luteolin-7-O-glucoside Research Articles

Preparation and Characterization of Copolymer Micelles for the Solubilization and In Vitro Release of Luteolin and Luteoloside.

Luteolin (LUT) and luteoloside (LUS) belong to flavonoids with high anticancer potential and were loaded into biodegradable diblock copolymer micelles of methoxy polyethylene glycol-polycaprolactone (mPEG5K-PCL10K), methoxy polyethylene glycol-polylactide-co-glycolide (mPEG5K-PLGA10K), and methoxy polyethylene glycol-polylactide (mPEG5K-PDLLA10K) by a self-assembly method, creating water-soluble LUT and LUS copolymer micelles, respectively. The solubilization formulations of the copolymer micelles were optimized with response surface methodology (RSM). The obtained drug micelles are torispherical under transmission electron microscope (TEM) with an average diameter of about 70nm. The mPEG5K-PLGA10K exhibited higher loading capacity for LUS which was 4.33%, and LUT- (or LUS)-loaded mPEG5K-PCL10K exhibited a better stability and encapsulation efficiency which was 65.1 and 55.8%, respectively. The in vitro drug release study showed above 47% of LUT was released from micelles at pH 7.4 PBS; however, no more than 35% of LUT was released at pH 6.4 PBS within 24h. Meanwhile, no more than 30% of LUS was released from micelles whether at pH 6.4 or 7.4 PBS solution within 24h.

Expression of Flavone Synthase II and Flavonoid 3'-Hydroxylase Is Associated with Color Variation in Tan-Colored Injured Leaves of Sorghum.

Sorghum (Sorghum bicolor L. Moench) exhibits various color changes in injured leaves in response to cutting stress. Here, we aimed to identify key genes for the light brown and dark brown color variations in tan-colored injured leaves of sorghum. For this purpose, sorghum M36001 (light brown injured leaves), Nakei-MS3B (purple), and a progeny, #7 (dark brown), from Nakei-MS3B × M36001, were used. Accumulated pigments were detected by using high-performance liquid chromatography: M36001 accumulated only apigenin in its light brown leaves; #7 accumulated both luteolin and a small amount of apigenin in its dark brown leaves, and Nakei-MS3B accumulated 3-deoxyanthocyanidins (apigeninidin and luteolinidin) in its purple leaves. Apigenin or luteolin glucoside derivatives were also accumulated, in different proportions. Differentially expressed genes before and after cutting stress were identified by using RNA sequencing (RNA-seq). Integration of our metabolic and RNA-seq analyses suggested that expression of only flavone synthase II (FNSII) led to the synthesis of apigenin in M36001, expression of both FNSII and flavonoid 3′-hydroxylase (F3′H) led to the synthesis of apigenin and luteolin in #7, and expression of both flavanone 4-reductase and F3′H led to the synthesis of 3-deoxyanthocyanidins in Nakei-MS3B. These results suggest that expression of FNSII is related to the synthesis of flavones (apigenin and luteolin) and the expression level of F3′H is related to the balance of apigenin and luteolin. Expression of FNSII and F3′H is thus associated with dark or light brown coloration in tan-colored injured leaves of sorghum.

Erratum to: Anti-inflammatory effects of luteolin and luteoloside from Taraxacum coreanum in RAW264.7 macrophage cells

The effects of luteolin (LT) and luteoloside (LS) from Taraxacum coreanum, using lipopolysaccharide (LPS)/interferon-gamma (IFN-γ)-induced RAW264.7 macrophage cells, on anti-inflammation were investigated. Our study was focused on the ethyl acetate fraction from T. coreanum (ETC) and its active compounds and their protective role against inflammation. The ETC and its active compounds, LT and LS, showed dose-dependent inhibitory activity against the production of nitric oxide (NO) and reactive oxygen species (ROS) in LPS/IFN-γ-stimulated RAW264.7 cells. In addition, ETC and its active compounds inactivated nuclear factor-kappa B and down-regulated inflammatory mediators. The results also showed that treatment with ETC, LT, and LS decrease pro-inflammatory cytokines, tumor necrosis factor-alpha, and interleukin-6. In conclusion, our studies indicated that ETC has anti-inflammatory activity owing to inhibition of NO/ROS generation and down-regulation of inflammatory mediators and cytokines. Moreover, LT and LS are bioactive compounds of ETC with protective effects against inflammation.

