In this paper, the hepatoprotective effects of 2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone (DMC) on CCl(4)-induced acute liver injury in Kunming mice were investigated. DMC was administered intraperitoneally (ip) (5, 10, or 20 mg/kg of body weight) for 7 days prior to the administration of CCl(4) (0.1%, ip). Pretreatment with DMC significantly decreased activities of serum hepatic enzymes, namely alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, alkaline phosphatase, γ-glutamyl transferase, and total bilirubin, and decreased the elevation of lipid peroxidation, malondialdehyde, reactive oxygen species, and protein carbonyl content. Pretreatment with DMC markedly increased activities of enzymatic antioxidants such as superoxide dismutase, catalase, glucose-6-phosphate dehydrogenase, glutathione peroxidase, glutathione S-transferase, and glutathione reductase and increased levels of nonenzymatic antioxidant markers such as reduced glutathione, total sulfhydryl groups, vitamin C, and vitamin E in liver. These results combined with liver histopathology demonstrate that DMC has potential hepatoprotective effects, which may be related to the attenuation of oxidative stress, accelerating the antioxidant cascade and inhibition of lipid peroxidation.

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Glucokinase (GK) activity, which is rapidly regulated by glucokinase regulatory protein (GKRP) in the liver, is crucial for blood glucose homeostasis. In this paper, the GK activation mechanisms of 1-deoxynojrimycin (DNJ), resveratrol (RES), oxyresveratrol (OXY), cyanidin-3-glucoside (C3G), and cyanidin-3-rutinoside (C3R) were compared. The results revealed that DNJ, RES, C3G, and C3R could differently improve glucose consumption and enhance intracellular GK activities. DNJ and RES significantly promoted GK translocation at 12.5 μM, whereas other ingredients showed moderate effects. DNJ, C3G, and C3R could rupture intramolecular hydrogen bonds of GK to accelerate its allosteric activation at early stage. RES and OXY could bind to a "hydrophobic pocket" on GK to stabilize the active GK at the final stage. Otherwise, RES, OXY, C3G, and C3R could interact with GKRP at the F1P binding site to promote GK dissociation and translocation. Enzymatic assay showed that RES (15-50 μM) and OXY (25-50 μM) could significantly enhance GK activities, which was caused by their binding properties with GK. Moreover, the most dramatic up-regulation effects on GK expression were observed in C3G and C3R groups. This work expounded the differences between GK activation mechanisms, and the new findings would help to develop new GK activators.

Context: Melanin plays an important role in preventing skin photoageing by blocking ultraviolet B (UVB). However, East Asian women prefer light and fair skin, therefore they want to keep their skin from photoageing and at the same time reduce the melanin in their skin. Chrysin is a kind of natural flavonoid with luxurious biological activities, which has a very promising effect on achieving this goal. Objective: To elucidate the effects and mechanisms of chrysin on photoageing and melanogenesis. Materials and methods: Human dermal fibroblasts (HDF) and B16 murine melanoma cells were incubated with chrysin (0-25 lM) for 48 h. Anti-photoageing activity was examined in HDF by assessment of synthesis/degradation of collagen I, antioxidative and antisenescent activities through ELISA and colorimetric method. Anti-melanogenesis activity was tested by assessment of melanin, tyrosinase (TYR), melanogenic proteins inhibition activities in B16 cells using colorimetric and ELISA method. Results: Chrysin increased collagen I secretion (50-121.54% at 6.25-25 lM) and chrysin showed anti-photoageing activity by decreasing the degradation of collagen I, repairing oxidation damage and reducing the rate of HDF senescence. Furthermore, chrysin exhibited inhibitory activities with 3.00-20.35% reduction of melanin content at 6.25-25 lM, and inhibited melanin synthesis through the inhibition of TYR activity and the suppression of melanogenic proteins (TYR, TYR-related protein-1/2 and microphthalmia-associated transcription factor) expressions. Discussion and conclusion: Chrysin may have potential for developing a functional cosmetic agent because of its anti-photoageing and anti-melanogenesis activities. ARTICLE HISTORY

A previous study reported that 2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone (DMC) had a potential hepatoprotective effect through preventing acute liver injury in mice. This study further evaluated the preventive effects of DMC on lipopolysaccharide (LPS)-stimulated hepatic inflammation and the underlying mechanism in liver macrophage. DMC significantly suppressed LPS-stimulated secretion and nucleocytoplasmic translocation of high-mobility group box 1 (HMGB1). DMC could dose-dependently reduce the phosphorylation of phosphatidylinositol 3-kinase (PI3K), protein kinase C alpha (PKCα), and phosphoinositide-dependent kinase 1 (PDK1). Furthermore, HMGB1 phosphorylation, the interaction between PKC and HMGB1, and the expression of HMGB1-dependent inflammation-related molecules were dose-dependently inhibited by DMC. Finally, DMC could target binding to the B box of HMGB1 by molecular modeling studies. All of these results indicated that DMC exhibited a potential protective effect against hepatitis probably via inhibiting HMGB1 secretion and blocking HMGB1 pro-inflammatory activity.