curcumin and Hypercholesterolemia

Hypercholesterolemia, as one of the major risk factors in development of cardiovascular diseases, is of mounting prevalence worldwide in recent years. Many nutraceuticals and phytochemical supplements serve as a promising complementary therapy in the management of hypercholesterolemia. Among them, spicy foods have attracted special attention. Plasma lipid-lowering activity of garlic, ginger, and turmeric have been well-studied in both humans and animals. Consumption of either 3 g/day of ginger or 2 g/day of curcumin for over 4 weeks effectively reduced blood cholesterol in hypercholesterolemia subjects. However, effects of chili and black peppers on blood cholesterol are studied little clinically. The present review is to summarize the findings of recent studies on the efficacy and mechanism of spicy foods and their primary bioactive components in management of hypercholesterolemia from preclinical studies to clinical trials.

Topics: Animals; Cholesterol; Curcuma; Garlic; Humans; Hypercholesterolemia; Spices; Zingiber officinale

We previously demonstrated that the combination of phytosterols (PS) and curcumin administered as dietary supplements significantly lowers LDL-cholesterol (LDL-C) more than either treatment alone. The aim of this study was to investigate the effects of this combination in a novel food (bread) on plasma lipid profiles in hypercholesterolaemic individuals. In a double-blinded, placebo-controlled, 2 × 2 factorial trial, participants were randomised to receive bread fortified with placebo (PL), 2.3 g PS (PS), 228 mg curcumin (CC) or a combination of 2.3 g PS and 228 mg CC (PS-CC) daily for four weeks. Primary outcomes were fasting plasma lipids [total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG)] and secondary outcomes were plasma LDL-particle (LDL-P) profile: LDL-P number and LDL-P size. Cardiovascular disease (CVD) risk (Framingham Risk Algorithm) was also explored. There was no significant difference between PL and CC or PS and PS-CC on blood lipids or CVD risk; therefore, groups were pooled for final analysis: the PL and CC group (PL-C, n = 36) and the PS and PS-CC group (PS-C, n = 39). PS-C significantly lowered TC (-0.52 mmol L-1, p < 0.0001), LDL-C (-0.49 mmol L-1, p < 0.0001) and CVD risk (-1.1 absolute %, p = 0.0005) compared to the PL-C group. Reductions from baseline in the PS-C group compared to that in the PL-C group were 7.6% and 10.6% for TC and LDL-C, respectively, and statistically significant (p < 0.0001). CVD-risk in the PS-C group reduced significantly (-12.7%) compared to that in the PL-C group (p = 0.0005). HDL-C and TG remained unchanged. The LDL-P number significantly decreased in the PS-C group by 124.33 nmol L-1 compared to that in the PL-C group (p = 0.005) and both groups showed a significant decrease in LDL-P size (p < 0.01); however, the absolute nm change in LDL-P size did not differ between groups and the percent change in LDL-P size in the PS-C group was borderline significant (-0.89%, p = 0.05) compared to that in the PL-C group. Regular consumption of PS-enriched bread with or without curcumin lowers blood cholesterol; however, curcumin alone did not influence blood lipids. Bread may be a convenient means of delivering PS with greater compliance for reducing the blood cholesterol concentration.

Topics: Adolescent; Adult; Aged; Australia; Bread; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Curcumin; Female; Humans; Hypercholesterolemia; Lipoproteins; Male; Middle Aged; Phytosterols; Triglycerides; Young Adult

Dietary phytosterols (PS) are well-known hypocholesterolaemic agents. Curcumin elicits hypolipidaemic and anti-inflammatory effects in preclinical studies, however, consistent findings in humans are lacking.. Concurrent PS and curcumin supplementation may exhibit enhanced hypocholesterolaemic and anti-inflammatory effects to optimise cardio-protection. The objective of this trial was to investigate the effects of dietary intervention with PS with or without curcumin on blood lipids (primary outcome) in hypercholesterolaemic individuals.. A double-blinded, randomised, placebo-controlled, 2 × 2 factorial trial was conducted in hypercholesterolaemic individuals. Participants received either placebo (PL, no phytosterols or curcumin), phytosterols (PS, 2 g/d), curcumin (CC, 200 mg/d) or a combination of PS and curcumin (PS-CC, 2 g/d-200 mg/d respectively) for four weeks. Primary outcomes included fasting total cholesterol (TC), LDL-cholesterol, HDL-cholesterol, triglycerides (TG), TC-to-HDL-C ratio (TC:HDL-C). Secondary outcomes included anthropometrics and fasting blood glucose concentrations.. Seventy participants with a mean (±SEM) fasting TC concentration of 6.57 ± 0.13 mmol/L completed the study (PL, n = 18; PS, n = 17; CC, n = 18; PS-CC, n = 17). PS and PS-CC supplementation significantly lowered TC, LDL-cholesterol and TC:HDL-C post-intervention (p < 0.05). Reductions from baseline in the PS group were 4.8% and 8.1% for TC and LDL-cholesterol respectively (p < 0.05). CC exhibited non-significant reduction (2.3% and 2.6%) in TC and LDL-C respectively, however, the PS-CC resulted in a greater reduction in TC (11.0%) and LDL-cholesterol (14.4%) than either of the treatments alone (p < 0.0001). The reduction in the PS-CC treatment was significantly greater compared to those for CC (p < 0.05) or PL (p < 0.01) alone. Plasma HDL-cholesterol and TG concentrations remained unchanged across all groups. No adverse side effects were reported.. The addition of curcumin to phytosterol therapy provides a complementary cholesterol-lowering effect that is larger than phytosterol therapy alone. Implications of these findings include the development of a single functional food containing both the active ingredients for enhanced lipid-lowering and compliance in hypercholesterolaemic individuals. ANZCTR identifier: 1261500095650.

