Inhibitory Effect of Carnosol on Phthalic Anhydride-Induced Atopic Dermatitis via Inhibition of STAT3

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.

Phloxine O, a Cosmetic Colorant, Suppresses the Expression of Thymic Stromal Lymphopoietin and Acute Dermatitis Symptoms in Mice

“…Enzyme-linked immunosorbent assays (ELISA) were performed as previously described ( Lee et al ., 2017 ). TSLP levels were determined using a DuoSet enzyme-linked immunosorbent assay (ELISA) kit (R&D systems, Minneapolis, MN, USA) following the manufacturer’s instructions.…”

Rosemary (Rosmarinus officinalis L., syn Salvia rosmarinus Spenn.) and Its Topical Applications: A Review

“…Mice with atopic dermatitis that were topically treated with carnosol showed a significant reduction in skin lesions compared with the control animals [ 26 ]. Atopic dermatitis is a chronic inflammation of the skin characterized by the presence of eczematous and pruritic lesions related to several factors, such as inflammatory cells, cytokines, and enzymes (e.g., STAT3, iNOS, and COX-2) [ 37 ].…”

“…The biological activities of secondary metabolites and extracts of R. officinalis were reported in studies investigating various effects such as its antitumor, antioxidant, anti-infectious, anti-inflammatory, and analgesic activities and effects on the central nervous system, endocrine system, disorders such as cardiac remodeling after myocardial infarction, body weight changes, dyslipidemia, cerebral ischemia, hepato-nephrotoxicity, stress, and anxiety [ 22 , 23 ]. The anti-inflammatory activity of rosemary has been attributed to the presence of carnosol and carnosic, rosmarinic, ursolic, oleanolic, and micromeric acids, which act synergistically [ 24 , 25 , 26 ]. Specifically, the anti-inflammatory effect was also attributed to the synergic effects of ursolic and micromeric acids present in rosemary extract.…”

Anti-Inflammatory Effects of Bee Venom on Phthalic Anhydride-Induced Atopic Dermatitis

“…Atopic dermatitis (AD) is a chronic inflammatory condition involving itchy skin (the most common type of eczema) [1], and is caused by several genetic and environmental factors [2]. Approximately 50% of patients with AD develop symptoms within their first year of life, and 95% experience symptoms by 5 years of age; however, AD can also occur in adults [3,4]. The diagnostic criteria for AD include evidence of itchy skin and 3 or more of the following: history of skin creases, hay fever or generally dry skin in the past year, onset of symptoms under 2 years, and visible flexural dermatitis [5].…”