Two new isoquinoline alkaloids from the seeds of Nandina domestica.

Two new isoquinoline alkaloids, 6 R,6aS-N-nantenine Nß-oxide (1), 6S,6aS-N-nantenine Nα-oxide (2), along with nine known alkaloids, nantenine (3), oxonantenine (4), protopine (5), nornantenine (6), N-methyl-laurotetanine (7), isocorydine (8), O-methyflavinantine (9), N-methyl-2,3,6-trimethoxymorphinan-dien-7-one Nß-oxide (10) and (+)-10-O-methylhernovine Nß-oxide (11) were isolated from the seeds of Nandina domestica. Their structures were elucidated by extensive analyses of spectroscopic data (IR, UV, HRESIMS, 1 D and 2 D NMR), ECD calculation and comparison with the related literatures. In addition, the cytotoxicity against A549 cells of these alkaloids was determined by the MTT assay.

ß-Carboline Alkaloids from the Seeds of Peganum harmala and Their Anti-HSV-2 Virus Activities.

Pegaharines A-G (1-6), six novel ß-carboline alkaloids representing three types of skeleton, were isolated from the seeds of Peganum harmala. Compound 1 is a peculiar ß-carboline alkaloid characterized by the unprecedented carbon skeleton of an azepine-indole system. Compounds 3-6 represent the first examples of heterodimers constructed from rare tetracyclic ß-carboline and classic tricyclic ß-carboline alkaloids. Compounds 1 and 2 were characterized by X-ray crystallography. Compound 4 exhibited strong antiviral activity against HSV-2, with an IC50 value of 2.12 ± 0.14 µM.

Six New Acylphloroglucinols from Dryopteris championii.

Six new acylphloroglucinols (1 - 6) were isolated from Dryopteris championii. Their structures were established on the basis of extensive analysis of spectroscopic data and comparison with reported data. The antibacterial activities of the isolates were evaluated against Staphylococcus aureus, Escherichia coli, Bacillus subtilis, and Dickeya zeae.

Sesquiterpene lactones from Elephantopus mollis and their anti-inflammatory activities.

Seven sesquiterpene lactones, 8-O-methacryloylelephanpane, 2,4-bis-O-methyl-8-O-methacryloylelephanpane, 4-O-ethyl-8-O-methacryloylelephanpane, 8-O-methacryloylisoelephanpane, 2-O-demethyltomenphantopin C, molephantin A, molephantin B, along with ten known ones, were isolated from Elephantopus mollis (Asteraceae). Their structures were elucidated by extensive analysis of spectroscopic data (IR, UV, HRESIMS, 1D and 2D NMR). The isolates were evaluated for their anti-inflammatory activities on LPS-stimulated RAW 264.7 cells, and all tested compounds exhibited potent anti-inflammatory effects with IC50 values of 0.57 ± 0.17 to 14.34 ± 1.61 µM, except that compound tomenphantopin C exhibited moderate anti-inflammatory activity with IC50 values of 59.97 ± 1.53 µM.

Diterpenoid Alkaloids from Delphinium ajacis and Their Anti-RSV Activities.

Five new diterpenoid alkaloids, ajacisines A-E (1-5), were isolated from Delphinium ajacis, along with seven known alkaloids (6-12). On the basis of their spectral data (IR, UV, HR-ESI-MS, 1D and 2D NMR) and chemical properties, the structures of compounds 1-12 were identified. All isolated compounds were evaluated for their in vitro antiviral activities against respiratory syncytial virus, and compounds 3-5 and 8 exhibited moderate to weak effects with IC50 values of 75.2 ± 1.1, 35.1 ± 0.6, 10.1 ± 0.3, and 50.2 ± 0.5 µM, respectively.

Depot-specific effects of treadmill running and rutin on white adipose tissue function in diet-induced obese mice

