Quince extract resists atherosclerosis in rats by down-regulating the EGFR/PI3K/Akt/GSK-3ß pathway.

We identified the effective components and the underlying mechanisms of Quince (Cydonia oblonga Mill, COM) extract against atherosclerosis. The effective components of COM extract were identified with UHPLC-Q-TOF-MS/MS. Network pharmacology was performed. A rat model of atherosclerosis induced by high-fat emulsion combined with vitamin D3 was established. The anti-atherosclerosis effect of COM extract was evaluated from various aspects such as blood lipid regulation, anti-oxidative stress, anti-inflammatory response, and vascular protection function. We identified 14 serum components of COM extract using UHPLC-Q-TOF-MS/MS. Through prediction, 573 targets were obtained, among which 224 targets were atherosclerosis specific targets. The key targets included GSK3ß, ESR1, EGFR, and HSP90AA1. The key signaling pathway was PI3K-Akt signaling pathway. Pharmacodynamics analysis showed that COM extract reduced the levels of TC, TG, and LDL-C as well as ALT and AST, while increased the level of HDL-C. Mechanistically, COM extract significantly increased serum SOD and GSH-Px activities, but decreased MDA content in atherosclerosis rats, showing antioxidant effects. Meanwhile, COM extract significantly down-regulated the levels of pro-inflammatory factors IL-1ß, IL-6, TNF-α and CRP, but up-regulated anti-inflammatory factor IL-10. Additionally, COM extract increased the levels of NO, eNOS, and 6-keto-PGF1α; whereas, decreased the levels of ET-1 and TXB2. Furthermore, COM extract significantly inhibited the mRNA and protein levels of EGFR, p-PI3K, p-AKT, GSK-3ß, Bax, and Caspase-3 as well as the Bax/Bcl-2 ratio. Conclusively, COM extract exerts hypolipidemic, anti-oxidative, anti-inflammatory, anti-thrombotic and vascular endothelium protective effects on atherosclerosis rat model, which may be related to the inhibition of EGFR/PI3K/AKT/GSK-3ß signaling pathway.

Sunflower pollen induces rapid excretion in bumble bees: Implications for host-pathogen interactions.

Host diet can have a profound effect on host-pathogen interactions, including indirect effects on pathogens mediated through host physiology. In bumble bees (Bombus impatiens), the consumption of sunflower (Helianthus annuus) pollen dramatically reduces infection by the gut protozoan pathogen Crithidia bombi. One hypothesis for the medicinal effect of sunflower pollen is that consumption changes host gut physiological function, causing rapid excretion that flushes C. bombi from the system. We tested the effect of pollen diet and C. bombi infection on gut transit properties using a 2x2 factorial experiment in which bees were infected with C. bombi or not and fed sunflower or wildflower pollen diet. We measured several non-mutually exclusive physiological processes that underlie the insect excretory system, including gut transit time, bi-hourly excretion rate, the total number of excretion events and the total volume of excrement. Sunflower pollen significantly reduced gut transit time in uninfected bees, and increased the total number of excretion events and volume of excrement by 66 % and 68 %, respectively, in both infected and uninfected bees. Here we show that a sunflower pollen diet can affect host physiology gut function, causing more rapid and greater excretion. These results provide important insight into a mechanism that could underlie the medicinal effect of sunflower pollen for bumble bees.

Empirical assessment of case-based methods for identification of drugs associated with upper gastrointestinal bleeding in the French National Healthcare System database (SNDS).

