Antilipotoxicity Activity of Osmanthus fragrans and Chrysanthemum morifolium Flower Extracts in Hepatocytes and Renal Glomerular Mesangial Cells.

The excess influx of free fatty acids (FFAs) into nonadipose tissues, such as those of liver and kidney, induces lipotoxicity leading to hepatic steatosis and renal dysfunction. The aim of this study was to investigate the protective effects of methanolic flower extracts of Osmanthus fragrans (OF) and Chrysanthemum morifolium (CM) against FFA-induced lipotoxicity in hepatocytes (human HepG2 cells) and renal glomerular mesangial cells (mouse SV40-Mes13 cells). The results showed that OF and CM significantly suppressed FFA-induced intracellular triacylglycerol accumulation via partially inhibiting the gene expression of sterol regulatory element-binding protein-1c (SREBP-1c) and glycerol-3-phosphate acyltransferase (GPAT) in HepG2 cells. Both extracts inhibited reactive oxygen species (ROS) generation by FFA-stimulated HepG2 cells. OF and CM also suppressed the mRNA expression of interleukin- (IL-) 1ß, IL-6, IL-8, tumor necrosis factor- (TNF-) α, and transforming growth factor- (TGF-) ß by HepG2 cells treated with conditioned medium derived from lipopolysaccharide-treated THP-1 monocytes. Furthermore, OF and CM effectively inhibited oleate-induced cellular lipid accumulation, TGF-ß secretion, and overexpression of fibronectin in mesangial cells. In conclusion, OF and CM possess hepatoprotective activity by inhibiting hepatic fat load and inflammation and renal protection by preventing FFA-induced mesangial extracellular matrix formation.

Flavones Isolated from Scutellariae radix Suppress Propionibacterium Acnes-Induced Cytokine Production In Vitro and In Vivo.

Scutellariae radix, the root of Scutellaria baicalensis, has long been applied in traditional formulations and modern herbal medications. Propionibacterium acnes (P. acnes) in follicles can trigger inflammation and lead to the symptom of inflammatory acnes vulgaris. This study was aimed at evaluating the effect of Scutellariae radix extract and purified components isolated from it on inflammation induced by P. acnes in vitro and in vivo. The results showed the ethyl acetate (EA) soluble fraction from the partition of crude ethanolic extract from Scutellariae radix inhibited P. acnes-induced interleukin IL-8 and IL-1ß production in human monocytic THP-1 cells. Seven flavones were isolated from the EA fraction by repeated chromatographies, and identified as 5,7-dihydroxy-6-methoxyflavone (FL1, oroxylin), 5,7-dihydroxy-8-methoxyflavone (FL2, wogonin), 5-hydroxy-7,8-dimethoxyflavone (FL3, 7-O-methylwogonin), 5,6'-dihydroxy-6,7,8,2'-tetramethoxy flavone (FL4, skullcapflavone II), 5,7,4'-trihydroxy-8-methoxyflavone (FL5), 5,2',6'-trihydroxy-7,8-dimethoxyflavone (FL6, viscidulin II), and 5,7,2',5'-tetrahydroxy-8,6'-dimethoxyflavone (FL7, ganhuangenin). They all significantly suppressed P. acnes-induced IL-8 and IL-1ß production in THP-1 cells, and FL2 exerted the strongest effect with half maximal inhibition (IC50) values of 8.7 and 4.9 µM, respectively. Concomitant intradermal injection of each of the seven flavones (20 µg) with P. acnes effectively attenuated P. acnes-induced ear swelling, and decreased the production of IL-6 and tumor necrosis factor-α in ear homogenates. Our results suggested that all the seven flavones can be potential therapeutic agents against P. acnes-induced skin inflammation.

Antioxidant, cell-protective, and anti-melanogenic activities of leaf extracts from wild bitter melon (Momordica charantia Linn. var. abbreviata Ser.) cultivars.

BACKGROUND: Several wild bitter melon (WBM; Momordica charantia Linn. var. abbreviata Ser.) cultivars were developed in Taiwan. However, little information is available regarding biological function of WBM leaf. Therefore, the objectives of this study were to investigate the nutrient content, antioxidant, cell protection and anti-melanogenic properties of wild bitter melon leaf. RESULTS: Methanolic leaf extracts were prepared from a variety and two cultivars of WBM. All extracts exerted potent nitric oxide and hydroxyl radical scavenging capacities. Furthermore, all extracts effectively reduce the production of reactive oxygen species and prevent cell death in UVB-irradiated HaCaT keratinocytes. The cell protective effect of leaf extract was also investigated by the prevention of HaCaT cells from sodium nitroprusside or menadione-induced toxicity, and significant cyto-protective activities were observed for all of them. Additionally, all extracts significantly suppressed tyrosinase activity and melanin levels in B16-F10 melanocytes. CONCLUSIONS: WBM leaf extract showed significant antioxidant, cyto-protective and anti-melanogenic activities. These findings suggested that WBM leaves may be beneficial for preventing the photo-oxidative damage and melanogenesis of skin.

