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Sargassum fusiforme (SF) is a popular edible brown macroalga found in Korea, Japan, and China and is known for its health-promoting properties. In this study, we used two sophisticated models to obtain optimized conditions for high antioxidant activity and metabolite profiling using high-resolution mass spectrometry. A four-factor central composite design was used to optimize the microwave-assisted extraction and achieve the maximum antioxidant activities of DPPH (Y1 : 28.01 % inhibition), ABTS (Y2 : 36.07 % inhibition), TPC (Y3 : 43.65 mg GAE/g), and TFC (Y4 : 17.67 mg CAE/g), which were achieved under the optimized extraction conditions of X1 : 47.67 %, X2 : 2.96 min, X3 : 139.54 °C, and X4 : 600.00 W. Moreover, over 79 secondary metabolites were tentatively identified, of which 12 compounds were reported for the first time in SF, including five phenolic (isopropyl 3-(3,4-dihydroxyphenyl)-2-hydroxypropanoate, 3,4-dihydroxyphenylglycol, scopoletin, caffeic acid 4-sulfate, and cinnamoyl glucose), two flavonoids (4’,7-dihydroxyisoflavone and naringenin), three phlorotannins (diphlorethohydroxycarmalol, dibenzodioxin-1,3,6,8-tetraol, and fucophlorethol), and two other compounds (dihydroxyphenylalanine and 5-hydroxybenzofuran2(3H)-one) being identified for the first time in optimized SF extract. These compounds may also be involved in improving the antioxidant potential of the extract. Therefore, optimized models can provide better estimates and predictive capabilities that would assist in finding new bioactive compounds with improved biological activities that can be further applied at a commercial level. [ABSTRACT FROM AUTHOR]

This study was performed to investigate the antioxidant activities of Nymphaea nouchali flower (NNF) extract and the underlying mechanism using RAW 264.7 cells. The presence of gallic acid, catechin, epicatechin, epigallocatechin, epicatechin gallate, caffeic acid, quercetin, and apigenin in the NNF was confirmed by high-performance liquid chromatography (HPLC). The extract had a very potent capacity to scavenge numerous free radicals. NNF extract was also able to prevent DNA damage and quench cellular reactive oxygen species (ROS) generation induced by tert-Butyl hydroperoxide (t-BHP) with no signs of toxicity. The NNF extract was able to augment the expression of both primary and phase II detoxifying enzyme, resulting in combat the oxidative stress. This is accomplished by phosphorylation of mitogen-activated protein kinase (MAP kinase) (p38 kinase and extracellular signal-regulated kinase (ERK)) followed by enhancing the nuclear translocation of the nuclear factor erythroid 2-related factor 2 (Nrf2). This attenuates cellular ROS generation and confers protection from cell death. Altogether, the results of current study revealed that Nymphaea nouchali flower could be a source of natural phytochemicals that could lead to the development of new therapeutic agents for preventing oxidative stress associated diseases and attenuating disease progression. [ABSTRACT FROM AUTHOR]

The leaves of Lannea coromandelica (Houtt.) Merr. are used in the Garo, Pahan, and Teli tribal communities of Bangladesh as a traditional medicinal plant to treat hepatitis, diabetes, ulcers, heart disease, and dysentery. However, there have been limited phytochemical and biological studies on the bark of L. coromandelica. This study aimed to investigate the antioxidant activities of L. coromandelica bark extract (LCBE) and the underlying mechanism using RAW 264.7 cells. The LCBE was analysed by high-pressure liquid chromatography (HPLC) to detect its key polyphenolic compounds. Various in vitro antioxidant assays were performed using RAW264.7 cells to assess the antioxidant effects of the LCBE and to understand the underlying molecular mechanism. HPLC revealed the presence of gallic acid, (-)-epigallocatechin-3-gallate, catechin, chlorogenic acid, and caffeic acid in the LCBE. The extract showed a very potent capacity to scavenge numerous free radicals through hydrogen atom transfer and/or electron donation and also quenched cellular reactive oxygen species (ROS) generation without showing any toxicity. The LCBE was found to combat the oxidative stress by enhancing the expression, at both transcriptional and translational levels, of primary antioxidant enzymes as well as phase II detoxifying enzymes, especially heme oxygenase 1, through the upregulation of the nuclear factor erythroid 2-related factor 2 (NRF2)-mediated pathway in RAW 264.7 cells via the phosphorylation of p38 kinase and c-Jun N-terminal kinase (JNK). The LCBE exhibited strong antioxidant activities and mitigated the cellular ROS production. These results provide scientific evidence of its potential as an ideal applicant for a cost-effective, readily available, and natural phytochemical, as well as a strategy for preventing diseases associated with oxidative stress and attenuating disease progress. [ABSTRACT FROM AUTHOR]

In this study, the anti-melanogenic effects of Heracleum moellendorffii Hance extract (HmHe) and the mechanisms through which it inhibits melanogenesis in melan-a cells were investigated. Mushroom tyrosinase (TYR) activity and melanin content as well as cellular tyrosinase activity were measured in the cells. mRNA and protein expression of microphthalmia-associated transcription factor (MITF), tyrosinase (TYR), TYR-related protein-1 (TYRP-1) and -2 were also examined. The results demonstrate that treatment with HmHe significantly inhibits mushroom tyrosinase activity. Furthermore, HmHe also markedly inhibits melanin production and intracellular tyrosinase activity. By suppressing the expression of TYR, TYRP-1, TYRP-2, and MITF, HmHe treatment antagonized melanin production in melan-a cells. Additionally, HmHe interfered with the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2, with reversal of HmHe-induced melanogenesis inhibition after treatment with specific inhibitor U0126. In summary, HmHe can be said to stimulate ERK1/2 phosphorylation and subsequent degradation of MITF, resulting in suppression of melanogenic enzymes and melanin production, possibly due to the presence of polyphenolic compounds. [ABSTRACT FROM AUTHOR]

