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2017 ; 25
(5
): 535-544
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Inhibitory Effect of Carnosol on Phthalic Anhydride-Induced Atopic Dermatitis via
Inhibition of STAT3
#MMPMID28655070
Lee DY
; Hwang CJ
; Choi JY
; Park MH
; Song MJ
; Oh KW
; Son DJ
; Lee SH
; Han SB
; Hong JT
Biomol Ther (Seoul)
2017[Sep]; 25
(5
): 535-544
PMID28655070
show ga
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/cm(2)) 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-?, IL-1?, 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.