Luteolin inhibits the release of glutamate in rat cerebrocortical nerve terminals

The present study investigated the effect and possible mechanism of luteolin, a food-derived flavonoid, on endogenous glutamate release in nerve terminals of rat cerebral cortex (synaptosomes). Luteolin inhibited the release of glutamate evoked by the K(+) channel blocker 4-aminopyridine (4-AP), and this phenomenon was concentration-dependent. The effect of luteolin on the evoked glutamate release was prevented by the chelation of the extracellular Ca(2+) ions and by the vesicular transporter inhibitor, but was insensitive to the glutamate transporter inhibitor. Luteolin decreased the 4-AP-induced increase in [Ca(2+)](C), whereas it did not alter 4-AP-mediated depolarization. Furthermore, the effect of luteolin on evoked glutamate release was abolished by blocking the Ca(v)2.2 (N-type) and Ca(v)2.1 (P/Q-type) channels, but not by blocking the ryanodine receptors or the mitochondrial Na(+)/Ca(2+) exchange. In addition, the inhibitory effect of luteolin on evoked glutamate release was prevented by the mitogen-activated/extracellular signal-regulated kinase (MEK) inhibitors. Western blot analyses showed that luteolin decreased the 4-AP-induced phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) and synapsin I, the main presynaptic target of ERK. Thus, it was concluded that luteolin inhibits glutamate release from rat cortical synaptosomes through the suppression of presynaptic voltage-dependent Ca(2+) entry and MEK/ERK signaling cascade.     

Absorption and excretion of luteolin and apigenin in rats after oral administration of Chrysanthemum morifolium extract

Chrysanthemum morifolium extract (CME) has the protective effect on cardiovascular diseases. Luteolin and apigenin are two major bioactive components in vivo when CME is orally administrated to experimental animal. The present paper shows the study of the absorption and excretion of luteolin and apigenin in rats after a single oral dose of CME (200 mg/kg). The levels of luteolin and apigenin in plasma, urine, feces, and bile were measured by HPLC after deconjugation with hydrochloric acid or beta-glucuronidase/sulfatase. The results showed that the plasma concentrations of luteolin and apigenin reached the highest peak level at 1.1 and 3.9 h after dosing, respectively. The area under the concentration-time curves (AUC) for luteolin and apigenin were 23.03 and 237.6 microg h mL-1, respectively. The total recovery of the dose was 37.9% (6.6% in urine; 31.3% in feces) for luteolin and 45.2% (16.6% in urine; 28.6% in feces) for apigenin. The cumulative luteolin and apigenin excreted in the bile was 2.05% and 6.34% of the dose, respectively. All of the results suggest apigenin may be absorbed more efficiently than luteolin in CME in rats, and both luteolin and apigenin have a slow elimination phase, with a quick absorption, so a possible accumulation of the two flavonoids in the body can be hypothesized.     

保水剂对岩溶石山土壤及金银花生长的影响

广西忻城县岩溶石山土壤具有土层浅薄贫瘠、保水性差、易干旱等特点。本试验选用高效农林保水剂、农作物果树抗旱保水剂、稷丰保水剂和旱宝贝MP-3005四种保水剂在移栽金银花扦插苗时施用,探讨了它们对忻城石山土壤物理性状及金银花生长的影响。结果表明:施用保水剂能降低土壤容重,提高土壤总孔隙度和毛管孔隙度,改良土壤结构,从而提高石山土壤持水能力;在石山土壤干旱时,高效农林、旱宝贝MP-3005两种保水剂能够促进金银花二级分枝生长,提高金银花幼苗存活率,保持金银花长势良好,有助于治理荒漠化石山和改善石山地区生态环境。     

Antiproliferative and chemopreventive effects of adlay seed on lung cancer in vitro and in vivo

This study examined the effects of different extracts of adlay seed on the growth of human lung cancer cells in vitro and in vivo. The data showed that a methanolic extract, but not a water extract, of adlay seed exerted an antiproliferative effect on A549 lung cancer cells by inducing cell cycle arrest and apoptosis. It was also found that tumor growth in vivo was inhibited by the methanolic extract in a dose-dependent manner. The chemopreventive effect of adlay seed on the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenesis in A/J mice was also investigated. Groups of mice were pre-fed with different diets, followed by feeding with NNK-containing drinking water for 8 months. The results indicated that feeding with diet containing 30% of powdered adlay seed reduced the number of surface lung tumors by approximately 50%. Taken together, these results indicate that the components of adlay seed exert an anticancer effect in vitro and in vivo and may be useful for the prevention of lung tumorigenesis.     

