Caffeic Acid Reduces Cutaneous Tumor Necrosis Factor Alpha (TNF-α), IL-6 and IL-1β Levels and Ameliorates Skin Edema in Acute and Chronic Model of Cutaneous Inflammation in Mice

Abstract

Caffeic acid (3,4-dihydroxycinnamic acid, CA) has been reported to have anti-inflammatory activity in animal models. However, the mechanisms underlying the anti-inflammatory effects of CA in skin inflammation are only partially understood. The present study was designed to investigate the effects and mechanisms of CA on acute and chronic skin inflammation in mice and the effect of CA in keratinocytes in vitro. The results showed that topical treatment with CA inhibited 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced skin edema in a dose-dependent manner, leading to substantial reductions in skin thickness and tissue weight, neutrophil-mediated myeloperoxidase activity, and various histopathological indicators. The CA treatment also significantly reduced the mRNA and protein levels of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and IL-1β at the application site, and the TNF-α production, the TNF-α-induced IL-6 and IL-1β production, and TNF-α-induced nuclear factor-kappa B (NF-κB) activation in human keratinocytes in vitro. Furthermore, CA was effective at reducing inflammatory damage induced by chronic TPA exposure. These results demonstrate that CA has anti-inflammatory activities in both acute and chronic contact dermatitis models via blockade of the mRNA and protein synthesis of these cytokines and neutrophil-mediated myeloperoxidase activity, and can target inflammatory mediators specifically in the keratinocytes. Taken together, the present results suggest that CA might be a therapeutic agent against inflammatory skin diseases.Key words 3,4-dihydroxycinnamic acid; pro-inflammatory cytokine; keratinocyte; 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced ear edema modelThe skin is an immune organ consisting of epidermal cells, i.e., keratinocytes and Langerhans cells.

Suppression of skin inflammation in keratinocytes and acute/chronic disease models by caffeic acid phenethyl ester

“…3). The effective dosages of CA in TPA-induced chronic inflammation model were 2, 4, and 6 % [28] whereas our results showed that CAPE was effective at 0.5 and 1 % in hapteninduced chronic dermatitis model (Fig. 5).…”

“…Moreover, CAPE was effective in vivo at the concentrations as low as 0.5 %. Recent report showed that the application of 6 % CA suppressed multiple TPA challenge-induced ear edema only by *24 % [28] while in our study, CAPE almost completely blocked TPA-induced ear edema at 0.5 % (Fig. 3).…”

A network pharmacology approach to determine active ingredients and rationality of herb combinations of Modified-Simiaowan for treatment of gout

“…Interestingly, Caffeic acid and Ferulic acid, the representative active ingredients in LJ (She and Zhu, 2008), exhibit low DL values, although their OB values meet the standards. They show potent antisepsis and anti-inflammatory effects (Ma et al, 2010;Zhang et al, 2014;Tang et al, 2014) and could be selected for further evaluation. Based on all these considerations, it was reasonable to believe that five could be listed as potential active ingredients.…”

Effect of Caffeic Acid on Ischemia-Reperfusion-Induced Acute Renal Failure in Rats

“…CA is also a potent 5-LOX inhibitor [9], as well as a potent antioxidant [10]. In the inflammatory process, CA has been demonstrated to downregulate NF-κB and inhibits tumor necrosis factor alpha (TNF-α), IL-6, IL-1β [11]. CA phenethyl ester, a derivative of CA, has been reported to protect IR-induced renal injury [12].…”