Anti-diabetic effects of luteolin and luteolin-7-O-glucoside on KK-A(y) mice.

Anti-diabetic potential of luteolin (LU) and luteolin-7-O-glucoside (LUG) were investigated in the amount of equimolar on KK-A(y) mice. The results showed that both of LU and LUG significantly improved blood glucose, HbA1c, insulin, and HOMR-IR levels. Anti-inflammatory and anti-oxidative effects of the LU and LUG were also proved. Furthermore, TGs in serum and liver were significantly decreased in the LU and LUG groups, as well as the mRNA expression of fat acid expression-related genes (SREBP-1c), compared to the basal diet group (CON). When compared the effects between the LU and LUG groups, TGs of the LU group were lower than those of the LUG group, accompanied with significantly decreased FAS activity and SREBP-1c expression in liver. These results suggested that both LU and LUG had positive effects of anti-diabetes on KK-A(y) mice, but LU more potently ameliorated diabetes than LUG, which might be attributed to the inhibitory of lipid synthesis.

Luteolin-7-glucoside inhibits IL-22/STAT3 pathway, reducing proliferation, acanthosis, and inflammation in keratinocytes and in mouse psoriatic model.

The epidermis is a dynamic tissue in which keratinocytes proliferate in the basal layer and undergo a tightly controlled differentiation while moving into the suprabasal layers. The balance between keratinocyte proliferation, differentiation, and death is essential, and its perturbation can result in pathological changes. Some common skin diseases, such as psoriasis, are characterized by hyperproliferation accompanied by inflammatory reactions, suggesting that molecules with topical anti-inflammatory and ROS scavenging abilities may be useful for their treatment. Here we investigate the potential of the flavone Luteolin-7-glucoside (LUT-7G) as a treatment for psoriasis. We show that LUT-7G leads to a modification of the cell cycle and the induction of keratinocyte differentiation, with modification of energy, fatty acid, and redox metabolism. LUT-7G treatment also neutralizes the proliferative stimulus induced by the proinflammatory cytokines IL-22 and IL-6 in HEKn. Moreover, in the Imiquimod (IMQ) mouse model of psoriasis, topical administration of LUT-7G leads to a marked reduction of acanthosis and re-expression of epidermal differentiation markers. Dissection of the IL-22 signalling pathway, activated by IMQ treatment, demonstrates that LUT-7G impairs the nuclear translocation of phosphorylated (activated) STAT3, blocking the IL-22 signalling cascade. Thus LUT-7G appears to be a promising compound for the treatment of hyperproliferative and inflammatory skin diseases, such as psoriasis.

Degradation kinetics of functional components of honeysuckle flowers during controlled-atmosphere heat pump drying

To investigate the change law of functional components and exterior color of honeysuckle flowers (HF) during controlled-atmosphere heat pump drying, nitrogen was used as drying medium in this study to reduce the oxygen concentration. The influences of drying temperature, HF’s loading amount and oxygen concentration on chlorogenic acid content, cynaroside content and L value (on behalf of browning degree) were explored, and the degradation kinetics models of chlorogenic acid and cynaroside were constructed. The results showed that chlorogenic acid content, cynaroside content and L value decreased with the rise of temperature, HF’s loading amount and oxygen concentration. The degradation kinetics models of chlorogenic acid and cynaroside during the drying process were established through introducing an exponent r related to time t in the first order reaction kinetics equation. The models had good fitting precision and can be used to predict the degradation law of chlorogenic acid and cynaroside. Keywords: honeysuckle flowers, controlled-atmosphere heat pump drying, chlorogenic acid, cynaroside, degradation kinetics DOI: 10.3965/j.ijabe.20160904.1940 Citation: Luo L, Yang B, Zhu W X, Ren G Y, Duan X, Kang X Y. Degradation kinetics of functional components of honeysuckle flowers during controlled-atmosphere heat pump drying. Int J Agric & Biol Eng, 2016; 9(4): 159－168.