Determination of water-soluble polyphenolic compounds in commercial herbal teas from Lamiaceae: peppermint, melissa, and sage

Chromatographic techniques (HPLC and HPTLC) were used for qualitative and quantitative determination of eriocitrin, luteolin 7-O-rutinoside, luteolin 7-O-beta-glucuronide, lithospermic acid, rosmarinic acid, and methyl rosmarinate together with other known compounds in commercial herbal teas from the Lamiaceae family: peppermint leaf (Menthae piperitae folium), melissa leaf (Melissae folium), and sage leaf (Salviae officinalis folium). Contents of analyzed compounds in infusions, the most popular forms, were established using a C18 column with acetonitrile-water-formic acid as a mobile phase. The HPLC method was validated for linearity, precision, and accuracy. Luteolin 7-O-beta-glucuronide and lithospermic acid were identified as new Mentha x piperita compounds. The investigated herbal teas delivered polyphenols in high amounts, up to 182.2 mg for the infusion of one peppermint tea bag.     

Intestinal ellagitannin metabolites ameliorate cytokine-induced inflammation and associated molecular markers in human colon fibroblasts

Pomegranate ellagitannins (ETs) are transformed in the gut to ellagic acid (EA) and its microbiota metabolites, urolithin A (Uro-A) and urolithin B (Uro-B). These compounds exert anti-inflammatory effects in vitro and in vivo. The aim of this study was to investigate the effects of Uro-A, Uro-B, and EA on colon fibroblasts, cells that play a key role in intestinal inflammation. CCD18-Co colon fibroblasts were exposed to a mixture of Uro-A, Uro-B, and EA, at concentrations comparable to those found in the colon (40 μM Uro-A, 5 μM Uro-B, 1 μM EA), both in the presence or in the absence of IL-1β (1 ng/mL) or TNF-α (50 ng/mL), and the effects on fibroblast migration and monocyte adhesion were determined. The levels of several growth factors and adhesion cytokines were also measured. The mixture of metabolites significantly inhibited colon fibroblast migration (～70%) and monocyte adhesion to fibroblasts (～50%). These effects were concomitant with a significant down-regulation of the levels of PGE(2), PAI-1, and IL-8, as well as other key regulators of cell migration and adhesion. Of the three metabolites tested, Uro-A exhibited the most significant anti-inflammatory effects. The results show that a combination of the ET metabolites found in colon, urolithins and EA, at concentrations achievable in the intestine after the consumption of pomegranate, was able to moderately improve the inflammatory response of colon fibroblasts and suggest that consumption of ET-containing foods has potential beneficial effects on gut inflammatory diseases.     

Cinnamon extract promotes type I collagen biosynthesis via activation of IGF-I signaling in human dermal fibroblasts

The breakdown of collagenous networks with aging results in hypoactive changes in the skin. Accordingly, reviving stagnant collagen synthesis can help protect dermal homeostasis against aging. We searched for type I collagen biosynthesis-inducing substances in various foods using human dermal fibroblasts and found that cinnamon extract facilitates collagen biosynthesis. Cinnamon extract potently up-regulated both mRNA and protein expression levels of type I collagen without cytotoxicity. We identified cinnamaldehyde as a major active component promoting the expression of collagen by HPLC and NMR analysis. Since insulin-like growth factor-I (IGF-I) is the most potent stimulator of collagen biosynthesis in fibroblasts, we examined the effect of cinnamaldehyde on IGF-I signaling. Treatment with cinnamaldehyde significantly increased the phosphorylation levels of the IGF-I receptor and its downstream signaling molecules such as insulin receptor substrate-1 and Erk1/2 in an IGF-I-independent manner. These results suggested that cinnamon extract is useful in antiaging treatment of skin.     

