Byoung Ok Cho

Blackberry extract attenuates oxidative stress through up-regulation of Nrf2-dependent antioxidant enzymes in carbon tetrachloride-treated rats.

The aim of this study was to investigate the protective ability of blackberry extract (BE) against oxidative stress in carbon tetrachloride (CCl(4))-treated rats. The results showed that treatment with BE attenuated lipid peroxidation that was increased by CCl(4) and also markedly recovered the activity of antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR), that were decreased by CCl(4). BE also elevated the protein expression levels of NF-E2-related factor-2 (Nrf2), CuZnSOD, MnSOD, GPx-1/2, and heme oxygenase-1 (HO-1), but not that of catalase. Furthermore, the administration of BE significantly attenuated the levels of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) that were increased by CCl(4). Therefore, the present study suggests that BE possesses significant protective effects against in vivo oxidative stress.

Anti-Inflammatory Effect of Mangostenone F in Lipopolysaccharide-Stimulated RAW264.7 Macrophages by Suppressing NF-κB and MAPK Activation

Mangostenone F (MF) is a natural xanthone isolated from Garcinia mangostana. However, little is known about the biological activities of MF. This study was designed to investigate the anti-inflammatory effect and underlying molecular mechanisms of MF in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. MF dose-dependently inhibited the production of NO, iNOS, and pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) in LPS-stimulated RAW264.7 macrophages. Moreover, MF decreased the NF-κB luciferase activity and NF-κB DNA binding capacity in LPS-stimulated RAW264.7 macrophages. Furthermore, MF suppressed the NF-κB activation by inhibiting the degradation of IκBα and nuclear translocation of p65 subunit of NF-κB. In addition, MF attenuated the AP-1 luciferase activity and phosphorylation of ERK, JNK, and p38 MAP kinases. Taken together, these results suggest that the anti-inflammatory effect of MF is associated with the suppression of NO production and iNOS expression through the down-regulation of NF-κB activation and MAPK signaling pathway in LPS-stimulated RAW264.7 macrophages.

Anti-inflammatory effect of austroinulin and 6-O-acetyl-austroinulin from Stevia rebaudiana in lipopolysaccharide-stimulated RAW264.7 macrophages.

Austroinulin (AI) and 6-O-acetyl-austroinulin (6-OAAI) are natural diterpenoids isolated from Stevia rebaudiana with anti-inflammatory activity. However, the mechanisms underlying their anti-inflammatory effects are not well understood. The purpose of this study was to investigate the effect of AI and 6-OAAI on nitric oxide (NO) production and their molecular mechanism in LPS-stimulated RAW264.7 macrophages. We found that AI and 6-OAAI inhibit the production of NO, iNOS, and pro-inflammatory cytokines (TNF-α, IL-6, IL-1β, and MCP-1) in LPS-stimulated RAW264.7 macrophages. In these same cells, AI and 6-OAAI also suppressed the phosphorylation of STAT1 and the production of interferon-beta (IFN-β). Moreover, treatment with AI and 6-OAAI inhibited the activation of interferon regulatory factor-3 (IRF3) and NF-κB. Taken together, our results suggest that AI and 6-OAAI inhibit NO production and iNOS expression by blocking the activation of STAT1, IRF3, and NF-κB in LPS-stimulated RAW264.7 macrophages.

Isoegomaketone Induces Apoptosis through Caspase-Dependent and Caspase-Independent Pathways in Human DLD1 Cells

Isoegomaketone (IK) is an essential oil component of Perilla frutescens (L.), but the mechanism by which IK induces apoptosis has never been studied. The purpose of this study was to elucidate the IK-induced apoptotic pathway in DLD1 human colon cancer cells. We observed that IK treatment over 24 h significantly inhibited cell viability in a dose-dependent manner. We also found that IK triggered cleavage of PARP. Moreover, IK treatment resulted in cleavage of caspase-8, -9, and -3 in a dose- and time-dependent manner. IK treatment also resulted in cleavage of Bid and translocation of Bax, and triggered the release of cytochrome c from the mitochondria to the cytoplasm. Furthermore, it resulted in the translocation of apoptosis inducing factor (AIF), a caspase-independent mitochondrial apoptosis factor, from the mitochondria into the nucleus. Overall, these results suggest that IK induces apoptosis through caspase-dependent and capase-independent pathways in DLD1 cells.