Topics: Anticholesteremic Agents; Cholesterol; Curcumin; Double-Blind Method; Drug Interactions; Female; Humans; Hypercholesterolemia; Male; Middle Aged; Phytosterols; Treatment Outcome; Triglycerides

Metabolic syndrome is an increasingly prevalent problem, not only in industrialized developed countries, but in developing countries as well. The modern healthcare to reduce the dysfunction of metabolic syndrome is burdened with great problems of unsafe medicines and certain degree of side effects. Medicinal plants and derived component products are becoming increasingly popular in modern society as natural alternatives to synthetic multiple drugs for the treatment of hypercholesterolemia and hypertriglyceridemia. The present research work was carried out to evaluate the zedoary (Curcuma zedoaria Roscoe.) herbal tea (ZHT) for antihypercholestrolemic and antilipidemic perspectives in discerning consumers.. Zedoary rhizome dried powder (ZRDP) after proximate composition analysis was used to prepared ZHT samples as T1 (500 mg ZRDP), T2 (1 g ZRDP) and T3 (1.5 g ZRDP) in 200 mL boiling water for 5 minutes, respectively. ZHT samples were characterized for total phenolic compounds (TPC), DPPH inhibition, total flavonoids, color tonality (L*, a* and b* value), pH, acidity, total soluble solids (TSS) and sensory acceptance. Thirty mild-hypercholestrolemic male human volunteers were randomly allocated to three groups (G1, G2 and G3) and each group consisting of 1o mild-hypercholestrolemic male human subjects. The volunteers were assigned ZHT samples for consecutive two months. The blood drawn for day 0, day 30 and day 60 after an overnight 12 h fast was analyzed for serum parameters such as total cholesterol (TC), high-density lipoprotein cholesterol (HDL-cholesterol), low-density lipoprotein cholesterol (LDL-cholesterol) and triglycerides (TG) concentration.. The ZRDP possessed abundantly the crude protein (13.5 ± 0.68 %), total dietary fiber (21.86 ± 0.71 %), acid detergent fiber (13.22 ± 0.44 %), neutral detergent fiber (18.68 ± 0.53 %) and mineral contents. Highest TPC, DPPH inhibition and total flavonoids values were observed 9.74 ± 0.64 (mg GAE/g DW), 47.28 ± 1.62 (%) and 17.12 ± 0.75 (QE mg/g), respectively in T3. L* value was significantly (p ≤ 0.05) low for T3 samples. In contrast, a* value and b* value was significantly (p ≤ 0.05) higher for T3 when compared with T1 and T2. T3 samples showed lower pH (5.13 ± 0.13) and higher acidity (0.25 ± 0.08) values than T1 (5.64 ± 0.25, 0.17 ± 0.05) and T2 (5.42 ± 0.21, 0.21 ± 0.06), respectively. Similarly, an increasing trend in TSS contents was observed. Sensory scores assigned to color, flavor, aroma and overall acceptability attributes varied in a quite narrow range for all ZHT samples. The lowest evaluation scores were recorded for T3 samples. The G3 showed the more reduction in body weight and BMI during efficacy study as compared to G1 and G2. The decrease in serum TC for G1, G2 and G3 on day 60 was observed 9 %, 14 % and 17 %, respectively when compared with reference value at day 0. The consumption of T3 resulted in significant increase (6.8 %) of HDL-cholesterol after two months. A trend in decrease of serum LDL-cholesterol (5.6 %) and TG (12.5 %) was also observed after consumption of T3 at day 60.. The results of the present study conclude that the strong phenolic contents and radical scavenging activity of zedoary rhizome have protective role against hypercholesterolemic and lipidemic conditions.