Experimental study on gastroprotective efficacy and mechanisms of luteolin-7-O-glucoside isolated from Ophiorrhiza mungos Linn. in different experimental models

The gastroprotective effect of luteolin-7-O-glucoside (LUT7G) on different ulcer models using rats including the indomethacin model, the ethanol-induced gastric ulcer model and the Shay ulcer model was examined. The ethanol-induced ulcer group showed significant increases in MPO, NO, iNOS, MMP-2, MMP-9, caspase-3, apoptosis, IL-6, TNF-α, IKK, NF-κB p65, and ICAM-1 and declines in PGE2, arginase, SOD, GSH, mucin, IL-10, eNOS, COX-1, HSP-70, and IκBα levels. However, LUT7G (25 mg/kg) pretreatment significantly reverted the pathophysiological levels of these biomarkers to near normal levels. The gastroprotective activity of LUT7G was abolished by pretreatment with SC560, rofecoxib, and L-NAME, demonstrating the participation of COX and NOS in LUT7G-facilitated gastroprotection against ethanol-induced ulcers. Convincingly, LUT7G (25 mg/kg) provided protective effects in the rat gastric mucosa against ethanol-induced gastric injury at least in part to antisecretory, anti-inflammatory, antioxidative, and antiapoptotic activity, and augmentation of PGE2, mucin and HSP-70 synthesis.

Metabolic Fate of Luteolin in Rats: Its Relationship to Anti-inflammatory Effect.

Luteolin is a naturally occurring flavone that reportedly has anti-inflammatory effects. Because most luteolin is conjugated following intestinal absorption, free luteolin is likely present at low levels in the body. Therefore, luteolin metabolites are presumably responsible for luteolin bioactivity. Here we confirmed that luteolin glucuronides, especially luteolin-3'-O-glucuronide, are the major metabolites found in plasma after oral administration of luteolin (aglycone) or luteolin glucoside (luteolin-7-O-glucoside) to rats. Luteolin-4'-O-glucuronide and luteolin-7-O-glucuronide were also detectable together with luteolin-3'-O-glucuronide in the liver, kidney, and small intestine. Next, we prepared these luteolin glucuronides and compared the anti-inflammatory effects of luteolin and luteolin glucuronides on gene expression in lipopolysaccharide-treated RAW264.7 cells. Luteolin glucuronides, especially luteolin-7-O-glucuronide, reduced expression of inflammatory genes in the cells, although their effects were weaker than those of luteolin. These results indicate that the active compound responsible for the anti-inflammatory effect of luteolin in vivo would be luteolin glucuronide and/or residual luteolin.

In Vitro and In Vivo α-Glucosidase and α-Amylase Inhibitory Effects of the Water Extract of Leaves of Pepper (Capcicum Annuum L. Cultivar Dangjo ) and the Active Constituent Luteolin 7-O-Glucoside

This study was conducted to evaluate the in vitro and in vivo hypoglycemic potential of the water extract of pepper (Capcicum annuum L. cultivar Dangjo) leaves (WEPL) and the active constituent luteolin 7-O-glucoside (LG) isolated from WEPL. WEPL showed in vitro α-glucosidase and α-amylase inhibitory activity. LG also showed a similar α-glucosidase and α-amylase inhibitory activity, suggesting that the ability of WEPL to inhibit both enzymes may be due to the presence of LG and other polyphenols in WEPL. Supporting this observation, both WEPL and LG significantly reduced blood glucose levels in streptozocin-induced diabetic mice when challenged with oral administration of sucrose, but not after oral glucose challenge. Hence, inhibition of α-glucosidase and α-amylase may possibly be one of the mechanisms for WEPL and LG to exert hypoglycemic activity, indicating that pepper leaves may be considered as a potential candidate for the management of type 2 diabetes mellitus. Practical Applications Leaves of pepper cultivars, including Dangjo pepper, are commonly consumed as food in Korea. The findings of this study demonstrate that the water extract of pepper leaves exhibits the capacity to inhibit carbohydrate hydrolyzing enzymes (α-glucosidase and α-amylase) in vitro and in vivo and these beneficial effects appear to be due to some specific bioactive compounds in pepper leaves, in particular luteolin 7-O-glucoside. Our preliminary observation provides a rationale for a possible use of pepper leaves for the management of postprandial hyperglycemia.

