Quality evaluation of Crataegus pinnatifida leaves by fingerprint combined with quantitative analysis of multi-components by single-marker / 中国药房

OBJECTIVE To establish the fingerprint and multi-component content determination method of Crataegus pinnatifida leaves from different producing areas， and to evaluate the quality of C. pinnatifida leaves and screen the differential markers. METHODS Seventy-eight batches of C. pinnatifida leaves were collected from Chengde of Hebei Province， Huludao of Liaoning Province， Yuncheng of Shanxi Province and Linyi of Shandong Province. High-performance liquid chromatography （HPLC） and Similarity Evaluation System for Traditional Chinese Medicine Chromatographic Fingerprints （2012 edition） were used to draw the fingerprints and conduct similarity evaluation. Grey correlation analysis， cluster analysis （CA）， principal component analysis （PCA） and orthogonal partial least squares-discriminant analysis （OPLS-DA） were performed by using SPSS 19.0， MetaboAnalyst 5.0 and SIMCA 14.1 software. The differential markers affecting the quality of C. pinnatifida leaves were screened with variable importance in the projection （VIP） value greater than 1 and the error line not exceeding the origin as the criterion. Using vitexin rhamnoside as an internal reference， the contents of chlorogenic acid， glucosylvitexin， hypericin and isoquercetin in 78 batches of C. pinnatifida leaves were determined by the same HPLC combined with quantitative analysis of multi- components by single-marker （QAMS）， and the results were compared with external standard method. RESULTS Eight common peaks were calibrated in the fingerprints for 78 batches of C. pinnatifida leaves from 4 producing areas. Five known components were identified， including chlorogenic acid （peak 1）， glucosylvitexin （peak 3）， vitexin rhamnoside （peak 4）， hypericin （peak 7） and isoquercetin （peak 8）； their similarities ranged from 0.871 to 0.998. Average relative correlations of samples from Chengde of Hebei Province， Huludao of Liaoning Province， Yuncheng of Shanxi Province and Linyi of Shandong Province were 0.538， 0.528， 0.462 and 0.435， respectively. CA and PCA showed that the samples from Chengde of Hebei Province and Huludao of Liaoning Province were roughly classified into one category， while the samples from Linyi of Shandong Province and Yuncheng of Shanxi Province were roughly classified into one category； VIP values of peak 1， 2， 3 and 5 were all greater than 1. By QAMS， the relative correction factors of chlorogenic acid， glucosylvitexin， hypericin and isoquercetin were 0.401， 0.993， 1.670 and 1.615 （RSD＜2%）. Compared with external standard method， except for isoquercetin in the two batches of samples （S39 and S41）， there was no significant difference in the content of each component in other batches of samples （the relative deviations≤ 5%）. CONCLUSIONS The established fingerprint and QAMS method are simple to operate and can be used to evaluate the quality of C. pinnatifida leaves. The sample from Chengde of Hebei Province is relatively good in quality. Chlorogenic acid （peak 1）， glucosylvitexin （peak 3）， and the corresponding components of peaks 2 and 5 may be differential markers affecting the quality of C. pinnatifida leaves.

Opposite Modulatory Effects of Crataegus aronia Aqueous Extract on Platelet Aggregation in Rats / 中国结合医学杂志

OBJECTIVES@#To reveal the mechanisms behind the dual effects of Crataegus aronia (C. aronia) aqueous extract on platelet aggregation by focusing on function, regulation, expression, and signaling of platelets P@*METHODS@#Adult male Wistar rats (120 ± 10 g) were classified as control received the vehicle, C. aronia (200 mg/kg), and C. aronia (2,000 mg/kg)-treated rats. After treatments for consecutive 7 days, hematological and molecular experiments were conducted to detect alterations in platelet aggregation, thromboxane B2 (THXB2) and intracellular reactive oxygen species (ROS) content; protein levels of P@*RESULTS@#At a concentration of 200 mg/kg, C. aronia inhibited platelet aggregation through multiple interconnected mechanisms including downregulation P@*CONCLUSION@#Oral administration of C. aronia at low dose inhibits platelet aggregation by reducing THXB2 release, expression of P-selectin and activating cAMP and Akt signaling through two major mechanisms including downregulation of P

