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Epigallocatechin-3-gallate (EGCG), a main catechin of green tea, has been suggested to inhibit hepatic gluconeogenesis. However, the exact role and related mechanism have not been established, In this study, we examined the role of EGCG in hepatic gluconeogenesis at concentrations that are reachable by ingestion of pure EGCG or green tea, and are not toxic to hepatocytes. Our results show in isolated hepatocytes that EGCG at relatively low concentrations (≤1 μM) inhibited glucose production via gluconeogenesis and expression of key gluconeogenic genes. EGCG was not toxic at these concentrations while demonstrating significant cytotoxicity at 10 μM and higher concentrations. EGCG at 1 μM or lower concentrations effective in suppressing hepatic gluconeogenesis did not activate the insulin signaling pathway, but activated 5′-AMP-activated protein kinase (AMPK). The EGCG suppression of hepatic gluconeogenesis was prevented by blockade of AMPK activity. In defining the mechanism by which EGCG activates AMPK, we found that the EGCG activation of AMPK was mediated by the Ca2+/calmodulin-dependent protein kinase kinase (CaMKK). Furthermore, our results show that the EGCG activation of AMPK and EGCG suppression of hepatic gluconeogenesis were both dependent on production of reactive oxygen species (ROS), which was a known activator of CaMKK. Together, our results demonstrate an inhibitory role for EGCG in hepatic gluconeogenesis and shed new light on the mechanism by which EGCG suppresses gluconeogenesis. [ABSTRACT FROM AUTHOR]

• A dammarane derivative (4-XL-PPD) was obtained by structural modification. • 4-XL-PPD showed much better anticancer activity than original compound AD-2 on cancer cells. • 4-XL-PPD-induction of apoptosis of can be attenuated by the ROS scavenger N-acetylcysteine in gastric carcinoma cells. • 4-XL-PPD inhibits migratory and invasive. (20 R)-Dammarane-3 β , 12 β , 20, 25-tetrol (25-OH-PPD) is a ginsenoside isolated from Panax ginseng (C. A. Meyer). Previous research shows that the compound exhibits anti-cancer activities on many human cancer cell lines. In an attempt to enhance 25-OH-PPD activity, some derivatives were synthesized. Through screening of the derivative compounds for anti-cancer activity against gastric carcinoma cells, 12 β - O -(L-Chloracetyl)-dammar-20(22)-ene-3 β , 25-diol (4-XL-PPD) was selected as a strong anti-cancer agent. In this study, the anti-cancer mechanisms of 4-XL-PPD were investigated. The results showed that compound 4-XL-PPD resulted in a concentration-dependent inhibition of cells viability in gastric cancer cells, without affecting the viability of normal cell (human gastric epithelial cell line-GES-1). In BGC-803 cancer cells, 4-XL-PPD triggered apoptosis, and stimulated reactive oxygen species production. Apoptosis can be attenuated by the reactive oxygen species scavenger N-acetylcysteine. Meantime, 4-XL-PPD effectively suppressed the migratory and invasive capabilities of BGC-803 cancer cell and inhibited the expression levels of proteins associated with migratory and invasive capabilities (MMP-2, MMP-9, E-cadherin and CD34). All the results suggest that 4-XL-PPD exhibited remarkable anticancer activity base on inducing apoptosis via generating reactive oxygen species and inhibiting migratory and invasive, which support development of 4-XL-PPD as a potential agent for cancer therapy. [ABSTRACT FROM AUTHOR]

(20R)-Dammarane-3 β , 12 β , 20, 25-tetrol (25-OH-PPD) is a ginsenoside isolated from Panax ginseng (C. A. Meyer). This compound exhibits anti-cancer activities on many human cancer cell lines. In this study, we investigated anti-cancer mechanisms of 12 β - O -( L -Chloracetyl)-dammar-20(22)-ene-3 β ,25-diol(12-Chloracetyl-PPD), a modified 25-OH-PPD. We found that compound 12-Chloracetyl-PPD resulted in a concentration-dependent inhibition of viability in prostate, breast, and gastric cancer cells, without affecting the viability of normal cell (human gastric epithelial cell line-GES-1, hair follicle dermal papilla cell line-HHDPC and rat myocardial cell line-H9C2). In MDA-MB-435 and C4-2B cancer cells, 12-Chloracetyl-PPD induced G2/M cell cycle arrest, down-regulated mouse double minute 2 (MDM2) expression, up-regulated p53 expression, triggered apoptosis, and stimulated reactive oxygen species production. Apoptosis can be attenuated by the reactive oxygen species scavenger N-acetylcysteine. Our results suggested that compound 12-Chloracetyl-PPD showed obvious anti-cancer activity based on delaying cell cycle arrest and inducing cell apoptosis by reactive oxygen species production, which supported development of 12-Chloracetyl-PPD as a potential agent for cancer chemotherapy. [ABSTRACT FROM AUTHOR]

A novel monolithic tree-branch-like copper-manganese oxides nanoarrays have been fabricated, exhibiting excellent periodate activation efficiency for the degradation of organic pollutants by synergistic effect between reduced copper and mixed-valence manganese species. [Display omitted] • A novel monolithic tree-branch-like copper-manganese oxides nanoarrays (CMM) was fabricated. • The Fenton-like microreactor CMM exhibits excellent catalytic activity for degradation of organic pollutants. • O 2 −, 1O 2 and OH were the major reactive radicals for 4-CP degradation in the CMM/NaIO 4 system. • The positive synergistic effect between reduced copper and mixed-valence manganese species for IO 4 - activation. Recently, considerable attention has been paid to develop novel Fenton-like oxidation systems for environmental remediation. The activation of periodate (NaIO 4) is a desirable oxidation process that drive redox reactions to produce abundant reactive oxygen species (ROS) by a suitable activator. This study reports a simple hydrothermal-calcination route for forming novel tree-branch-like copper-manganese oxides (CuMnO x @MnO x , CMM) nanoarrays, and the production of radical species from NaIO 4 induced by CMM for the removal of rhodamine B and 4-chlorophenol from wastewater. The synergistic effects of Cu oxides and Mn oxides composite significantly elevated the activation of periodate, exhibited excellent degradation performance in the CMM/NaIO 4. Furthermore, reduced copper species and mixed-valence manganese species play a major role in reaction via XPS analysis. Additionally, the underlying degradation mechanism of this work was systematically researched by radical quenching tests and EPR analysis. Superoxide anion radical (O 2 −) was the major free radicals in this system, simultaneously the production of non-radical singlet oxygen (1O 2) via the electron transfer, which are contributed to remove organic pollutants. This work provides a facile way for fabricating monolithic multi-component metal oxides, and new insights into understand activation mechanism of manganese-based periodate activator. [ABSTRACT FROM AUTHOR]