PURPOSE: Upper gastrointestinal bleeding (UGIB) is a severe and frequent drug-related event. In order to enable efficient drug safety alert generation in the French National Healthcare System database (SNDS), we assessed and calibrated empirically case-based designs to identify drug associated with UGIB risk. METHODS: All cases of UGIB were extracted from SNDS (2009-2014) using two definitions. Positive and negative drug controls were used to compare 196 self-controlled case series (SCCS), case-control (CC) and case-population (CP) design variants. Each variant was evaluated in a 1/10th population sample using area under the receiver operating curve (AUC) and mean square error (MSE). Parameters that had major impacts on results were identified through logistic regression. Optimal designs were replicated in the unsampled population. RESULTS: Using a specific UGIB definition, AUCs ranged from 0.64 to 0.80, 0.44 to 0.61 and 0.50 to 0.67, for SCCS, CC and CP, respectively. MSE ranged from 0.07 to 0.39, 0.83 to 1.33 and 1.96 to 4.6, respectively. Univariate regressions showed that high AUCs were achieved with SCCS with multiple drug adjustment and a 30-day risk window starting at exposure. The top-performing SCCS variant in the unsampled population yielded an AUC = 0.84 and MSE = 0.14, with 10/36 negative controls presenting significant estimates. CONCLUSIONS: SCCS adjusting for multiple drugs and using a 30-day risk window has the potential to generate UGIB-related alerts in the SNDS and hypotheses on its potential population impact. Negative control implementation highlighted that low systematic error was generated but that protopathic bias and confounding by indication remained unaddressed issues.

Coronary Risks Associated with Diclofenac and Other NSAIDs: An Update.

The risk of coronary events with non-steroidal anti-inflammatory drugs has been the subject of much debate since the original trial of rofecoxib raised the issue. Since then, over almost 20 years, such risks have been shown in clinical trials of long-term high-dose users, and in observational studies comparing users with non-users. The roles of cyclooxygenase (COX)-2/COX-1 selectivity and COX-2 inhibitory potency have been proposed to explain this increased risk of myocardial infarction (MI). Among NSAIDs, diclofenac appeared to be associated with a relatively higher risk of MI, similar to that of rofecoxib, compatible with the drug's high COX-2 inhibitory potency. Recent studies have resulted in further information being available. A study in the Danish healthcare system using active comparators found a slightly increased risk of MI in healthy persons. However, risk decreased with increasing baseline cardiovascular risk, to the point that in patients at high cardiovascular risk, there was no additional risk associated with diclofenac compared with paracetamol or other NSAIDs. The other major study, from the SOS project, studied several million persons in four countries in Europe, comparing the use of many NSAIDs with non-use. That study found a slightly increased risk with diclofenac compared with non-use, but this was not different from other NSAIDs. Comparing risks with selectivity or potency found no effect of either. These studies refute the main hypotheses to explain the coronary risk of NSAIDs. Finding risk in healthy low-risk patients only questions the reality of a link between the use of the drugs and the occurrence of MI in these conditions. Biases or confounding may be the major reason for small increases in cardiovascular risks in healthy users of NSAIDs in real life.

Comparative Real-Life Effectiveness and Safety of Dabigatran or Rivaroxaban vs. Vitamin K Antagonists: A High-Dimensional Propensity Score Matched New Users Cohort Study in the French National Healthcare Data System SNDS.

BACKGROUND: Clinical trials have indicated that the direct-acting oral anticoagulants dabigatran and rivaroxaban have better risk/benefit profiles than do vitamin K antagonists (VKAs) for stroke prevention in non-valvular atrial fibrillation (NVAF). OBJECTIVE: Our objective was to compare the 1-year real-life risk of major clinical events with dabigatran or rivaroxaban versus VKAs for NVAF. METHODS: This was a high-dimensional propensity score (hdPS)-matched cohort study of new users of dabigatran, rivaroxaban or VKAs for NVAF in the French national healthcare systems database in 2013 followed-up for 1 year [22]. Hazard ratios (HRs) with 95% confidence intervals (CIs) for clinical events and death were determined during exposure. RESULTS: In 2013, a total of 103,101 new anticoagulant users had definite NVAF: 44,653 VKA, 27,060 dabigatran, and 31,388 rivaroxaban. In matched populations, HRs were as follows for dabigatran versus VKAs (20,489 per group): stroke and systemic embolism (SSE) 0.75 (95% CI 0.63-0.88), clinically relevant bleeding (CRB) 0.58 (95% CI 0.51-0.66), hemorrhagic stroke (HS) 0.22 (95% CI 0.14-0.36), gastrointestinal bleeding (GIB) 0.98 (95% CI 0.80-1.19), acute coronary syndrome (ACS) 0.79 (95% CI 0.65-0.95), death 0.74 (95% CI 0.67-0.82), composite (any of the above) 0.71 (95% CI 0.66-0.76). For matched rivaroxaban versus VKA (23,053 per group) HRs were as follows: SSE 0.98 (95% CI 0.85-1.14), CRB 0.83 (95% CI 0.75-0.92), HS 0.65 (95% CI 0.49-0.87), GIB 1.08 (95% CI 0.90-1.30), ACS 0.84 (95% CI 0.71-1.00), death 0.77 (95% CI 0.71-0.84), composite 0.84 (95% CI 0.79-0.89). Numbers needed to treat to observe one fewer death were 49 ± 0.05 with dabigatran or rivaroxaban versus VKAs. CONCLUSION: Consistent with results from clinical trials and other observational studies, dabigatran and rivaroxaban were at least as effective and safer than VKAs for the prevention of thromboembolic events in NVAF over 1 year in the French population. STUDY REGISTRATION: European Medicines Agency EUPAS 13017 (www.encepp.eu) Clinicaltrials.gov id NCT02785354.