The modified nanocrystalline cellulose for hydrophobic drug delivery

In this work, torispherical nanocrystalline cellulose (NCC) was synthesized, and firstly modified with a cationic surfactant cetyltrimethylammonium bromide (CTMAB). It was proved that the kinetics of NCC adsorbing CTMAB followed the pseudo-second-order kinetics equation, and the adsorption isotherm model followed Freundlich which was multi molecular layer adsorption model. The morphology and structure of NCC and CTMAB-coated NCC were characterized by transmission electron microscopy (TEM) and X-ray powder diffraction (XRD). Stabilities of NCC and CTMAB-coated NCC were assayed by zeta potential. The results showed that NCC in CTMAB solution was well-dispersed and stable. Moreover, the drug loading and release performance of CTMAB-coated NCC were studied using luteolin (LUT) and luteoloside (LUS) as model drugs.

Anti-inflammatory activity of the aerial parts of Platycodon grandiflorum and its constituents in LPS-stimulated RAW264.7 macrophages

Platycodon grandiflorum A. DC. (Campanulaceae) grows as a perennial herb, and is widely distributed or cultivated in Korea, Japan and China. Platycodi Radix, the dried root of P. grandiflorum has been used as an antitussive, expectorant and drainage medicine in the traditional herbal medicine [1]. Lipopolysaccharides (LPSs) induce the production of inflammatory mediators such as iNOS, COX-2, TNF-α, IL-1, and IL-6 in macrophages. Therefore, reducing the expression levels of LPS-inducible inflammatory mediators is considered as an effective way to evaluate anti-inflammatory activity [2]. In order to compare the anti-inflammatory activity of solvent fractions from the aerial parts of P. grandiflorum on LPS-stimulated macrophages, the EtOH extract was consecutively partitioned with CH2Cl2, EtOAc and n-BuOH, and the levels of inflammatory mediators such as NO, TNF-α and IL-6 were evaluated. The anti-inflammatory activity potential of the solvent fractions was in the order of n-BuOH>EtOAc>CH2Cl2>H2O. The BuOH fraction strongly regulated NO, TNF-α and IL-6, and especially showed potent inhibition of the production of NO and IL-6 in LPS -stimulated RAW264.7 cells (IC50: 6.7 and 8.1 µg/mL, respectively). Seven known phenolic compounds were isolated from the BuOH and EtOAc fractions, which showed comparatively higher activity than the other fractions. The known compounds were identified as luteolin 7-glucoside, 3'-rhamnoside, apigenin 7-glucoside, 4'-rhamnoside, luteolin 7-(6"-O-acetyl)-glucoside, luteolin 7-glucoside, apigenin 7-glucoside, chlorogenic acid, and luteolin. The isolated compounds revealed inhibitory effects on NO, TNF-α and IL-6 production at concentrations of IC50 below 25, 60 and 38 µg/mL, respectively.

Phytochemical analysis with the antioxidant and aldose reductase inhibitory capacities of Tephrosia humilis aerial parts’ extracts

The aerial parts of Tephrosia humilis were tested about their antioxidant potential, their ability to inhibit the aldose/aldehyde reductase enzymes and their phenolic content. The plant material was exhaustively extracted with petroleum ether, dichloromethane and methanol, consecutively. The concentrated methanol extract was re-extracted, successively, with diethyl ether, ethyl acetate and n-butanol. All extracts showed significant antioxidant capacity, but the most effective was the ethyl acetate extract. As about the aldose reductase inhibition, all fractions, except the aqueous, were strong inhibitors of the enzyme, with the n-butanolic and ethyl acetate fractions to inhibit the enzyme above 75%. These findings provide support to the ethnopharmacological usage of the plant as antioxidant and validate its potential to act against the long-term diabetic complications. The phytochemical analysis showed the presence of 1,4-dihydroxy-3,4-(epoxyethano)-5-cyclohexene(1), cleroindicin E(2), lupeol(3), methyl p-coumarate(4), methyl 4-hydroxybenzoate(5), prunin(6), 5,7,2ʹ,5ʹ-tetrahydroxyflavanone 7-rutinoside(7), protocatechuic acid(8), luteolin 7-glucoside(9), apigenin(10), naringin(11), rhoifolin(12) and luteolin 7-glucuronate(13).

