astaxanthine and Hyperlipidemias

Astaxanthin has been reported to improve dyslipidemia and metabolic syndrome in animals, but such effects in humans are not well known.. Placebo-controlled astaxanthin administration at doses of 0, 6, 12, 18 mg/day for 12 weeks was randomly allocated to 61 non-obese subjects with fasting serum triglyceride of 120-200mg/dl and without diabetes and hypertension, aged 25-60 years.. In before and after tests, body mass index (BMI) and LDL-cholesterol were unaffected at all doses, however, triglyceride decreased, while HDL-cholesterol increased significantly. Multiple comparison tests showed that 12 and 18 mg/day doses significantly reduced triglyceride, and 6 and 12 mg doses significantly increased HDL-cholesterol. Serum adiponectin was increased by astaxanthin (12 and 18 mg/day), and changes of adiponectin correlated positively with HDL-cholesterol changes independent of age and BMI.. This first-ever randomized, placebo-controlled human study suggests that astaxanthin consumption ameliorates triglyceride and HDL-cholesterol in correlation with increased adiponectin in humans.

Topics: Adiponectin; Adult; Cholesterol, HDL; Female; Humans; Hyperlipidemias; Male; Middle Aged; Triglycerides; Xanthophylls

Inhibition of HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase, the rate rate-determining enzyme for the biogenesis of cholesterol is known to show antineoplastic effects. Therefore, this study investigates the in-silico HMG-CoA reductase (HMGCR)-inhibitory and in-vivo anti-lipidaemic/anticancer effects of carotenoids from Spondias mombin.. Carotenoids from S. mombin leaves were characterized with the aid of liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS). The characterized phytochemicals were obtained from PubChem. They were docked into the orthosteric site of human HMGCR (Protein Data Bank code 1HW8) using AutoDock 4.0 suites. DMBA (7,12-dimethylbenz[a]anthracene) model of breast cancer was treated with the carotenoids extract from S. mombin (100 mg/kg and 200 mg/kg doses) to assess its anti-lipidaemic cum anticancer effects.. Carotenoids from S. mombin; beta-carotene-15,15'-epoxide, astaxanthin and 7,7',8,8'-tetrahydro-β-β-carotene demonstrate HMGCR inhibition. They form hydrophobic interactions with key residues within the catalytic domain of HMGCR. The carotenoids extract exhibits anti-lipidaemic/anticancer effects, lowering serum triglyceride, LDL and cholesterol concentration. It increases HDL concentration and downregulates the expression of HMGR, AFP, CEACAM-3, BRCA-1 and HIF-1 mRNAs.. Carotenoids from S. mombin demonstrate HMG-CoA reductase (HMGCR) inhibition, anti-lipidaemic, and anticancer effects. The inhibition of HMGCR by the carotenoids extract further poses it as a potential anti-hypercholesterolaemia compounds.

Topics: Acyl Coenzyme A; Anacardiaceae; Animals; Anticholesteremic Agents; Antineoplastic Agents, Phytogenic; beta Carotene; Breast; Breast Neoplasms; Carotenoids; Down-Regulation; Female; Humans; Hydroxymethylglutaryl CoA Reductases; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Hyperlipidemias; Hypolipidemic Agents; Lipids; Molecular Docking Simulation; Phytotherapy; Plant Extracts; Rats, Wistar; Xanthophylls