Effectiveness and Safety of Rivaroxaban 15 or 20 mg Versus Vitamin K Antagonists in Nonvalvular Atrial Fibrillation.

Background and Purpose- We compared the 1-year safety and effectiveness of rivaroxaban 15 mg (R15) or rivaroxaban 20 mg (R20) to vitamin K antagonists (VKAs) in patients with nonvalvular atrial fibrillation. Methods- New user cohort study of patients dispensed R15 or R20 versus VKA in 2013 or 2014 for nonvalvular atrial fibrillation, followed 1 year in the French Système National des Données de Santé (66 million people). R15 and R20 users were matched 1:1 with VKA users on sex, age, date of first drug dispensing, and high-dimensional propensity score. Hazard ratios (95% CIs) for stroke and systemic embolism, major bleeding, and death were computed using Cox proportional hazards or models by Fine and Gray during exposure. Results- In 31 171 matched R20 and VKA, mean age, 71; 62% men; 76% with CHA2DS2-VASc ≥2; 5% HAS-BLED >3 (hypertension, abnormal renal and liver function, stroke, bleeding, labile INR, elderly, drugs or alcohol); incidence rates for stroke and systemic embolism were 1.5% and 1.9% (hazard ratio, 0.79 [0.69-0.90]); major bleeding, 1.5% and 2.2% (0.67 [0.59-0.77]); death, 3.9% and 5.8% (0.67 [0.61-0.73]). In 23 314 matched R15 and VKA patients, mean age, 80; 47% men; 93% with CHA2DS2-VASc ≥2 and 9% with HAS-BLED >3; incidence rates of stroke and systemic embolism were 2.3% and 2.1% (1.05 [0.92-1.21]); major bleeding, 2.4% and 2.9% (0.84 [0.74-0.96]); death, 9.1% and 10.8% (0.85 [0.79-0.90]). Numbers needed to treat to observe one fewer death (NNT) were 46 for R15 and 61 for R20. Conclusions- In real life in France over 2013 to 2015, R15 and R20 were at least as effective and safer than VKA. Clinical Trial Registration- URL: http://www.encepp.eu. Unique identifier: EUPAS14567.

A review of Algerian medicinal plants used in the treatment of diabetes.

ETHNOPHARMACOLOGICAL RELEVANCE: Plants are traditionally used in Algeria to treat many disorders, including diabetes mellitus. Knowledge of the plants that are used may provide insight on their properties, for further exploration. This study reviewed all the available published and unpublished reports concerning the use of herbal medicines in the treatment of diabetes in Algeria. AIM OF THE STUDY: To describe the plants used in Algeria to treat diabetes, as reported in the literature. MATERIAL AND METHODS: Systematic review of ethnobotanical papers published in the medical literature, from literature databases (Pubmed, Web of Science), as well as Google, for English, French and Arabic -language publication, and a manual search of local libraries and bookshops, as well as the university repository of PhD and master's theses. The reference lists of the papers retrieved were also examined for further papers. RESULTS: Many plants are cited in the ethnobotanical surveys, but only very few pharmacological studies were found. In the ethnobotanical surveys, 171 plants were reported, from 58 families of which the most often cited were Asteraceae, Lamiaceae and Apiaceae. The plants with the best evidence of use and activity are: Anabasis articulata (Forssk.) Moq., Trigonella foenum-graecum L., Centaurium erythraea Rafn, Artemisia herba-alba Asso, Marrubium vulgare L., Agathophora alopecuroides (Delile) Fenzl ex Bunge, Anabasis articulata (Forssk.) Moq., Hammada elegans (Bunge) Botsch., Helianthemum kahiricum Delile, Salsola baryosma (Schult.) Dandy, Salsola vermiculata L., Olea europaea L. CONCLUSION: Traditional herbal medicines are still very much used in Algeria to control diabetes. However they are generally poorly characterized and none have been properly tested in man. There is a need for systematic evaluation of the more commonly used plants to confirm their antidiabetic activity, identify possible mechanimss of action, and recommend best use.

