Chemical Distance Measurement and System Pharmacology Approach Uncover the Novel Protective Effects of Biotransformed Ginsenoside C-Mc against UVB-Irradiated Photoaging.

Long-term exposure to ultraviolet light induces photoaging and may eventually increase the risk of skin carcinogenesis. Rare minor ginsenosides isolating from traditional medicine Panax (ginseng) have shown biomedical efficacy as antioxidation and antiphotodamage agents. However, due to the difficulty of component extraction and wide variety of ginsenoside, the identification of active antiphotoaging ginsenoside remains a huge challenge. In this study, we proposed a novel in silico approach to identify potential compound against photoaging from 82 ginsenosides. Specifically, we calculated the shortest distance between unknown and known antiphotoaging ginsenoside set in the chemical space and applied chemical structure similarity assessment, drug-likeness screening, and ADMET evaluation for the candidates. We highlighted three rare minor ginsenosides (C-Mc, Mx, and F2) that possess high potential as antiphotoaging agents. Among them, C-Mc deriving from American ginseng (Panax quinquefolius L.) was validated by wet-lab experimental assays and showed significant antioxidant and cytoprotective activity against UVB-induced photodamage in human dermal fibroblasts. Furthermore, system pharmacology analysis was conducted to explore the therapeutic targets and molecular mechanisms through integrating global drug-target network, high quality photoaging-related gene profile from multiomics data, and skin tissue-specific expression protein network. In combination with in vitro assays, we found that C-Mc suppressed MMP production through regulating the MAPK/AP-1/NF-κB pathway and expedited collagen synthesis via the TGF-ß/Smad pathway, as well as enhanced the expression of Nrf2/ARE to hold a balance of endogenous oxidation. Overall, this study offers an effective drug discovery framework combining in silico prediction and in vitro validation, uncovering that ginsenoside C-Mc has potential antiphotoaging properties and might be a novel natural agent for use in oral drug, skincare products, or functional food.

Antiphotoaging and Antimelanogenesis Properties of Ginsenoside C-Y, a Ginsenoside Rb2 Metabolite from American Ginseng PDD-ginsenoside.

Ginsenosides are compounds responsible for the primary pharmacological effects of American ginseng. Compound-Y (C-Y) is a minor ginsenoside and a metabolite of Panax ginseng. In this study, we investigated the protective effect of ginsenoside UVB-irradiated NHDFs and its potential for use as an antihyperpigmentation agent through ginsenoside C-Y as a functional food and cosmetic ingredient. Ginsenoside C-Y is a natural antioxidant isolated from the American ginseng PDD-ginsenoside. Our data showed that ginsenoside C-Y block UVB-exposed ROS, restrict MMP-1 production and promote procollagen type I synthesis. Interestingly, ginsenoside C-Y suppresses UVB-exposed VEGF, and TNF-α secretion, could be related with NFAT signal path. Ginsenoside C-Y has exhibited photoaging effects by increasing TGF-ß1 level, fortifying Nrf2 nuclear translocation and restricting AP-1 and MAPK phosphorylation. Assessment of the melanogenic response indicated that ginsenoside C-Y inhibited melanin secretion and tyrosinase activity and decreased melanin content in Melan-a and zebrafish embryos. These results suggest that ginsenoside C-Y can be used as a potential botanical agent to protect premature skin from UVB-induced photodamage and prevent skin hyperpigmentation.

Photoprotective and Anti-Inflammatory Properties of Vina-Ginsenoside R7 Ameliorate Ultraviolet B-Induced Photodamage in Normal Human Dermal Fibroblasts.

Vina-ginsenoside R7 (R7) has been exhibited to engage in multiple pharmacological activities, such as antioxidant and anti-inflammatory activities. However, no photoaging-related studies have been performed on R7. Research is being conducted with the aim of assessing whether treatment with R7 has a protective effect on UVB-induced photoaging skin. Our results show that UVB exposure directly reduces matrix metalloproteinase (MMP) secretion through R7 by restraining the AP-1/MAPK pathway and blocks extracellular matrix (ECM) expression degradation. In addition, R7 improves the expression of transforming growth factor beta 1 (TGF-ß1), and type I procollagen also facilitates the synthesis of collagen by the TGF-ß/Smad signal transduction pathway. Finally, R7 valid blocks nuclear factor-κB (NF-κB) activation and enhances antioxidative stress capacity through activated nuclear factor (erythroid derived 2)-like 2 (Nrf2). In particular, the application of R7 restrains pro-inflammatory cytokines (TNF-α, IL-6, iNOS), which trigger ECM, degrade enzyme production, and suppress vascular endothelial growth factor (VEGF) secretion. In conclusion, R7 may constitute a promising cosmetic ingredient that can protect against skin photodamage resulting from detrimental UVB irradiation.

Glaciecola amylolytica sp. nov., an amylase-producing bacterium isolated from seawater.

