5-Hydroxymethylfurfural from black garlic extract prevents TNFα-induced monocytic cell adhesion to HUVECs by suppression of vascular cell adhesion molecule-1 expression, reactive oxygen species generation and NF-κB activation.

5-Hydroxymethylfurfural (5-HMF) is a common Maillard reaction product; the reaction occurs during heat-processing and the preparation of many types of foods and beverages. Although 5-HMF has been proposed to have harmful effects, recently, its beneficial effects, including antioxidant, cytoprotective and antitumor effects have become increasingly apparent. It was found recently that a chloroform extract of aged black garlic shows antiinflammatory properties when administered to human umbilical vein endothelial cells (HUVECs). This study investigated the antiinflammatory potential of 5-HMF purified from the chloroform extract of aged black garlic in tumor necrosis factor-α (TNF-α)-stimulated HUVECs. Treatment of HUVECs with 5-HMF strongly suppressed TNF-α-induced cell surface and total protein expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular cell adhesion molecule-1 (ICAM-1) as well as their mRNA expression. In addition, 5-HMF significantly inhibited TNF-α-induced reactive oxygen species formation, and markedly reduced THP-1 monocyte adhesion to TNF-α-stimulated HUVECs. Furthermore, 5-HMF significantly inhibited NF-κB transcription factor activation in TNF-α-stimulated HUVECs. The data provide new evidence of the antiinflammatory properties of 5-HMF in support of its potential therapeutic use for the prevention and management of vascular diseases such as atherosclerosis through mechanisms involving the inhibition of VCAM-1 expression and NF-κB activation in vascular endothelial cells.

Identification of a novel compound that inhibits iNOS and COX-2 expression in LPS-stimulated macrophages from Schisandra chinensis.

A novel alpha-iso-cubebenol, which has anti-inflammatory effects in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages, was isolated from the fruits of Schisandra chinensis. alpha-iso-cubebenolinhibited LPS-induced nitric oxide (NO) and prostaglandin E(2) (PGE(2)) production. Consistent with these findings, alpha-iso-cubebenol also reduced the LPS-induced expression of inducible nitric oxide synthase and cyclooxygenase-2 at the protein and mRNA levels in a concentration-dependent manner. alpha-iso-cubebenol also inhibited LPS-induced nuclear translocation of the NF-kappaB p65 subunit. Furthermore, alpha-iso-cubebenol suppressed the phosphorylation of ERK, JNK, and p38 kinase induced by LPS. Since the novel alpha-iso-cubebenol blocked the production of several pro-inflammatory mediators induced by LPS in macrophages, the molecule can be useful material for the development of anti-inflammatory agents against bacterial infections or endotoxin.

Association between Obesity and Neighborhood Socioeconomic Status in Korean Adolescents Based on the 2013 Korea Youth Risk Behavior Web-Based Survey.

BACKGROUND: An increase in the obese adolescent population is being recognized as a serious medical and social problem. The present study aimed to examine the association between neighborhood socioeconomic status (SES) and obesity in Korean adolescents based on total available resources and local social inequality models. METHODS: The present study used data from the 2013 Korea Youth Risk Behavior Web-based Survey in analyzing 72,438 Korean adolescents aged 12-18. The analysis investigated obesity odds ratio (OR) according to neighborhood SES adjusted for age and individual SES indices, which included family affluence scale (FAS), education level of parents, cohabitation with parents, and weekly allowance. Obesity OR was investigated according to neighborhood SES by FAS, and according to FAS by neighborhood SES. RESULTS: After adjusting for age and individual SES variables, there was no significant association between neighborhood SES and adolescent obesity for either boys or girls. However, girls in the high FAS group showed a pattern of lower neighborhood SES being associated with a significant increase in risk of obesity; in the high neighborhood SES group, boys showed a pattern of higher FAS being associated with a significant increase in risk of obesity, whereas girls show a pattern of decrease. CONCLUSION: Although limited, the present study demonstrated that some girl groups exhibited a pattern of lower neighborhood SES being associated with an increase in risk of obesity, as well as a gender-based difference in risk of obesity by individual SES. Therefore, measures to prevent adolescent obesity should be established with consideration for differences in risk according to individual and neighborhood SES.

The Relationship between Body Fat Percent and Bone Mineral Density in Korean Adolescents: The Fifth Korea National Health and Nutrition Examination Survey (KNHANES V-1), 2010.