Terpenoids from leaves of Chinese hawthorn / 中国中药杂志

Fifteen compounds were isolated from the 70% EtOH extract of leaves of Chinese hawthorn(Crataegus pinnatifida var. major) by various purification steps, and their structures were determined as 2α,3α,12β,19α,-tetrahydroxyursan-13β,28-olide(1),euscaphic acid(2), tormentic acid(3), ursolic acid(4), pomolic acid(5), corosolic acid(6), maslinic acid(7), linalyl rutinoside(8),(Z)-3-hexenyl β-D-glucoside(9),(3S, 6S)-cis-linalool-3,7-oxide-β-D-glucopyranoside(10), pisumionoside(11), icariside B6(12), byzantionoside B(13),(6R,7E,9R)-9-Hydroxy-4,7-megastigmadien-3-one 9-O-β-D-glucopyranoside(14) and(6S,7E,9R)-6,9-dihydroxy-4,7-megastigmadien-3-one 9-O-β-D-glucopyranoside(15) mainly based on the mass spectrum(MS) and nuclear magnetic resonance(NMR) spectroscopic techniques, of which compound 1 was a new pentacyclic triterpene, and compounds 2, 5, 6, 8, 10, 13 and 15 were isolated form this plant for the first time.

Different development phase of transcriptome analysis from Crataegus pinnatifida Bge. and cloning, structure and function prediction of squalene epoxidase involved in triterpenic acid biosynthesis / 药学学报

italic>Crataegus pinnatifida is a traditional Chinese medicine, which contains organic acids, triterpenoid acids and other active components, has important medicinal and edible value. In order to study the difference of gene expression level in different developmental stages of hawthorn and explore the genes of active ingredient biosynthesis in Crataegus pinnatifida, high-throughput Illumina HiSeq 2000 technology were used to conduct transcriptome sequencing and bioinformatics analysis on Crataegus pinnatifida fruits from the same origin at different developmental stages. 78 496 Unigenes with an average length of 941 nt were obtained by Trinity software. Among them, 58 395 Unigenes can be annotated by NR, NT, Swiss prot, KEGG, COG, GO and other public databases. KEGG pathway analysis showed that 52 Unigenes encoding 15 key enzymes involved in the citric acid cycle. There are 62 Unigenes were involved in the triterpene biosynthesis pathway of Crataegus pinnatifida. Two key enzymes SQE of triterpenoid metabolism pathway in Crataegus pinnatifida were cloned and performed bioinformatic analysis. The results showed that ORF of CpSQE1 and CpSQE2 were 1 594 bp and 1 597 bp, respectively, encoding 530 and 531 amino acids. The molecular weight of proteins was 57.6 kDa and 57.5 kDa. Bioinformatics analysis showed that both CpSQE1 and CpSQE2 proteins have a PLN02985 superfamily conserved domain, belonging to the squalene monooxygenase superfamily. The phylogenetic tree shows that CpSQE1 and CpSQE2 are clustered together with SQE with squalene epoxidase function in other plants. This study provides a research basis for further exploring the key genes in the biosynthesis process of hawthorn active ingredients and analyzing the regulation pathway of its active ingredient biosynthesis.

Cloning and prokaryotic expression analysis of squalene synthase CpSQS1 and CpSQS2 from Crataegus pinnatifida / 中国中药杂志