A Gram-stain-negative, aerobic, non-motile and coccus-shaped bacterium (THG-3.7T) was isolated from seawater. Growth occurred at 10-30 °C (optimum 25 °C), at pH 6-8 (optimum 7) and in the presence of 1-8 % (w/v) NaCl (optimum 4 %). Based on 16S rRNA gene sequence analysis, the nearest phylogenetic neighbours of strain THG-3.7T were identified as Paraglaciecola mesophila DSM 15026T (95.3 % similarity), Glaciecola pallidula DSM 14239T (95.2 %), Paraglaciecola aquimarina KCTC 32108T (95.1 %), Paraglaciecola arctica KACC 14537T (94.9 %), Glaciecola nitratireducens KCTC 12276T (94.7 %) and Paraglaciecola psychrophila CGMCC 1.6130T (94.7 %). 16S rRNA gene sequence similarities among strain THG-3.7T and other species were lower than 94.7 %. The polar lipids were phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, one unidentified lipid and one unidentified aminolipid. The quinone system was composed of Q-8. The major fatty acids were C16 : 0, C18 : 1ω7c and summed feature 3 (C16 : 1ω7c and/or iso-C15 : 0 2-OH). The DNA G+C content of strain THG-3.7T was 47.9 mol%. On the basis of the data presented, strain THG-3.7T represents a novel species of the genus Glaciecola, for which the name Glaciecola amylolytica sp. nov. is proposed. The type strain is THG-3.7T (=KACC 19478T=CCTCC AB 2017258T).

Helianthus annuus L. flower prevents UVB-induced photodamage in human dermal fibroblasts by regulating the MAPK/AP-1, NFAT, and Nrf2 signaling pathways.

BACKGROUND: Excessive ultraviolet radiation usually causes skin photoaging, inflammation, and even photocarcinogenesis. UV radiation-generated reactive oxygen species (ROS) are a major contributing factor to photodamage. The flowers of Helianthus annuus L. have been reported to possess strong anti-inflammatory and antioxidant activity. However, there are few reports on the use of H. annuus L. to relieve UVB-induced photoaging. PURPOSE: In this study, we evaluated the protective effect of a 50% ethanol extract of H. annuus L. flower (HAF) against UVB-induced photodamage using normal human dermal fibroblasts. METHODS: The secretion of ROS, interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), matrix metalloproteinases (MMPs), procollagen type I, and transforming growth factor-ß1 (TGF-ß1) was measured with kits. The messenger RNA levels of COX-2, iNOS, and TGF-α were measured by RT-PCR. The AP-1, MAPK, NFAT, and Nrf2 pathways were investigated by Western blot analysis. RESULTS: HAF extract significantly blocked UVB-induced ROS and MMP (MMP-1 and MMP-3) production and procollagen type I reduction. Further study demonstrated that the photoaging inhibitory actions were related to promotion of Nrf2 nuclear translocation, upregulation of TGF-ß1 level, and downregulation of AP-1 and MAPK phosphorylation. Importantly, HAF effectively inhibited UVB-induced VEGF and inflammatory cytokines such as IL-6, COX-2, iNOS, and TNF-α secretion, which might be involved in the regulation of the NFAT signaling pathway. CONCLUSION: Our results indicate that HAF is a useful botanical source protecting against UVB-mediated skin photodamage.

Ginsenoside C-Mx Isolated from Notoginseng Stem-leaf Ginsenosides Attenuates Ultraviolet B-mediated Photoaging in Human Dermal Fibroblasts.

Notoginseng is a traditional herbal medicine widely used for medicinal therapy in Asia, as it contains numerous ginsenosides with pharmacological effects. In this study, we submitted Notoginseng stem-leaf (NGL) ginsenosides to an enzyme to create a reaction with the monomer products of ginsenoside C-Mx and then investigated the ability of ginsenoside C-Mx to protect the skin against ultraviolet B-induced injury in normal human dermal fibroblasts (NHDFs). Ginsenoside C-Mx alleviated UVB-induced intracellular reactive oxygen species (ROS), MMP-1 and IL-6 expression while accelerating TGF-ß and procollagen type I secretion. In addition, ginsenoside C-Mx reversed UVB-induced procollagen type I reduction by regulating the TGF-ß/Smad signaling pathway. Moreover, ginsenoside C-Mx inhibited activation of AP-1 transcription factor, an inducer of MMPs. Ginsenoside C-Mx displayed an outstanding antioxidant capacity, increasing expression of cytoprotective antioxidants such as HO-1 and NQO-1 expression by enhancing the nuclear accumulation of Nrf2. Interestingly, application of ginsenoside C-Mx treatment (1, 10, 20 µm) significantly diminished UVB-induced suppressed NF-κB expression, decreasing the over-released inflammatory cytokines. Taken together, our findings indicated that ginsenoside C-Mx may act as a promising natural cosmetic ingredient for prevention and treatment of UVB-induced skin damage.