Anti-inflammatory activity of myricetin from Diospyros lotus through suppression of NF-κB and STAT1 activation and Nrf2-mediated HO-1 induction in lipopolysaccharide-stimulated RAW264.7 macrophages

Diospyros lotus is traditionally used for the treatment of diabetes, diarrhea, tumor, and hypertension. The purpose of this study was to investigate the anti-inflammatory effect and underlying molecular mechanisms of myricetin in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Myricetin dose-dependently suppressed the production of pro-inflammatory mediators (NO, iNOS, PGE2, and COX-2) in LPS-stimulated RAW264.7 macrophages. Myricetin administration decreased the production of NO, iNOS, TNF-α, IL-6, and IL-12 in mice. Myricetin decreased NF-κB activation by suppressing the degradation of IκBα, nuclear translocation of p65 subunit of NF-κB, and NF-κB DNA binding activity in LPS-stimulated RAW264.7 macrophages. Moreover, myricetin attenuated the phosphorylation of STAT1 and the production of IFN-β in LPS-stimulated RAW264.7 macrophages. Furthermore, myricetin induced the expression of HO-1 through Nrf2 translocation. In conclusion, these results suggest that myricetin inhibits the production of pro-inflammatory mediators through the suppression of NF-κB and STAT1 activation and induction of Nrf2-mediated HO-1 expression in LPS-stimulated RAW264.7 macrophages. Graphical abstract This study has elucidated the anti-inflammatory effects of myricetin in in vitro and in vivo.

Protective effects of grape stem extract against UVB-induced damage in C57BL mice skin

Humans have become exposed to another form of a trait which is ultraviolet B (UVB) radiation reaching the earths surface. This has become a major source of oxidative stress that ultimately leads to inflammation, DNA damage, photoaging and pigmentation disorders etc. Although several studies have shown the photo-protective role of different grape parts like the fruits and seeds, little or no data demonstrating the in vivo photo-protective role of grape stem, which is the most discarded part of the grape are available. We evaluated the protective influence of grape stem extract against UVB-induced oxidative damage in C57BL mice characterized by epidermal hyperplasia, pigmentation, collagen degradation and inflammation. Grape stem extract was administered topically 1week before UVB irradiation (120mJ/cm2) and continued until the termination of the experiment. A group of non-irradiated mice and a group of irradiated mice topically administered with propylene were used as a negative and positive control. Epidermal thickness, pigmentation, erythema, mast cell and neutrophil infiltration, collagen degradation and COX-2, Nrf2, and HO-1 expressions were evaluated. Grape stem extract markedly recovered skin damage induced by the UVB radiation through the prevention of epidermal hyperplasia, pigmentation, erythema, mast cell and neutrophil infiltrations, collagen degradation and COX-2, Nrf2, and HO-1 expressions. Our study demonstrated for the first time in C57BL mice that grape stem extract reduces UVB-induced oxidative damage and hence can play a protective role in skin photo-damage.

3-deoxysilybin exerts anti-inflammatory effects by suppressing NF-κB activation in lipopolysaccharide-stimulated RAW264.7 macrophages

3-deoxysilybin (3-DS), also known as (–)-isosilandrin A, is a natural flavonoid of Silybum marianum. This study was designed to investigate the anti-inflammatory effect and the underlying molecular mechanisms of 3-DS in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. 3-DS dose-dependently inhibited the production of NO and the expression of iNOS in LPS-stimulated RAW264.7 macrophages. 3-DS also inhibited the production of pro-inflammatory cytokines (MCP-1, TNF-α, IL-6, and IL-1β) in LPS-stimulated RAW264.7 macrophages. Moreover, 3-DS decreased the NF-κB DNA binding activity in LPS-stimulated RAW264.7 macrophages. Furthermore, 3-DS suppressed NF-κB activation by inhibiting the degradation of IκBα and nuclear translocation of p65 subunit of NF-κB in LPS-stimulated RAW264.7 macrophages. Taken together, the present study suggests for the first time that 3-DS may exhibit an anti-inflammatory effect through the suppression of NF-κB transcriptional activation in LPS-stimulated RAW264.7 macrophages. Graphical Abstract Possible model for anti-inflammatory effect by 3-deoxysilybin in RAW264.7 macrophages.