In order to understand the structural characteristics of squalene synthase genes in the triterpenoids biosynthesis pathway of Crataegus pinnatifida, the squalene synthase genes of C. pinnatifida was cloned and analyzed by bioinformatics and prokaryotic expression. Two squalene synthase genes CpSQS1 and CpSQS2 were cloned from C. pinnatifida fruit by RT-PCR. The ORF length of CpSQS1 and CpSQS2 were 1 239 bp and 1 233 bp respectively, encoding 412 aa and 410 aa respectively. CpSQS1 and CpSQS2 were predicted to be stable acidic proteins by online tools. The secondary structure was mainly composed of α-helix structure, and the tertiary structure was predicted by homology modeling. Structural functional domain analysis showed that 35-367 aa of CpSQS1 and CpSQS2 cDNA containing conserved trans-isoprenyl pyrophosphate synthase domains. Transmembrane domain analysis predicted that two transmembrane domains were founded in CpSQS1 and CpSQS2. The squalene synthase amino sequence of C. pinnatifida had higher homology with the known SQS of Salvia miltiorrhiza and Glycyrrhiza glabra. Phylogenetic tree analysis showed that CpSQS1 and CpSQS2 were clustered into one branch of MdSQS1 and MdSQS2, which were consistent with the phylogenetic rule. Prokaryotic expression vector pGEX-4 T-1-CpSQS1 and pGEX-4 T-1-CpSQS2 were transformed into Escherichia coli Transetta(DE3) for induction, and the target protein was successfully expressed at 65 kDa. The expression levels of CpSQS2 were significantly higher than that of CpSQS1 in three different developmental stages of C. pinnatifida. In this study, the full-length cDNA sequences of C. pinnatifida SQS1 and SQS2 were cloned and analyzed for the first time, which provided the foundation for further study on the metabolic pathway of C. pinnatifida triterpenoids.

Antihypoxic activities of Crataegus pentaegyn and Crataegus microphylla fruits-an in vivo assay

ABSTRACT The aim of this study was to evaluate anti-hypoxia activity of polyphenolic extracts of Crataegus microphylla and Crataegus pentaegyn on mice. Three experimental models of hypoxia were considered, including asphyctic hypoxia, haemic hypoxia, and circulatory hypoxia. Polyphenolic extract of both plants exhibited significant anti-hypoxic activity and prolonged animal survival time. Anti-hypoia activity of C. pentaegyn was found to be superior to that of C. microphylla in circulatory and asphyctic hypoxia. Antihypoxic activity of these extracts may be attributed to their phenolic compounds.

Differential therapeutic effects of Crataegus aronia and simvastatin on the hepatocyte ultrastructure in hepatic steatosis / Efectos terapéuticos diferenciales de Crataegus aronia y simvastatina sobre la estructura del hepatocito en la esteatosis hepática

Complications of fat accumulation in liver, hepatic steatosis such as liver cirrhosis and liver failure are among the common public health problems. We sought to investigate the damage to the hepatocyte ultrastructure induced by high fat diets (HFD) and compared the therapeutic effects at the cellular level of two antioxidant and lipid lowering agents; Crataegus aronia extracts and simvastatin on hepatic steatosis. Rats were either fed with HFD (model group) or low fat diets (LFD) (control group) for 15 weeks before being sacrificed and therapeutic groups started the treatment with these agents after week 11 until the sacrifice day. Harvested liver tissues were examined using transmission electron microscopy (TEM) and liver homogenates were assayed for markers of anti-oxidative stress that are known to be modulated in liver injury. TEM examinations of the model group showed a profound damage to the hepatocytes compared to the control group as demonstrated by steatosis, damaged mitochondria and vaculated cytoplasm, disrupted rough and smooth endoplasmic reticulum and nuclear membrane, dilated intercellular space between hepatocytes, and alterations in lysosomes. In addition, HFD ameliorated the anti-oxidant glutathione (GSH) and augmented the oxidative stress TBARS biomarkers. Both Crataegus aronia and simvastatin significantly reduced lipids and TBARS, and treated damage to hepatic cells, but hepatocyte structures were differentially responded to these agents. However, only Crataegus aronia induced GSH (p=0.001). We conclude that HFD-induced hepatic steatosis caused a substantial damage to the hepatocyte's ultrastructures, and Crataegus aronia and simvastatin treatments differentially reversed hepatic injuries.

