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.
The phosphoinositol 3-kinase/Akt pathway plays a critical role in oncogenesis and the dysregulation of this pathway through loss of PTEN is a particularly common phenomenon in aggressive prostate cancers. Several recent studies have indicated that ursolic acid (UA), a pentacyclic triterpenoid, and its derivatives inhibit the growth of cancer cells by cell cycle arrest and the stimulation of apoptosis. In the present study, we report a novel autophagic response of UA in PTEN-deficient PC3 prostate cancer cells. As one of the major types of programmed cell death, autophagy has been observed in response to several anticancer drugs and demonstrated to be responsible for cell death. UA-induced autophagy in PC3 cells is associated with the reduced cell viability and the enhanced expression of LC3-II, an autophagosome marker in mammals, and monodansylcadaverine incorporation into autolysosomes. Furthermore, we found that UA exhibited anti-proliferative effects characterized by G1 phase arrest and autophagy at an early stage that precedes apoptosis. We also show that UA-induced autophagy in PC3 cells are mediated through the Beclin-1 and Akt/mTOR pathways. Inhibition of autophagy by either 3-methyladenine or Beclin-1/Atg5 small interfering RNA enhanced UA-induced apoptosis. Taken together, our data suggest that autophagy functions as a survival mechanism in PC3 cells against UA-induced apoptosis and a rational for the use of autophagy inhibitors in combination with UA as a novel modality of cancer therapy.
Background
Protocatechuic acid has reported containing antioxidant effects. However, information on its other biological activities such as anti‐wrinkle properties is limited
Aims
The objective of this study was to evaluate an antioxidant, collagen synthesis, MMP‐1 inhibition (in vitro), and anti‐wrinkle (in vivo) effects of protocatechuic acid (PCA) as a potent ingredient for wrinkle‐care cosmetic.
Methods
Antioxidant effect was evaluated based on its scavenging activity for free radicals (DPPH, ABTS+). To evaluate the anti‐skin aging potency of PCA, levels of MMP‐1 and type I procollagen were measured using an ELISA kit in cultured human dermal fibroblasts. To further investigate if PCA could increase collagen synthesis, full‐thickness human skin explants were immunostained with an anti‐collagen I antibody. In an in vivo study, 22 female subjects were enrolled in a placebo‐controlled trial. Facial wrinkle, especially crow’s feet around eyes, was treated with lotion‐containing 0.02% PCA for 8 weeks and compared with the placebo.
Results
In in vitro study, PCA showed high antioxidant activ ity. PCA also showed potential to induce the synthesis of type I collagen in human dermal fibroblast and skin explants. It inhibited MMP‐1 secretion from UVA‐irradiated human dermal fibroblast. An in vivo study, treatment with lotion‐containing 0.02% PCA for 8 weeks significantly reduced the percentage of all skin wrinkle parameters.
Conclusion
Based on the results of in vitro assays and in vivo skin testing in human subjects, PCA shows potential in anti‐wrinkle or anti‐skin aging treatments.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.