Wild bitter melon (Momordica charantia Linn. var. abbreviata Ser.) extract and its bioactive components suppress Propionibacterium acnes-induced inflammation.

In this study, we aimed to evaluate the inhibitory effect of wild bitter melons (WBM; Momordica charantia Linn. var. abbreviata Ser.) on Propionibacterium acnes-induced inflammation and to identify the bioactive components. Our results showed that ethyl acetate (EA) extract of WBM fruit in vitro potently suppressed pro-inflammatory cytokine and matrix metalloproteinase (MMP)-9 levels in P. acnes-stimulated THP-1 cells. Furthermore, concomitant intradermal injection of WBM EA extract in mice effectively attenuated P. acnes-induced ear swelling and granulomatous inflammation. To further investigate the bioactive components, we found that both saponifiable (S) and nonsaponifiable (NS) fractions of WBM EA extract significantly suppressed pro-inflammatory cytokine and MMP-9 levels. Phytol and lutein, identified in the NS fraction, also inhibited cytokine production. Moreover, S and NS fractions of EA extract, phytol and lutein, activated peroxisome proliferator-activated receptor (PPAR) α and ß in the transactivation assay. Our results suggested that PPARα or PPARγ signalling may contribute, at least in part, to the anti-inflammatory activity of WBM.

Docosahexaenoic acid attenuates VCAM-1 expression and NF-κB activation in TNF-α-treated human aortic endothelial cells.

This study was conducted to test the hypothesis that n-3 polyunsaturated fatty acids are able to down-regulate expression of adhesion molecules and nuclear factor-κB (NF-κB) activation in vascular endothelial cells, in addition to reducing atherosclerotic lesions in vivo. We report here that docosahexaenoic acid (DHA) reduces atherosclerotic lesions in the aortic arteries of apolipoprotein E knockout (apoE(-/-)) mice. Consistent with the observation in animal study, DHA inhibited THP-1 cell adhesion to tumor necrosis factor α (TNF-α)-activated human aortic endothelial cells (HAECs). Expression of vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1) on the cell surface of HAECs was determined by cell-surface enzyme-linked immunosorbent assay. DHA and eicosapentaenoic acid decreased VCAM-1 expression in a dose-dependent manner in TNF-α treated HAECs, while cis-linoleic acid and arachidonic acid did not have any significant effect on either VCAM-1 or ICAM-1 expression. Moreover, DHA significantly reduced VCAM-1 protein expression in the cell lysates of TNF-α-treated HAECs, as determined by Western blot analysis. In line with NF-κB signaling pathway, DHA suppressed the TNF-α-activated IκBα phosphorylation and degradation as well as IκB kinase-ß phosphorylation. Subsequently, translocation of the NF-κB (p50/p65) and AP-1 (c-Fos/c-Jun) subunits was down-regulated by DHA in the nucleus of HAECs. These results suggest that DHA negatively regulates TNF-α-induced VCAM-1 expression through attenuation of NF-κB signaling pathway and AP-1 activation. This study provides evidence that DHA may contribute to the prevention of atherosclerosis and inflammatory diseases in vivo.

Sesamin attenuates intercellular cell adhesion molecule-1 expression in vitro in TNF-alpha-treated human aortic endothelial cells and in vivo in apolipoprotein-E-deficient mice.

Sesame lignans have antioxidative and anti-inflammatory properties. We focused on the effects of the lignans sesamin and sesamol on the expression of endothelial-leukocyte adhesion molecules in tumor necrosis factor-alpha (TNF-alpha)-treated human aortic endothelial cells (HAECs). When HAECs were pretreated with sesamin (10 or 100 microM), the TNF-alpha-induced expression of intercellular cell adhesion molecule-1 (ICAM-1) was significantly reduced (35 or 70% decrease, respectively) by Western blotting. Sesamol was less effective at inhibiting ICAM-1 expression (30% decrease at 100 microM). Sesamin and sesamol reduced the marked TNF-alpha-induced increase in human antigen R (HuR) translocation and the interaction between HuR and the 3'UTR of ICAM-1 mRNA. Both significantly reduced the binding of monocytes to TNF-alpha-stimulated HAECs. Sesamin significantly attenuated TNF-alpha-induced ICAM-1 expression and cell adhesion by downregulation of extracellular signal-regulated kinase 1/2 and p38. Furthermore, in vivo, sesamin attenuated intimal thickening and ICAM-1 expression seen in aortas of apolipoprotein-E-deficient mice. Taken together, these data suggest that sesamin inhibits TNF-alpha-induced extracellular signal-regulated kinase/p38 phosphorylation, nuclear translocation of NF-kappaB p65, cytoplasmic translocalization of HuR and thereby suppresses ICAM-1 expression, resulting in reduced adhesion of leukocytes. These results also suggest that sesamin may prevent the development of atherosclerosis and inflammatory responses.