The effects of antioxidants on ocular blood flow in patients with glaucoma.

PURPOSE: To investigate the effects of an antioxidant dietary supplement that includes Ginkgo biloba, on retinal and retrobulbar blood flow in patients with open-angle glaucoma (OAG). METHODS: Forty-five patients with confirmed OAG were enroled in a randomized, double blinded, placebo-controlled cross-over study. Baseline and postadministration measurements of intraocular pressure (IOP), ocular perfusion pressure (OPP), retrobulbar blood flow, and retinal capillary blood flow were non-invasively measured (ultrasound and laser Doppler modalities, respectively) before and one month after antioxidant nutraceuticals and placebo administration. Changes in measurements between the active supplement and placebo arms were evaluated using paired t-tests, with p < 0.05 considered statistically significant. RESULTS: Antioxidant supplementation produced a statistically significant increase in peak systolic and/or end diastolic blood flow velocities in all retrobulbar blood vessels compared to placebo. Vascular resistance was also reduced in central retinal and nasal short posterior ciliary arteries following antioxidant administration. Additionally, antioxidant supplementation increased superior and inferior temporal retinal capillary mean blood flow and the ratio of active to non-active retina capillaries compared to placebo. CONCLUSION: One-month oral administration of antioxidants produced increases in biomarkers of ocular blood flow within retinal and retrobulbar vascular beds in patients with OAG.

Constituents and Antioxidant Activity of Bleeding Sap from Various Xinjiang Grapes.

OBJECTIVE: Wine grape sap or bleeding sap of grapes (GBS) is commonly used in Xinjiang (China) for therapeutic aims. Do variations in composition related to region and variety affect its properties? METHODS: GBS samples originating in various parts of Xinjiang (Turpan, Hotan, Kashgar, and Atush) were tested for phenols and polyphenols, polysaccharides, saponin, proteins, individual amino acids, and minerals. Their antioxidant activity was measured using ascorbic acid as reference. RESULTS: Polyphenol content varied from 2.6 to 6.6 mg/L, polysaccharides 18.3-816 mg/L, saponin 6.25-106 mg/L, and protein 3.0-22.4 mg/L. Mineral elements and amino acids ranged from 6.20 to 201.2 mg/L and 0.06-118.7 mg/L, respectively. ·OH scavenging ability varied from 70% to over 90%, higher than Vitamin C. Grapes from Turpan had lower antioxidant activity than other grapes even though the polyphenol content was generally higher. CONCLUSION: Bleeding sap of Xinjiang grape is rich in amino acids, polysaccharides, polyphenols, and protein. The contents are different according to the origin, related possibly to species, climate, and environment. Antioxidant effects were not correlated with polyphenol content. SUMMARY: Antioxidant activity of plants or plant extracts is often associated with polyphenolsBleeding sap of grapes has strong antioxidant propertiesBleeding sap from different grape varieties from different parts of Xinjiang (China) had different polyphenol concentrationsThere was no correlation of polyphenol concentrations with antioxidant activity. Abbreviations used: GBS: Bleeding sap of grapes; PITC: phenyl isothiocyanate.

The national healthcare system claims databases in France, SNIIRAM and EGB: Powerful tools for pharmacoepidemiology.

