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The hepatoprotective effect of 10% ethanolic extract of Curdrania tricuspidata (CTE) was investigated in HepG2/2E1 cells and C57BL/6 J mice. When compared ethanol-only treated HepG2/2E1 cells, pretreatment of CTE prevented increased intra-cellular reactive oxygen species levels and decreased antioxidant activities by ethanol-induced oxidative stress. In C57BL/6 J mice, CTE at a dose of 250 mg/kg/day was administered for 10 days, with ethanol (5 g/kg/day) administered for the final 3 days. Pretreatment with CTE prevented the elevated activities of serum aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase caused by ethanol-induced hepatic damage. CTE-treated mice displayed a reduced level of malondialdehyde and increased antioxidant activities of catalase, glutathione S-transferase, glutathione peroxidase, and superoxide dismutase, as well as a reduced level of glutathione as compared with ethanol-only-treated mice. CTE-treated mice exhibited significant inhibition of CYP2E1 activities and expression. These results suggest that CTE could be a useful agent for the prevention of ethanol-induced oxidative damage in the liver, elevating antioxidative potentials and alleviating oxidative stress by suppressing CYP2El.

Histone acetyltransferase (HAT) inhibitors (HATi) isolated from dietary compounds have been shown to suppress inflammatory signaling, which contributes to rheumatoid arthritis. Here, we identified a novel HATi in Punica granatum L. known as delphinidin (DP). DP did not affect the activity of other epigenetic enzymes (histone deacetylase, histone methyltransferase, or sirtuin1). DP specifically inhibited the HAT activities of p300/CBP. It also inhibited p65 acetylation in MH7A cells, a human rheumatoid arthritis synovial cell line. DP-induced hypoacetylation was accompanied by cytosolic accumulation of p65 and nuclear localization of IKBα. Accordingly, DP treatment inhibited TNFα-stimulated increases in NF-κB function and expression of NF-κB target genes in these cells. Importantly, DP suppressed lipopolysaccharide-induced pro-inflammatory cytokine expression in Jurkat T lymphocytes, demonstrating that HATi efficiently suppresses cytokine-mediated immune responses. Together, these results show that the HATi activity of DP counters anti-inflammatory signaling by blocking p65 acetylation and that this compound may be useful in preventing inflammatory arthritis.

Perilla frutescens is an annual herbaceous plant native to Asia, where its leaves are used in Asian gourmet food. Our previous study showed that the inhibition of γ-glutamylcysteine synthetase (γ-GCS) activity was remarkably recovered by pretreatment with perilla leaf extract (PLE). The objective was to fractionise PLE, and to identify the active component that is responsible for the enhancement of γ-GCS activity and glutathione (GSH) concentration. Among the five fractions from PLE, PLE-III of the ethyl acetate fraction showed the highest γ-GCS activity in a HepG2 cell experiment, and was further chromatographed. The purified compound, which enhanced γ-GCS activity, was finally identified as caffeic acid. We first report the enhancement of γ-GCS activity and GSH level in HepG2 cells by caffeic acid obtained from PLE. Our results suggest that caffeic acid may be a key factor in the chemopreventive potential of perilla leaf components by increasing de novo synthesis of GSH.

Ethnopharmacological relevance: Rosa rugosa Thunb. (Rosaceae) has been traditionally used for treatments of diabetes, chronic inflammatory diseases, pain, and anticancer in Korea. Aim of study: We investigate the inhibitory effect of histone acetyltransferase activity from the methanol extract of stems of Rosa rugosa on androgen receptor-mediated transcriptional regulation. Materials and methods: For the present study, Rosa rugosa methanol extract (RRME) was obtained from stem part of Rosa rugosa using methanol extraction. Histone acetyltransferase assay were performed to measure the inhibitory effect on acetylation, reporter assay, real-time PCR and ChIP assay were performed to measure androgen receptor-mediated transcriptional regulation, and MTT test were performed to measure cell viability. Results: RRME inhibited both p300 and CBP (60–70% at 100g/ml) activity. We show RRME mediates agonist-dependent androgen receptor (AR) activation and suppresses antagonist-dependent inhibition. RRME treatment also decreased transcription of AR regulated genes and also reduced histone H3 and AR acetylation in the promoters of prostate-specific antigen (PSA) and -2-microglobulin (B2M). Finally, RRME treatment reduced the growth of LNCaP, a human prostate cancer cell line. Conclusion: These results demonstrate RRME is a potent HAT inhibitor, which reduced AR and histone acetylation leading to decreased AR-mediated transcription and reduced LNCaP cell growth. © 2008 Elsevier Ireland Ltd. All rights reserved.