BACKGROUND: The relationships of total and regional body fat percent with bone mineral density (BMD) in Korean adolescents were examined using the Fifth Korea National Health and Nutrition Examination Survey (KNHANES V-1), 2010. METHODS: Body fat percent at whole body (WBFP), trunk (TBFP), and extremities (both upper and lower extremities fat mass/body weight, EBFP), ratio of trunk fat mass to extremities fat mass (TEFR), and BMD at whole body, total femur, and lumbar spine were measured by dual energy X-ray absorptiometry in a population-based sample of 433 boys and 362 girls, aged 12 to 18 years. The analyses were conducted using linear regression analysis with complex sampling design. RESULTS: After adjusting for confounders such as age, height, weight, serum 25-(OH) vitamin D concentration, energy intake, calcium intake, physical activity, and menarche status for girls, WBFP, TBFP, and EBFP were inversely associated with whole and regional BMD in both sexes (P < 0.05). TEFR was positively associated with whole and regional BMD in boys after adjusting for confounders, while it was negatively associated in girls (P < 0.05). However, the associations were non-significant when bone mass-free lean mass was adjusted instead of bodyweight except for a positive association between TEFR and BMD in boys. CONCLUSION: In Korean adolescents, total and regional body fat percent is not independently associated with BMD after adjusting for bone mass-free lean mass but higher fat in trunk as compared to extremities may be protective for BMD in boys.

In vitro and in vivo anticancer effects of Lithospermum erythrorhizon extract on B16F10 murine melanoma.

ETHNOPHARMACOLOGICAL RELEVANCE: Lithospermum erythrorhizon has long been used in traditional Asian medicine for the treatment of diseases including skin cancer. In this study, hexane extract from the roots of Lithospermum erythrorhizon (LEH) was chemically characterized and its anticancer activity was tested against the most aggressive form of skin cancer. MATERIALS AND METHODS: The in vitro anticancer studies viz. cell growth, cell cycle and apoptosis, and the expression of tumor regulating proteins were analyzed against B16F10 melanoma cells. In addition, C57BL/6 mice models were used to evaluate the in vivo anticancer potential of LEH. Mice were intraperitoneally injected with LEH at doses of 0.1 and 10mg/kg every 3 days. The tumor inhibition ratio was determined after 21 days of treatment and the histopathological analyses of the tumor tissues were compared. Further, LEH was purified and its active compounds were structurally elucidated and identified by NMR spectra and quantified by HPLC analyses. RESULTS: LEH effectively inhibits the growth of melanoma cells with an IC(50) of 2.73µg/ml. Cell cycle analysis revealed that LEH increased the percentage of cells in sub-G1 phase by dose dependent manner. LEH exhibited down regulation of anti-apoptotic Bcl-2 family proteins and up regulation of apoptotic Bax protein expression. Importantly, LEH induced cleavage of poly (ADP-ribose) polymerase (PARP) and activated the caspase cascade (caspase 3) with this cleavage mediating the apoptosis of B16F10 cells. LEH treatment at a dose of 10mg/kg for 21 days in experimental mice implanted with tumors resulted in significant reduction of the tumor growth (43%) and weight (36%). Histopathology analysis of LEH treated tumor tissues showed evidence of increased necrotic cells in a concentration dependent manner. Meanwhile, five naphthoquinone compounds [Shikonin (1); Deoxyshikonin (2); ß-Hydroxyisovalerylshikonin (3); Acetylshikonin (4) and Isobutyrylshikonin (5)] were purified from LEH and responsible for its anticancer activity. CONCLUSION: LEH induced apoptosis in B16F10 cells by activation of caspase 3 and inducing sub-G1 cell cycle arrest. LEH exhibited both in vitro and in vivo anticancer activity. Shikonin derivatives in the LEH are responsible for the anticancer activity.

Schisandra chinensis α-iso-cubebenol induces heme oxygenase-1 expression through PI3K/Akt and Nrf2 signaling and has anti-inflammatory activity in Porphyromonas gingivalis lipopolysaccharide-stimulated macrophages.

Heme oxygenase-1 (HO-1) is a potent anti-inflammatory molecule that regulates pro-inflammatory mediators. Several studies have indicated that HO-1 expression is induced by a variety of stimuli such as lipopolysaccharide (LPS), cytokines, oxidative stress, and antioxidant phytochemicals. In this study, we assessed the anti-inflammatory effects of a novel α-iso-cubebenol isolated from dried fruits of Schisandra chinensis in human macrophage THP-1 cells and investigated the involvement of HO-1 signaling. We first observed that α-iso-cubebenol induced HO-1 mRNA and protein expression in a dose- and time-dependent manner via activation of erythroid-specific nuclear factor-regulated factor 2 (Nrf2). We also found that α-iso-cubebenol induced phosphorylation of phosphoinositide 3-kinase (PI3K)/Akt and extracellular-regulated kinase (ERK) in a time-dependent manner. Furthermore, treatment of THP-1 cells with inhibitors and siRNA specific for PI3K/Akt and ERK decreased the expression of HO-1. These results suggested that α-iso-cubebenol induced HO-1 expression through the activation of PI3K/Akt, ERK, and Nrf2 signaling. Next, α-iso-cubebenol strongly inhibited Porphyromonas gingivalis LPS-stimulated pro-inflammatory cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, and IL-12). Moreover, we observed that α-iso-cubebenol treatment inhibited nuclear levels and activity of NF-κB in a dose-dependent manner. Additionally, treatment with tin-protoporphyrin (SnPP), a selective inhibitor of HO-1, reversed the α-iso-cubebenol-mediated inhibition of P. gingivalis LPS-induced pro-inflammatory cytokines. Hence, α-iso-cubebenol might induce anti-inflammatory effects on P. gingivalis LPS-stimulated human THP-1 macrophages by mediating the activation of PI3k/Akt and ERK that leads to over-expression of HO-1 and Nrf-2. These findings suggest that α-iso-cubebenol may be considered as a novel therapeutic agent to ameliorate periodontitis.