Topics: Adult; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Curcuma; Humans; Hypercholesterolemia; Hypolipidemic Agents; Lipoproteins, HDL; Male; Teas, Herbal; Triglycerides

Recently, ginger has been used in traditional Chinese medicine as an herbal therapy for treating several cardiovascular diseases, however, information on its mechanism of action is limited. The present study assessed the effect of two ginger varieties (Zingiber officinale and Curcuma longa) on the arginase activity, atherogenic index, levels of liver thiobarbituric acid reactive substances (TBARSs), and plasma lipids in rats fed with a high-cholesterol (2%) diet for 14 days. Following the treatment period, it was found that feeding a high-cholesterol diet to rats caused significant (p < 0.05) increases in arginase activity, atherogenic index, levels of TBARS, total cholesterol (TC), triglycerides (TGs), and low-density lipoprotein cholesterol (LDL-C) with a concomitant decrease in high-density lipoprotein cholesterol (HDL-C). However, both ginger and turmeric (2% and 4%) caused significant (p < 0.05) decreases in arginase activity and the atherogenic index, and prevented hypercholesterolemia by decreasing the TC, TGs, and LDL-C while increasing the HDL-C when compared with the controls. In conclusion, dietary supplementation with both types of rhizomes (ginger and turmeric) inhibited arginase activity and prevented hypercholesterolemia in rats that received a high-cholesterol diet. Therefore, these activities of ginger and turmeric represent possible mechanisms underlying its use in herbal medicine to treat several cardiovascular diseases.

Topics: Animals; Arginase; Curcuma; Hypercholesterolemia; Lipids; Liver; Male; Phytotherapy; Plant Extracts; Rats; Rhizome; Thiobarbituric Acid Reactive Substances; Zingiber officinale

The anti-atherogenic potentials of total ginger (Zingiber officinale) extract (TGE) or curcuminoids extracted from turmeric (Curcuma longa), members of family Zingiberaceae, were compared in hypercholesterolaemia. Rabbits were fed either normal or atherogenic diet. The rabbits on atherogenic diet received treatments with TGE or curcumenoids and placebo concurrently for 6 weeks (n = 6). The anti-atherogenic effects of curcuminoids and ginger are mediated via multiple mechanisms. This effect was correlated with their ability to lower cholesteryl ester transfer protein activity. Ginger extract exerted preferential effects on plasma lipids, reverse cholesterol transport, cholesterol synthesis and inflammatory status. Curcuminoids, however, showed superior antioxidant activity.

Topics: Animals; Antioxidants; Cholesterol Ester Transfer Proteins; Curcuma; Curcumin; Diet, Atherogenic; Disease Models, Animal; Hypercholesterolemia; Hypolipidemic Agents; Inflammation; Liver; Oxidative Stress; Plant Extracts; Rabbits; Zingiber officinale

Curcumin has been demonstrated as having numerous desirable characteristics, such as antioxidant, anti-inflammatory, and antiatherogenic activities. We report the hypocholesterolemic effect and molecular mechanism of curcumin.. We found that curcumin enhanced LDL receptor (LDLR) level on the cell surface, as well as LDLR activity; however, LDLR transcription and mRNA stability were not affected. Furthermore, we found that proprotein convertase subtilisin/kexin type 9 (PCSK9) gene was downregulated at the transcriptional level by curcumin, leading to an increase in LDL uptake in HepG2 cells. The curcumin-responsive element of the PCSK9 promoter, a binding site for hepatocyte nuclear factor 1α (HNF-1α), was also identified. We demonstrated that curcumin reduced the nuclear abundance of hepatocyte nuclear factor 1α, resulting in its attenuated interaction with the PCSK9 promoter and leading to a downregulation of PCSK9 expression. Finally, we showed that curcumin decreased the statin-induced PCSK9 expression and potentially synergized with statin administration.. Current results indicate that curcumin suppression of PCSK9 expression is associated with increases in cell-surface LDLR and LDLR activity in hepatic cells and it acts in a molecular mechanism that is distinct from the statins. Curcumin exhibits hypolipidemic activity and may serve as a useful supplement to statin treatment for hypercholesterolemia.

