Antagonizing Effects and Mechanisms of Afzelin against UVB-Induced Cell Damage

Abstract

Ultraviolet (UV) radiation induces DNA damage, oxidative stress, and inflammatory processes in human keratinocytes, resulting in skin inflammation, photoaging, and photocarcinogenesis. Adequate protection of skin against the harmful effects of UV irradiation is essential. Therefore, in this study, we investigated the protective effects of afzelin, one of the flavonoids, against UV irradiation in human keratinocytes and epidermal equivalent models. Spectrophotometric measurements revealed that the afzelin extinction maxima were in the UVB and UVA range, and UV transmission below 376 nm was <10%, indicating UV-absorbing activity of afzelin. In the phototoxicity assay using the 3T3 NRU phototoxicity test (3T3-NRU-PT), afzelin presented a tendency to no phototoxic potential. In addition, in order to investigate cellular functions of afzelin itself, cells were treated with afzelin after UVB irradiation. In human keratinocyte, afzelin effectively inhibited the UVB-mediated increase in lipid peroxidation and the formation of cyclobutane pyrimidine dimers. Afzelin also inhibited UVB-induced cell death in human keratinocytes by inhibiting intrinsic apoptotic signaling. Furthermore, afzelin showed inhibitory effects on UVB-induced release of pro-inflammatory mediators such as interleukin-6, tumor necrosis factor-α, and prostaglandin-E2 in human keratinocytes by interfering with the p38 kinase pathway. Using an epidermal equivalent model exposed to UVB radiation, anti-apoptotic activity of afzelin was also confirmed together with a photoprotective effect at the morphological level. Taken together, our results suggest that afzelin has several cellular activities such as DNA-protective, antioxidant, and anti-inflammatory as well as UV-absorbing activity and may protect human skin from UVB-induced damage by a combination of UV-absorbing and cellular activities.

Intraperitoneally administered biliverdin protects against UVB-induced skin photo-damage in hairless mice

“…Both the TBARS and SOD levels may be used as markers of oxidative stress. Most products and vitamin-based treatments used to prevent skin aging involve antioxidation properties [27][28][29]. In this study, the data suggest that overexposure to UVB irradiation leads to increased TBARS level and decreased SOD level, resulting in significant skin damage.…”

Nrf2- and Bach1 May Play a Role in the Modulation of Ultraviolet A-Induced Oxidative Stress by Acetyl-11-Keto-β-Boswellic Acid in Skin Keratinocytes

“…A number of natural products from plants like phenolics and flavonoids [17], peanut sprout extracts [31], and afzelin [32], etc., have been reported as very useful chemoprevention against oxidative stress. Our present study provides evidence that the plant derivative AKBA is a promising regimen for chemoprevention through activation of the Nrf2-ARE-driven antioxidant pathway; researchers showed that AKBA suppresses tumorigenesis, inflammation, and neuroprotection [8,33].…”

Afzelin exhibits anti-cancer activity against androgen-sensitive LNCaP and androgen-independent PC-3 prostate cancer cells through the inhibition of LIM domain kinase 1

“…Afzelin has been reported to exhibit antioxidant, DNA-protective, ultra-violet radiation-absorbing and antiinflammatory properties (36). In addition, a recent study revealed that afzelin inhibits breast cancer cell proliferation by stimulating apoptosis (5).…”