1-Iodohexadecane Alleviates 2,4-Dinitrochlorobenzene-Induced Atopic Dermatitis in Mice: Possible Involvements of the Skin Barrier and Mast Cell SNARE Proteins

Abstract

Atopic dermatitis (AD) is a chronic inflammatory dermal disease with symptoms that include inflammation, itching, and dry skin. 1-Iodohexadecane is known as a component of Chrysanthemum boreale essential oil that has an inhibitory effect on AD-like lesions. However, its effects on AD-related pathological events have not been investigated. Here, we explored the effects of 1-iodohexadecane on AD lesion-related in vitro and in vivo responses and the mechanism involved using human keratinocytes (HaCaT cells), mast cells (RBL-2H3 cells), and a 2,4-dinitrochlorobenzene (DNCB)-induced mouse model (male BALB/c) of AD. Protein analyses were performed by immunoblotting or immunohistochemistry. In RBL-2H3 cells, 1-iodohexadecane inhibited immunoglobulin E-induced releases of histamine and β-hexosaminidase and the expression of VAMP8 protein (vesicle-associated membrane proteins 8; a soluble N-ethylmaleimide-sensitive factor attachment protein receptor [SNARE] protein). In HaCaT cells, 1-iodohexadecane enhanced filaggrin and loricrin expressions; in DNCB-treated mice, it improved AD-like skin lesions, reduced epidermal thickness, mast cell infiltration, and increased filaggrin and loricrin expressions (skin barrier proteins). In addition, 1-iodohexadecane reduced the β-hexosaminidase level in the serum of DNCB-applied mice. These results suggest that 1-iodohexadecane may ameliorate AD lesion severity by disrupting SNARE protein-linked degranulation and/or by enhancing the expressions of skin barrier-related proteins, and that 1-iodohexadecane has therapeutic potential for the treatment of AD.

The genus Chrysanthemum: Phylogeny, biodiversity, phytometabolites, and chemodiversity

“…Chrysanthemum plants have a wide range of pharmacological activities ( Figure 9 ; Supplementary Table S1 ). In recent years, the main studied taxa include CM ( Khan et al, 2020 ), C. indicum ( Tian et al, 2020 ), C. boreale ( Kim et al, 2022 ) and C. zawadskii ( Kim et al, 2019 ), among others. The most reported activity of Chrysanthemum is its anti-inflammatory and immunomodulatory effects ( Xue et al, 2021 ; Kim et al, 2022 ), which are consistent with traditional efficacy; it also shows great potential for improving chronic metabolic diseases, neurodegenerative diseases, etc.…”

“…In recent years, the main studied taxa include CM ( Khan et al, 2020 ), C. indicum ( Tian et al, 2020 ), C. boreale ( Kim et al, 2022 ) and C. zawadskii ( Kim et al, 2019 ), among others. The most reported activity of Chrysanthemum is its anti-inflammatory and immunomodulatory effects ( Xue et al, 2021 ; Kim et al, 2022 ), which are consistent with traditional efficacy; it also shows great potential for improving chronic metabolic diseases, neurodegenerative diseases, etc. As the main active ingredients, flavonoids, phenolic acids and terpenoids may be the principal material basis for these effects.…”

“…Plant pharmacophylogeny is an interdisciplinary subject that integrates plant systematics, phytochemistry, TCM, pharmacology and other multidisciplinary knowledge systems Xiao, 2017, 2020), and plays an important role in guiding the conservation, development and utilization of medicinal plant resources. The core idea of plant pharmacophylogeny is that species in adjacent phylogenetic groups have relatively close genetic characteristics; the similar gene sequences lead to relatively close biosynthetic pathways of various phytometabolites in closely related taxa, manifesting a high degree of similarity in the chemical composition, i.e., (1) specific secondary metabolites are more likely to be distributed in multiple species that are genetically close and (2) natural products in closely related taxa have higher similarity in molecular skeleton composition and the relationship of derivation (Liu et al, 2021b). The similarity of the above two tiers of chemicals is manifested in the overall similarity of biological activity or therapeutic effect in clinical application.…”

Metabolites and Bioactivity of the Marine Xestospongia Sponges (Porifera, Demospongiae, Haplosclerida) of Southeast Asian Waters

“…1-iodohexadecane (hexadecyl iodide or cetyl iodide) ( 33 ) reduced 2,4-Dinitrochlorobenzene-Induced Atopic Dermatitis (AD) (a chronic inflammatory dermal) in mice. The treatment with bioactive alkane at a concentration of 100μg/mL for 21 days improved AD-like skin lesions, suppressed epidermal thickness and elevated filaggrin [ 76 , 77 ]. The above-mentioned long-chain fatty acids from X. testudinaria are displayed in Figure 7 .…”

Vesicle trafficking and vesicle fusion: mechanisms, biological functions, and their implications for potential disease therapy

“…Atopic dermatitis is a chronic inflammatory dermal disease caused by histamine with symptoms including inflammation, itching, and dry skin. 1-Iodohexadecane treatment significantly decreased VAMP8 expression level, therefore reduced histamine release in mast cells and alleviates the symptoms for the mice with atopic dermatitis [ 437 ]. In another study, peptides derived from various SNARE motifs, such as a N-terminal-mimicking peptides derived from VAMP8, was investigated for their potential inhibitory effects against the formation of SNARE complex and mast cell degranulation [ 438 ].…”