Topics: Cell Membrane; Cholesterol, LDL; Curcumin; Down-Regulation; Drug Synergism; Gene Expression Regulation, Neoplastic; Hep G2 Cells; Hepatocyte Nuclear Factor 1-alpha; Hepatocytes; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Proprotein Convertase 9; Proprotein Convertases; Receptors, LDL; RNA, Messenger; Serine Endopeptidases; Transcription, Genetic

Curcumin, the yellow substance found in turmeric, possesses antioxidant, anti-inflammation, anticancer, and lipid-lowering properties. Because we hypothesized that curcumin could ameliorate the development of atherosclerosis, the present study focused on the effects and potential mechanisms of curcumin consumption on high-cholesterol diet-induced atherosclerosis in rabbits. During our study, New Zealand white rabbits were fed 1 of 3 experimental diets: a normal diet, a normal diet enriched with 1% cholesterol (HCD), or an HCD supplemented with 0.2% curcumin. At the end of 8 weeks, blood samples were collected to determine the levels of serum lipids, cytokines, and soluble adhesion molecule levels. Gene expression of adhesion molecules and matrix metalloproteinases (MMPs) in aortas were measured by quantitative real-time polymerase chain reaction and Western blot. Compared with the HCD group, rabbits fed an HCD supplemented with 0.2% curcumin had significantly less aortic lesion areas and neointima thickening. Curcumin reduced the levels of total cholesterol, triglyceride, low-density lipoprotein cholesterol, and oxidized low-density lipoprotein cholesterol in serum by 30.7%, 41.3%, 30.4%, and 66.9% (all P < .05), respectively, but did not affect high-density lipoprotein cholesterol levels. In addition, curcumin attenuated HCD-induced CD36 expression, circulating inflammatory cytokines, and soluble adhesive molecule levels. Curcumin reduced the mRNA and protein expression of intracellular adhesion molecule-1, vascular cell adhesion molecule-1, P-selectin, and monocyte chemotactic protein-1, and it inhibited HCD-induced up-regulation of MMP-1, MMP-2, and MMP-9. Our results demonstrate that curcumin exerts an antiatherosclerotic effect, which is mediated by multiple mechanisms that include lowering serum lipids and oxidized low-density lipoprotein, thus modulating the proinflammatory cytokine levels and altering adhesion molecules and MMP gene expression.

Topics: Animals; Antioxidants; Aorta; Atherosclerosis; CD36 Antigens; Cell Adhesion Molecules; Chemokine CCL2; Cholesterol; Curcuma; Curcumin; Cytokines; Hypercholesterolemia; Intercellular Adhesion Molecule-1; Male; Matrix Metalloproteinases; P-Selectin; Phytotherapy; Plant Extracts; Rabbits; RNA, Messenger; Triglycerides; Up-Regulation; Vascular Cell Adhesion Molecule-1

Essential oil components from turmeric (Curcuma longa L.) are documented for neuroprotective, anti-cancer, anti-thrombotic and antioxidant effects. The present study aimed to investigate the disease-modifying potential of curcuma oil (C. oil), a lipophilic component from C. longa L., in hyperlipidaemic hamsters. Male golden Syrian hamsters were fed a chow or high-cholesterol (HC) and fat-rich diet with or without C. oil (30, 100 and 300 mg/kg) for 28 d. In HC diet-fed hamsters, C. oil significantly reduced plasma total cholesterol, LDL-cholesterol and TAG, and increased HDL-cholesterol when compared with the HC group. Similar group comparisons showed that C. oil treatment reduced hepatic cholesterol and oxidative stress, and improved liver function. Hyperlipidaemia-induced platelet activation, vascular dysfunction and repressed eNOS mRNA expression were restored by the C. oil treatment. Furthermore, aortic cholesterol accumulation and CD68 expression were also reduced in the C. oil-treated group. The effect of C. oil at 300 mg/kg was comparable with the standard drug ezetimibe. Delving into the probable anti-hyperlipidaemic mechanism at the transcript level, the C. oil-treated groups fed the chow and HC diets were compared with the chow diet-fed group. The C. oil treatment significantly increased the hepatic expression of PPARa, LXRa, CYP7A1, ABCA1, ABCG5, ABCG8 and LPL accompanied by reduced SREBP-2 and HMGCR expression. C. oil also enhanced ABCA1, ABCG5 and ABCG8 expression and suppressed NPC1L1 expression in the jejunum. In the present study, C. oil demonstrated an anti-hyperlipidaemic effect and reduced lipid-induced oxidative stress, platelet activation and vascular dysfunction. The anti-hyperlipidaemic effect exhibited by C. oil seems to be mediated by the modulation of PPARa, LXRa and associated genes involved in lipid metabolism and transport.

