Diallyl trisulfide (DATS) protects cardiac cells against advanced glycation end-product-induced apoptosis by enhancing FoxO3A-dependent upregulation of miRNA-210.

Diabetic cardiomyopathy is a common complication of diabetes, resulting in cardiac hypertrophy and heart failure associated with excessive reactive oxygen species and mitochondria-mediated apoptosis generation. Mitogen-activated protein kinase-c-Jun N-terminal kinase (MAPK-JNK), regulated by microRNA (miR)-210, affects mitochondrial function and is activated by advanced glycation end-products (AGE) in cardiac cells. Diallyl trisulfide (DATS), an antioxidant in garlic oil, inhibits stress-induced cardiac apoptosis. This study examined whether DATS enhances miR-210 expression to attenuate cardiac apoptosis. We investigated the DATS-mediated attenuation mechanism of AGE-enhanced cardiac apoptosis by modulating miR-210 and its upstream transcriptional regulator, FoxO3a. We found FoxO3a binding sites in the miR-210 promoter region. Our results indicated that DATS treatment inhibited AGE-induced JNK activation, phosphoprotein c-Jun nuclear transactivation, and cardiac apoptosis and reversed the AGE-induced reduction in cardiac miR-210 levels. The luciferase activity after DATS treatment was significantly lower than that of the control and was reversed following AGE treatment. We also showed that FoxO3a, upregulated by DATS treatment, may bind to the miR-210 promoter to enhance its expression and downregulates JNK expression to attenuate AGE-induced cardiac apoptosis. Oral administration of DATS enhanced FoxO3a expression in the heart and reduced diabetes-induced heart apoptosis. Our findings indicate that DATS mediates AGE-induced cardiac cell apoptosis attenuation by promoting FoxO3a nuclear transactivation to enhance miR-210 expression and regulate JNK activation. Our results suggest that DATS can be used as a cardioprotective agent, and miR-210 is a critical regulator in inhibiting diabetic cardiomyopathy.

Paeoniflorin found in Paeonia lactiflora root extract inhibits melanogenesis by regulating melanin-related signal transduction in B16F10 cells.

BACKGROUND: Skin pigmentation is modulated by various processes, with melanogenesis playing a key role. Melanin is synthesized by the catalysis of melanogenesis-related enzymes, such as tyrosinase and tyrosine-related proteins TRP-1 and TRP-2. Paeoniflorin is the main bioactive component of Paeonia suffruticosa Andr., Paeonia lactiflora., or Paeonia veitchii Lynch and has been used for centuries for its anti-inflammatory, anti-oxidant, and anti-carcinogenic properties. AIMS & METHODS: In this study, melanin biosynthesis in mouse melanoma (B16F10) cells was induced using α-melanocyte-stimulating hormone (α-MSH), and then cells were co-treated with paeoniflorin to evaluate its potential anti-melanogenic effect. RESULTS: α-MSH stimulation increased melanin content, tyrosinase activity, and melanogenesis-related markers in a dose-dependent manner. However, treatment with paeoniflorin reversed α-MSH-induced upregulation of melanin content and tyrosinase activity. Furthermore, paeoniflorin inhibited cAMP response element-binding protein activation and TRP-1, TRP-2, and microphthalmia-associated transcription factor protein expression in α-MSH-stimulated B16F10 cells. CONCLUSION: Overall, these findings show the potential of paeoniflorin as a depigmenting agent for cosmetic products.

Seven traditional Chinese herbal extracts fermented by Lactobacillus rhamnosus provide anti-pigmentation effects by regulating the CREB/MITF/tyrosinase pathway.

Skin pigmentation is resulted from several processes, such as melanin synthesis transportation and abnormal melanin accumulation in keratinocytes. Various studies have suggested that seven traditional Chinese herbal extracts from Atractylodes macrocephala, Paeonia lactiflora, Bletilla striata, Poria cocos, Dictamnus dasycarpus, Ampelopsis japonica and Tribulus terrestris (which we collectively named ChiBai), show several protective effects toward skin-related diseases. Lactobacillus rhamnosus, a lactic acid bacterium, has been reported to treat skin inflammation and atopic dermatitis. In this study, the broth produced by the cofermentation of ChiBai with Lactobacillus rhamnosus was studied for its effects on skin pigmentation through in vitro and in vitro experiments. In the in vitro experiments, we found that the fermented broth of ChiBai (FB-ChiBai) suppressed alpha-melanocyte stimulating hormone (α-MSH)-induced melanogenesis in B16F0 murine melanoma cells without any cytotoxicity at a concentration of 0.5%. FB-ChiBai significantly attenuated melanin production, tyrosinase activities and melanogenesis-related signaling pathways. Treatment with FB-ChiBai also reduced the nuclear translocation and promoter binding activities of MITF. In the in vivo experiments, FB-ChiBai was topically applied to the dorsal skin of C57BL/6J nude mice and concurrently irradiated with UVB, three times a week for 8 weeks. The results indicated that FB-ChiBai alleviated UVB-induced hyperpigmentation by reducing epidermal hyperplasia and inhibiting the CREB/MITF/tyrosinase pathway. In conclusion, our data indicated that the anti-melanogenic effects of FB-ChiBai are mediated by the inhibition of CREB/MITF/tyrosinase signaling pathway. The findings suggest that FB-ChiBai can protect against UV-B irradiation and that it might be used as an agent in cosmetic products to protect against UVB-induced hyperpigmentation.

Extracts of Jasminum sambac flowers fermented by Lactobacillus rhamnosus inhibit H2 O2 - and UVB-induced aging in human dermal fibroblasts.

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/H2 O2 -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/H2 O2 -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/H2 O2 -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/H2 O2 -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/H2 O2 -induced dermal cell aging and may be considered a promising ingredient in skin aging therapy.

Roles of p38α and p38ß mitogen­activated protein kinase isoforms in human malignant melanoma A375 cells.

Skin cancer is one of the most common cancers worldwide. Melanoma accounts for ~5% of skin cancers but causes the large majority of skin cancer­related deaths. Recent discoveries have shown that the mitogen­activated 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 p38ß, 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 epithelial­mesenchymal transition markers, such as matrix metallopeptidase (MMP) 2, MMP9, twist family bHLH transcription factor 1, snail family transcriptional repressor 1 and vimentin, while mesenchymal­epithelial transition markers, such as E­cadherin, 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 senescence­like features, but not cell cycle arrest. Expression of the senescence markers p16, p21, p53 and ß­galactosidase was upregulated, and an increase in the number of senescence­associated ß­galactosidase­positive cells was observed in a p38α knockdown stable clone. However, no significant difference was found between control and p38ß stable knockdown cells. Taken together, the present results suggested that p38α knockdown impaired migration and proliferation, and increased senescence, in A375 melanoma cells. However, p38ß 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.