Five New Diarylbutyrolactones and Sesquilignans from Saussurea medusa and Their Inhibitory Effects on LPS-induced NO Production.

Five new diarylbutyrolactones and sesquilignans (1A/1B:  - 4: ), including one pair of enantiomers (1A/1B: ), together with 10 known analogues (5:  - 14: ), were isolated from the whole plants of Saussurea medusa. Compound 1: was found to possess an unusual 7,8'-diarylbutyrolactone lignan structure. Separation by chiral HPLC analysis led to the isolation of one pair of enantiomers, (+)-1A: and (-)-1B: . The structures of the new compounds were elucidated by extensive spectroscopic data. All compounds, except compounds 5, 7: and 9: , were isolated from S. medusa for the first time. Moreover, compounds 1:  -  4, 8: and 10:  - 14: had never been obtained from the genus Saussurea previously. Compounds (+)- 1A, 2, 5, 7: , and 9:  - 11: were found to inhibit the lipopolysaccharide (LPS)-induced release of NO by RAW264.7 cells with IC50 values ranging from 10.1 ± 1.8 to 41.7 ± 2.1 µM. Molecular docking and iNOS expression experiments were performed to examine the interactions between the active compounds and the iNOS enzyme.

Three Pairs of Novel Enantiomeric 8-O-4' Type Neolignans from Saussurea medusa and Their Anti-inflammatory Effects In Vitro.

Three pairs of novel enantiomeric 8-O-4' type neolignans (1a/1b−3a/3b), together with seven known analogues (4−10), were isolated from the whole plants of Saussurea medusa. Their structures were elucidated by extensive spectroscopic data analysis and electric circular dichroism (ECD) calculations after chiral separations. All compounds were obtained from S. medusa for the first time, and compounds 1−3 and 5−10 had never been obtained from the genus Saussurea previously. The anti-inflammatory activities of the compounds were evaluated by determining their inhibitory activities on the production of NO and inducible nitric oxide synthase (iNOS) expression in LPS-stimulated RAW 264.7 cells. Compounds (+)-1a, (−)-1b and 5−7 inhibited NO production and had IC50 values ranging from 14.3 ± 1.6 to 41.4 ± 3.1 µM. Compound 7 induced a dose-dependent reduction in the expression of iNOS in LPS-treated RAW 264.7 cells. Molecular docking experiments showed that all active compounds exhibited excellent docking scores (<−7.0 kcal/mol) with iNOS. Therefore, compounds (+)-1a, (−)-1b and 5−7 isolated from the whole plants of S. medusa may have therapeutic potential in inflammatory diseases.

Two new monoterpenes from Sibiraea laevigata.

Two new monoterpenes, 3-(2-oxo-4-methyl-3-pentenyl)furan-5H-2-one (1) and 3-[(2E)-4-hydroxyl-4-methyl-2-pentenyl)]furan-5H-2-one (2), along with eight known compounds (3-10), were isolated from the stalks and infructescence of Sibiraea laevigata. Their structures were elucidated by spectroscopic methods including extensive 1D and 2D NMR techniques. In addition, all of these isolates were evaluated for their cytotoxic and antioxidant activities. The results showed that compounds 5-7 displayed cytotoxicity with IC50 values ranging from 34.8 to 43.2 µg ml-1 against tumor cell lines. Furthermore, 5 and 9 showed antioxidant activities.

[Chemical Constituents from Roots of Gentiana straminea of Tibetan Medicine].

Objective: To investigate the chemical constituent from the roots of Gentiana straminea. Methods: The constituents were separated by microporous resin,silica gel,Sephadex LH-20 and preparative column chromatography and their structures were elucidated by NMR and MS spectral methods. Results: Twelve chemical constituents were isolated from the roots of Gentiana straminea and their structures were identified as daucosterol( 1),ß-sitosterol( 2),ursolic acid( 3),sweroside( 4),swertiamarin( 5),gentiopicroside( 6),6'-O-acetyl-gentiopicroside( 7),6'-O-ß-D-glucopyranosyl-sweroside( 8),protocatech uic aldehyde( 9),protocatechuic acid( 10),methyl gallate( 11) and dibutyl phthalate( 12). Conclusion: The compounds 8,9,10,11 and 12 are obtained from this plant for the first time.