Topics: Animals; Anticholesteremic Agents; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Aorta; Cholesterol, Dietary; Cricetinae; Curcuma; Hypercholesterolemia; Jejunum; Liver; Liver X Receptors; Male; Mesocricetus; Nitric Oxide Synthase Type III; Oils, Volatile; Orphan Nuclear Receptors; Oxidative Stress; Phytotherapy; Plant Preparations; Platelet Activation; PPAR alpha; RNA, Messenger; Triglycerides; Vascular Diseases

An extract of Curcuma longa was tested in hypercholesterolemic rats to investigate its potential therapeutic effect on vascular conditions. Four experimental groups were used: normal diet (ND) control group, high cholesterol diet (HCD) group, and HCD subgroups supplemented with turmeric extract at 100 or 300 mg/kg of body weight (HCD100Tur and HCD300Tur groups, respectively). Turmeric extract was fed orally to animals, and dietary treatments lasted for 28 days. Hypercholesterolemia developed in the HCD, HCD100Tur, and HCD300Tur rats. Segments of the thoracic aorta were isolated, and an organ bath experiment was used to assess the vasorelaxation capability among all rats. Rats fed only HCD showed a marked decrease in acetylcholine-induced vasorelaxation compared with ND control rats. The HCD100Tur and HCD300Tur rats showed significant improvement in vasorelaxation compared with HCD rats. When vasorelaxation was induced by high concentrations of sodium nitroprusside, no differences in vasorelaxation were observed among the four groups of rats. A mechanistic study showed that HCD100Tur and HCD300Tur rats had significantly higher levels of the antioxidant enzymes superoxide dismutase and glutathione peroxidase than HCD rats. The transcript levels of heat shock protein 70 (hsp70), bcl2, bax-α, caspase (casp3), and glyceraldehyde 3-phosphate dehydrogenase in aortic tissues indicated that hypercholesterolemia significantly increased the expression of bax-α and casp3 but down-regulated bcl2 expression compared with the control group. Turmeric increased the expression of hsp70 and bcl2 but greatly reduced casp3 expression, indicating that turmeric improves vasorelaxation of the aorta in hypercholesterolemic rats by increasing antioxidant enzyme activities and likely suppressing apoptosis.

Topics: Animals; Aorta, Thoracic; Caspase 3; Curcuma; Gene Expression; HSP70 Heat-Shock Proteins; Humans; Hypercholesterolemia; In Vitro Techniques; Male; Plant Extracts; Rats; Rats, Sprague-Dawley; Vasodilation

In this study we examined the antioxidant effect of curcumin on lipid oxidation in vitro and in vivo. In vitro, curcumin at 5 microgM concentration completely prevented low-density lipoprotein (LDL) oxidation by CuS0(4), indicating that curcumin is an effective antioxidant in vitro. In vivo, feeding a pure cholesterol (PC)-rich diet to rabbits significantly increased the plasma and liver lipids as well as thiobarbituric acid reactive substances (TBARS) levels. Addition of curcumin to the PC diet did not show any effect on either plasma lipid and TBARS or liver lipids. Liver TBARS tended to decrease but that decrease was not significant. Erythrocyte glutathione peroxidase (GSH-Px) activity was significantly decreased while catalase activity was significantly increased in rabbits fed a PC diet. The addition of curcumin to a PC diet did not show any significant effect on erythrocyte enzyme activities compared to the rabbits fed a PC diet. The liver GSH-Px and catalase activities were significantly decreased in rabbits fed a PC diet, but the addition of curcumin to the PC diet enhanced the liver GSH-Px activity, which became nonsignificantly different from the control group. These results were discussed considering that curcumin may not be well absorbed and it did not reach a level high enough in vivo to overcome the severe hypercholesterolemia and oxidative stress produced by the PC-rich diet.

Topics: Alkaloids; Animals; Antioxidants; Benzodioxoles; Catalase; Cholesterol, Dietary; Curcumin; Glutathione Peroxidase; Hypercholesterolemia; Lipid Peroxidation; Lipids; Lipoproteins, LDL; Liver; Male; Oxidation-Reduction; Oxidative Stress; Piperidines; Polyunsaturated Alkamides; Rabbits

Curcuma comosa has been known to have potential use in cardiovascular diseases, but its immunoregulatory role in atherosclerosis development and liver toxicity has not been well studied. We therefore investigated the effects of Curcuma comosa on the expression of atherosclerosis-related cytokine genes in rabbits fed a high-cholesterol diet.. Twelve male New Zealand White rabbits were treated with 1.0% cholesterol for one month and were subsequently treated with 0.5% cholesterol either alone, or in combination with 5mg/kg/day of simvastatin or with 400mg/kg/day of Curcuma comosa powder for three months. The expression of IL-1, MCP-1, TNF-α, IL-10, and TGF-β in the isolated abdominal aorta and liver were determined by real-time RT-PCR. Liver toxicity was determined by hepatic enzyme activity.. Curcuma comosa significantly decreased the expression of pro-inflammatory cytokines, leading to a stronger reduction in IL-1, MCP-1, and TNF-α expression compared to that was suppressed by simvastatin treatment. However, neither Curcuma comosa nor simvastatin affected the expression of anti-inflammation cytokines. In the liver, Curcuma comosa insignificantly decreased the expression of pro-inflammatory cytokines and significantly increased the expression of the anti-inflammatory cytokine IL-10 without altering the activity of hepatic enzymes. In contrast, simvastatin significantly increased the MCP-1 and TNF-α expressions and serum ALT level, without affecting the expression of anti-inflammatory cytokines.. In this study, we demonstrated that Curcuma comosa exerts anti-inflammatory activity in the aorta and liver without causing liver toxicity, indicating that Curcuma comosa is a potential candidate as an alternative agent in cardiovascular disease therapy.