The French health care system is based on universal coverage by one of several health care insurance plans. The SNIIRAM database merges anonymous information of reimbursed claims from all these plans, linked to the national hospital-discharge summaries database system (PMSI) and the national death registry. It now covers 98.8% of the French population, over 66 million persons, from birth (or immigration) to death (or emigration), making it possibly the world's largest continuous homogeneous claims database. The database includes demographic data; health care encounters such as physician or paramedical visits, medicines, medical devices, and lab tests (without results); chronic medical conditions (ICD10 codes); hospitalisations with ICD10 codes for primary, linked and associated diagnoses, date and duration, procedures, diagnostic-related groups, and cost coding; date but currently not cause of death. The power of the database is correlatively great, and its representativeness is near perfect, since it essentially includes the whole country's population. The main difficulty in using the database, beyond its sheer size and complexity, is the administrative process necessary to access it. Recent legislative advances are making this easier. EGB (Echantillon Généraliste de Bénéficiaires) is the 1/97th random permanent representative sample of SNIIRAM, with planned 20-year longitudinal data (10 years at this time). Access time is 1 to 3 months, but its power is less (780 000 subjects). This is enough to study common issues with older drugs but may be limited for new products or rare events.

News from Tartary: an ethnopharmacological approach to drug and therapeutic discovery.

Ethnopharmacology aims to identify new therapeutic agents based on their traditional use. It begins by the identification of disease states, and of the traditional therapies for these, most commonly herbals. Herbals of interest are selected from ethnopharmacological surveys, and tested on experimental models of the diseases of interest. Once the activity of the traditional remedy is demonstrated, including dose-dependence, if possible comparatively to reference medications, the active ingredients can be explored, if possible using bioguided extraction. Identified molecules can then be further developed as medicinal products or pharmaceutical medicines (e.g., artemisine), or the herbal product can be developed as such (e.g. St John's wort). We provide examples of various study programmes, concerning the antiplatelet and antithrombotic effects of Armagnac extracts from Southwest France; antithrombotic and antihypertensive effects of extracts of Ocimum basilicum L; antithrombotic, antihypertensive and antihyperlipidemic effects of Cydonia oblonga; Antiproliferative and antithrombotic effects of Abnorma Savda Munziq of traditional Uyghur medicine; and the antidiabetic and hepatoprotective effects of Centaurium erythraea Rafn, Artemisia herba-alba Asso and Trigonella foenum-graecum L., all in collaboration between University of Bordeaux, France, Xinjiang Medical University in Urumqi, China and University Mentouri in Constantine, Algeria.

Effect of Centaurium erythraea Rafn, Artemisia herba-alba Asso and Trigonella foenum-graecum L. on liver fat accumulation in C57BL/6J mice with high-fat diet-induced type 2 diabetes.

ETHNOPHARMACOLOGICAL RELEVANCE: Centaurium erythraea Rafn (CE), Artemisia herba-alba Asso (AHA) and Trigonella foenum-graecum L. (TFG) are traditionally used to treat type 2 diabetes in Algeria, previous studies have found that extracts of these plants were effective to treat or prevent experimental diabetes induced by high-fat diet (HFD). AIM OF THE STUDY: Describe the additional effects of these extracts on lipid tissue deposition in HFD. MATERIALS AND METHODS: Male C57BL/6J mice were fed with HFD to induce type 2 Diabetes. Groups of mice were given plant extracts orally at 2g/kg/bodyweight daily for 20 weeks during establishment of diabetes, or for 18 weeks after confirmation of diabetes at the 17th week. Liver and other tissue samples were stained with Oil Red O. RESULTS: Liver steatosis was confirmed with HFD. CE, AHA and TFG extracts improved liver steatosis by the end of the preventive (20 weeks) and curative periods (35 weeks). This was most marked for CE extract (p<0.05), less so with TFG and AHA. No steatosis was found in other tissues. CONCLUSION: CE extract had a clear hepatoprotective effect in this mouse model of diet-induced type 2 diabetes. AHA and TFG had a minimal or no significant effect on steatosis. Beyond its effect as an antidiabetic agent, CE may also be promising to prevent or treat non-alcoholic liver steatosis.

Effects of Cydonia oblonga Miller leaf and fruit flavonoids on blood lipids and anti-oxydant potential in hyperlipidemia rats.