Associations of platelet-activating factor acetylhydrolase (PAF-AH) gene polymorphisms with circulating PAF-AH levels and risk of coronary heart disease or blood stasis syndrome in the Chinese Han population.

The circulating level of platelet-activating factor acetylhydrolase (PAF-AH) is a novel biomarker to predict the presence of coronary heart disease. PAF-AH gene polymorphisms may be responsible for the variance of circulating PAF-AH levels in individuals. However, the association of PAF-AH gene polymorphisms with circulating PAF-AH levels and the susceptibility to coronary heart disease (CHD) remains unsolved. Blood stasis syndrome (BSS) of CHD is the most common type of TCM syndromes, and a previous study discovered its relationship with the elevated circulating PAF-AH levels. However, the association of gene polymorphisms and CHD with BSS is unclear at present. In this study, four polymorphisms (R92H, I198T, A379V, V279F) of the PAF-AH gene were genotyped in 570 CHD patients, of which 299 had BSS. In addition, 317 unaffected individuals from the same hospitals served as controls. Plasma PAF-AH levels were measured in 155 controls and 271 CHD patients selected randomly, including 139 CHD patients with BSS. In the Chinese Han population, plasma PAF-AH levels in CHD patients with BSS or without BSS were significantly higher (12.9 ± 6.5 and 11.1 ± 5.0 µM, respectively) than in controls (9.3 ± 5.2 µM); this difference still remained significant after adjustment for traditional risk factors or the inflammatory factors. The R92H polymorphism was highly related to the plasma PAF-AH levels and the risk of CHD, especially among patients with BSS, even with the adjustment for the effects of traditional factors. The I198T polymorphism was highly associated with risk of CHD with BSS, but was associated with neither the risk of CHD with no BSS nor with elevated plasma PAF-AH levels.

Separation and purification of five phenylpropanoid glycosides from Lamiophlomis rotata (Benth.) Kudo by a macroporous resin column combined with high-speed counter-current chromatography.

Five phenylethanoid glycosides (PhGs), forsythoside B, verbascoside, alyssonoside, isoverbascoside, and leucosceptoside B, were isolated and purified from Lamiophlomis rotata (Benth.) Kudo by high-speed counter-current chromatography (HSCCC) combined with macroporous resin (MR) column separation. In the present study, the two-phase solvent system composed of ethyl acetate/n-butanol/water (13:3:10, v/v/v) was used for HSCCC separation. A total of 27 mg of forsythoside B, 41 mg of verbascoside, 29 mg of alyssonoside, 23 mg of isoverbascoside, and 13 mg of leucosceptoside B with purities of 97.7, 99.2, 99.5, 99.3, and 97.3%, respectively, were obtained in a one-step separation within 4 h from 150 mg of crude extract. The recoveries of the five PhGs after MR-HSCCC separation were 74.5, 76.5, 72.5, 76.4, and 77.0%, respectively. The chemical structures of all five compounds were identified by (1) H and (13) C NMR spectroscopy.

Megastigmane sesquiterpenoids from Saussurea medusa and their anti-inflammatory activities.

Objectives: An ethanol extract of the whole plants of Saussurea medusa had been investigated to find novel anti-inflammatory sesquiterpenoids. Methods: Extensive spectroscopic data and chemical methods were applied to elucidate the structures of the compounds. Results: One new megastigmane sesquiterpenoid (1), along with 11 known analogues (2-12), were obtained from S. medusa. All isolates, except compounds 3 and 6, were mentioned from the studied plant for the first time. Compounds 1, 2, 4, 5, 7, 8 and 12 were firstly isolated from the genus Saussurea. Compounds 2, 9 and 10 were found to inhibit the lipopolysaccharide (LPS)-induced release of NO by RAW264.7 cells with IC50 values ranging from 21.1 ± 1.7 to 46.7 ± 1.9 µM. Furthermore, iNOS expression experiment was performed to examine the interactions between the active compounds and the iNOS enzyme.

