Abstract
Kaempferol, a bioflavonoid present in fruits and vegetables, has a variety of antioxidant and anti-inflammatory capacities, but the functional role of kaempferol in oxidative skin dermal damage has yet to be well studied. In this study, we examine the role of kaempferol during the inflammation and cell death caused by 12-O-tetradecanoylphorbol-13-acetate (TPA) in normal human dermal fibroblasts (NHDF). TPA (5 μM) significantly induced cytotoxicity of NHDF, where a robust increase in the interleukin (IL)-1β mRNA among the various pro-inflammatory cytokines. The skin fibroblastic cytotoxicity and IL-1β expression induced by TPA were significantly ameliorated by a treatment with 100 nM of kaempferol. Kaempferol blocked the production of the intracellular reactive oxygen species (ROS) responsible for the phosphorylation of c-Jun N-terminal kinase (JNK) induced by TPA. Interestingly, we found that kaempferol inhibited the phosphorylation of nuclear factor-kappa B (NF-κB) and the inhibitor NF-κB (IκBα), which are necessary for the expression of cleaved caspase-3 and the IL-1β secretion in TPA-treated NHDF. These results suggest that kaempferol is a functional agent that blocks the signaling cascade of the skin fibroblastic inflammatory response and cytotoxicity triggered by TPA.
Highlights
Introduction iationsHuman skin has the two layers consisting of epidermis and the dermis, where dermal fibroblasts play an important role in the secretion of inflammatory mediators against chemical and microbial agents, maintaining the structural and mechanical properties of fibers by producing a dense extracellular matrix protein [1,2]. 12-O-tetradecanoyl phorbol13-acetate (TPA), known as a phorbol ester, is a potent inflammagen that elicits skin edema and the cellular response of inflammation in response to the infiltration of neutrophils [3].Increasing evidence has suggested that TPA is a tumor promoter that potentiates epidermal hyperplasia by producing reactive oxygen species (ROS) to create the oxidative stress responsible for the many human diseases [3,4]
The increases in the expression (Figure 1E) and secretion of IL-1β (Figure 1F) induced by TPA markedly blocked by treatment with kaempferol (100 nM). These results demonstrate that the strong potential of kaempferol as a therapeutic agent on skin dermal fibroblastic cytotoxicity and inflammation triggered by TPA
Our findings suggest that TPA triggers skin dermal fibroblastic damage and that kaempferol neutralizes the apoptotic and inflammatory pathways induced by TPA through the inhibition of Jun N-terminal kinase (JNK)-dependent IκBα/Nuclear factor-kappa B (NF-κB) activation occurring due to the production of ROS (Figure 5E)
Summary
Increasing evidence has suggested that TPA is a tumor promoter that potentiates epidermal hyperplasia by producing reactive oxygen species (ROS) to create the oxidative stress responsible for the many human diseases [3,4]. The mechanism of oxidative stress by which TPA induces the skin fibroblastic inflammation and cytotoxicity in the promoting of dermal damage had not yet been explored. Given that the accumulation of oxidative molecular damage due to ROS generation in dermal fibroblasts evokes the activation of apoptotic signaling proteins and causes the abnormal expression of proinflammatory cytokines associated with various skin aging manifestations [6,8], many previous reports have suggested that dietary antioxidant intake such as phenolic compounds, flavonoids, and α-tocopherol ameliorates the risk of many types of inflammatory skin diseases [9,10]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call