White adipose tissue (WAT) is a critical organ involved in regulating metabolic homeostasis under obese condition. Strategies that could positively affect WAT function would hold promise for fighting against obesity and its complications. The aim of the present study is to explore the effects of treadmill exercise training and rutin intervention on adipose tissue function from diet-induced obese (DIO) mice and whether fat depot-specific effects existed. In epididymal adipose tissue, high-fat diet (HFD) resulted in reduction in adiponectin mRNA expression, peroxisome proliferator-activated receptors (PPAR)-γ and DsbA-L protein expression, elevation in endoplasmic reticulum (ER) stress markers including 78 kDa glucose-regulated protein (GRP-78), C/EBP homologous protein (CHOP) and p-c-Jun N-terminal kinase (JNK). Isoproterenol-stimulated lipolysis and insulin stimulated Akt phosphorylation ex vivo were blunted from HFD group. The combination of rutin with exercise (HRE) completely restored GRP78 and p-JNK protein expression to normal levels, as well as blunted signaling ex vivo. In inguinal adipose tissue, HFD led to increased adiponectin mRNA expression, PPAR-γ, GRP78, and p-JNK protein expression, and reduction in DsbA-L. HRE is effective for restoring p-JNK, PPAR-γ, and DsbA-L. In conclusion, depot-specific effects may exist in regard to the effects of rutin and exercise on key molecules involved in regulating adipose tissue function (i.e., ER stress markers, PPAR-γ and DsbA-L, adiponectin expression, and secretion, ex vivo catecholamine stimulated lipolysis and insulin stimulated Akt phosphorylation) from DIO mice (AU)

No disponible

Effects of 8-Week Hatha Yoga Training on Metabolic and Inflammatory Markers in Healthy, Female Chinese Subjects: A Randomized Clinical Trial.

We aimed to determine the effects of an 8 wk Hatha yoga training on blood glucose, insulin, lipid profiles, endothelial microparticles (EMPs), and inflammatory status in healthy, lean, and female Chinese subjects. A total of 30 healthy, female Chinese subjects were recruited and randomized into control or yoga practice group. The yoga practice included 8 wks of yoga practice (2 times/wk) for a total of 16 times. Fasting blood samples were collected before and after yoga training. Plasma was isolated for the measurement of lipid profiles, glucose, insulin, EMPs, and inflammatory cytokines. Whole blood was cultured ex vivo and stimulated with lipopolysaccharide (LPS) and Pam3Cys-SK4. Peripheral blood mononuclear cells (PBMCs) were isolated for the measurement of TLR2 and TLR4 protein expression. Yoga practice significantly reduced plasma cholesterol, LDL-cholesterol, insulin levels, and CD31+/CD42b- EMPs. Cultured whole blood from the yoga group has reduced proinflammatory cytokines secretion both at unstimulated condition and when stimulated with Pam3Cys-SK4; this might be associated with reduced TLR2 protein expression in PBMCs after yoga training. Hatha yoga practice in healthy Chinese female subjects could improve hallmarks related to MetS; thus it can be considered as an ancillary intervention in the primary MetS prevention for the healthy population. This trial is registered with ChiCTR-IOR-14005747.

Depot-specific effects of treadmill running and rutin on white adipose tissue function in diet-induced obese mice.

White adipose tissue (WAT) is a critical organ involved in regulating metabolic homeostasis under obese condition. Strategies that could positively affect WAT function would hold promise for fighting against obesity and its complications. The aim of the present study is to explore the effects of treadmill exercise training and rutin intervention on adipose tissue function from diet-induced obese (DIO) mice and whether fat depot-specific effects existed. In epididymal adipose tissue, high-fat diet (HFD) resulted in reduction in adiponectin mRNA expression, peroxisome proliferator-activated receptors (PPAR)-γ and DsbA-L protein expression, elevation in endoplasmic reticulum (ER) stress markers including 78 kDa glucose-regulated protein (GRP-78), C/EBP homologous protein (CHOP) and p-c-Jun N-terminal kinase (JNK). Isoproterenol-stimulated lipolysis and insulin stimulated Akt phosphorylation ex vivo were blunted from HFD group. The combination of rutin with exercise (HRE) completely restored GRP78 and p-JNK protein expression to normal levels, as well as blunted signaling ex vivo. In inguinal adipose tissue, HFD led to increased adiponectin mRNA expression, PPAR-γ, GRP78, and p-JNK protein expression, and reduction in DsbA-L. HRE is effective for restoring p-JNK, PPAR-γ, and DsbA-L. In conclusion, depot-specific effects may exist in regard to the effects of rutin and exercise on key molecules involved in regulating adipose tissue function (i.e., ER stress markers, PPAR-γ and DsbA-L, adiponectin expression, and secretion, ex vivo catecholamine stimulated lipolysis and insulin stimulated Akt phosphorylation) from DIO mice.

[Chemical Constituents from Syzygium samarangense Branches and Leaves].