A meta-analysis on the impact of disease-specific education programs on health outcomes for patients with chronic obstructive pulmonary disease.

Disease-specific education programs have become an important factor in the treatment and care of chronic conditions, such as heart failure and diabetes mellitus. However, the effectiveness of these educational methods on chronic obstructive pulmonary disease (COPD) remains unclear. The objective of this meta-analysis was to evaluate whether disease-specific education programs were beneficial to health-related quality of life (HRQoL) variables and other long-term health outcomes in patients with COPD. Using electronic databases (PubMed, Cochrane Library, Science Direct, Chinese Biomedical Data System, China National Knowledge Infrastructure, and Wanfang Database) and individual searches (published and unpublished Chinese studies), we identified 12 randomized controlled trials (RCTs; English and/or Chinese) from 1991 to 2011. A meta-analysis on these studies revealed a positive relationship between disease-specific education programs and HRQoL scores (as measured by the St. George's Respiratory Questionnaire). Moreover, educational programs were associated with increased knowledge about COPD, improved disease management skills, inhaler adherence, and decreased COPD-related emergency department visits and hospital admissions, as well as long-term effects on improving COPD patients' health outcomes. Although significant effects were not detected across all HRQoL variables and health measures, our findings suggest that education programs have the potential to be a valuable intervention for COPD patients. Our results provide a foundation for future research in this area, which we recommend as including more rigorously designed, large, randomized studies.

[A case control study of influential factors or the Han population with coronary heart disease of blood stasis syndrome in Fuzhou area].

OBJECTIVE: To study main factors and the influencing extent of the susceptibility of the Han population with coronary heart disease (CHD) of blood stasis syndrome (BSS) in Fuzhou area. METHODS: A case control study was employed in Fujian People's Hospital from August 2009 to January 2010. Patients with recent attack of CHD of BSS and of CHD of non-BSS, as well as patients without CHD of non-BSS were recruited as subjects. Correlated factors with CHD were collected using questionnaire and laboratory examinations. The correlation and the correlation strength between each factor and CHD of BSS were analyzed using one-way and multiple-factor unconditional Logistic regression methods. RESULTS: Of the 403 patients in line with inclusion criteria, there were 176 patients with CHD of BSS, 123 with CHD of non-BSS, and 104 without CHD of non-BSS. Results of one-way analysis were reported as follows. Senility, mental labors, hypertension, excessive consumption of oil and salt, depression, stress, past relevant medical history, abnormal prothrombin time (PT), and abnormal hematocrit (HCT) were high-risk factors for CHD of BSS. Regular physical exercise and adequate sleep were protective factors. Except for the effects by age and sex, mental labors, hypertension, excessive consumption of oil and salt, depression, stress, past relevant medical history were still risk factors for CHD of BSS, with the correlation strength (OR value, 95% CI) being 1.902 (95% CI 1.222-2.959), 2.221 (95% CI 1.181-4.176), 2.945 (95% CI 1.781 4.871), 1.794 (95% CI 1.114-2.890), 3.462 (95% CI 1.555-7.712), 1.517 (95% Cl 1.082-2.128), and 3.159 (95% CI 1.732-5.764). In the comparison between those with CHD of BBS and those with CHD of non-BBS, excessive consumption of salt and meat, and stress were the risk factors for BSS. After the effects by age and sex were adjusted, the OR value were still 1.586 (95% CI 1.051-2.393), 1.801 (95% CI 1.191-2.723), and 1.386 (95% CI 1.024-1.876). CONCLUSIONS: When compared with the population of non-BSS, the predisposing factors for the Han population with CHD of BSS in Fuzhou area covered mental labors, hypertension, excessive consumption of oil and salt, depression, stress, and past relevant medical history. Compared with other syndrome types in Chinese medicine, positive correlation existed between BSS and excessive consumption of salt and meat, as well as stress.