Oxidative damage is implicated in the pathogenesis of various liver injuries. In the present study the ability of Pycnogenol (PYC) as an antioxidant to protect against CCl4-induced oxidative stress and hepatotoxicity in rats was investigated. Four experimental groups of six rats each were constructed: a vehicle control group received the respective vehicles (distilled water and corn oil) only; a CCl4 group received a 14-day repeated intraperitoneal (i.p.) dose of distilled water and then a single oral dose of CCl4 at 1.25 ml/kg; and the CCl4&PYC 10 and CCl4&PYC 20 groups received a 14-day repeated i.p. dose of PYC 10 and 20 mg/kg, respectively, and then a single oral dose of CCl4 at 1.25 ml/kg. Hepatotoxicity was assessed 24 h after the CCl4 treatment by measurement of serum aminotransferase (AST) and alanine aminotransferase (ALT) activities, hepatic malondialdehyde (MDA) and glutathione (GSH) concentrations, and catalase, superoxide dismutase (SOD), and glutathione-S-transferase (GST) activities. The results were confirmed histopathologically. The single oral dose of CCl4 produced significantly elevated levels of serum AST and ALT activities. Histopathological examinations showed extensive liver injuries, characterized by extensive hepatocellular degeneration/necrosis, fatty changes, inflammatory cell infiltration, congestion, and sinusoidal dilatation. In addition, an increased MDA concentration and decreased GSH, catalase, SOD, and GST were observed in the hepatic tissues. On the contrary, PYC treatment prior to the administration of CCl4 significantly prevented the CCl4-induced hepatotoxicity, including the elevation of serum AST and ALT activities and histopathological hepatic lesions, in a dose-dependent manner. Moreover, MDA and GSH levels and catalase, SOD, and GST activities in hepatic tissues were not affected by administration of CCl4, indicating that the pretreatment of PYC efficiently protects against CCl4-induced oxidative damage in rats. The results indicate that PYC has a protective effect against acute hepatotoxicity induced by the administration of CCl4 in rats, and that the hepatoprotective effects of PYC may be due to both the inhibition of lipid peroxidation and the increase of antioxidant activity.

In this study, two quercetin-α- d -glucopyranosides were synthesized via the acceptor reaction of a glucansucrase obtained from Leuconostoc mesenteroides B-1299CB, with quercetin and sucrose. The two transfer products were purified via HPLC, and the structures of the products were identified as quercetin-4′-O-α- d -glucopyranoside (Q-G1) and quercetin-3′-O-α- d -glucopyranoside (Q-G1′), in accordance with the results of 1H, 13C, HSQC, H-H COSY, HMBC analyses. The primary product (Q-G1) evidenced slower effects on DPPH radical-scavenging activity (SC50 = 25.2 μM) than was seen with quercetin (SC50 = 6.5 μM). The water solubility of Q-G1 was 12.7 mM, whereas the quercetin was barely soluble in water. The Ki value of Q-G1 (674.5 μM) was almost identical to that of quercetin (673.3 μM) with regard to tyrosinase inhibition effects.

For the overproduction of 5-aminolevulinic acid (ALA) from recombinant Escherichia coli, the inhibition of ALA dehydratase on both small scale by using an eppendorf tube, and on a large scale by using a fermenter, the in vitro glycation and the inactivation of enzymes on the ALA dehydratase under several experimental conditions were investigated. The presence of 0.5–10 mM of d -glucose caused a concentration-dependent inhibition of recombinant E. coli ALA dehydratase activity. The ALA dehydratase levels were dependent on the pH of the medium, with the maximal activities occurring at 8.0. The inhibition constant, Ki, of intracellular ALA dehydratase by d -glucose and levulinic acid (LA) were 1.02 and 0.32 mM, respectively. The addition of 10 mM of d -glucose drastically inhibited the ALA dehydratase activity (85% inhibition), in turn, the highest level of extracellular ALA production (3.8 g/l) was achieved. Based upon those results, we concluded that d -glucose decreased the ALA dehydratase activity both by the competitive inhibition with substrate and by the inactivation of enzyme protein, and that the inactivation of ALA dehydratase by d -glucose may require glycation metabolism of d -glucose at least in part.