OBJECTIVE: To study the effects of Cydonia oblonga Miller (COM) total flavonoids (TF) from leaves and fruit on the blood lipid and antioxidant potentials using hyperlipidaemic rat models. METHODS: Hyperlipidaemic rat models were created with high-lipid emulsion. Rats were distributed into normal controls, hyperlipidaemic models, and daily high (160mg/kg), medium (80mg/kg) and low (40mg/kg) TF from leaves and fruit and simvastatin (5mg/kg) groups. After four weeks, serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), alanine aminotransferase (ALT), aspartate aminotransferase (AST), as well as hepatic superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) were measured. RESULTS: Compared with the hyperlipidaemic model group, TF significantly reduced serum TC, TG, LDL-C (P<0.01), ALT and AST (P<0.01 or P<0.05) and increased HDL-C (P<0.05 or P<0.01). TF also reduced MDA (P<0.01 or P<0.01). CONCLUSION: COM total flavonoids can effectively regulate the metabolism of lipids, and remove oxygen free radicals. This confirms its potential value in the prevention and treatment of hyperlipidaemia.

Traditional Uighur Medicine Karapxa decoction, inhibits liver xanthine oxidase and reduces serum uric acid concentrations in hyperuricemic mice and scavenges free radicals in vitro.

BACKGROUND: Karapxa decoction (KD) is a Traditional Uighur Medicine used for hepatitis, cholecystitis, gastralgia, oedema, gout and arthralgia. Because of its purported effect in gout, its effects were tested in hyperuricemic mice models induced by yeast extract paste or potassium oxonate, as well as its capacity to scavenge free radicals in vitro. METHODS: Hyperuricemia was induced in mice by yeast extract paste or potassium oxonate. KD was given orally for 14 days at 200, 400 and 800 mg/kg/day, with Allopurinol 10 mg/kg/day as positive control. Serum uric acid (UA), and liver xanthine oxidase activity (XO) were measured. Scavenging activity of KD on 1, 1-diphenyl-2-picrylhydrazyl radicals (DPP•), nitric oxide (•NO), superoxide (O2•-), efficiency against lipid peroxidation, and XO inhibition were determined in vitro. RESULTS: KD inhibited liver XO activity and reduced serum uric acid in hyperuricemic mice. KD also showed noticeable antioxidant activity, scavenging free radicals (DPP•, •NO and O2•-). It was effective against lipid peroxidation and inhibited XO in vitro. CONCLUSIONS: This study supports the traditional use of Karapxa decoction to treat hyperuricemia and gout.

Burnout: evaluation of the efficacy and tolerability of TARGET 1® for professional fatigue syndrome (burnout).

OBJECTIVE: To study the effect of a dietary supplement (TARGET 1®: a combination of casozepine, taurine, Eleutherococcus senticosus and extramel) on burnout symptomatology. METHODS: A 12-week, double-blind, randomized, placebo-controlled trial was conducted in workers engaged in professional contact with patients, students or clients. All were affected by burnout syndrome based on a score of ≥4 on the Burnout Measure Scale (BMS-10). The primary outcome measure was the change in the BMS-10 score; secondary outcome measures included the change in the Maslach's Burnout Inventory scale-Human Service Survey (MBI-HSS) score and the Beck Depression Inventory. Five scores were evaluated. RESULTS: Eighty-seven participants were enrolled in the study: 44 received the active formulation (verum group); 43 received placebo. After 12 weeks' supplementation, the placebo group showed significant improvements in scores for BMS-10, MBI-HSS fatigue and the Beck Depression Inventory, but MBI-HSS depersonalization and task management were not improved; the verum group showed significant improvements in all five scores. The verum group consistently showed significantly greater improvements in scores than the placebo group. CONCLUSIONS: TARGET 1® significantly improved the symptoms of burnout after 12 weeks' use.

Effect of traditional Uyghur medicine abnormal Savda Munziq extract on rabbit platelet aggregation in vitro and rat arteriovenous shunt thrombosis in vivo.