18个品种蓝靛果营养成分分析及综合品质评价

为了研究不同品种蓝靛果各指标的差异，确定影响其品质的关键指标，对不同品种蓝靛果进行综合评价并分类。以18个品种蓝靛果为研究对象，基于百粒质量、可溶性固形物含量、含水率、总酸、可溶性糖、糖酸比、总酚、总黄酮、花色苷、维生素C、铁、钙、感官评分、胰脂肪酶抑制率等各项指标的差异，通过相关性分析、主成分分析，建立一套综合评价蓝靛果品质的方法，并结合热图聚类分析将18个品种的蓝靛果进行分类，根据各类蓝靛果特点分析其潜在应用方向。测定结果显示不同品种蓝靛果多项指标存在显著差异（P＜0.05），经各指标之间相关性分析可得总酸与总酚、总黄酮以及花色苷含量之间呈显著正相关（P＜0.05），胰脂肪酶抑制率与总酸含量呈极显著正相关（P＜0.01），与花色苷含量呈显著正相关（P＜0.05），感官评分与百粒质量呈显著正相关（P＜0.05）。经主成分分析，提取出5个主成分，累计贡献率达84.524%，总酸、总酚、总黄酮、花色苷含量以及胰脂肪酶抑制率是评价蓝靛果品质的关键指标。根据综合评价函数计算综合得分，排名前五的品种分别是"谢列娜"（42.38）、"蓓蕾"（41.04）、"别列里"（39.26）、"乌兰"（35.38）和"炭火"（34.56），此5种蓝靛果品质优良，可用于选育新品种或定向育种。经热图聚类分析可将18个品种蓝靛果分为Ⅰ、Ⅱ、Ⅲ类，各分别含有4、5、9个品种。第Ⅰ类蓝靛果适宜鲜食；第Ⅱ类蓝靛果适合开发具有辅助降脂功能的保健食品；第Ⅲ类蓝靛果适宜开发成休闲食品，其中"阿索里""1-100-82""33-11-82"和"蓝纺锤"适合开发果汁、果酒等产品，"蓝色温柔""伊利亚特""托米奇卡""瓦秀岗""炭火"适合加工果酱、果脯、罐头等产品。研究结果为蓝靛果的定向育种提供一定参考，为不同品种蓝靛果的开发利用提供理论依据，也为蓝靛果等浆果品质分析、综合评价及合理分类提供系统可靠的方法。     

A synthetic naringenin derivative, 5-hydroxy-7,4'-diacetyloxyflavanone-N-phenyl hydrazone (N101-43), induces apoptosis through up-regulation of Fas/FasL expression and inhibition of PI3K/Akt signaling pathways in non-small-cell lung cancer cells

Naringenin, a well-known naturally occurring flavonone, demonstrates cytotoxicity in a variety of human cancer cell lines; its inhibitory effects on tumor growth have spurred interest in its therapeutic application. In this study, naringenin was derivatized to produce more effective small-molecule inhibitors of cancer cell proliferation, and the anticancer effects of its derivative, 5-hydroxy-7,4'-diacetyloxyflavanone-N-phenyl hydrazone (N101-43), in non-small-cell lung cancer (NSCLC) cell lines NCI-H460, A549, and NCI-H1299 were investigated. Naringenin itself possesses no cytotoxicity against lung cancer cells. In contrast, N101-43 inhibits proliferation of both NCI-H460 and A549 cell lines; this capacity is lost in p53-lacking NCI-H1299 cells. N101-43 induces apoptosis via sub-G1 cell-cycle arrest in NCI-H460 and via G0/G1 arrest in A549 cells. Expression of apoptosis and cell-cycle regulatory factors is altered: Cyclins A and D1 and phospho-pRb are down-regulated, but expression of CDK inhibitors such as p21, p27, and p53 is enhanced by N101-43 treatment; N101-43 also increases expression levels of the extrinsic death receptor Fas and its binding partner FasL. Furthermore, N101-43 treatment diminishes levels of cell survival factors such as PI3K and p-Akt dose-dependently, and N101-43 additionally induces cleavage of the pro-apoptotic factors caspase-3, caspase-8, and poly ADP-ribose polymerase (PARP). Cumulatively, these investigations show that the naringenin derivative N101-43 induces apoptosis via up-regulation of Fas/FasL expression, activation of caspase cascades, and inhibition of PI3K/Akt survival signaling pathways in NCI-H460 and A549 cells. In conclusion, these data indicate that N101-43 may have potential as an anticancer agent in NSCLC.     