OBJECTIVE: To investigate the chemical constituents from the branches and leaves of Syzygium samarangense. METHODS: The dried branches and leaves of Syzygium samarangense were powdered and extracted with 95% ethanol, then partitioned with petroleum ether, chloroform and ethyl acetate. The chloroform fraction was subjected to silica gel, Sephdex L-20 and preparative HPLC. The structures were identified by physicochemical properties and spectral data. RESULTS: 14 compounds were respectively isolated and identified as ursolic aldehyde(1), betulin(2), betulinic aldehyde(3), betulinic acid(4), lupeol(5), ß-sitosterol(6), 5, 7-dihydroxy-6-methylflavanone(7), 2', 4'-dihydroxy-6'-methoxy-3'-methyldihydrochalcone (8), 2', 4'-dihydroxy-6'-methoxy-3'-methylchalcone (9), 5, 7-dihydroxy-6, 8-dimethylflavanone (10), 5, 7-dihydroxyflavanone (11), 2', 4'-dihydroxy-6'-methoxy-3', 5'-dimethyldihydrochalcone (12), 2'-hydroxy-4', 6'-dimethoxy-3'-methylchalcone(13) and p-hydroxyb6nzaldehyde(14). CONCLUSION: Compounds 1 - 4 and 14 are isolated from this plant for the first time.

New Phloroglucinol Derivatives from the Fruit Tree Syzygium jambos and Their Cytotoxic and Antioxidant Activities.

Seven new phloroglucinol derivatives (1-7) were isolated from the fruit tree Syzygium jambos together with four known triterpenoids (8-11) and two known flavones (12 and 13). According to the spectroscopic analyses (infrared, electrospray ionization mass spectrometry (ESIMS), high-resolution ESIMS, 1D and 2D nuclear magnetic resonance), the structures of compounds 1-7 were elucidated as jambone A (1), jambone B (2), jambone C (3), jambone D (4), jambone E (5), jambone F (6), and jambone G (7). All the isolates were determined for their cytotoxic activities on melanoma cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and compounds 10 and 11 showed potent activities. Moreover, compounds 1, 2, 4-7, 12, and 13 exhibited weak antioxidant activities under ferric-reducing antioxidant power and 2,2-diphenyl-1-picryhydrazyl radical-scavenging assays.

Effects of treadmill running and rutin on lipolytic signaling pathways and TRPV4 protein expression in the adipose tissue of diet-induced obese mice.

To explore the effects of rutin and exercise on high-fat diet (HFD)-induced disrupted lipolytic signaling, adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) signaling, transient receptor potential cation channel subfamily V member 4 (TRPV4) and its associated protein expression, and whether depot-specific effects existed. C57BL/6J mice were randomized into five groups: chow group, HFD, HFD plus rutin intervention group (HR), HFD combined with treadmill running group (HE), and HFD combined with treadmill running and rutin intervention group (HRE). At the end of the 16-week intervention, lipolytic markers, AMPK signaling pathways, TRPV4, and peroxisome proliferator-activated receptor gamma coactivator 1α + ß (PGC-1α + ß) from adipose tissue were measured by western blotting. In epididymal adipose tissue, HFD resulted in significant reduction in the phosphorylation of hormone sensitive lipase at serine660 (p-HSL660), perilipin A, phosphoenolpyruvate carboxykinase (PEPCK), p-AMPK, and p-acetyl-CoA carboxylase (ACC) protein expression. Exercise intervention and exercise plus rutin completely restored p-HSL660, perilipin A, PEPCK, p-AMPK, and p-ACC protein expression to normal level. HFD and HR groups have reduced expression of PGC-1α + ß, exercise, and exercise plus rutin completely restored PGC-1α + ß expression to normal level. In subcutaneous adipose tissue, HFD elevated TRPV4, exercise, and exercise plus rutin completely reduced TRPV4 to normal level. HR, HE, and HRE group have increased PGC-1α + ß. In conclusion, depot-specific effects existed in regards to how rutin and exercise affect lipolytic signaling and p-AMPK, as well as TRPV4 and PGC-1α + ß expression.

Effect of vitamin D supplementation on the level of circulating high-sensitivity C-reactive protein: a meta-analysis of randomized controlled trials.