Diospyros lotus leaf and grapefruit stem extract synergistically ameliorate atopic dermatitis-like skin lesion in mice by suppressing infiltration of mast cells in skin lesions

Atopic dermatitis, a chronic relapsing and pruritic inflammation of the skin also thought to be involved in, or caused by immune system destruction is an upsetting health problem due to its continuously increasing incidence especially in developed countries. Mast cell infiltration in atopic dermatitis skin lesions and its IgE-mediated activation releases various cytokines and chemokines that have been implicated in the pathogenesis of atopic dermatitis. This study was aimed at investigating synergistic anti-inflammatory, anti-pruritic and anti-atopic dermatitis effects of Diospyros lotus leaf extract (DLE) and Muscat bailey A grapefruit stem extract (GFSE) in atopic dermatitis-like induced skin lesions in mice. Combinations of DLE and GFSE inhibited TNF-α and IL-6 production more than DLE or GFSE in PMA plus calcium ionophore A23187-activated HMC-1 cells. DLE and GFSE synergistically inhibited compound 48/80-induced dermal infiltration of mast cells and reduced scratching behavior than DLE or GFSE. Furthermore, DLE and GFSE synergistically showed a stronger ameliorative effect in skin lesions by reducing clinical scores; dermal infiltration of mast cells; ear and dorsal skin thickness; serum IgE and IL-4 production in atopic dermatitis-like mice. Collectively, these results suggest that DLE and GFSE synergistically exhibit anti-atopic dermatitis effects in atopic dermatitis-like skin lesions in mice.

Cyanidin-3-glucoside ameliorates CCl4-induced liver injury in mice

The protective effect of cyanidin-3-glucoside (C3G) against carbon tetrachloride (CCl4)-induced liver injury in mice was investigated. Administration of C3G attenuated the levels of serum aspartate aminotransferase, alanine aminotransferase, and liver lipid peroxidation in CCl4-treated mice. Histopathological examination of mouse livers showed that C3G reduced the incidence of liver lesions induced by CCl4. Moreover, C3G prevented DNA damage and decreased the protein levels of γ-H2AX in CCl4-treated mouse livers. C3G also increased the activity of the antioxidant enzymes superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase, which were decreased due to CCl4 administration in CCl4-treated mouse livers. C3G inhibited the expression levels of IL-6 and iNOS in CCl4-treated mice. C3G apparently protects the liver from CCl4-induced hepatic damage through antioxidant and anti-inflammatory mechanisms.

Ameliorative effects of Diospyros lotus leaf extract against UVB-induced skin damage in BALB/c mice

The aim of this study was to investigate the protective effect of Diospyros lotus leaf extract (DLE) on UVB-induced skin damage in mice. UVB irradiation of mice skin incurred significant damage to mice skin; increased thiobarbituric acid-reactive substance level; decreased superoxide dismutase; and glutathione levels in mice skin tissues. More so, UVB irradiation led to collagen degradation and infiltration of mast cell and neutrophils into mice skin leading to inflammation. However, topical application of DLE significantly reversed these conditions with the result comparable to l-ascorbic acid. Myricitrin, gallic acid, astragalin, myricetin-3-O-glactosside, and myricetin through high-performance liquid chromatography analysis were further determined to be the primary active compounds in DLE. In conclusion, our study showed that DLE has potentials as local therapeutic materials against skin damage by inhibiting oxidative stress and UVB-induced skin damage.