Anti-inflammatory and antifibrotic effects of naringenin in diabetic mice

Renal protective effects of naringenin at 0.5, 1, and 2% of the diet in diabetic mice were examined. Naringenin supplemented at 1 and 2% increased its deposit in liver and kidney of diabetic mice. Compared with the diabetic control group, naringenin treatments at 1 and 2% lowered plasma levels of glucose and blood urea nitrogen, as well as increased insulin level and creatinine clearance (P < 0.05). Naringenin treatments dose-dependently reduced renal tumor necrosis factor-α level and expression (P < 0.05) but only at 1 and 2% significantly decreased production and expression of interleukin (IL)-1β, IL-6, and monocyte chemoattractant protein-1 (P < 0.05). Naringenin intake at 2% decreased renal formation and expression of type IV collagen, fibronectin, and transforming growth factor-β1 (P < 0.05). This compound at 1 and 2% lowered protein kinase C activity and suppressed nuclear factor κB (NF-κB) p65 activity, mRNA expression, and protein production in kidney. However, this agent only at 2% diminished NF-κB p50 activity, mRNA expression, and protein production (P < 0.05). These results indicate that naringenin could attenuate diabetic nephropathy via its anti-inflammatory and antifibrotic activities.     

Composition of liquid rice hull smoke and anti-inflammatory effects in mice

A new liquid rice hull smoke extract with a smoky aroma and sugar-like odor prepared by pyrolysis of rice hulls followed by liquefaction of the resulting smoke contained 161 compounds characterized by GC/MS. Antioxidative, antiallergic, and anti-inflammatory activities of the extract were assessed in vitro and in vivo. At pH 5, the extract inhibited 1-diphenyl-2-picrylhydrazyl (DPPH) free radicals and suppressed nitric oxide (NO) and β-hexosaminidase releases from lipopolysaccharide (LPS)-induced RAW264.7 mouse macrophage leukemia cells and ionophore A23187-stimulated RBL-2H3 rat basophilic cells without significant cytotoxicity. 12-O-Tetradecanolylphorbol-13-acetate (TPA) was applied to the ears of CD-1 mice to induce inflammation (edema), which was accompanied by increases in a series of biomarkers. Topical application of 1% of the extract as well as feeding mice a standard diet with 1% extract for two weeks significantly reduced the expression of biomarkers associated with the TPA-induced inflammation. These include tumor necrosis factor-α (TNF-α), IL-1β, interleukin-1β (IL-1β), interleukin-6 (IL-6), leukotriene B(4) (LTB(4)), prostaglandin E(2) (PGE(2)), myeloperoxidase (MPO). These in vitro and in vivo findings demonstrate the potential value of rice hull smoke extract derived from a major agricultural byproduct to serve as a new biomaterial for the improvement of food quality and safety and the environment.     

Antioxidant,prooxidant, and cytotoxic activities of solvent-fractionated dandelion (Taraxacum officinale) flower extracts in vitro

This study was conducted to investigate the chemical antioxidant and bioactive properties of the water (WF) and ethyl acetate fractions (EAF) derived from dandelion (Taraxacum officinale) flower extract (DFE). HPLC analysis showed the presence of both luteolin and luteolin 7-glucoside in the DFE, which contributed to noted in vitro antioxidant and Caco-2 cell cytotoxic activities. Both WF and EAF of DFE exhibited free radical scavenging activities in a stable 2,2-diphenyl-1-picrylhydrazyl radical model and reduced the breakage of supercoiled DNA strand induced by both non-site-specific and site-specific hydroxyl radical. Oxidation of structured phosphatidylcholine liposome induced by peroxyl radical was reduced in the presence of both EAF and WF. EAF had greater (p < 0.05) affinity to scavenge peroxyl radical than WF, as measured by the formation of conjugated diene. At low concentration, prooxidant activity of both fractions was observed in Cu(2+)-induced structured liposome and hLDL oxidation models, thus indicating that the reducing power of the DFE had resulted in generation of reactive cuprous ion. However, at high concentrations the EAF did not promote oxidation in the presence of Cu(2+), suggesting that the free radical scavenging activity of this fraction was sufficient to minimize the potential oxidative mechanism attributed to the metal ion reducing activity associated with prooxidant activity.     

