UV radiation and H2O2 are the primary factors that cause skin aging. Both trigger oxidative stress and cellular aging. It has been reported that deacetylase silent information regulator 1 (SIRT1), a longevity gene, enhances activation of NF-E2-related factor-2 (Nrf2), as well as its downstream key antioxidant gene hemeoxygenase-1 (HO-1), to protect cells against oxidative damage by deacetylating the transcription coactivator PPARγ coactivator-1α (PGC-1α). Galangin, a flavonoid, possesses anti-oxidative and anti-inflammatory potential. In the present study, we applied Ultraviolet B/H2O2-induced human dermal fibroblast damage as an in vitro model and UVB-induced photoaging of C57BL/6J nude mice as an in vivo model to investigate the underlying dermo-protective mechanisms of galangin. Our results indicated that galangin treatment attenuates H2O2/UVB-induced cell viability reduction, dermal aging, and SIRT1/PGC-1α/Nrf2 signaling activation. Furthermore, galangin treatment enhanced Nrf2 activation and nuclear accumulation, in addition to inhibiting Nrf2 degradation. Interestingly, upregulation of antioxidant response element luciferase activity following galangin treatment indicated the transcriptional activation of Nrf2. However, knockdown of SIRT1, PGC-1α, or Nrf2 by siRNA reversed the antioxidant and anti-aging effects of galangin. In vivo evidence further showed that galangin treatment, at doses of 12 and 24 mg/kg on the dorsal skin cells of nude mice resulted in considerably reduced UVB-induced epidermal hyperplasia and skin senescence, and promoted SIRT1/PGC-1α/Nrf2 signaling. Furthermore, enhanced nuclear localization of Nrf2 was observed in galangin-treated mice following UVB irradiation. In conclusion, our data indicated that galangin exerts anti-photoaging and antioxidant effects by promoting SIRT1/PGC-1α/Nrf2 signaling. Therefore, galangin is a potentially promising agent for cosmetic skin care products against UV-induced skin aging.

Chronic high-glucose exposure results in the production of advanced glycation end-products (AGEs) leading to reactive oxygen species (ROS) generation, which contributes to the development of diabetic cardiomyopathy. PKCδ activation leading to ROS production and mitochondrial dysfunction involved in AGE-induced cardiomyocyte apoptosis was reported in our previous study. Diallyl trisulfide (DATS) is a natural cytoprotective compound under various stress conditions. In this study, the cardioprotective effect of DATS against rat streptozotocin (STZ)-induced diabetic mellitus (DM) and AGE-induced H9c2 cardiomyoblast cell/neonatal rat ventricular myocyte (NRVM) damage was assessed. We observed that DATS treatment led to a dose-dependent increase in cell viability and decreased levels of ROS, inhibition of PKCδ activation, and recuded apoptosis-related proteins. Most importantly, DATS reduced PKCδ mitochondrial translocation induced by AGE. However, apoptosis was not inhibited by DATS in cells transfected with PKCδ-wild type (WT). Inhibition of PKCδ by PKCδ-kinase-deficient (KD) or rottlerin not only inhibited cardiac PKCδ activation but also attenuated cardiac cell apoptosis. Interestingly, overexpression of PKCδ-WT plasmids reversed the inhibitory effects of DATS on PKCδ activation and apoptosis in cardiac cells exposed to AGE, indicating that DATS may inhibit AGE-induced apoptosis by downregulating PKCδ activation. Similar results were observed in AGE-induced NRVM cells and STZ-treated DM rats following DATS administration. Taken together, our results suggested that DATS reduced AGE-induced cardiomyocyte apoptosis by eliminating ROS and downstream PKCδ signaling, suggesting that DATS has potential in diabetic cardiomyopathy (DCM) treatment.

