Parnassin, a Novel Therapeutic Peptide, Alleviates Skin Lesions in a DNCB-Induced Atopic Dermatitis Mouse Model

Abstract

Atopic dermatitis (AD) is a chronic inflammatory skin disease which requires continuous treatment due to its relapsing nature. The current treatment includes steroids and nonsteroidal agents targeting inflammation but long-term administration causes various side effects such as skin atrophy, hirsutism, hypertension and diarrhea. Thus, there is an unmet need for safer and effective therapeutic agents in the treatment of AD. Peptides are small biomolecule drugs which are highly potent and remarkably have less side effects. Parnassin is a tetrapeptide with predicted anti-microbial activity curated from Parnassius bremeri transcriptome data. In this study, we confirmed the effect of parnassin on AD using a DNCB-induced AD mouse model and TNF-α/IFN-γ-stimulated HaCaT cells. In the AD mouse model, topical administration of parnassin improved skin lesions and symptoms in AD mice, such as epidermal thickening and mast cell infiltration, similar to the existing treatment, dexamethasone, and did not affect body weight, or the size and weight of spleen. In TNF-α/IFN-γ-stimulated HaCaT cells, parnassin inhibited the expression of Th2-type chemokine CCL17 and CCL22 genes by suppressing JAK2 and p38 MAPK signaling kinases and their downstream transcription factor STAT1. Parnassin also significantly reduced the gene expression of TSLP and IL-31, which are pruritus-inducing cytokines. These findings suggested that parnassin alleviates AD-like lesions via its immunomodulatory effects and can be used as a candidate drug for the prevention and treatment of AD because it is safer than existing treatments.

Anti-Atopic Dermatitis Effect of TPS240, a Novel Therapeutic Peptide, via Suppression of NF-κB and STAT3 Activation

“…4.1. Peptide Synthesis TPS240 (KQYR) was synthesized and purified at Lugen Sci Co., Ltd. (Bucheon, Republic of Korea) according to previously described methods [20]. The peptide was dissolved in distilled phosphate-buffered saline (PBS) at a concentration of 1 mg/mL.…”

“…Peptide drugs are gaining momentum as antimicrobials and anti-inflammatory modulators for several diseases, notably inflammatory bowel disease, autoimmune diseases, neurological diseases, and tumors [14,15]. Previously, peptides such as AES16-2M, human β-defensins, collagen tripeptide, and parnassin showed anti-inflammatory effects and attenuated AD-like symptoms [16][17][18][19][20].…”

“…In our previous study, we reported that parnassin, a novel peptide curated from Parnassius bremeri (P. bremeri, red-spotted Apollo butterfly), is effective in improving atopic dermatitis [20]. For further study, modifications were made to increase the activity of parnassin.…”