Vitamin D might elicit protective effects against cardiovascular disease by decreasing the level of circulating high-sensitivity C-reactive protein (hs-CRP), an inflammatory marker. Thus, we conducted a meta-analysis of randomized controlled trials to evaluate the association of vitamin D supplementation with circulating hs-CRP level. A systematic literature search was conducted in September 2013 (updated in February 2014) via PubMed, Web of Science, and Cochrane library to identify eligible studies. Either a fixed-effects or a random-effects model was used to calculate pooled effects. The results of the meta-analysis of 10 trials involving a total of 924 participants showed that vitamin D supplementation significantly decreased the circulating hs-CRP level by 1.08 mg/L (95% CI, -2.13, -0.03), with the evidence of heterogeneity. Subgroup analysis suggested a higher reduction of 2.21 mg/L (95% CI, -3.50, -0.92) among participants with baseline hs-CRP level ≥5 mg/L. Meta-regression analysis further revealed that baseline hs-CRP level, supplemental dose of vitamin D and intervention duration together may be attributed to the heterogeneity across studies. In summary, vitamin D supplementation is beneficial for the reduction of circulating hs-CRP. However, the result should be interpreted with caution because of the evidence of heterogeneity.

Crystal structure of betulinic acid methanol monosolvate.

The title compound [systematic name: 3ß-hy-droxy-lup-20(29)-en-28-oic acid methanol monosolvate], C30H48O3·CH3OH, is a solvent pseudopolymorph of a naturally occurring plant-derived lupane-type penta-cyclic triterpenoid, which was isolated from the traditional Chinese medicinal plant Syzygium jambos (L.) Alston. The dihedral angle between the planes of the carb-oxy-lic acid group and the olefinic group is 12.17 (18)°. The A/B, B/C, C/D and D/E ring junctions are all trans-fused. In the crystal, O-H⋯O hydrogen bonds involving the hy-droxy and carb-oxy-lic acid groups and the methanol solvent mol-ecule give rise to a two-dimensional network structure lying parallel to (001).

[Characteristics of sediment phosphorus in the Jiulong River-Reservoir system and its ecological significance].

Sediment phosphorus (P) content and component ratio from 16 sites along the North Jiulong River-reservoir system were analyzed using the Standard Measurement and Test (SMT) procedure. The spatial pattern and characteristics of sediment P and its ecological significance in the Jiulong River-reservoir system were examined in combination with water measurement and watershed information. Total P content in sediments ranged from 387 to 2092 mg x kg(-1) with an average of 1032 mg x kg(-1). Inorganic phosphorus (IP) dominated P in sediment, accounting for 48%-98% of TP, and Fe/Al-bound phosphorus (Fe/Al-P) took 43%-99% of IP. The spatial pattern of sediment showed that TP and Fe/Al-P were higher in upstream and lower in downstream, corresponding to the spatial variation of surface water P and land-based loads from animal waste, human waste and fertilizer loss. Spatial variation of TP in sediment was controlled by Fe/AI-P along the North Jiulong River. The P-rich sediment with a great release potential due to the high ratio of Fe/ Al-P, the typical spatial pattern, and the lower N/P ratio observed in upstream water (where phytoplankton growth tends to be weakly limited by phosphorus), are likely to explain the fact that algal blooms first appear in the upstream and then spread to downstream reservoirs along the North Jiulong River. Present findings concerning sediment P characteristics indicate an important regulating effect and the ecological significance on the process of algal blooms in the Jiulong River.

Ultrasensitive detection of drug-resistant pandemic 2009 (H1N1) influenza A virus by rare-variant-sensitive high-resolution melting-curve analysis.

Oseltamivir (Tamiflu), an oral neuraminidase inhibitor, has been widely used to treat pandemic 2009 (H1N1) influenza A. Although a majority of 2009 (H1N1) influenza A virus remains oseltamivir susceptible, the threat of resistance due to the His275Tyr mutation is highlighted by the limitations of alternative therapies and the potential for rapid, global fixation of this mutation in the circulating influenza A virus population. In order to better understand the emergence of resistance, we developed a rare-variant-sensitive high-resolution melting-curve analysis method (RVS-HRM) that is able to detect the His275Tyr oseltamivir resistance mutation to 0.5% in a background of susceptible virus. We applied RVS-HRM to clinical specimens from patients who developed oseltamivir resistance and demonstrated the ultrasensitive detection of influenza A virus N1 neuraminidase quasispecies. Interestingly, we were unable to detect the oseltamivir resistance mutation in pretreatment samples, suggesting that resistant virus does not reach even this very low detection threshold until exposed to selective drug pressure. Thus, patients naive to oseltamivir are most likely to be susceptible when this drug is used as a first-line treatment modality.

Gynura procumbens Merr. decreases blood pressure in rats by vasodilatation via inhibition of calcium channels.