Olive leaf components apigenin 7-glucoside and luteolin 7-glucoside direct human hematopoietic stem cell differentiation towards erythroid lineage

The generation of blood cellular components from hematopoietic stem cells is important for the therapy of a broad spectrum of hematological disorders. In recent years, several lines of evidence suggested that certain nutrients, vitamins and flavonoids may have important roles in controlling the stem cell fate decision by maintaining their self-renewal or stimulating the lineage-specific differentiation. In this study, main olive leaf phytochemicals oleuropein (Olp), apigenin 7-glucoside (Api7G) and luteolin 7-glucoside (Lut7G) were investigated for their potential effects on hematopoietic stem cell differentiation using both phenotypic and molecular analysis. Oleuropein and the combination of the three compounds enhanced the differentiation of CD34+ cells into myelomonocytic cells and lymphocytes progenitors and inhibited the commitment to megakaryocytic and erythroid lineages. Treatment with Lut7G stimulated both the erythroid and the myeloid differentiation, while treatment with Api7G specifically induced the differentiation of CD34+ cells towards the erythroid lineage and inhibited the myeloid differentiation. Erythroid differentiation induced by Api7G and Lut7G treatments was confirmed by the increase in hemoglobin genes expressions (α-hemoglobin, β-hemoglobin and γ-hemoglobin) and erythroid transcription factor GATA1 expression. As revealed by microarray analysis, the mechanisms underlying the erythroid differentiation-inducing effect of Api7G on hematopoietic stem cells involves the activation of JAK/STAT signaling pathway. These findings prove the differentiation-inducing effects of olive leaf compounds on hematopoietic stem cells and highlight their potential use in the ex vivo generation of blood cells.

Protection of Luteolin-7-O-Glucoside Against Doxorubicin-Induced Injury Through PTEN/Akt and ERK Pathway in H9c2 Cells.

Luteolin-7-O-glucoside (LUTG) was isolated from the plants of Dracocephalum tanguticum Maxim. Previous research has showed that LUTG pretreatment had a significant protective effect against doxorubicin (DOX)-induced cardiotoxicity by reducing intracellular calcium overload and leakage of creatine kinase and lactate dehydrogenase. But the underlying mechanisms have not been completely elucidated. In the present study, we investigated the effects of LUTG on H9c2 cell morphology, viability, apoptosis, reactive oxygen species generation, and the mitochondrial transmembrane potentials. The expression of p-PTEN, p-Akt, p-ERK, p-mTOR, and p-GSK-3β were detected by Western blotting. Compared with DOX alone treatment group, the morphological injury and apoptosis of the cells in groups treated by DOX plus LUTG were alleviated, cell viability was increased, ROS generation was lowered remarkably, and mitochondrial depolarization was mitigated. In DOX group, the expression of p-PTEN was lower than normal group and the expression of p-Akt and p-ERK was higher than normal group. In the groups treated with LUTG (20μM), the expression of p-PTEN was upregulated and the expression of p-Akt, p-ERK, p-mTOR, and p-GSK-3β was downregulated. These results indicated that the protective effects of LUTG against DOX-induced cardiotoxicity may be related to anti-apoptosis through PTEN/Akt and ERK pathway.