[Determining the content of trace element in Potentilla parvifolia Fisch at different altitudes].

Determining the content of Ca, Fe, Mn, Zn, Cu and Mg in Potentilla parvifolia Fisch by atomic absorption spectrometry was studied. Recovery and RSD of the method is 98.3%-103.2% and 1.21%-3.01% respectively, and the method is rapid and precise. The order of the content in Potentilla parvifolia Fisch is Mg>Ca>Fe>Mn>Zn>Cu. There is not a relation between altitude and content. The mean of the content of Mg, Ca and Fe is 5079.641, 2760.188 and 1070.297 mg * kg(-1) respectively. The result of Potentilla parvifolia Fisch can provide theoretical basis for medicine research.

Antioxidant and α-glucosidase inhibitory ingredients identified from Jerusalem artichoke flowers.

Jerusalem artichoke (JA, Helianthus tuberosus L.) has been researched extensively due to its wide range of uses, but there are limited studies on its flowers. In this study, we report the first detailed phytochemical study on JA flowers, which yielded 21 compounds. Compound 4 was identified as a major water-soluble yellow pigment of JA flowers. In addition, the methanol extract of JA flowers and the isolates were evaluated for their antioxidant and α-glucosidase inhibitory activities. Among the tested compounds, compound 13 showed the strongest ABTS+ free radical scavenging activity with SC50 value of 2.30 ± 0.13 µg/mL, and compound 6 showed most potent α-glucosidase inhibitory activity with inhibition rate of 60.0% ± 10.3% at a concentration of 250 µg/mL. Results showed that methanol extract of JA flowers exhibited antioxidant and α-glucosidase inhibitory activities which could be attributed to its phenolic ingredients including chlorogenic acid derivatives, flavonoids and phenols.

8-isopentenyl isoflavone derivatives from the whole herb of Sphaerophysa salsula.

Phytochemical studies on the whole herb of Sphaerophysa salsula has resulted in the discovery of one new 8-isopentenyl isoflavone derivative, named sphaerosin s2 (3-(8-(2-hydroxypropan-2-yl)-3,4-dihydro-2H-furo[2,3-h]chromen-3-yl)-2,6-dimethoxyphenol) (1), along with four know 8-isopentenyl isoflavone derivatives (2-5). Compounds (2, 4 and 5) were isolated for the first time from this species. Their structures were elucidated on the basis of ESI-MS, UV, IR, 1D NMR and 2D NMR data.

Separation of antioxidant and α-glucosidase inhibitory flavonoids from the aerial parts of Asterothamnus centrali-asiaticus.

A new flavonoid, along with 16 known ones, was separated from the aerial parts of Asterothamnus centrali-asiaticus. Their structures were elucidated by extensive spectroscopic methods, including 1D and 2D NMR techniques and HRESIMS. To confirm the structure of the new compound, computational prediction of its 13C chemical shifts was performed. All of the 17 flavonoids were reported from A. centrali-asiaticus for the first time. In addition, all flavonoids were evaluated for their antioxidant and α-glucosidase inhibitory activities. The results showed that 10 of them exhibited antioxidant activity. Meanwhile, four flavonoids displayed α-glucosidase inhibitory effect with IC50 values ranging from 38.9 to 299.7 µM.

Association of platelet-activating factor receptor gene rs5938 (G/T) and rs313152 (T/C) polymorphisms with coronary heart disease and blood stasis syndrome in a Chinese Han population.