Las complicaciones de la acumulación de grasa en el hígado, la esteatosis hepática como la cirrosis hepática y la insuficiencia hepática se encuentran entre los problemas comunes de salud pública. Se intentó investigar el daño a la ultraestructura de los hepatocitos inducido por la dieta alta en grasas (DAG) y se compararon los efectos terapéuticos a nivel celular de dos antioxidantes y agentes hipolipemiantes; Extracto de Crataegus aronia y simvastatina sobre esteatosis hepática. Las ratas fueron alimentadas con DAG (grupo modelo) o dieta baja en grasa (DBG) (grupo control) durante 15 semanas antes de sacrificarse y los grupos terapéuticos comenzaron el tratamiento con estos agentes después de la semana 11 hasta el día del sacrificio. Se examinaron los tejidos hepáticos usando microscopía electrónica de transmisión (MET) y se analizaron homogeneizados de hígado para marcadores de estrés anti-oxidativo, que se sabe están modulados en la lesión hepática. Los exámenes MET del grupo DAG mostraron un grave daño de los hepatocitos en comparación con el grupo control, demostrado por esteatosis, daño mitocondrial y citoplasma vacío, retículo endoplásmico rugoso y liso y membrana nuclear, el espacio intercelular dilatado entre hepatocitos y alteraciones en los lisosomas. Además, DAG mejoró el anti-oxidante glutatión (GSH) y aumentó el estrés oxidativo TBARS biomarcadores. Tanto Crataegus aronia como simvastatina redujeron significativamente los lípidos y TBARS, trataron el daño a las células hepáticas, pero las estructuras de hepatocitos respondieron diferencialmente a estos agentes. Sin embargo, sólo Crataegus aronia indujo GSH (p = 0,001). Concluimos que la esteatosis hepática inducida por HFD causó un daño sustancial a la ultraestructura del hepatocito y los tratamientos de Crataegus aronia y simvastatina diferenciaron las lesiones hepáticas.

Study on Enrichment Process of Total Flavonoids from Crataegus pinnatifida Bge, with Macroporous Resin / 中国生化药物杂志

Objective To study the optimal technology parameters of the enrichment process for total flavonoids of Crataegus pinnatifida Bge,with macroporous Resin. Methods The enrichment process was studied by orthogonal experiment design using orthogonal from L9(34) with the content of total flavonoids from Crataegus pinnatifida Bge,as indexes, the factors such as adsorption capacity, the column diameter-height ratio, eluant volume and adsorption time were investigated. Results The optimum elution parameters were as follows: the eluant volume of 60% alcohol—the wet resin amount (g)—the sample volume (mL) was 2:1, the sample was 4:1, the column diameter-height ratio was 1:6 , the adsorption time was 1h, respectively. Conclusion This process enriching the total flavonoids of Crataegus pinnatifida Bge,is feasible.

Spectrum-effect relationship of triglyceride-lowering fraction of Crataegus pinnatifida fruit / 中草药

Objective: To investigate the correlation between UPLC fingerprints of triglyceride (TG)-lowering fraction of Crataegus pinnatifida fruit and its efficacy. Methods: In vitro digestion model for TG was applied to screen the TG-lowering fraction of C. pinnatifida fruit. The fingerprints of TG-lowering fraction of 12 batches of hawthorn fruits from different habitats were established by UPLC. And the partial least squares regression (PLSR) analysis was used to explore the correlation between peak areas of UPLC fingerprints and TG content. Results: Flavonoids rich fraction of C. pinnatifida fruit exhibited stronger TG decreasing activity than other fractions. Eleven common peaks of the active fraction were selected. Peaks 1 (procyanidins dimers B), 3 (procyanidins C1), 4 (procyanidins dimers B), 5 (rutin), 6 (hyperoside), 7 (isoquercitrin), and 8 (procyanidins dimers B) had positive effect on TG decreasing activity, while peaks 2 (epicatechin), 10 (quercitin), and 11 (5-O-caffeoyl quinic acid butyl ester) had negative effect. Conclusion: The TG-lowering effect is closely related to flavonoids.