Contribution of the main polyphenols of Thymus mastichina subsp. mastichina to its antioxidant properties

The antioxidant activity and phenol content of 14 populations of Thymus mastichina grown in an experimental plot, was analyzed by DPPH, FRAP and Folin-Ciocalteu method to define their antioxidant activity. Polyphenols were analyzed by HPLC-DAD and the relationship between polyphenols and antioxidant capacity was established. Populations means for DPPH activity ranges were 44–98mgTE/gDW while FRAP antioxidant capacity was 52–115mgTE/gDW. Total phenol content ranged between 11 and 38mg of CAE/g DW for the different populations. The polyphenols identified were: chlorogenic acid, caffeic acid, rosmarinic acid, luteolin glucoside and luteolin. The main polyphenols were rosmarinic acid, ranging from 1.7 to 43mg/g DW, one unidentified polyphenol designated as Peak 3 (0.53–15LEeqmg/g) and luteolin glucoside ranging from 0.96 to 19LEeqmg/g. Rosmarinic acid contributed mainly to the FRAP antioxidant capacity and to the total phenols, while peak 3 contributed mainly to the DPPH assay. Luteolin, chlorogenic acid and caffeic acid had a range of 0–2.7, 0.07–2.2, 0–0.46mg/g DW, respectively. The study showed high intra-populations variability and above all high inter-populations variability. The Carrocera population had the highest antioxidant activity and amount of phenols and it could be selected for its content.

Effects on Liver Lipid Metabolism of the Naturally Occurring Dietary Flavone Luteolin-7-glucoside.

Disruptions in whole-body lipid metabolism can lead to the onset of several pathologies such as nonalcoholic fatty liver disease (NAFLD) and cardiovascular diseases (CVDs). The present study aimed at elucidating the molecular mechanisms behind the lipid-lowering effects of the flavone luteolin-7-glucoside (L7G) which we previously showed to improve plasma lipid profile in rats. L7G is abundant in plant foods of Mediterranean diet such as aromatic plants used as herbs. Results show that dietary supplementation with L7G for one week induced the expression of peroxisome proliferator-activated receptor-alpha (PPAR-α) and of its target gene carnitine palmitoyl transferase 1 (CPT-1) in rat liver. L7G showed a tendency to decrease the hepatic expression of sterol regulatory element-binding protein-1 (SREBP-1), without affecting fatty acid synthase (FAS) protein levels. Although SREBP-2 and LDLr mRNA levels did not change, the expression of HMG CoA reductase (HMGCR) was significantly repressed by L7G. L7G also inhibited this enzyme's in vitro activity in a dose dependent manner, but only at high and not physiologically relevant concentrations. These results add new evidence that the flavone luteolin-7-glucoside may help in preventing metabolic diseases and clarify the mechanisms underlying the beneficial health effects of diets rich in fruits and vegetables.

Quantitative comparison of caffeoylquinic acids and flavonoids in Chrysanthemum morifolium flowers and their sulfur-fumigated products by three-channel liquid chromatography with electrochemical detection.

For the determination of seven caffeoylquinic acids [neochlorogenic acid (NcA), cryptochlorogenic acid (CcA), chlorogenic acid (CA), caffeic acid (CfA), isochlorogenic acid A (Ic A), isochlorogenic acid B (Ic B), isochlorogenic acid C (Ic C)] and two flavonoids [luteolin 7-O-glucoside (LtG) and luteolin (Lt)], a three-channel liquid chromatography with electrochemical detection (LC-3ECD) method was established. Chromatographic peak heights were proportional to each concentration, ranging from 2.5 to 100 ng/mL for NcA, CA, CcA, and CfA, and ranging from 2.5 to 250 ng/mL for LtG, Ic B, Ic A, Ic C, and Lt, respectively. The present LC-3ECD method was applied to the quantitative analysis of caffeoylquinic acids and flavonoids in four cultivars of Chrysanthemum morifolium flowers and their sulfur-fumigated products. It was found that 60% of LtG and more than 47% of caffeoylquinic acids were lost during the sulfur fumigation processing. Sulfur fumigation showed a destructive effect on the C. morifolium flowers. In addition, principle component analyses (PCA) were performed using the results of the quantitative analysis of caffeoylquinic acids and flavonoids to compare the "sameness" and "differences" of these analytes in C. morifolium flowers and the sulfur-fumigated products. PCA score plots showed that the four cultivars of C. morifolium flowers were clearly classified into four groups, and that significant differences were also found between the non-fumigated C. morifolium flowers and the sulfur-fumigated products. Therefore, it was demonstrated that the present LC-3ECD method coupled with PCA is applicable to the variation analysis of different C. morifolium flower samples.