OBJECTIVE: To explore the association of the platelet-activating factor receptor (PAFR) gene rs5938, rs313152 and rs76744145 polymorphisms with coronary heart disease (CHD) and blood stasis syndrome (BSS) of CHD in Chinese Han population. METHODS: A total of 570 CHD patients (299 with BSS and 271 with non-BSS) and 317 controls were enrolled. The PAFR gene rs5938, rs313152 and rs76744145 polymorphisms were genotyped using the multiplex SNaPshot technology. The statistical analysis was conducted using a multiple variable logistic regression model. RESULTS: Significant differences were detected in the genotypes frequency distributions of the rs5938 (P<0.01), but not the rs313152 (P>0.05), between the controls and CHD patients. Individuals with an rs5938 or rs313152 mutated allele had a low risk for CHD [adjusted odds ratio (aOR)=0.35, 95% confidence interval (CI): 0.23 to 0.56, P<0.01; aOR=0.65, 95% CI: 0.46 to 0.91, P<0.05, respectively]. After the CHD patients were stratified as BSS or non-BSS according to their Chinese medicine patterns, the rs5938 polymorphism mutated alleles had a significant association with a low risk for BSS of CHD (aOR=0.32, 95% CI: 0.18 to 0.57, P<0.01) and non-BSS of CHD (aOR=0.31, 95% CI: 0.17 to 0.55, P<0.01). The rs313152 polymorphism was associated with a low risk for BSS (aOR=0.51, 95% CI: 0.33 to 0.79, P<0.01), but not for non-BSS (aOR=1.22, 95% CI: 0.81 to 1.85, P<0.05). Furthermore, the interaction effect of the rs5938 and rs313152 polymorphisms for BSS of CHD was significantly based on an aOR value associated with the combination of the rs5938 GT genotype with the rs313152 TC genotype of 0.27 (95% CI: 0.1 to 0.7, P<0.01). CONCLUSION: The PAFR gene rs5938 or rs313152 polymorphisms might be a potential biomarker for susceptibility to CHD, especially to BSS of CHD in Chinese Han population.

Antioxidants and α-glucosidase inhibitors from "Liucha" (young leaves and shoots of Sibiraea laevigata).

The young leaves and shoots of Sibiraea laevigata, known as "Liucha", are used as tea by Tibetans to improve digestion after meals. Long-term consumption of "Liucha" will cause weight loss. In present work, we reported on the isolation and NMR and chemical analysis-based elucidation of seven new sorbitol O-caffeic acid ester derivatives named sorbitol esters A-G (1-7) and eighteen known phenolic compounds from S. laevigata. All of the isolates were evaluated for their antioxidant and α-glucosidase inhibitory activities. Among them sorbitol ester A (1), sorbitol ester D (4), sorbitol ester F (6), sorbitol ester G (7), isoferulic acid (15), methyl caffeate (18), trans-p-hydroxycinnamic acid (19), and kaempferol 3-O-ß-d-(6″-E-p-coumaroyl)-glucopyranoside (25) showed more potent α-glucosidase inhibitory activity than the clinical drug acarbose.

Isolation and identification of antioxidant and α-glucosidase inhibitory compounds from fruit juice of Nitraria tangutorum.

Nitraria tangutorum Bor., having edible berries, is valued for reputed health benefits in Qinghai-Tibet plateau. The phytochemical research on the fruit juice of N. tangutorum led to the isolation of twenty-six compounds including five new compounds, tangutorids A-D (1, 2, 3a, and 3b), and (3E,5E)-7-O-ß-glucosyl-4-(2-methoxy-2-oxoethyl)hepta-3,5-dienoic acid (15). The structures of these compounds were elucidated through comprehensive spectroscopic analyses. Tangutorids A-F were the first examples of glucose-derived ß-carbolines from natural products. The biogenetic pathways of 1-8 were proposed to involve Pictet-Spengler reactions and described starting from the co-isolated tryptophan (10) and corresponding aldehydes. All isolates were evaluated for their antioxidant and α-glucosidase inhibitory activities. Compounds 21, 22, and 24 showed antioxidant activity with SC50 values ranging from 12.2±1.9 to 30.4±2.7µg/mL, and compound 1 showed strong α-glucosidase inhibitory effect with IC50 value of 63.3±4.6µg/mL.

