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 Ocimum basilicum L. on cyclo-oxygenase isoforms and prostaglandins involved in thrombosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Ocimum basilicum L. (OBL) is a plant used in traditional Uyghur medicine for the treatment and prevention of cardiovascular disease. In previous studies we had found an antihypertensive and antithrombotic effect suggestive of an effect on prostaglandins, which we attempt to document here. MATERIALS AND METHODS: 6-keto-PGF1α, the metabolite of prostacyclin, and PGE2 were measured in the supernatant of human umbilical vein endothelial cells (HUVEC) and basal or LPS-stimulated mouse coeliac macrophage cultures exposed to OBL ethanol (OBL-E) extracts and petroleum ether, chloroform, ethylacetate and butanol (PE, C, EA, B) fractions. In addition, 6-keto-PGF1α and thromboxane B2 (TXB2) were measured in a rat model of thromboangiitis obliterans exposed or not to OBL. RESULTS: Short-term exposure to OBL-E dose-dependently increased 6-keto-PGF1α from HUVEC, and long-term (24h) exposure decreased it. OBL-C and OBL-B increased 6-keto-PGF1α, whereas the other fractions tended to decrease it after 24h exposure. The extract and all fractions decreased basal and stimulated PGE2 production, but only OBL-EA and OBL-B reduced PGE2 in stimulated cultures to concentrations below the unstimulated values (P<0.05). In vivo OBL increased 6-keto-PGF1α and decreased TXB2. CONCLUSION: OBL and its extracts increased 6-keto-PGF1α and reduced PGE2 and TXB2 production in a dose and time-related manner. This could indicate simultaneous inhibition of COX-2 and stimulation of endothelial COX-1. The butanol fraction seemed most promising in this respect.

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.

Effect of Cydonia oblonga Mill. leaf extract on serum lipids and liver function in a rat model of hyperlipidaemia.

ETHNOPHARMACOLOGICAL RELEVANCE: Cydonia oblonga Mill. leaves are traditionally used in Uyghur medicine to treat or prevent cardiovascular disease. Beyond a demonstrated effect on thrombosis, we tested it for an effect on dyslipidemia, in a rat model of hyperlipidemia. METHODS: Seventy healthy Sprague Dawley rats were randomly divided into 6 groups: normal controls, model controls, simvastatin, and low-, medium- and high-dose Cydonia oblonga Mill. leaf extracts (COM), orally for 56 days. The normal controls were fed a normal diet, all other groups a high fat diet. Rat weights were recorded over time. Total cholesterol (TC), triglycerides (TG), low and high-density lipoproteins (LDL, HDL), as well as AST, ALT and total protein (TP) were measured in serum at the end of the study. The antioxidant capacity of glutathione peroxidase (GSH-PX), superoxide dismutase (SOD), malondialdehyde (MDA) was measured in liver samples, along with lipoprotein lipase (LPL), and hepatic lipase (HL). Liver pathology was described. RESULTS: COM dose-dependently reduced TC, TG, LDL-C and MDA, inhibited the activity of ALT, AST and LPS, increased HDL-C content, increased the activity of SOD, GSH-PX, LPL and HL, and reduced liver steatosis in hyperlipidaemia rats, which was significant at medium and high doses. The effect of COM was similar to that of simvastatin except for increased LPL and HL which were reduced by COM but not by simvastatin. CONCLUSION: Cydonia oblonga Mill. leaf extracts have hypolipidaemic and hepatoprotective effects, probably related to increasing antioxidant capacity and lipoprotein metabolism in the liver, and inhibition of lipogenesis.