We investigated the antioxidative activity of LX519290, a derivative of L-allo threonine, in vitro and in vivo. To evaluate the antioxidative activity of LX519290, we performed several in vitro assays (2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,20-azino-bis-(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) radical-scavenging assays, a ferric reducing antioxidant power assay, cupric-reducing antioxidant capacity, and oxygen radical absorbance capacity assay) and evaluated inhibition against the generation of nitric oxide (NO) and reactive oxygen species (ROS) in murine macrophage (RAW264.7) cells. The results showed that LX519290 possessed very strong radical scavenging activity and reducing power, and inhibited NO and ROS generation in a dose-dependent manner without showing any cytotoxicity. LX519290 treatment also increased the total thiol content and glutathione S-transferases (GST) activities in RAW264.7 cells. Finally, we also determined whether LX519290 affects the mRNA levels of antioxidant enzymes in vitro and in vivo. The expression of superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) were markedly higher in the sample-treated group than in the oxidative stress group. LX519290 treatment also increased the transcriptional and translational activities of NF-E2-related factor-2 (Nrf-2) with corresponding increases in the transcriptional and translational activities of haeme oxygenase-1 (HO-1). Collectively, the data demonstrated that LX519290 has potent antioxidative activity, decreases NO and ROS generation, increases total thiol content and GST activities in RAW264.7 cells, and increases the transcriptional and translational levels of antioxidant enzymes in vitro and in vivo. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the effect of ethyl acetate fraction of Euryale ferox seed extracts (Efse-EA) on melanogenesis in immortalized mouse melanocyte cell line, melan-a. Efse-EA showed strong dose-dependent mushroom tyrosinase inhibitory activity. Treatment of melan-a cells with 30 μg/mL Efse-EA produced strong inhibition of cellular tyrosinase and melanin synthesis. Efse-EA significantly reduced the levels of melanogenesis-related proteins, such as tyrosinase, tyrosinase-related proteins 1 and 2, and microphthalmia-associated transcription factor. Because Efse-EA treatment reduced tyrosinase protein levels without changing its mRNA expression, we investigated whether this decrease was related to proteasomal or lysosomal degradation of tyrosinase. We found that chloroquine, a lysosomal proteolysis inhibitor, almost completely abolished both the down-regulation of tyrosinase and the inhibition of melanin synthesis induced by Efse-EA. These results suggested that Efse-EA may contribute to the inhibition of melanogenesis by altering lysosomal degradation of tyrosinase, and that this extract may provide a new cosmetic skin-whitening agent. [ABSTRACT FROM AUTHOR]

Multinucleated osteoclasts differentiate from hematopoietic progenitors of the monocyte/macrophage lineage. Because of its pivotal role in bone resorption, regulation of osteoclast differentiation is a potential therapeutic approach to the treatment of erosive bone disease. In this study, we have found that fucoidan, a sulfated polysaccharide extracted from brown seaweed, inhibited osteoclast differentiation. In particular, addition of fucoidan into the early stage osteoclast cultures significantly inhibited receptor activator of nuclear factor kappa B (NF-κB) ligand (RANKL)-induced osteoclast formation, thus suggesting that fucoidan affects osteoclast progenitors. Furthermore, fucoidan significantly inhibited the activation of RANKL-dependent mitogen-activated protein kinases (MAPKs) such as JNK, ERK, and p38, and also c-Fos and NFATc1, which are crucial transcription factors for osteoclastogenesis. In addition, the activation of NF-κB, which is an upstream transcription factor modulating NFATc1 expression, was alleviated in the fucoidan-treated cells. These results collectively suggest that fucoidan inhibits osteoclastogenesis from bone marrow macrophages by inhibiting RANKL-induced p38, JNK, ERK and NF-κB activation, and by downregulating the expression of genes that partake in both osteoclast differentiation and resorption. [ABSTRACT FROM AUTHOR]

The development of antimelanogenic agents is important for the prevention of serious aesthetic problems such as melasmas, freckles, age spots, and chloasmas. In the course of screening for melanin synthesis inhibitors, we found that the culture broth from an insect morphopathogenic fungus, Beauveria bassiana CS1029, exhibits potent antimelanogenic activity. We isolated and purified an active metabolite and identified it as S-(-)-10,11-dihydroxyfarnesoic acid methyl ester (dhFAME), an insect juvenile hormone. To address whether dhFAME inhibits melanin synthesis, we first measured the size of the melanin biosynthesis inhibition zone caused by dhFAME. dhFAME also showed inhibitory activity against mushroom tyrosinase in Melan-a cells. Intracellular, dose-dependent tyrosinase inhibition activity was also confirmed by zymography. In addition, we showed that dhFAME strongly inhibits melanin synthesis in Melan-a cells. Furthermore, we compared levels of TYR, TRP-1, TRP-2, MITF, and MC1R mRNA expression by reverse-transcription polymerase chain reaction and showed that treatment of Melan-a cells with 35 µM dhFAME led to an 11-fold decrease in TYR expression, a 6-fold decrease in TRP-2 expression, and a 5-fold decrease in MITF expression. Together, these results indicate that dhFAME is a potent inhibitor of melanin synthesis that can potentially be used for cosmetic biomaterial(s). [ABSTRACT FROM AUTHOR]