Astaxanthin (ASTX) is a xanthophyll carotenoid that reduces hemostasis in hyperlipidemic organisms. Its antihemostatic mechanisms remain unclear.. The effects of ASTX on coagulation, the fibrinolytic system and platelet aggregation were investigated in hyperlipidemic rats.. Different doses of ASTX (5, 10 and 30 mg/kg/day, p.o.) were administered for four weeks to high-fat diet-induced hyperlipidemic rats. Serum lipid and lipoprotein levels were measured with an automatic biochemical analyzer. The prothrombin time (PT), activated partial thromboplastin time (APTT) and maximum platelet aggregation rate (MAR) were determined by a coagulation analyzer. The activities of the tissue-type plasminogen activator (t-PA), type-1 plasminogen activator inhibitor (PAI-1) and endothelial nitric oxide synthase (eNOS), as well as the levels of thromboxane B(2) [TXB(2)], 6-keto prostaglandin F(1α) [6-keto-PGF(1α)] and platelet granule membrane protein (GMP-140), were measured with enzyme-linked immunosorbent assay kits. Gene and protein expression levels were analyzed by reverse transcriptase polymerase chain reaction and Western blot, respectively.. ASTX (30 mg/kg) treatment in hyperlipidemic rats reduced serum TG (0.58 ± 0.14 versus 1.12 ± 0.24 mmol/L), serum TC (1.77 ± 0.22 versus 2.24 ± 0.21 mmol/L), serum LDL-C (1.13 ± 0.32 versus 2.04 ± 0.48 mmol/L), serum MDA (69%), plasma MAR (55%), serum TXB2/6-keto-PGF1α (34%) and serum GMP-140 levels (25%), plasma PAI-1 activity (48%) and downregulated the mRNA (33%) and protein (23%) expression of aorta eNOS, the mRNA (79%) and protein (72%) expression levels of aorta PAI-1. However, ASTX (30 mg/kg/d) treatment increased serum SOD activity (2.1 fold), serum GPx activity (1.8 fold), plasma PT (1.3 fold), plasma APTT (1.7 fold), serum NO (1.4-fold), serum 6-keto-PGF1α (1.3 fold).. ASTX reduced blood coagulation and platelet aggregation and promoted fibrinolytic activity in hyperlipidemic rats. These activities were closely correlated with ASTX, maintaining the balance of t-PA/PAI-1, NO/ROS and TXA2/PGI2 in vivo.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Anticoagulants; Biomarkers; Blood Coagulation; Diet, High-Fat; Disease Models, Animal; Dose-Response Relationship, Drug; Fibrinolysis; Fibrinolytic Agents; Hyperlipidemias; Lipid Peroxidation; Lipids; Male; Nitric Oxide; Nitric Oxide Synthase Type III; P-Selectin; Partial Thromboplastin Time; Plasminogen Activator Inhibitor 1; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Prothrombin Time; Rats, Sprague-Dawley; Thromboxane B2; Time Factors; Tissue Plasminogen Activator; Xanthophylls

The composition of atherosclerotic plaques, not just macroscopical lesion size, has been implicated in their susceptibility to rupture and the risk of thrombus formation. By focusing on the quality of lipids, macrophages, apoptosis, collagen, metalloproteinase expression and plaque integrity, we evaluated the possible anti-atherosclerotic effect of the antioxidants alpha-tocopherol and astaxanthin in Watanabe heritable hyperlipidemic (WHHL) rabbits. Thirty-one WHHL rabbits were divided into three groups and were fed a standard diet, as controls (N =10), or a standard diet with the addition of 500 mg alpha-tocopherol per kg feed (N =11) or 100 mg astaxanthin per kg feed (N =10) for 24 weeks. We found that both antioxidants, particularly astaxanthin, significantly decreased macrophage infiltration in the plaques although they did not affect lipid accumulation. All lesions in the astaxanthin-treated rabbits were classified as early plaques according to the distribution of collagen and smooth muscle cells. Both antioxidants also improved plaque stability and significantly diminished apoptosis, which mainly occurred in macrophages, matrix metalloproteinase three expressions and plaque ruptures. Although neither antioxidant altered the positive correlations between the lesion size and lipid accumulation, the lesion size and apoptosis were only positively correlated in the control group. Astaxanthin and alpha-tocopherol may improve plaque stability by decreasing macrophage infiltration and apoptosis in this atherosclerotic setting. Apoptosis reduction by alpha-tocopherol and astaxanthin may be a new anti-atherogenic property of these antioxidants.

Topics: alpha-Tocopherol; Animals; Antioxidants; Aorta, Thoracic; Apoptosis; Arteriosclerosis; beta Carotene; Cell Movement; Collagen; Hyperlipidemias; Lipid Peroxidation; Lipids; Macrophages; Matrix Metalloproteinase 3; Rabbits; Xanthophylls