It is well known that ultraviolet light activates mitogen-activated protein (MAP) kinase by increasing the reactive oxygen species (ROS) in the body, enhancing activating protein 1(AP-1) complexes (c-Jun and c-Fos), increasing matrix metalloproteinases (MMPs) and degrading collagen and elastin. In this study, we confirmed that polyphenolic rich Spatholobus suberectus (SS) stem extracts suppressed ultraviolet (UV)-induced photo-aging. The major active components of SS stem extracts were identified as gallic acid, catechin, vanillic acid, syringic acid and epicatechin. The aqueous and ethanolic extracts of the stem of SS (SSW and SSE, respectively) significantly reduced the elastase enzyme activity. Moreover, both extracts were suppressed the ROS generation and cellular damage induced by UVB in HaCaT cells. Our results also revealed that SSE could regulate the expression of MMPs, tissue inhibitor of matrix metalloproteinase (TIMP)-1, collagen type I alpha 1 (COL1A1), elastin (ELN) and hyaluronan synthase 2 (HAS2) at their transcriptional and translational level. Furthermore, SSE was blocked the UVB-induced phosphorylation of mitogen-activated protein kinases (MAPKs), nuclear factor-kappa B (NF-κB) and c-Jun. Moreover, combination of syringic acid, epicatechin and vanillic acid showed strong synergistic effects on elastase inhibition activity, in which the combination index (CI) was 0.28. Overall, these results strongly suggest that the polyphenolics of SSE exert anti-ageing potential as a natural biomaterial to inhibit UVB-induced photo-aging.
As part of our continuous effort to find potential anti-inflammatory agents from endophytic fungi, a Fusarium solani strain, isolated from the plant Aponogeton undulatus Roxb., was investigated. Cerevisterol (CRVS) was identified from endophytic fungi, a Fusarium solani strain, and moreover exhibited anti-inflammatory activity. However, the underlying mode of action remains poorly understood. The aim of this study is to reveal the potential mechanisms of CRVS against inflammation on a molecular level in LPS-activated RAW 264.7 peritoneal macrophage cells. CRVS was isolated from F. solani and characterized based on spectral data analysis. The MTT assay was performed to measure cell viability in CRVS-treated macrophages. Anti-inflammatory activity was assessed by measurement of nitric oxide (NO) and prostaglandin E2 (PGE2) levels, as well as the production of various cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and -6 (IL-6) in LPS-stimulated macrophages. RT-PCR and immunoblotting analyses were done to examine the expression of various inflammatory response genes. A reporter gene assay was conducted to measure the level of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and activator protein-1 (AP-1) transactivation. CRVS suppresses the LPS-induced production of NO and PGE2, which is a plausible mechanism for this effect is by reducing the expression of iNOS and COX-2. CRVS also decreases the expression of pro-inflammatory cytokines, such as TNF-α, IL-6, and IL-1β. CRVS halted the nuclear translocation of NF-κB by blocking the phosphorylation of inhibitory protein κBα (IκBα) and suppressing NF-κB transactivation. The mitogen-activated protein kinases (MAPK) signaling pathways are also suppressed. CRVS treatment also inhibited the transactivation of AP-1 and the phosphorylation of c-Fos. Furthermore, CRVS could induce the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) by down-regulating Kelch-like ECH-associated protein 1 (Keap-1) and up-regulating hemeoxygenases-1 (HO-1) expression. The results suggest that CRVS acts as a natural agent for treating inflammatory diseases by targeting an MAPK, NF-κB, AP-1, and Nrf2-mediated HO-1 signaling cascade.
Ultraviolet B (UVB) irradiation is viewed as the principal inducer of skin photo-aging, associated with acceleration of collagen degradation and upregulation of matrix metalloproteinases (MMPs). The ethnic groups of southern/western China use Fuzhuan brick-tea (FBT) as a beverage and as a nutritional supplement. In this study, we scrutinized the antagonistic effects of aqueous extract of Fuzhuan-brick tea (FBTA) on skin photo-aging in UVB-exposed human keratinocyte (HaCaT) cells. FBTA exhibited strong antioxidant activity and quenched UVB-induced generation of cellular reactive oxygen species (ROS) without showing any toxicity. FBTA was capable of combating oxidative stress by augmenting messenger RNA (mRNA) and protein levels of both phase I and phase II detoxifying enzymes, especially heme oxygenase 1 (HO-1), by upregulating the nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated pathway in HaCaT cells via the phosphorylation of p38 and extracellular signal-regulated kinase (ERK). FBTA also downregulated the expression of matrix metalloproteinase-1 (MMP-1) while upregulating type I procollagen by modulating Nrf2 signaling in UVB-irradiated HaCaT cells. Collectively, our results show that FBTA might be useful as a functional food while being a good candidate in the development of cosmetic products and medicines for the remedy of UVB-induced skin photo-aging.
In this study, we investigate the immunomodulatory effects of a novel antimicrobial peptide, YD1, isolated from Kimchi, in both in vitro and in vivo models. We establish that YD1 exerts its anti-inflammatory effects via up-regulation of the Nrf2 pathway, resulting in the production of HO-1, which suppresses activation of the NF-κB pathway, including the subsequent proinflammatory cytokines IL-1β, IL-6, and TNF-α. We also found that YD1 robustly suppresses nitric oxide (NO) and prostaglandin E2 (PGE2) production by down-regulating the expression of the upstream genes, iNOS and COX-2, acting as a strong antioxidant. Collectively, YD1 exhibits vigorous anti-inflammatory and antioxidant activity, presenting it as an interesting potential therapeutic agent.