Rapid determination of oleanolic acid and ursolic acid in eight kinds of Chinese materia medica by HPLC / 中草药

Objective: To establish a method of rapid analysis for simultaneous determination of oleanolic acid and ursolic acid in Chinese materia medica (CMM) of Verbena officinalis, Ligustrum lucidum, Prunella vulgaris, Hedyotis diffusa, Patrinia scabiosaefolia, Eriobotrya japonica, Crataegus pinnatifida, Chaenomeles Fructus papaya. Methods: The analyses of preparation were conducted by accelerated solvent extraction (ASE), methanol was used as solvent extraction, and the static extraction time was 6 min. Separation was carried out on Acclaim C30 Thermo column with acetonitrile and 0.2% acetic acid (85:15) as mobile phase, flow rate was 0.3 mL/min, and UV detection wavelength was set at 205 nm. Results: After 10 min sample extraction time, oleanolic acid and ursolic acid reached baseline separation, and no sample matrix was interfered, the linear correlation coefficient was over 0.999, the average recovery between 95.8% and 102.7%; Compared to Chinese Pharmacopoeia 2015, the determination of average mass fraction difference was 3.7% and 5.8%. Conclusion: This method is simple, fast, and suitable for the analysis of these drugs, and it can be used for content determination of oleanolic acid and ursolic acid for eight kinds of CMM.

Study on quality standard of Wujin capsules / 药学实践杂志

Objective To establish the qualitative and quantitative analytic method for quality control of Wujin capsules.Methods Curcuma wenyujin Y.H.Chen et C.Ling and Crataegus pinnatifida Bge.in Wujin capsules were identified by TLC method.The content of tenacissoside H was determined by HPLC.Chromatographic separation was achieved at Waters Xbridge C18 column (100 mm× 3.0 mm, 3.5 μm) with an evaporative light scattering detector (ELSD).Acetonitrile and H2O were used as the mobile phase for isocratic elution.Results The qualitative identification by TLC was specific.The well separated clear spots were exhibited on each thin layer plate.Tenacissoside H had a linear equation in the range of 11.60-580.00 μg/ml(r=0.999 0).The average recovery was 101.54％.Conclusion The TLC identification of Curcuma wenyujin Y.H.Chen et C.Ling and Crataegus pinnatifida Bge.was simple and well established.The HPLC-ELSD method was specific,sensitive and reliable.Those methods can be used for the quality control of Wujin capsules.

Effects of Ethanol Extract of Crataegus Pinnatifida Bge. Var. major N. E. Br. from Heilongjiang Province on Hemodynamics of Acute Myocardial Ischemia and Platelet Aggregation in Rats / 中国药师

Objective: To observe the effect of ethanol extract of Crataegus Pinnatifida Bge. Var. major N. E. Br. from Hei-longjiang province on hemodynamics of acute myocardial ischemia caused by ligation and platelet aggregation induced by isoproterenol. Methods:After the model establishment of acute myocardial ischemia by ligation in rats, the systolic blood pressure ( SBP) ,diastolic blood pressure ( DBP ) , heart rate ( HR ) , left ventricular systolic pressure ( LVSP ) , left ventricular end-diastolic pressure ( LV-EDP) , left ventricular peak systolic ( +) and diastolic ( -) rate ( ± dp ·dt max-1 ) were recorded. Meanwhile, the acute myocar-dial ischemia model induced by isoproterenol was established. The platelet aggregation was measured by a platelet aggregation instru-ment. Results:The ethanol extract of Crataegus Pinnatifida Bge. Var. major N. E. Br. from Heilongjiang province could significantly increase the SBP, DBP, LVSP, +dp · dtmax-1 and HR, and reduce LVEDP,-dp·dtmax-1 in high dose group with statistical sig-nificance (P<0. 05). The medium dose group had small impact on the DBP, while showed statistically significant effect on the other hemodynamic indices. The low dose group had statistically significant effect on the SBP, LVSP and ± dp·dtmax-1 (P<0. 05), while showed no notable effects on the other indices. The results of aggregation rate in 1 min and 5 min after the determination and the maxi-mum one in the high and medium dose groups showed that the ethanol extract could significantly inhibit the platelet aggregation with sta-tistical significance (P<0. 05). Conclusion:The ethanol extract of Crataegus Pinnatifida Bge. Var. major N. E. Br. can improve the blood flow of acute myocardial ischemia in rats and reduce platelet aggregation after ischemia.

