The small molecule rhodomyrtone suppresses TNF-α and IL-17A-induced keratinocyte inflammatory responses: A potential new therapeutic for psoriasis

Abstract

Psoriasis is a common skin disease pathogenically driven by TNF and IL-17A-induced epidermal hyperproliferation and inflammatory responses. The ongoing need for new therapeutic agents for psoriasis has highlighted medicinal plants as sources of phytochemicals useful for treating psoriatic disease. Rhodomyrtone, a bioactive phytochemical from Rhodomyrtus tomentosa, has well-established anti-proliferative activities. This study assessed the potential of rhodomyrtone for curtailing TNF/IL-17A-driven inflammation. Stimulating human skin organ cultures with TNF+IL-17A to model the skin inflammation in psoriasis, we found that rhodomyrtone significantly decreased inflammatory gene expression and the expression and secretion of inflammatory proteins, assessed by qRT-PCR, immunohistochemistry and ELISA assays respectively. RNA-seq analysis of monolayer primary keratinocytes treated with IL-17A/TNF showed that rhodomyrtone inhibited 724/1587 transcripts >2-fold altered by IL-17A/TNF (p<0.01), a number of which were confirmed at the mRNA and protein level. Suggesting that rhodomyrtone acts by modulating MAP kinase and NF-κB signaling pathways, rhodomyrtone inhibited TNF-induced ERK, JNK, p38, and NF-κBp65 phosphorylation. Finally, assessing the in vivo anti-inflammatory potential of rhodomyrtone, we examined its effects on imiquimod-induced skin inflammation in mice, finding rhodomyrtone reversed imiquimod-induced skin hyperplasia and epidermal thickening (p< 0.001). Taken together, these results suggest that rhodomyrtone may be useful in preventing or slowing the progression of inflammatory skin disease.

The Health Beneficial Properties of Rhodomyrtus tomentosa as Potential Functional Food

“…Moreover, it attenuated imiquimod-induced skin inflammation in mice. The data supported the efficacy of rhodomyrtone for treating psoriasis through the inhibition of keratinocyte hyperproliferation [54]. These results indicate that R. tomentosa and its components exert anti-inflammatory effects that open up the possibility of using these natural products for further development of health beneficial products regarding prevention and/or treatment of inflammation.…”

Review—Current Concepts in Inflammatory Skin Diseases Evolved by Transcriptome Analysis: In-Depth Analysis of Atopic Dermatitis and Psoriasis

“…Interestingly, using an unsupervised clustering algorithm, non-lesional and as effectively treated determined specimens as well as lesional and relapse samples clustered pairwise together stating their respective similarities in molecular profiles [223]. Evaluating treatment response may not only be valuable in systemic treatments but also in radiation-based approaches like narrow band UVB irradiation (NB-UVB) [224] or topical agents like ferulic acid [225], indirubin [43], or rhodomyrtone [226]. For instance, NB-UVB irradiation was shown to exhibit systemic effects by restoring expression of the transcription factor CEBPB in PBMCs of treated patients [224].…”

Apoptotic or Antiproliferative Activity of Natural Products against Keratinocytes for the Treatment of Psoriasis

“…tomentosa extract, which demonstrates antibacterial, anti-inflammatory, and immunomodulatory properties [128]. Chorachoo et al [129] investigated whether rhodomyrtone could affect the proliferation, growth arrest, and apoptosis of HaCaT. The antiproliferative percentage of HaCaT was 13.6%~61.6% after 24-h incubation with rhodomyrtone at 2~32 μg/mL.…”