Biomolecules & Therapeutics  
Inhibitory Effect of Carnosol on Phthalic Anhydride-Induced Atopic Dermatitis via Inhibition of STAT3
Do Yeon Lee1, Chul Ju Hwang1, Ji Yeon Choi1, Mi Hee Park1, Min Ji Song1, Ki Wan Oh1, Dong Ju Son1, Seung Hwa Lee2, Sang Bae Han1 and Jin Tae Hong1,*
1College of Pharmacy and Medical Research Center,
2Department of Industrial Cosmetics, Chungbuk National University, Cheongju 28160, Republic of Korea
E-mail: jinthong@chungbuk.ac.kr
Tel: +82-43-261-2813, Fax: +82-43-268-2732
Received: January 17, 2017; Revised: April 19, 2017; Accepted: May 2, 2017; Published online: June 27, 2017.
© The Korean Society of Applied Pharmacology. All rights reserved.

Abstract
Carnosol is a phenolic antioxidant present in rosemary (Rosmarinus officinalis). It is known for anti-inflammatory effects, analgesic activity and anti-cancer effects. However, no study has been dedicated yet to its effect on atopic dermatitis (AD). Here, we show that carnosol effectively inhibited LPS-induced nitric oxide (NO) generation and expression of inflammatory marker proteins (iNOS and COX-2) in RAW 264.7 cells. In addition, carnosol effectively inhibits the phosphorylation of STAT3 and DNA binding activity in RAW 264.7 cells. Pull down assay and docking model analysis showed that carnosol directly binds to the DNA binding domain (DBD) of STAT3. We next examined the anti-atopic activity of carnosol (0.05 µg/cm2) using 5% Phthalic anhydride (PA)-induced AD model in HR1 mice. Carnosol treatment significantly reduced 5% PA-induced AD like skin inflammation in skin tissues compared with control mice. Moreover, carnosol treatment inhibits the expression of iNOS and COX-2 in skin tissue. In addition, the levels of TNF-α, IL-1β, and Immunoglobulin-E in blood serum was significantly decreased in carnosol treated mice compared with those of 5% PA treated group. Furthermore, the activation of STAT3 in skin tissue was decreased in carnosol treated mice compared with control mice. In conclusion, these findings suggest that carnosol exhibited a potential anti-AD activity by inhibiting pro-inflammatory mediators through suppression of STAT3 activation via direct binding to DBD of STAT3.
Keywords: Atopic dermatitis, STAT3, Carnosol


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