Simultaneous Determination of Six Effective Components in Crataegus pinnatifida by Quantitative Analysis of Multi-components by Single Marker / 中国药房

OBJECTIVE:To establish a method for the simultaneous determination of chlorogenic acid,vitexin glucoside,vi-texin rhamnoside,vitexin,rutin and hyperoside in Crataegus pinnatifida. METHODS:With reference peak of vitexin glucoside, HPLC was conducted to calculate the relative correction factor(RCF)of chlorogenic acid,vitexin glucoside,vitexin rhamnoside, vitexin,rutin and hyperoside,then the contents of above-mentioned 5 components in C. pinnatifida were calculated. The column was Agilent ZORBAX SB C18 with mobile phase of 0.1% formic acid-acetonitrile-tetrahydrofuran (gradient elution) at a flow rate of 1.0 ml/min,the detection wavelength was 350 nm,column temperature was 30 ℃,and the injection volume was 10 μl. RE-SULTS:The linear range was 12.50-400.0 μg for chlorogenic acid(r=0.999 8),25.00-800.0 μg for vitexin glucoside(r=0.999 9), 31.25-1 000.0 μg for vitexin rhamnoside(r=0.999 9),6.470-260.0 μg for vitexin(r=0.999 9),2.50-80.0 μg for rutin(r=0.999 8) and 9.375-300.0 μg for hyperoside(r=0.999 9);RSDs of precision,stability and reproducibility tests were lower than 2.0%;re-coveries were 99.2%-103.9%(RSD=1.6%,n=6),97.9%-100.8%(RSD=1.2%,n=6),99.2%-100.8%(RSD=0.5%,n=6), 97.3%-101.3%(RSD=1.5%,n=6),98.0%-103.0%(RSD=1.9%,n=6)and 95.5%-101.5%(RSD=2.2%,n=6). RCFs of vitex-in glucoside with chlorogenic acid,vitexin rhamnoside,vitexin,rutin and hyperoside were 1.119,1.009,0.706,1.063 and 0.830, respectively. CONCLUSIONS:The method is simple with good precision,stability and reproducibility,and it can be sued for the simultaneous determination of 6 components in C. pinnatifida.

Total Flavone of Hawthorn Leaf inhibits neuronal apoptosis in brain tissue of rat models of chronic cerebral ischemia / 中国组织工程研究

BACKGROUND: Cerebrovascular disease often causes dysfunction of the brain nerve, and nerve cel apoptosis is the important factor of cerebral nerve dysfunction. The excessive expression of c-fos can block the transduction of intracelular signal so that producing some apoptosis-promoting factors, which involve in nerve cel apoptosis process after ischemia injury of brain. Bcl-2 is an inhibited factor. It might to be the key to treat ischemic cerebrovascular disease by inhibiting or reducing the apoptosis of nerve cels after ischemia injury. OBJECTIVE: To investigate the therapeutic effect and mechanism of the Total Flavone of Hawthorn Leaf on chronic cerebral ischemia rats. METHODS: A total of 72 healthy male Sprague-Dawley rats were randomly divided into sham surgery group, model group, Total Flavone of Hawthorn Leaf group and ginkgo leaf group. Permanent bilateral carotid artery ligation was used to prepare chronic cerebral ischemia model in the model group, Total Flavone of Hawthorn Leaf group and ginkgo leaf group. Total Flavone of Hawthorn Leaf group and ginkgo leaf group respectively received 140 mg/kg Total Flavone of Hawthorn Leaf and 12.3 mg/kg ginkgo leaf intragastricaly for 36 days from 36 days after model induction. Model group and sham surgery group received 3.5 mL/kg physiological saline intragastricaly. RESULTS AND CONCLUSION: Compared with the model group, the expression of c-fos protein significantly deceased in the Total Flavone of Hawthorn Leaf group (P 0.05). These data indicated that the protective effect of Total Flavone of Hawthorn Leaf on chronic cerebral ischemia was associated with its inhibition of neuronal apoptosis. Its mechanism of anti-apoptosis might be associated with up-regulating expression of Bcl-2, down-regulating expression of c-fos and decreasing Ca2+ content in brain.