Effect of intestinal production of equol on menopausal symptoms in women treated with soy isoflavones.

OBJECTIVE: To evaluate the effect of soy isoflavones on menopausal symptoms in women who do and who do not produce equol, a daidzein metabolite. METHOD: A randomized, double-blind, placebo-controlled clinical trial was conducted over 6 months with 96 healthy menopausal women. After taking take 135 mg of isoflavones daily for 1 week, the women in the study group were assigned to the equol-producing (EP) or the non-EP group according to the presence or absence of equol in their urine. Menopausal symptoms were evaluated using a modified Kupperman Index. RESULT: Compared with the placebo group, the scores for hot flashes and excessive sweating were significantly reduced after 3 months, and the scores for weakness, palpitations, limb paresthesia, and total symptoms after 6 months, in the EP group only. CONCLUSIONS: Isoflavone supplementation improves menopausal symptoms only in women with the ability to produce equol.

Sesame ingestion affects sex hormones, antioxidant status, and blood lipids in postmenopausal women.

Sesame ingestion has been shown to improve blood lipids in humans and antioxidative ability in animals. Sesamin, a sesame lignan, was recently reported to be converted by intestinal microflora to enterolactone, a compound with estrogenic activity and also an enterometabolite of flaxseed lignans, which are known to be phytoestrogens. Whether sesame can be a source of phytoestrogens is unknown. This study was designed to investigate the effect of sesame ingestion on blood sex hormones, lipids, tocopherol, and ex vivo LDL oxidation in postmenopausal women. Twenty-six healthy subjects attended, and 24 completed, this randomized, placebo-controlled, crossover study. Half of them consumed 50 g sesame seed powder daily for 5 wk, followed by a 3-wk washout period, then a 5-wk 50-g rice powder placebo period. The other half received the 2 supplements in reverse order. After sesame treatment, plasma total cholesterol (TC), LDL-C, the ratio of LDL-C to HDL-C, thiobarbituric acid reactive substances in oxidized LDL, and serum dehydroepiandrosterone sulfate decreased significantly by 5, 10, 6, 23, and 18%, respectively. The ratio of alpha- and gamma-tocopherol to TC increased significantly by 18 and 73%, respectively. All of these variables differed significantly between the 2 treatments. Serum sex hormone-binding globulin and urinary 2-hydroxyestrone (n = 8) increased significantly by 15 and 72%, respectively, after sesame treatment, and these concentrations tended to differ (P = 0.065 and P = 0.090, respectively) from those after the placebo treatment. These results suggest that sesame ingestion benefits postmenopausal women by improving blood lipids, antioxidant status, and possibly sex hormone status.

Estrogenic effect of yam ingestion in healthy postmenopausal women.

OBJECTIVE: Yam (Dioscorea) has been used to treat menopausal symptom folklorically. This study was to investigate the effects of yam ingestion on lipids, antioxidant status, and sex hormones in postmenopausal women. METHODS: Twenty-four apparently healthy postmenopausal women were recruited to replace their staple food (rice for the most part) with 390 g of yam (Dioscorea alata) in 2 of 3 meals per day for 30 days and 22 completed the study. Fasting blood and first morning urine samples were collected before and after yam intervention for the analyses of blood lipids, sex hormones, urinary estrogen metabolites and oxidant stress biomarker. The design was a one arm, pre-post study. A similar study of postmenopausal women (n = 19) fed 240 g of sweet potato for 41 days was included as a control study. Serum levels of estrone, estradiol and SHBG were analyzed for this control group. RESULTS: After yam ingestion, there were significant increases in serum concentrations of estrone (26%), sex hormone binding globulin (SHBG) (9.5%), and near significant increase in estradiol (27%). No significant changes were observed in serum concentrations of dehydroepiandrosterone sulfate, androstenedione, testosterone, follicular stimulating hormone, and luteinizing hormone. Free androgen index estimated from the ratio of serum concentrations of total testosterone to SHBG decreased. Urinary concentrations of the genotoxic metabolite of estrogen, 16alpha-hydroxyestrone decreased significantly by 37%. Plasma cholesterol concentration decreased significantly by 5.9%. Lag time of low-density lipoprotein oxidation prolonged significantly by 5.8% and urinary isoprostane levels decreased significantly by 42%. For the control subjects fed with sweet potato, all three hormone parameters measured were not changed after intervention. CONCLUSION: Although the exact mechanism is not clear, replacing two thirds of staple food with yam for 30 days improves the status of sex hormones, lipids, and antioxidants. These effects might reduce the risk of breast cancer and cardiovascular diseases in postmenopausal women.