OBJECTIVE: Abnormal Savda Munziq (ASMq) is a standard herbal preparation used in Uyghur traditional medicine to fight chronic diseases including cardiovascular, but its specific effects on thrombosis and platelet aggregation are unknown. METHODS: Rabbit platelets were incubated with ASMq extract (10, 20, 40 µg/ml) for 15, 30, or 60 min, and aggregation was induced with ADP and collagen. In vivo, ASMq extract 2.97 g/kg, 5.94g/kg, 11.88 g/kg per os daily for 15 days were tested on thrombus wet weight in a rat model of arterio-venous bypass thrombosis. Plasma thromboxane B2 (TXB2) and 6-keto-PGF1a (6PG) were measured by radioimmunoassay. Aspirin (12 µg/ml and 5mg/kg) and saline were used as control in both experiments. RESULTS: ASMq inhibited ADP and collagen-induced aggregation in vitro in a dose-dependent manner that increased over time, to a maximum of 6.4 ± 1.3% and 21.6 ± 4.0% for ADP and collagen, respectively, at one hour׳s incubation with the highest concentration, whereas the effects of aspirin (34.5 ± 2.2% and 41.9 ± 2.5%, respectively) were stable over time. In vivo, ASMq inhibited thrombus formation dose-dependently, by 70% at the highest dose, compared to 67% with aspirin. ASMq essentially did not change prostaglandin production, compared to the clear inhibition by aspirin. CONCLUSION: Abnormal Savda Munziq extract inhibits dose-dependent platelet aggregation with ADP or collagen in vitro and thrombosis in vivo to values similar to those of aspirin, though unlike aspirin this effect does not seem mediated by an inhibition of cyclo-oxygenase.

Effect of Bridelia ferruginea Benth (Euphorbiaceae) ethyl acetate and acetone fractions on insulin resistance in fructose drinking mice.

ETHNOPHARMACOLOGICAL RELEVANCE: The root of Bridelia ferruginea is traditionally used as a treatment for type 2 diabetes. The present study was investigated to evaluate the effect of Bridelia ferruginea root bark fractions on some markers of type 2 diabetes on fructose drinking mice. MATERIALS AND METHODS: Mice received a solution of fructose 15% during 42 days ad libitum; at the 15th day to the 42nd day, they received distilled water for fructose drinking control group, metformin 50 mg/kg per day or fractions 50 mg/kg per day for treatment groups. The normal control group received only distilled water during the experiment. After 6 weeks of experiment, OGTT, fasting blood glucose, plasma insulin, triglycerides (TG), total cholesterol, AST and ALT levels were measured. RESULTS: Fructose drinking control group (F) showed significant (p<0.001) increase of glucose tolerance, plasma levels of total cholesterol, triglycerides and insulin index for insulin resistance (Homeostasis Model Assessment ratio HOMA-IR) as compared to normal control mice. In treated groups, there was a significant reduction of glucose intolerance respectively 74% (p<0.001), 25% (p<0.5) and 92% (p<0.001) for ethyl acetate fraction, acetone fraction and metformin at the same dose of 50 mg/kg per day during 4 weeks administration. In ethyl acetate fraction and metformin treated groups, biochemical parameters and insulin index were significantly (p<0.001) lower than that of fructose drinking control group. CONCLUSIONS: This indicates that Bridelia ferruginea root bark ethyl acetate fraction improved insulin resistance as metformin significantly in type 2 diabetes.

Effects of Cydonia oblonga Miller extracts on blood hemostasis, coagulation and fibrinolysis in mice, and experimental thrombosis in rats.

INTRODUCTION: Cydonia oblonga Miller (COM) is traditionally used in Uyghur medicine for the prevention of cardiovascular disease. The present study is designed to explore the effects of COM extracts on models and markers of thrombosis and related biomarkers. MATERIALS AND METHODS: 20, 40, 80 mg/kg/day COM aqueous extracts and 5mg/kg/day aspirin, orally for 14 days were compared to untreated controls in mice on bleeding and clotting times, using the tail cutting and glass slide methods and for death rates in collagen-epinephrine pulmonary thrombosis, thrombolysis in vitro and euglobulin lysis time (ELT). In rats, common carotid artery FeCl3-induced thrombus and inferior vena cava thrombosis occlusion time, plasma concentrations of thromboxane B2 (TXB2) and 6-keto-prostaglandine F1α (6-keto-PGF1α) were measured. RESULTS AND CONCLUSION: Compared to controls, COM extracts dose-dependently prolonged bleeding by 2.17, 2.78 and 3.63 times, vs. aspirin 2.58, and the clotting time by 1.44, 2.47 and 2.48 times, vs. aspirin 1.91. COM reduced pulmonary embolus mortality by 27, 40 and 53%, vs. 47% for aspirin. COM dose-dependently increased thrombolysis by 45, 55 and 63%, vs. 56% for aspirin, and shortened ELT to 71, 61 and 43%, vs. 43% for aspirin. In rats, venous occlusion time was prolonged. Arterial and venous thrombus weights were dose-dependently reduced in COM groups. TXB2 decreased and 6-keto-PGF1α increased with COM and aspirin, with an association between 6-keto-PGF1α/TXB2 and arterial or venous thrombus weight for all products, and for occlusion time with COM but not for aspirin. CONCLUSION: We confirm the experimental effects of COM on hemostasis and thrombosis. Further exploration of putative clinical effects appear justified.

