Haeng Jeon Hur

Quercetin, the active phenolic component in kiwifruit, prevents hydrogen peroxide-induced inhibition of gap-junction intercellular communication

We evaluated the effects of the two main kiwifruit cultivars (gold kiwifruit (GOK) and green kiwifruit (GRK)) and their active phenolic compound, quercetin, on H2O2-induced inhibition of gap-junction intercellular communication (GJIC) in WB-F344 rat liver epithelial cells. We found that both GOK and GRK protect WB-F344 cells from H2O2-induced inhibition of GJIC. The extracellular signal-regulated protein kinase 1/2 (ERK1/2)-connexin 43 (Cx43) signalling pathway is crucial for the regulation of GJIC, and both GOK and GRK blocked the H2O2-induced phosphorylation of Cx43 and ERK1/2 in WB-F344 cells. Quercetin alone attenuated the H2O2-mediated ERK1/2-Cx43 signalling pathway and consequently reversed H2O2-mediated inhibition of GJIC in WB-F344 cells. A free radical-scavenging assay using 1,1-diphenyl-2-picrylhydrazyl showed that the scavenging activity of quercetin was higher than that of a synthetic antioxidant, butylated hydroxytoluene, per mol, suggesting that the chemopreventive effect of quercetin on H2O2-mediated inhibition of ERK1/2-Cx43 signalling and GJIC may be mediated through its free radical-scavenging activity. Since the carcinogenicity of reactive oxygen species such as H2O2 is attributable to the inhibition of GJIC, GOK, GRK and quercetin may have chemopreventive potential by preventing the inhibition of GJIC.

Phenolic Phytochemicals Derived from Red Pine (Pinus densiflora) Inhibit the Invasion and Migration of SK‐Hep‐1 Human Hepatocellular Carcinoma Cells

Abstract:  Considerable attention has recently been focused on identifying chemopreventive phytochemicals derived from medicinal plants. Here, we analyzed phenolic phytochemicals from red pine (RP) leaves and found epigallocatechin gallate (EGCG) and epigallocatechin (EGC), and catechin gallate (CG) as their major phenolic phytochemicals. This article also investigated whether RP leaf extract and its phenolic phytochemicals inhibit the invasion of SK‐Hep‐1 human hepatocellular carcinoma cells (SK‐Hep‐1 cells). RP suppressed the invasion and the migration of SK‐Hep‐1 cells. EGCG and CG also inhibited the invasion and migration, with EGC exhibiting a lower efficacy. Matrix metalloproteinases (MMPs), particularly gelatinase‐A (MMP‐2) and gelatinase‐B (MMP‐9), degrade components of the basement membrane and are strongly implicated in invasion and metastasis formation of malignant tumors. RP suppressed both MMP‐2 and MMP‐9 activities. EGCG and CG reduced the activities of MMP‐9 and MMP‐2 in a dose‐dependent manner, with EGC exhibiting a lower efficacy on both MMPs. Our results suggest that RP inhibits tumor invasion and migration, which may be attributed to the effects of EGCG and CG. In particular, EGCG plays a key role in the efficacy of RP against hepatocarcinogenesis.

Peonidin inhibits phorbol-ester-induced COX-2 expression and transformation in JB6 P+ cells by blocking phosphorylation of ERK-1 and -2

Abstract:  Abnormal upregulation of cyclooxygenase‐2 (COX‐2) has been frequently observed in various types of transformed and cancerous cells. Numerous anti‐inflammatory agents have been shown to exert chemopreventive effects by targeting COX‐2, a rate‐limiting enzyme involved in the inflammatory process. Anthocyanins are naturally occurring polyphenolic compounds that endow various fruits, vegetables, and plants with intense colors. Peonidin is another representative anthocyanidin, but its chemopreventive potential has not been fully described. This article investigated the effect of peonidin on 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA)‐induced COX‐2 expression and transformation in JB6 P+ mouse epidermal cells (JB6 P+ cells). Treatment of JB6 P+ cells with peonidin inhibited TPA‐induced COX‐2 expression, and also decreased TPA‐induced neoplastic transformation and blocked TPA‐induced phosphorylation of extracellular signal‐regulated kinases (ERKs) in the cells. The inhibition of the signaling mechanism regulating the activation of ERKs strongly suggests that peonidin exhibits chemopreventive as well as anti‐inflammatory activities.

Honokiol Improves Liver Steatosis in Ovariectomized Mice

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease, and is associated with the development of metabolic syndrome. Postmenopausal women with estrogen deficiency are at a higher risk of progression to NAFLD. Estrogen has a protective effect against the progression of the disease. Currently, there are no safe and effective treatments for these liver diseases in postmenopausal women. Honokiol (Ho), a bioactive natural product derived from Magnolia spp, has anti-inflammatory, anti-angiogenic, and anti-oxidative properties. In our study, we investigated the beneficial effects of Ho on NAFLD in ovariectomized (OVX) mice. We divided the mice into four groups, as follows: SHAM, OVX, OVX+β-estradiol (0.4 mg/kg of bodyweight), and OVX+Ho (50 mg/kg of diet). Mice were fed diets with/without Ho for 12 weeks. The bodyweight, epidermal fat, and weights of liver tissue were lower in the OVX group than in the other groups. Ho improved hepatic steatosis and reduced proinflammatory cytokine levels. Moreover, Ho markedly downregulated plasma lipid levels. Our results indicate that Ho ameliorated OVX-induced fatty liver and inflammation, as well as associated lipid metabolism. These findings suggest that Ho may be hepatoprotective against NAFLD in postmenopausal women.

Studies on the Anti-Oxidative Function of trans-Cinnamaldehyde-Included β-Cyclodextrin Complex

trans-Cinnamaldehyde (tCIN), an active compound found in cinnamon, is well known for its antioxidant, anticancer, and anti-inflammatory activities. The β-cyclodextrin (β-CD) oligomer has been used for a variety of applications in nanotechnology, including pharmaceutical and cosmetic applications. Here, we aimed to evaluate the anti-inflammatory and antioxidant effects of tCIN self-included in β-CD complexes (CIs) in lipopolysaccharide (LPS)-treated murine RAW 264.7 macrophages. RAW 264.7 macrophages were treated with increasing concentrations of β-CD, tCIN, or CIs for different times. β-CD alone did not affect the production of nitric oxide (NO) or reactive oxygen species (ROS). However, both tCIN and CI significantly reduced NO and ROS production. Thus, CIs may have strong anti-inflammatory and antioxidant effects, similar to those of tCIN when used alone.