Anti-inflammatory effect of heme oxygenase-1 toward Porphyromonas gingivalis lipopolysaccharide in macrophages exposed to gomisins A, G, and J.

Periodontitis, a chronic inflammatory periodontal disease that develops from gingivitis, is caused by periodontal pathogenic bacteria such as Porphyromonas gingivalis. Recent studies have focused on the antioxidant, anti-human immunodeficiency virus, anticarcinogenic, and anti-inflammatory properties of gomisins. However, the anti-inflammatory activities of gomisin plants through heme oxygenase-1 (HO-1) signals remain poorly defined. We found that gomisins' anti-inflammatory activity occurs via the induction of HO-1 expression. Gomisins G and J inhibit the production of the pro-inflammatory cytokines tumor necrosis factor-α, interleukin-1ß, and interleukin-6 and also block nuclear factor-κB activation in Raw264.7 cells stimulated with P. gingivalis lipopolysaccharide. Furthermore, pro-inflammatory cytokine production is inhibited through the induction of HO-1 expression. HO-1 expression is induced by all gomisins, but their anti-inflammatory activity via HO-1 signaling is observed with gomisins G and J, and not A. We found that gomisins G and J extracted from Schisandria chinensis can inhibit the P. gingivalis lipopolysaccharide induced-inflammatory responses in Raw264.7 cells.

Upregulation of heme oxygenase-1 via PI3K/Akt and Nrf-2 signaling pathways mediates the anti-inflammatory activity of Schisandrin in Porphyromonas gingivalis LPS-stimulated macrophages.

The lipopolysaccharide (LPS) of Porphyromonas gingivalis is thought to induce periodontitis. In this study, we isolated Schisandrin from the dried fruits of Schisandra chinensis and examined the anti-inflammatory effect of Schisandrin in macrophages stimulated with LPS from P. gingivalis. First, Schisandrin inhibited LPS-induced pro-inflammatory cytokines, including TNF-α, IL-1ß, and IL-6. And Schisandrin suppressed the nuclear translocation and activity of NF-κB and phosphorylation of IκBα in LPS-stimulated RAW 264.7 cells. Next, the presence of a selective inhibitor of HO-1 (SnPP) and a siRNA specific for HO-1 inhibited Schisandrin-mediated anti-inflammatory activity. Furthermore, Schisandrin induced HO-1 expression of RAW 264.7 cells through Nrf-2, PI3K/Akt, and ERK activation. Therefore, these results suggest that the anti-inflammatory effects of Schisandrin on P. gingivalis LPS-stimulated RAW 264.7 cells may be due to a reduction of NF-κB activity and induction of the expression of HO-1, leading to TNF-α, IL-1ß, and IL-6 down-regulation.

Apoptosis induction of human leukemia U937 cells by gomisin N, a dibenzocyclooctadiene lignan, isolated from Schizandra chinensis Baill.

We compared the pro-apoptotic effect of two dibenzocyclooctadiene lignans, gomisin A and gomisin N, isolated from Schizandra chinensis Baill, in U937 human promyelocytic leukemia cells in vitro. Gomisin N, but not gomisin A, inhibited cell growth in a dose-dependent manner, which was associated with the induction of apoptosis. The increase in apoptosis that was induced by gomisin N was correlated with down-regulation of anti-apoptotic Bcl-2 expression, a decrease in the mitochondrial membrane potential (MMP) and a release of cytochrome c from the mitochondria into the cytosol. Furthermore, gomisin N induced the proteolytic activation of caspase-9 and -3 and a concomitant degradation of poly(ADP-ribose) polymerase. However, caspase-8 was not activated and cleavage of Bid was not observed in gomisin N-treated U937 cells. The cytotoxic effects and apoptotic characteristics induced by gomisin N were significantly inhibited by z-DEVD-fmk, a caspase-3 inhibitor, demonstrating the important role that caspase-3 plays in the process. We conclude that gomisin N induces the apoptosis of U937 cells through a signaling cascade of mitochondria-mediated intrinsic caspase pathways and gomisin N may be a useful chemotherapeutic agent.