Effect of Cydonia oblonga Mill. leaf extracts or captopril on blood pressure and related biomarkers in renal hypertensive rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Cydonia oblonga Mill. (COM) is used in traditional Uyghur medicine to treat or prevent cardiovascular disease. In a previous study COM leaf extracts were found to be active in renal hypertensive rats (RHR). The present study tests the dose-dependence of the effect of ethanol leaf extracts on hypertension and on biomarkers associated with blood pressure control, such as angiotensin-II (AII), plasma renin activity (PRA), apelin-12 (A), endothelin (ET) and nitric oxide (NO), compared to captopril. METHODS: Two-kidney one-clip (2K1C) Goldblatt model rats were divided randomly into six groups: sham, model, captopril 25 mg/kg, COM leaf extract 80, 160 and 320 mg/kg (n=10 each). Drugs were administered orally daily for eight weeks. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured before treatment and every 2 weeks. Blood and kidney samples were collected after the last treatment to measure AII, PRA, A, ET and NO. RESULTS: RHR had increased blood pressure, AII, A, PRA, ET and decreased NO. Treatment with captopril reduced blood pressure, AII, A, PRA, and ET, though not quite to normal values. COM leaf extracts significantly and dose-dependently reduced blood pressure, AII, A, RA and ET, whereas NO was increased. The highest dose of COM had the same effects as captopril. CONCLUSION: The effects of COM extracts on blood pressure and biomarkers were dose-dependent and at the highest dose similar to those of captopril. This suggests an action of COM on the renin-angiotensin system, which could explain its antihypertensive effect.

Effect of Cydonia oblonga Mill. fruit and leaf extracts on blood pressure and blood rheology in renal hypertensive rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Quince, Cydonia oblonga Mill. (COM), is used in traditional Uyghur medicine to treat or prevent cardiovascular diseases. Uyghur people have greater longevity and lower blood pressure than other central Asian populations. We therefore tested COM fruit and leaf extracts on blood pressure and rheology in renal hypertensive rats (RHR). MATERIALS AND METHODS: Two-kidney, one-clip (2K1C) renal hypertensive rats were divided randomly into eleven groups: sham, model, and model treated with daily doses of 80 and 160mg/kg aqueous or ethanol extracts of COM fruit or leaves, or 25mg/kg captopril (n=10 per group), given orally once daily for 8 weeks. Blood pressure was measured before treatment and every 2 weeks thereafter. Blood rheology was tested after 8 weeks. RESULTS: Model rats had higher blood pressure than sham 8 weeks after the procedure (systolic blood pressure 193±7 vs. 138±8mmHg, p<0.05). Those treated with captopril had decreased blood pressure within 2 weeks but that did not return to the level found in the sham group at 8 weeks (167±7, p<0.05 vs. model). With the COM extracts, the effect on blood pressure was notable after 4 weeks. At 8 weeks blood pressure was similar with captopril and with 160mg ethanol leaf extract (166±4, p<0.05 vs. model), the most effective of the extracts. Model rats had higher blood viscosity and lower erythrocyte deformability than sham. Captopril had little effect on blood rheology; whereas COM extracts reduced whole blood viscosity and improved erythrocyte deformability to levels approaching those found in sham. CONCLUSIONS: COM extracts have antihypertensive activity in renal hypertensive rats. The additional effect on rheology, compared to captopril, may convey added interest. Further studies of these effects in man appear warranted.