Allicin Ameliorates IMQ-induced psoriasis-like Skin Inflammation Via
Disturbing the Interaction of Keratinocytes with IL-17A
Abstract
Background and Purpose: Psoriasis is an inflammatory skin disease of
chronic recurrence mediated by the interaction between IL-17 and
keratinocytes, which sustains a vicious circle of inflammation.
Currently, there is no safe and effective natural medicine for the
clinical treatment of psoriasis. Given its prominent anti-proliferative
and anti-inflammatory properties, we investigated the mechanism of
allicin improving psoriasis. Experimental Design: Pharmacodynamics and
toxicology experimental studies were estimated after topical
administration of allicin on the skin of mice. Changes in inflammatory
factors expression were analyzed by qPCR and immunohistochemistry after
topical treatment with allicin in mice with psoriasis-like lesions
induced by imiquimod. The impacts of allicin on proliferation and
apoptosis of keratinocytes were analyzed by CCK8 assay and flow
cytometry. The interaction between IL-17A and keratinocytes was studied
using HaCaT cells, and the mechanism of action of allicin was explored
by Western Blot. Transcriptomic changes following the action of allicin
were probed by RNA-seq. Key Results: Our study demonstrated that allicin
significantly improved the epidermal structure by inhibiting excessive
proliferation and evasion of apoptosis of keratinocytes. Furthermore,
allicin reduced the secretion of inflammatory cytokines (IL-17A/F,
IL-22, IL-12, IL-20), chemokines (CXCL2, CXCL5, CCL20), and
antibacterial peptides (S100A8/9). Mechanistically, allicin directly
inhibited the IL-17-induced TRAF6/MAPK/NF-κB and STAT3/NF-κB signaling
cascades in keratinocytes, thus breaking the positive inflammation
feedback and alleviating imiquimod-induced psoriasis-like dermatitis in
mice. Importantly, topical administration of allicin did not cause skin
allergy, and the safety and adaptability of long-term application were
verified.