Skin cancer is one of the most common cancers worldwide. Melanoma accounts for ~5% of skin cancers but causes the large majority of skin cancer-related deaths. Recent discoveries have shown that the mitogen-activated protein kinase (MAPK) signaling pathway is critical for melanoma development and progression. Many oncogenic pathways that cause melanoma tumorigenesis have been identified, most of which are due to RAF/MEK/ERK (MAPK) pathway activation. However, the precise role of p38 remains unclear. Using specific short hairpin (sh) RNA to silence p38α and p38β, the present findings demonstrated that p38α was a crucial factor in regulating cell migration in the A375 melanoma cell line. Silencing p38α downregulated the expression of epithelial-mesenchymal transition markers, such as matrix metallopeptidase (MMP) 2, MMP9, twist family bHLH transcription factor 1, snail family transcriptional repressor 1 and vimentin, while mesenchymal-epithelial transition markers, such as E-cadherin, were upregulated. Of note, the results also demonstrated that p38α silencing impaired vascular endothelial growth factor expression, which regulates tumor angiogenesis. Furthermore, p38α knockdown inhibited cell proliferation in melanoma cells. In addition, silencing p38α induced senescence-like features, but not cell cycle arrest. Expression of the senescence markers p16, p21, p53 and β-galactosidase was upregulated, and an increase in the number of senescence-associated β-galactosidase-positive cells was observed in a p38α knockdown stable clone. However, no significant difference was found between control and p38β stable knockdown cells. Taken together, the present results suggested that p38α knockdown impaired migration and proliferation, and increased senescence, in A375 melanoma cells. However, p38β may not be involved in melanoma tumorigenesis. Therefore, targeting p38α may be a valuable approach towards inhibiting tumor growth and metastasis in patients with melanoma.

This study aimed to investigate the mechanism underlying the protective effects of galangin against H 2 O 2 /UVB-induced damage using in vitro and in vivo models of photodamage. Moreover, we identified the involvement of miRNA regulation in this process. The H 2 O 2 /UVB-treated HS68 human dermal fibroblasts and UVB-induced C57BL/6J nude mice were used as in vitro and in vivo models of photodamage. The results showed that galangin treatment alleviated H 2 O 2 /UVB-induced reduction in cell viability, TGFβ/Smad signaling impairment, and dermal aging. Based on the results of microRNA array analyses and database searches, hsa-miR-4535 was identified as a potential candidate miRNA that targets Smad4. In vitro , galangin treatment activated Smad2/3/4 complex and inhibited hsa-miR-4535 expression in H2O2/UVB-exposed cells. In vivo , topical application of low (12 mg/kg) and high doses (24 mg/kg) of galangin to the dorsal skin of C57BL/6J nude mice significantly alleviated UVB-induced skin photodamage by promoting TGFβ/Smad collagen synthesis signaling, reducing epidermal hyperplasia, wrinkle formation, and skin senescence, as well as inhibiting hsa-miR-4535 expression. Taken together, our findings indicate a link between hsa-miR-4535 and TGFβ/Smad collagen synthesis signaling and suggest these factors to be involved in the photo-protective mechanism of galangin in dermal fibroblasts against H 2 O 2 /UVB-induced aging. The evidence indicated that galangin with anti-aging properties can be considered as a supplement in skin care products.

Ultraviolet (UV) irradiation is a crucial factor that leads to skin photoaging and results in increased DNA damage, oxidative stress, and collagen degradation. Jasmine flowers have been utilized as a traditional medicine in Asia to treat various diseases, including dermatitis, diarrhea, and fever. Furthermore, the fermented broth of Lactobacillus rhamnosus has been reported to exert protective effects on the skin. In the present study, jasmine flower extract was fermented with L. rhamnosus. We investigated the antioxidant and collagen‐promoting effects on UVB/H2O2‐induced HS68 dermal fibroblast cell damage. The results indicated that treatment with the fermented flower extracts of Jasminum sambac (F‐FEJS) could enhance the viability of HS68 cells. Furthermore, the UVB/H2O2‐induced excessive production of reactive oxygen species, degradation of collagen, activation of MAPKs, including P38, ERK, and JNK, and premature senescence were remarkably attenuated by F‐FEJS in dermal fibroblast cells. The nuclear accumulation of p‐c‐jun, which is downstream of MAPK, and the inactivation of p‐smad2/3, which is one of the crucial transcription factors that enhance collagen synthesis, were reversed in response to F‐FEJS treatment in UVB/H2O2‐exposed cells. Notably, the expression of antioxidant genes, such as HO‐1, and the nuclear translocation of Nrf2 were further enhanced by F‐FEJS in UVB/H2O2‐treated cells. Interestingly, the F‐FEJS‐induced increase in ARE luciferase activity indicated the activation of Nrf2/ARE signaling. In conclusion, our findings demonstrated that F‐FEJS can effectively ameliorate UVB/H2O2‐induced dermal cell aging and may be considered a promising ingredient in skin aging therapy.