A new isocoumarin from the aerial parts of Aconitum gymnandrum.

A new isocoumarin, along with 10 known compounds, was isolated from the aerial parts of Aconitum gymnandrum. Their structures were elucidated by spectroscopic methods including extensive 1D and 2D NMR techniques. Among the known compounds, compound 11 was obtained as a natural product for the first time, which was previously reported as a synthetic product. In addition, compounds 1-5, 7 and 9 were tested for their cytotoxicity against four human cancer cell lines. The results showed that compounds 3, 4 and 7 displayed cytotoxicity against lung cancer A549 and gastric cancer MGC80, respectively, whereas 5 and 9 showed selective cytotoxicity against hepatocellular carcinoma HepG2.

Isolation and Identification of Saponins from the Natural Pasturage Asterothamnus centrali-asiaticus Employing Preparative Two-Dimensional Reversed-Phase Liquid Chromatography/Hydrophilic Interaction Chromatography.

Asterothamnus centrali-asiaticus, a kind of characteristic shrub abundant in grassland and desert areas, has been used as forage fodder for camels and goats in Central Asia, and this plant also plays a critical role in the maintenance of desert grassland ecosystems as a result of its tolerance to poor soils and sand burial. However, its chemical composition has been rarely reported. In this study, phytochemical investigation of this pasturage was performed and three new triterpenoid saponins (1-3) were isolated together with nine known triterpenoid saponins (4-12) using preparative two-dimensional reversed-phase liquid chromatography/hydrophilic interaction chromatography (2D RPLC/HILIC). Their structures were elucidated via diverse spectroscopic analyses, including infrared (IR) spectrometry, high-resolution electrospray ionization mass spectrometry (HR-ESIMS), and one-dimensional (1D) and 2D nuclear magnetic resonance (NMR). All isolated triterpenoid saponins (1-12) were reported from this genus for the first time, and they were further evaluated for their cytotoxicity against four cancer cell lines (A549, HepG2, MGC-803, and MFC), which indicated that compound 11 showed potent cytotoxicity against the HepG2 cell line, with an IC50 value of 6.85 µg/mL.

Elevated plasma platelet activating factor, platelet activating factor acetylhydrolase levels and risk of coronary heart disease or blood stasis syndrome of coronary heart disease in Chinese: a case control study: a case-control study.

The purpose of the study was to explore the association between plasma platelet activating factor (PAF) and platelet activating factor acetylhydrolase (PAF-AH) levels and risk of coronary heart disease (CHD) or blood stasis syndrome (BSS) of CHD. Questionnaire, routine clinical assays and plasma levels of PAF, PAF-AH and inflammatory factors hs-CRP and IL-6 were investigated or measured for 120 controls and 150 CHD patients (66 non-BSS and 84 BSS). Plasma PAF levels were higher in CHD patients [49.7 (34.8-73.2 pg/mL)] than in controls [23.8 (14.9-42.3 pg/mL)] (P < 0.001), and in BSS [56.0 (40.1-86.1 pg/mL)] than in non-BSS [47.4 (29.0-67.4 pg/mL)] (P = 0.027). Similarly, plasma PAF-AH levels were higher in CHD patients [11.5 (7.5-15.6 µmol/L)] than in controls [8.1 (5.4-12.6 µmol/L)] (P < 0.001), and in BSS [13.4 (8.7-18.5 µmol/L)] than in non-BSS [9.5 (7.3-14.3 µmol/L)] (P = 0.014). After adjustment for the confounded effects of inflammatory factors or conventional risk factors, plasma PAF and PAF-AH levels still had a significant difference between CHD patients and controls, but plasma PAF-AH rather than PAF levels had a significant difference between BSS and non-BSS. Elevated plasma PAF level contributed to the risk of CHD rather than BSS, and elevated plasma PAF-AH level was an independent risk factor of CHD and BSS.