Effect of Olive Leaf Components on the Proliferation and Viability of Hematopoietic Stem Cells

Hematopoietic stem cells (HSCs) transplantation and/or the infusion of hematopoietic cells are currently the best alternative for the treatment of a wide variety of hematological disorders. Therefore, novel modulators of HSCs fate continue to be identified in an attempt to optimize the in vitro culture of these cells. In this study, main olive leaf components, oleuropein, apigenin 7-glucoside, and luteolin 7-glucoside, and their combination, were investigated for their effect on the proliferation and viability of CD34+ hematopoietic cells. Results of the MTT assay and flow cytometric evaluation of cell viability indicated that high concentrations of up to 50 μM of olive leaf phytochemicals did not decrease CD34+ cell proliferation or viability, except for apigenin 7-glucoside which showed a slight decrease in cell proliferation. This decrease is caused by a decrease in the growth rate of CD34+ cells rather than by cell death as revealed by the cell viability results. These findings suggest that olive leaf phytochemicals, used alone or in combination, are not cytotoxic on HSCs and provide the first evidence for the potential use of olive leaf compounds as supplements to CD34+ cell culture for further investigations of their effects on the self-renewal or differentiation of HSCs.

Predicting the structural preferences of luteolin-7-O-β-d-glucoside in the gas phase: An application of the hybrid MCMM/QM approach

The hybrid Monte-Carlo multiple minimum/quantum mechanical approach, which includes fully random conformational searches and high-level quantum mechanical calculations, is employed to predict the low-lying conformers of luteolin-7-O-β-d-glucoside (L7G) in the gas phase. The conformational searches allow a large number of reasonable initial geometries to be generated. In order to save the optimization time, the step-by-step classification is applied to reduce the number of possible conformations. The structural analysis of L7G suggests that hydrogen bonds play an important role in the structural stability. Meanwhile, forming cooperative intra-ring hydrogen bonds could further lower the relative energies. Compared with L4′G, the glycosidic dihedral angles of L7G distribute extensively. Conformer of L7G prefers a loose geometry because of the lack of the constraint from inter-ring hydrogen bonds. However, the glycosidic dihedral angles of L4′G are limited in a small range due to the inter-ring hydrogen bonds between luteolin and glucose rings. A comparison of L7G and L4′G reveals the influence of the glycosidic linkage on the distribution of glycosidic dihedral angles.

Effects of luteolin 7-glucoside and its aglicone luteolin in liver lipid metabolism and plasma lipoproteins

Flavonoids as luteolin (L) and luteolin-7-glucoside (L7G) are polyphenols abundant in human diet, and are present in vegetables such as celery and green pepper; being particularly abundant in herbs of the genus Salvia (family Laminaceae). These compounds have been associated with various biological activities including modulating blood cholesterol levels, and lipid-lowering properties [1]. In the present study, we fed rats with standard chow supplemented with L7G (2 mg/kg), and found that this compound modulates lipid metabolism in the liver through induction of PPARα and CPT1, important β-oxidation regulators, while decreasing mRNA levels of HMGCoA reductase, the limiting enzyme cholesterol endogenous synthesis. These effects induced by L7G could prevent fatty liver disease and dyslipidemia. In agreement with this, diet supplementation with L7G decreased total and LDL cholesterol levels, improving plasma lipid profile in healthy rats. Although L7G is the form in which this compound is most abundant in nature, there are reports of low bioavailability of flavonoids and particularly of the glycosylated forms that are believed to undergo deglycosylation upon intestinal absorption. In order to compare effects of both, luteolin and his glicone, luteolin-7-glucoside, we tested them in vitro, using HepG2 cell line. The results show that not only treatment with L7G, but also with L increase PPARα which gives the first insights on the effect on β-oxidation regulation by both L and L7G in human hepatocytes; and show that both compounds, in vitro, have comparable effects at this level.