Topics: Animals; Aorta, Abdominal; Atherosclerosis; Base Sequence; Cholesterol, Dietary; Curcuma; Cytokines; DNA Primers; Hypercholesterolemia; Liver; Liver Function Tests; Male; Plants, Medicinal; Rabbits; Reverse Transcriptase Polymerase Chain Reaction

Culinary herbs and spices have been widely used for their hypoglycemic, lipid-lowering, and anti-inflammatory activities. This study examined the physiologic activity of hydrophilic components using extracts of turmeric or laurel leaf powder. Aqueous extracts of turmeric and laurel showed potent inhibitory activity against fructose-mediated glycation with antioxidant ability against low-density lipoprotein (LDL) oxidation and radical scavenging activity. The turmeric and laurel extracts had potent cholesteryl ester transfer protein (CETP) inhibitory ability (up to 23% and 40% inhibition, respectively) at a final concentration of 10 μg/mL. The turmeric and laurel extracts inhibited the cellular uptake of oxidized LDL into macrophages, which is the initial step in atherogenesis. For in vivo testing, zebrafish consumed a high cholesterol diet (HCD) (final concentration, 4% [wt/wt]) with or without turmeric or laurel powder (final concentration, 10% [wt/wt]). The turmeric and laurel groups had a 14% and 12% decrease, respectively, in the weight and height ratios compared to the HCD group. The plasma total cholesterol level was significantly lower in the turmeric and laurel groups (48% and 28% less, respectively, than in the HCD group). Plasma triglycerides were more markedly reduced in the turmeric and laurel groups than in the HCD group (68% and 56% less, respectively, than the HCD group). In conclusion, the hydrophilic extracts of turmeric and laurel potently suppressed the incidence of atherosclerosis via a strong antioxidant potential, prevention of apolipoprotein A-I glycation and LDL phagocytosis, and inhibition of CETP. Consumption of turmeric and laurel extracts exhibited hypolipidemic and antioxidant activities in a hypercholesterolemic zebrafish model.

Topics: Animals; Antioxidants; Apolipoprotein A-I; Atherosclerosis; Biological Transport; Cholesterol Ester Transfer Proteins; Cholesterol, Dietary; Cholesterol, LDL; Curcuma; Disease Models, Animal; Fructose; Hypercholesterolemia; Hypolipidemic Agents; Laurus; Lipid Metabolism; Lipid Peroxidation; Macrophages; Phagocytosis; Phytotherapy; Plant Extracts; Zebrafish

The extract of Curcuma longa, better known as turmeric, was orally administered to experimental rats that were fed a high-cholesterol diet to investigate whether it could regulate plasma lipids and cholesterol levels and possibly improve hepatic conditions. With turmeric supplements, rats showed a significant decrease in total plasma cholesterol and low-density lipoprotein cholesterol but an increase in high-density lipoprotein cholesterol when compared with rats that were fed a high-cholesterol diet alone. Fatty liver developed in hypercholesterolemic rats with the high-cholesterol diet treatment, and this condition was markedly improved when rats were provided with turmeric supplements at 100 mg/kg or 300 mg/kg of body mass. The turmeric treatment resulted in a significant decrease in the total amount of hepatic lipid. Histological staining of liver tissues with Sudan III and hematoxylin showed that rats fed with a high-cholesterol diet alone had more and larger granular fat bodies than rats having turmeric extract supplementation in their high-cholesterol diet. Reverse-transcription polymerase chain reaction was used to assess the expression levels of enzymes involved in fat metabolism and cellular homeostasis in experimental rat livers. The results showed that rats fed a high-cholesterol diet supplemented with turmeric extract had a significant increase in the expression of cholesterol 7 α-hydroxylase, hemeoxygenase 1, and low-density lipoprotein receptors but a significant decrease in 3-hydroxy-3-methyl-glutaryl-CoA reductase level when compared with rats fed a normal or high-cholesterol diet, showing that turmeric prevents hypercholesterolemia and the formation of fatty liver by the modulation of expressions of enzymes that are important to cholesterol metabolism..   Turmeric may be considered a functional food for regulating plasma cholesterol levels and preventing the development of fatty liver in people who frequently consume a high-cholesterol diet.