Organic acids, sugars, vitamin C content and some pomological characteristics of eleven hawthorn species (Crataegus spp) from Turkey

BACKGROUND: The Hawthorn (Crateagus sp.) mostly occurs around the temperate region of the world with a high number of species, producing a fruit with numerous beneficial effects for human health. The aim of the study was to determine organic acid and sugar contents in the fruit of a number of hawthorn species grown in Erzincan province of Turkey. RESULTS: Citric acid was the predominant organic acid in all hawthorn species and C. pseudoheterophylla had the highest citric acid content (23.688 g/100 g). There were not statistically significant differences among hawthorn species (except C. atrosanguinea Pojark) in terms of fumaric acid content. C. pontica C.Koch had a higher content of vitamin C (9.418 mg/100 g) compared to other species. Fructose was the predominant sugar component in all species and C. monogyna subsp. monogyna Joiq had the highest fructose content (18.378 g/100 g). CONCLUSIONS: The high fruit quality of the studied species indicates the importance of this fruit in human nutrition as a natural source. The study revealed that there were differences in terms of fruit characteristics among hawthorn species and thus better quality hawthorn genotypes can be selected within the species. Hence, this study is considered to be a valuable reference for forthcoming studies. The high fruit quality of the studied species indicates the importance of this fruit in human nutrition as a natural source.

Prognostic Factors for Patients with Congestive Heart Failure – An Extended Evaluation of the SPICE-Study.

Aims: Controlled clinical trials collect huge amounts of high quality data. It is a waste of information to evaluate these data only for the efficacy and safety of the investigational medication. We propose extended evaluations of large trials for scientific purposes, especially to find the most important risk factors of the disease or variables which are associated with risk to have the disease. Methodology: The SPICE study is a controlled, randomised, completely masked trial that has investigated the efficacy of the Crataegus product WSÒ 1442 in 2681 randomised patients with congestive heart failure (CHF). It was initiated and sponsored by Dr. Willmar Schwabe Pharmaceuticals. Results have already been published. We asked the sponsor to send us the data for an extended evaluation which was performed with a multivariate Cox regression model to find risk factors for the composite endpoint cardiac death, non-fatal myocardial infarction or hospitalisation due to progressive heart failure. Results: Most important risk factors are lower New York Heart Association (NYHA) function class, younger age and higher left ventricular ejection fraction. Patients had less cardiac events when taking glycosides, antiarrhythmics, nitrates, diuretics, beta blockers and calcium antagonists, so patients with a high number of cardiovascular medication have a poorer prognosis. Three scenarios for the interpretation of cardioactive medications as “risk” are presented. We assume that symptoms leading to the indication of a specific cardioactive medication are the risk. This risk is only partly balanced by medication intake. In general, the intake of cardioactive medication is associated with the risk to have the disease. Conclusion: An extended evaluation of large clinical studies finds out what is important for the outcome besides specific efficacy of the investigational drug. This is usually not the scope of pharmaceutical companies, but useful for science, doctors and patients.

Isolation of cytotoxic compounds from the seeds of Crataegus pinnatifida / 中国天然药物

AIM@#To study the chemical constituents and bioactivity of the seeds of Crataegus pinnatifida.@*METHODS@#The chemical constituents were isolated and purified by macroporous adsorptive resin D101, silica gel, and ODS column chromatography, and preparative HPLC. Their structures were elucidated on the basis of spectroscopic methods. In addition, the cytotoxic activities of compounds 1-4 were investigated on OPM2 and RPMI-8226 cells.@*RESULTS@#Four compounds were obtained and their structures were identified as (7S, 8S)-4-[2-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-1-(hydroxymethyl)ethoxy]-3, 5-dimethoxybenzaldehyde (1), (+)-balanophonin (2), erythro-guaiacylglycerol-β-coniferyl aldehyde ether (3), buddlenol A (4).@*CONCLUSION@#Compound 1 is a novel norlignan, while compounds 1-4 exhibited marginal inhibition on the proliferation of OPM2 and RPMI-8226 cells.