Oleuropein ameliorates acute colitis in mice

Oleuropein, the major secoiridoid in olive tree leaves, possesses a wide range of health promoting properties. It has recently been shown to exhibit anti-inflammatory activity. We have evaluated the effect of oleuropein on dextran sulfate sodium (DSS)-induced experimental colitis in mice in order to provide insight into its mechanisms of action. Oral administration of oleuropein notably attenuated the extent and severity of acute colitis while reducing neutrophil infiltration; production of NO, IL-1β, IL-6, and TNF-α; expression of iNOS, COX-2, and MMP-9; and the translocation of the NF-κB p65 subunit to the nucleus in colon tissue. In LPS-stimulated peritoneal macrophages, the oleuropein metabolite, hydroxytyrosol, was shown to inhibit NO production, iNOS expression, NF-κB p65 subunit translocation, mRNA expression, and the release of IL-1β, IL-6, and TNF-α. These results suggest that the effect of oleuropein on DSS-induced colitis is associated with a decrease in the production of interleukins and expression of proteins, principally through reduction of NF-κB activation.     

转化生长因子β1基因(TGF-β1)外显子2的单核苷酸多态性及其与两个山羊品种产羔数的相关分析

为寻找与山羊(Capra hircus)产羔数密切相关的分子标记,加快山羊育种进程,研究转化生长因子β1基因(TGF-β1)遗传多态性与山羊产羔数的相关性,根据牛的TGF-β1基因序列设计3对引物,采用PCR-SSCP.和DNA测序技术检测山羊TGF-β1基因外显子2和内含子3的多态性,同时用最小二乘法研究了其多态性与产羔数的关系。结果表明,在波尔山羊和陕南白山羊中,仅第二外显子148bp位点碱基发生A→G的突变,导致苏氨酸(Thr)变为丙氨酸(Ala);多态位点均以A为优势等位基因,基因频率分别为0.530和0.648。在波尔山羊的1～3胎产羔数中,AB型个体的产羔数显著高于BB和AA型个体(P<0.05);在第四胎产羔数和平均产羔数中,AB型个体的产羔数显著高于AA(P<0.05),显著高于BB(P<0.05);BB型个体的平均产羔数显著高于AA型(P<0.05)。在陕南白山羊中,AB型个体的2～4胎产羔数和平均产羔数显著高于AA和BB型个体(P<0.05);在第一胎中,AB型个体显著高于AA型个体(P<0.05)。研究结果表明TGF-β1基因多态位点与产羔数显著相关,可以用于山羊分子遗传育种的候选基因。     

Phytochemical composition, anti-inflammatory, and antiproliferative activity of whole wheat flour

Whole wheat flour from five wheat cultivars was evaluated for phenolic, carotenoid, and tocopherol compositions as well as anti-inflammatory and antiproliferative activities against HT-29 cells. The total ferulic acid content ranged from 452 to 731 μg/g among the five cultivars and was primarily present in the insoluble-bound form. Lutein was the only carotenoid detected and ranged from 1.5 to 4.0 μg/g, and α-tocopherol levels ranged from 12 to 61 μg/g. Extracts of four cultivars demonstrated significant anti-inflammatory activity, measured as inhibition of interleukin-1β (IL-1β) mRNA expression; however, none of the extracts inhibited tumor necrosis factor-α (TNF-α) mRNA expression, a second indicator of anti-inflammatory activity. Proliferation of HT-29 adenocarcinoma cells was inhibited by extracts from all cultivars at the dose of 100 mg botanical equivalent/mL. The cultivar WestBred 936 had the greatest antiproliferative activity at lower concentrations (20 and 50 mg botanical equivalent/mL), had the greatest anti-inflammatory effect against IL-1β, and also had the highest levels of ferulic acid and α-tocopherol. This research shows that whole wheat flours of these five cultivars varied significantly in their contents of phenolics, carotenoids, and α-tocopherol as well as in their anti-inflammatory and antiproliferative potentials, suggesting the possibility that wheat varieties can be selected based on potential health benefits.     