Topics: Animals; Anticholesteremic Agents; Cholesterol 7-alpha-Hydroxylase; Curcuma; Dose-Response Relationship, Drug; Fatty Liver; Gene Expression Regulation; Heme Oxygenase (Decyclizing); Hydroxymethylglutaryl CoA Reductases; Hypercholesterolemia; Isoenzymes; Lipid Metabolism; Liver; Male; Plant Extracts; Random Allocation; Rats; Rats, Sprague-Dawley; Receptors, LDL; Rhizome

To evaluate the efficacy of the curcumin-coating stent (CCS) on the inhibition of restenosis in a rabbit iliac artery stent model.. Curcumin, pigment naturally acquired from the rhizome of the plant curcuma longa, is known to have antiproliferative, antimigratory, and anti-inflammatory effects. However, it is still unclear that curcumin can inhibit neointimal proliferation of the injured vessel.. Dose-dependent inhibition of cell growth was observed over a dose range from 10 nM to 10 microM. CCS was prepared by a dip-coating method (high-dose: HD, low-dose: LD). The release profile of the HD CCS showed that drug release persisted until day 21. Scanning electron microscopy of the CCS showed an intact surface of the stent even after expansion. To test the efficacy of CCS in vivo, LD CCS, HD CCS, and bare metal stents (BMS) were implanted in random order in one iliac artery (N = 30 arteries) of male New Zealand White rabbits (N = 15).. After 28 days, the LD and HD CCS groups had a 43% and 55% reduction in the neointimal area, compared with the BMS group (BMS 3.3 +/- 1.0 mm(2), LD 1.9 +/- 0.8 mm(2), and HD 0.9 +/- 0.5 mm(2), P < 0.05). There appeared to be no cytotoxicity related to curcumin at the indicated doses.. Curcumin, a natural compound in the human diet, seems to be a safe and effective candidate drug for use in a drug-eluting stent for the prevention of stent restenosis following angioplasty.

Topics: Angioplasty, Balloon; Animals; Arterial Occlusive Diseases; Becaplermin; Cardiovascular Agents; Cell Movement; Cell Proliferation; Cells, Cultured; Coated Materials, Biocompatible; Constriction, Pathologic; Curcumin; Disease Models, Animal; Dose-Response Relationship, Drug; Drug-Eluting Stents; Hypercholesterolemia; Iliac Artery; Male; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Platelet-Derived Growth Factor; Prosthesis Design; Proto-Oncogene Proteins c-sis; Rabbits; Rats; Rats, Sprague-Dawley; Surface Properties; Time Factors

Type II diabetes mellitus (T2DM) is often accompanied by non-alcoholic steatohepatitis (NASH) and associated with hypercholesterolemia, that is, increased levels of plasma low-density lipoprotein (LDL) and oxidized LDL (ox-LDL). Approximately one-third of NASH develops hepatic fibrosis. The role of hypercholesterolemia in T2DM and NASH-associated hepatic fibrogenesis remains obscure. We previously reported that the phytochemical curcumin inhibited the activation of hepatic stellate cells (HSCs), the major effector cells during hepatic fibrogenesis, and protected the liver from fibrogenesis in vitro and in vivo. The aims of this study are to evaluate the role of ox-LDL in activation of HSCs, to assess curcumin effects on eliminating the role of ox-LDL, and to further explore the underlying mechanisms. In this report, we observe that ox-LDL alters the expression of genes closely relevant to HSC activation, which is eliminated by curcumin. Curcumin suppresses gene expression of lectin-like oxidized LDL receptor-1 (LOX-1), leading to the blockade of the transport of extracellular ox-LDL into cells. This suppressive effect of curcumin results from the interruption of Wnt signaling and the activation of peroxisome proliferator-activated receptor-gamma (PPARgamma). In conclusion, these results support our initial hypothesis and demonstrate that ox-LDL stimulates HSC activation, which is eliminated by curcumin by suppressing lox-1 expression by interrupting Wnt signaling and stimulating PPARgamma activity. These results provide novel insights into the role of ox-LDL in T2DM and NASH-associated hepatic fibrogenesis and mechanisms by which curcumin suppresses ox-LDL-induced HSC activation, as well as the implication of curcumin in the treatment of T2DM and NASH-associated hepatic fibrosis.