INTRODUCTION: Gynura procumbens has been shown to decrease blood pressure via inhibition of the angiotensinconverting enzyme. However, other mechanisms that may contribute to the hypotensive effect have not been studied. OBJECTIVES: To investigate the cardiovascular effects of a butanolic fraction of Gynura procumbens in rats. METHODS: Anaesthetized rats were given intravenous bolus injections of butanolic fraction at doses of 2.5-20 mg/kg in vivo. The effect of butanolic fraction on vascular reactivity was recorded in isolated rat aortic rings in vitro. RESULTS: Intravenous administrations of butanolic fraction elicited significant (p < 0.001) and dose-dependent decreases in the mean arterial pressure. However, a significant (p < 0.05) decrease in the heart rate was observed only at the higher doses (10 and 20 mg/kg). In isolated preparations of rat aortic rings, phenylephrine (1 × 10⁻6 M)- or potassium chloride (8 × 10⁻² M)-precontracted endothelium-intact and -denuded tissue; butanolic fraction (1 × 10⁻6 - 1 × 10⁻¹ g/ml) induced similar concentration-dependent relaxation of the vessels. In the presence of 2.5 × 10⁻³ and 5.0 × 10⁻³ g/ml butanolic fraction, the contractions induced by phenylephrine (1 × 10⁻9-3 × 10⁻5 M) and potassium chloride (1 × 10⁻² - 8 × 10⁻² M) were significantly antagonized. The calcium-induced vasocontractions (1 × 10⁻4-1 × 10⁻²M) were antagonized by butanolic fraction concentration-dependently in calcium-free and high potassium (6×10⁻² M) medium, as well as in calcium- and potassium-free medium containing 1×10⁻6 M phenylephrine. However, the contractions induced by noradrenaline (1 × 10⁻6 M) and caffeine (4.5 × 10⁻² M) were not affected by butanolic fraction. CONCLUSION: Butanolic fraction contains putative hypotensive compounds that appear to inhibit calcium influx via receptor-operated and/or voltage-dependent calcium channels to cause vasodilation and a consequent fall in blood pressure.

Gynura procumbens Merr. decreases blood pressure in rats by vasodilatation via inhibition of calcium channels

INTRODUCTION: Gynura procumbens has been shown to decrease blood pressure via inhibition of the angiotensinconverting enzyme. However, other mechanisms that may contribute to the hypotensive effect have not been studied. OBJECTIVES: To investigate the cardiovascular effects of a butanolic fraction of Gynura procumbens in rats. METHODS: Anaesthetized rats were given intravenous bolus injections of butanolic fraction at doses of 2.5-20 mg/kg in vivo. The effect of butanolic fraction on vascular reactivity was recorded in isolated rat aortic rings in vitro. RESULTS: Intravenous administrations of butanolic fraction elicited significant (p<0.001) and dose-dependent decreases in the mean arterial pressure. However, a significant (p<0.05) decrease in the heart rate was observed only at the higher doses (10 and 20 mg/kg). In isolated preparations of rat aortic rings, phenylephrine (1×10-6 M)- or potassium chloride (8×10-2 M)-precontracted endothelium-intact and -denuded tissue; butanolic fraction (1×10-6-1×10-1 g/ml) induced similar concentration-dependent relaxation of the vessels. In the presence of 2.5×10-3 and 5.0×10-3 g/ml butanolic fraction, the contractions induced by phenylephrine (1×10-9-3×10-5 M) and potassium chloride (1×10-2-8×10-2 M) were significantly antagonized. The calcium-induced vasocontractions (1×10-4-1×10-2 M) were antagonized by butanolic fraction concentration-dependently in calcium-free and high potassium (6×10-2 M) medium, as well as in calcium- and potassium-free medium containing 1×10-6 M phenylephrine. However, the contractions induced by noradrenaline (1×10-6 M) and caffeine (4.5×10-2 M) were not affected by butanolic fraction. CONCLUSION: Butanolic fraction contains putative hypotensive compounds that appear to inhibit calcium influx via receptor-operated and/or voltage-dependent calcium channels to cause vasodilation and a consequent fall in blood pressure.

[Chemical constituents of Hyperricum monogynum].

OBJECTIVE: To investigate the chemical constituents from the aerial parts of Hyperricum monogynum. METHOD: Compounds were isolated by various column chromatography and identified by spectral analysis. RESULT: Ten compounds were isolated and identified as quercetin, quercitrin, hyperoside, rutin, (-)-epicatechin, 3,5-dihydroxy-1-methoxy-xanthone, 3,4-O-isopropylidenyl shikimic acid, shikimic acid, daucosterol, and oleanoic acid. CONCLUSION: All compounds were isolated from this plant for the first time.