Pharmacokinetic study of isoquercitrin in rat plasma after intravenous administration at three different doses

The aim of this study is to develop a simple and specific HPLC method using vitexin as the internal standard to investigate the pharmacokinetics of isoquercitrin (ISOQ) after three different doses administrated intravenously to rats. The pharmacokinetic parameters were calculated by both compartmental and non-compartmental approaches. The results showed that ISOQ fitted a three-compartment open model. The values of AUC increased proportionally within the range of 5-10 mg·kg-1. Moreover, a half-life, b half-life, ªCL, MRT0-t and MRT0→∞ of ISOQ in rats showed significant differences between 20 mg·kg-1 and other doses, indicating that ISOQ presented dose-dependent pharmacokinetics in the range of 5-10 mg·kg-1 and non-linear pharmacokinetics at higher doses.

O objetivo deste estudo é desenvolver um método simples e específico de HPLC usando vitexina como padrão interno para investigar a farmacocinética do isoquercitrina (ISOQ) após três doses diferentes administradas por via intravenosa a ratos. Os parâmetros farmacocinéticos foram calculados pelas abordagens compartimental e não compartimental. Os resultados mostraram que ISOQ se encaixa no modelo de três compartimentos. Os valores de AUC aumentaram proporcionalmente na faixa de 5-10 mg·kg-1. Além disso, a meia-vida, b meia-vida, ªCL, MRT0-t and MRT0→∞ de ISOQ em ratos mostraram diferenças significativas entre 20 mg·kg-1 e outras doses, o que significa que ISOQ apresenta farmacocinética dose-dependente no intervalo de 5-10 mg·kg-1 e farmacocinética não linear em doses mais elevadas.

The genus Crataegus: chemical and pharmacological perspectives

Traditional drugs have become a subject of world importance, with both medicinal and economical implications. A regular and widespread use of herbs throughout the world has increased serious concerns over their quality, safety and efficacy. Thus, a proper scientific evidence or assessment has become the criteria for acceptance of traditional health claims. Plants of the genus Crataegus, Rosaceae, are widely distributed and have long been used in folk medicine for the treatment of various ailments such as heart (cardiovascular disorders), central nervous system, immune system, eyes, reproductive system, liver, kidney etc. It also exhibits wide range of cytotoxic, gastroprotective, anti-inflammatory, anti-HIV and antimicrobial activities. Phytochemicals like oligomeric procyanidins, flavonoids, triterpenes, polysaccharides, catecholamines have been identified in the genus and many of these have been evaluated for biological activities. This review presents comprehensive information on the chemistry and pharmacology of the genus together with the traditional uses of many of its plants. In addition, this review discusses the clinical trials and regulatory status of various Crataegus plants along with the scope for future research in this aspect.

Ethnomedicinal and phytopharmacological potential of Crataegus oxyacantha Linn. - A review

Traditional herbal medicines are practiced in the entire world and their ethnopharmacological records reveal that most of the people of the world have been using plants, animals, micro-organisms and minerals for treating various diseases. Crataegus oxyacantha (C. oxyacantha) Linn. (Rosaceae) commonly known as Hawthorn is an official plant in Homeopathic System of Medicine to treat various conditions of cardiovascular system. In recent times, this drug has been subjected to phytochemical, pharmacological, pre-clinical and clinical investigations and many new investigations have been indicated. Current review finds ethnomedicinal and phytopharmacological potential of leaves, flowers, berries, bark etc. for exploring the immense medicinal potential of Hawthorn. At the same time, studies to evaluate the dosage, toxicity and interactions with drugs and herbs on simultaneous use, which is imperative for optimal and safe utilization of this plant, are explained. There are few comprehensive reports available on clinical use of Hawthorn in chronic heart failure patients have shown promising results.