Analysis of the Potential Topical Anti-Inflammatory Activity of Averrhoa carambola L. in Mice.

Inflammatory skin disorders, such as psoriasis and atopic dermatitis, are very common in the population; however, the treatments currently available are not well tolerated and are often ineffective. Averrhoa carambola L. (Oxalidaceae) is an Asian tree that has been used in traditional folk medicine in the treatment of several skin disorders. The present study evaluates the topical anti-inflammatory effects of the crude ethanolic extract of A. carambola leaves, its hexane, ethyl acetate, and butanol fractions and two isolated flavonoids on skin inflammation. Anti-inflammatory activity was measured using a croton oil-induced ear edema model of inflammation in mice. Topically applied ethanolic extract reduced edema in a dose-dependent manner, resulting in a maximum inhibition of 73 ± 3% and an ID(50) value of 0.05 (range: 0.02-0.13) mg/ear. Myeloperoxidase (MPO) activity was also inhibited by the extract, resulting in a maximum inhibition of 60 ± 6% (0.6 mg/ear). All of the fractions tested caused inhibition of edema formation and of MPO activity. Treatment with the ethyl acetate fraction was the most effective, resulting in inhibition levels of 75 ± 5 and 54 ± 8% for edema formation and MPO activity, respectively. However, treatment of mice with isolated compounds [apigenin-6-C-ß-l-fucopyranoside and apigenin-6-C-(2″-O-α-l-rhamnopyranosyl)-ß-l-fucopyranoside] did not yield successful results. Apigenin-6-C-(2″-O-α-l-rhamnopyranosyl)-ß-l-fucopyranoside caused only a mild reduction in edema formation (28 ± 11%). Taken together, these preliminary results support the popular use of A. carambola as an anti-inflammatory agent and open up new possibilities for its use in skin disorders.

Role of TRPA1 receptors in skin inflammation induced by volatile chemical irritants in mice.

Contact dermatitis is a very common inflammatory reaction in the skin, causing not only aesthetic problems but also loss functionality at work. The molecular mechanisms of contact dermatitis induced by chemical irritants are still unclear. Considering that transient receptor potential channels (TRP) may induce neurogenic inflammation and the exacerbation of inflammatory responses, here we investigated the role of transient receptor potential channel ankyrin type-1 (TRPA1) in skin inflammation evoked by chemical irritants. Ear oedema and nociceptive responses elicited by the topical application of xylene and toluene were measured in Swiss mice, wild type and TRPA1 knockout (Trpa1-/-) C57BL/6 mice. Histological analyses were performed in mice subjected to the ear oedema assay. Topical application of xylene and toluene in the mouse ear induced an edematogenic response (0.113 ±â€¯0.008 mm and 0.067 ±â€¯0.011 mm), compared to vehicle (0.008 ±â€¯0.008 mm), assessed by ear thickness measurements and histological analyses. These responses were prevented by topical pretreatment with a selective TRPA1 antagonist, HC-030031 (% inhibition: xylene 36.8 ±â€¯9.4% and toluene 50.7 ±â€¯11.0%), and by the genetic deletion of TRPA1 ((% inhibition: xylene 66.6 ±â€¯16.7% and toluene 75 ±â€¯0%). In addition, the topical application of xylene and toluene to the mouse paw elicited nociceptive responses, which were significantly reduced by oral treatment with HC-030031 ((% of inhibition: 84.9 ±â€¯1.3% and 27.1 ±â€¯8.0%, respectively); nociceptive responses were almost completely abolished in Trpa1-/-mice. Our data suggest that the activation of TRPA1 could be involved in some of the symptoms of irritant-mediated contact dermatitis, such as oedema, pain and neurogenic inflammation.

The involvement of TRPA1 channel activation in the inflammatory response evoked by topical application of cinnamaldehyde to mice.

AIMS: In the present work, we characterize the inflammatory process induced by the topical application of cinnamaldehyde on the skin of mice and verify the participation of transient receptor potential A1 TRPA1 receptors in this process. MAIN METHODS: We measured mouse ear edema and sensitization/desensitization after topical application of cinnamaldehyde or/and capsaicin. We also quantified cellular infiltration through myeloperoxidase (MPO) activity and histological and immunohistochemical analyses and evaluated the expression of TRPV1 and TRPA1 by western blot. KEY FINDINGS: Cinnamaldehyde induced ear edema in mice (1-6µg/ear) with a maximum effect of 4µg/ear. Cinnamaldehyde promoted leukocyte infiltration as detected by increasing MPO activity and confirmed by histological analyses. The edema and cellular infiltration evoked by the application of 4µg/ear of cinnamaldehyde were prevented by topical application of ruthenium red, a non-selective TRP antagonist as well as camphor and HC030031, two TRPA1 receptor antagonists. Cinnamaldehyde-induced edema, but not cellular infiltration, was prevented by topical application of the tachykinin NK1 antagonist, aprepitant, indicating a neuropeptide release phenomenon in this process. Additionally, we observed that repeated topical applications of cinnamaldehyde did not induce changes in sensitization or desensitization with respect to the edema response. Interestingly, repeated treatment with the TRPV1 agonist, capsaicin, abrogated it edematogenic response, confirming the desensitization process and partially decreasing the cinnamaldehyde-induced edema, suggesting the involvement of capsaicin-sensitive fibers. SIGNIFICANCE: Our data demonstrate that the topical application of cinnamaldehyde produces an inflammatory response that is dependent on TRPA1 receptor stimulation.