Antioxidant and anti-inflammatory activities of selected medicinal plants containing phenolic and flavonoid compounds

The antioxidant, anti-inflammatory, and cytotoxic activities of water and ethanol extracts of 14 Chinese medicinal plants were investigated and also their total phenolics and flavonoid contents measured. The antioxidant activity was evaluated in a biological assay using Saccharomyces cerevisiae , whereas the radical scavenging activity was measured using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method. Total phenolics and flavonoid contents were estimated by Folin-Ciocalteu and aluminum chloride methods, respectively. The anti-inflammatory activities of the plant extracts were determined by measuring the inhibition of production of nitric oxide (NO) and TNF-α in LPS and IFN-γ activated RAW 264.7 macrophages. Their cytotoxic activities against macrophages were determined by Alamar Blue assay. Four plants, namely, Scutellaria baicalensis , Taxillus chinensis , Rheum officinale , and Sophora japonica , showed significant antioxidant activity in both yeast model and also free radical scavenging methods. The ethanol extract of S. japonica showed highest levels of phenolics and flavonoids (91.33 GAE mg/g and 151.86 QE mg/g, respectively). A positive linear correlation between antioxidant activity and the total phenolics and flavonoid contents indicates that these compounds are likely to be the main antioxidants contributing to the observed activities. Five plant extracts (S. baicalensis, T. chinensis, S. japonica, Mahonia fortunei , and Sophora flavescens ) exhibited significant anti-inflammatory activity by in vitro inhibition of the production of NO and TNF-α with low IC(50) values. These findings suggest that some of the medicinal herbs studied in this paper are good sources of antioxidants.     

Inhibition of Lipopolysaccharide (LPS)-induced inflammatory responses by Sargassum hemiphyllum sulfated polysaccharide extract in RAW 264.7 macrophage cells

Sargassum hemiphyllum , a kind of brown seaweed generally found along coastlines in East Asia, has long served as a traditional Chinese medicine. S. hemiphyllum has shown an anti-inflammatory effect; however, its mechanism has not been elucidated clearly. This study explored S. hemiphyllum for its biomedical effects. S. hemiphyllum sulfated polysaccharide extract (SHSP) was first prepared; the mouse macrophage cell line (RAW 264.7) activated by lipopolysaccharide (LPS) was used as a model system. The secretion profiles of pro-inflammatory cytokines, including IL-1β, IL-6, TNF-α, and NO, were found significantly to be reduced in 1-5 mg/mL dose ranges of SHSP treatments. RT-PCR analysis suggested SHSP inhibits the LPS-induced mRNA expressions of IL-β, iNOS, and COX-2 in a dose-dependent manner. At protein levels, Western blot analysis demonstrated a similar result for NF-κB (p65) in cytosol/nuclear. Taken together, the anti-inflammatory properties of SHSP may be attributed to the down-regulation of NF-κB in nucleus.     

Structures of new triterpenoids and cytotoxicity activities of the isolated major compounds from the fruit of Momordica charantia L

Two new cucurbitane-type triterpene glycosides, charantagenins D (1) and E (2), and one new sterol, 7-oxo-stigmasta-5,25-diene-3-O-β-d-glucopyranoside (3), were isolated from the fruit of Momordica charantia L. together with another eight known compounds. Their structures were determined on the basis of spectral analysis. Cytotoxicity activities of the isolated major compounds were evaluated against lung cancer cell line A549, glioblastoma cell line U87, and hepatoma carcinoma cell line Hep3B by using a 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) in vitro assay. Results showed compounds 1 and 7 (goyaglycoside d) with an -OMe substituent group in the side chain exhibited significant cytotoxic activities against cancer cells. Impressively, the IC(50) values of the new compound 1 to A549, U87, and Hep3B were 1.07, 1.08, and 14.01 μmol/L, respectively, which were much lower than those of other tested compounds.