlying mechanisms in cells. IPA attenuated the DNCB-induced increase in the serum concentrations of IgE and thymic stromal lymphopoietin (TSLP), and in the mRNA levels of thymus and activation regulated chemokine(TARC), macrophage derived chemokine (MDC), interleukin-4 (IL-4), interleukin-5 (IL-5), interleukin-13 (IL-13), tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) in mice. Histopathological analysis showed that IPA reduced the epidermal/dermal thickness and inflammatory and mast cell infiltration of ear tissue. In addition, IPA attenuated the phosphorylation of NF-κB and IκBα, and the degradation of IκBα in ear lesions. Furthermore, IPA treatment suppressed TNF-α/IFN-γ-induced TARC expression by inhibiting the NF-κB activation in cells. Phosphorylation of extracellular signalregulated protein kinase (ERK1/2) and the signal transducer and activator of transcription 1 (STAT1), the upstream signaling proteins, was reduced by IPA treatment in HaCaT cells. In conclusion, IPA ameliorated AD-like skin symptoms by regulating cytokine and chemokine production and so has therapeutic potential for AD-like skin lesions.
Competing Interests: The authors declare no conflict of interest.

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Nos. NRF-2020R1A2C1007764, NRF-2020R1I1A1A01055488 National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP)

Keywords: IgE; NF-κB; TARC; atopic dermatitis-like skin lesions; impressic acid

0 (3,11-dihydroxylup-20(29)-en-28-oic acid)
0 (Cytokines)
0 (NF-kappa B)
0 (STAT1 Transcription Factor)
0 (Triterpenes)

Date Created: 20210303 Date Completed: 20210419 Latest Revision: 20210419

20221213

PMC7956308

10.3390/ijms22052334

33652742