Eswara Rao Puppala
Psoriasis is a chronic inflammatory and proliferative skin disease characterized by pathological skin lesions which significantly impact the quality of life. Perillyl alcohol (POH) is a hydroxylated monoterpene, naturally found in essential oils like Lavandula augustifolia, Prunus avium etc. Recent studies have been proven that inhibitors of farnesyltransferase enzyme showed significant anti-psoriatic activity. POH is one such natural molecule having anti-proliferative, anti-inflammatory and anti-oxidant properties by inhibiting farnesyltransferase enzyme which further down regulates the NF-κB and STAT3 via Ras/Raf/MAPK pathway. Hence, in the current study we aimed to investigate the effect of POH on IMQ induced psoriatic like skin inflammation model in Balb/C mice. It was found that POH (200 mg/kg, topical application) has reduced the epidermal hyperplasia, psoriasis area and severity index (PASI) scoring; splenomegaly. Further, POH treatment has decreased the pro-inflammatory serum cytokine levels such as IL-6, IL-12/23, TNF-α and IL-1β and also reduced the expression levels of various inflammatory proteins, COX-2, iNOS, IL-17A, IL-22, NF-кB and STAT3 evidenced by Immunoblotting from skin samples. The levels of endogenous antioxidants like GSH, SOD, and Nrf2 were restored to normal levels upon POH treatment. POH downregulated the proteins levels of TLR7, TLR8, CyclinD1 and mRNA expression of Bcl-2 in the mice. POH has ameliorated the hyper-keratosis and acanthosis which was evidenced by histopathology. Immuno-fluorescence data revealed that POH has decreased the levels of Ki67, NF-кB-p-65 and STAT3 levels in skin tissues. Collectively, our results suggest that POH has a promising therapeutic application for ameliorating psoriasis-like skin inflammation.