Topics: Animals; Blotting, Western; Coloring Agents; Curcumin; Diabetes Mellitus, Type 2; Gene Expression Regulation; Gene Silencing; Hepatic Stellate Cells; Hypercholesterolemia; Lipoproteins, LDL; Liver Cirrhosis; Male; Mutagenesis, Site-Directed; PPAR gamma; Rats; Rats, Sprague-Dawley; Receptors, Oxidized LDL

Health beneficial hypolipidemic and antioxidant influences of dietary spice principles--curcumin, capsaicin alone and in combination included in the diet for 8 weeks were evaluated in induced hypercholesterolemic rats, in order to verify if there is any additive or synergistic effect of these two bioactive compounds. Dietary curcumin (0.2%), capsaicin (0.015%) or their combination significantly countered the hypercholesterolemia brought about by high cholesterol feeding. Hepatic cholesterol was lowered by dietary spice principles only in normal rats. Liver triglyceride levels were lowered in both normal and hypercholesterolemic rats by capsaicin. Curcumin and capsaicin lowered hepatic and blood lipid peroxides in hypercholesterolemic rats, while the effect in blood was additive with their combination. Hepatic ascorbic acid was enhanced by dietary spice principles in normal rats; glutathione was enhanced by their combination only in hypercholesterolemic rats. Activities of serum glutathione reductase, glutathione transferase and catalase and hepatic glutathione reductase in normal rats and serum glutathione peroxidase in hypercholesterolemic rats were enhanced by dietary spice principles. While dietary curcumin and capsaicin normalized the changes in the levels of antioxidant molecules and activities of antioxidant enzymes to a significant extent, this effect was not generally additive when given in combination, and was higher than the individual effects only in a few instances.

Topics: Animals; Antioxidants; Capsaicin; Cholesterol, Dietary; Curcumin; Female; Glutathione Reductase; Hypercholesterolemia; Hypolipidemic Agents; Lipid Metabolism; Lipids; Liver; Rats; Rats, Wistar; Sulfhydryl Compounds

Topics: Alzheimer Disease; Antioxidants; Capsaicin; Cinnamomum zeylanicum; Curcumin; Cystic Fibrosis; Health Promotion; Humans; Hypercholesterolemia; Neoplasms; Phytotherapy; Plant Structures; Plants, Medicinal; Salvia officinalis; Spices

In rats rendered hypercholesterolaemic by maintaining them on a cholesterol-enriched diet (0.5 %) for 8 weeks, as a result of alteration in membrane structural lipids, erythrocytes were observed to be deformed and become more fragile. This deformity and fragility was partially reversed by the two dietary spice principles, curcumin and capsaicin, and the spice, garlic, by virtue of their ability to lower the extent of hypercholesterolaemia. A further insight into the factors that might have reduced the fluidity of erythrocytes in hypercholesterolaemic rats revealed changes in fatty acid profile of the membranes, phospholipid composition of the membrane bilayer, reduced Ca(2+),Mg(2+)-ATPase, and reduction in the sensitivity of erythrocytes to concanavaline A. Dietary capsaicin appeared to counter these changes partially in hypercholesterolaemic rats. Electron spin resonance (ESR) spectra and fluorescence anisotropy parameters also revealed altered fluidity of erythrocytes in hypercholesterolaemic rats. Dietary capsaicin and curcumin significantly reversed this alteration. Scanning electron microscopic examination revealed that the echinocyte population was increased in the erythrocytes of hypercholesterolaemic rats, and this was significantly countered by dietary capsaicin. The membrane protein profile and the active cation efflux appeared to be unaffected in the hypercholesterolaemic situation.

Topics: Adenosine Triphosphatases; Animals; Capsaicin; Curcumin; Erythrocyte Deformability; Erythrocyte Membrane; Erythrocytes; Fatty Acids; Female; Fluorescence Polarization; Garlic; Hypercholesterolemia; Membrane Fluidity; Microscopy, Electron, Scanning; Phospholipids; Rats; Rats, Wistar; Spices

Curcumin (a component of turmeric) has long been used as a spice and food-coloring agent. In experimental animals, curcumin has shown anti-diabetic, anti-inflammatory, cytotoxic and anti-oxidant properties.. The possible hypolipidemic effect of curcumin was investigated in rats fed a high-cholesterol diet (HCD). The lipid profile and activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were assessed in serum, as well as anti-oxidant parameters in liver tissues.. Feeding the animals a high cholesterol diet (HCD) for 7 consecutive days (1 ml 100 g(-1)) resulted in marked hypercholesterolemia, increased serum level of low-density lipoprotein cholesterol (LDL-C), but a decreased serum high-density lipoprotein cholesterol (HDL-C). Curcumin admixed with the diet (0.5% w/w) decreased serum total cholesterol (TC) by about 21% and LDL-C by 42.5%, but it increased serum HDL by 50%. The atherogenic indices (LDL-C/HDL-C and TC/HDL-C) were reduced by 52% and 35%, respectively. Curcumin also decreased the enzyme activities of serum AST and ALT, which were increased in HCD animals.. Curcumin showed an obvious hypocholesterolemic effect that could be due to an effect on cholesterol absorption, degradation or elimination, but not due to an anti-oxidant mechanism. This could be supported by the finding in our study that neither HCD nor curcumin-admixed HCD had any effects on the liver content of glutathione (GSH) or superoxide dismutase (SOD) activity. Thus one could argue that ingestion of curcumin-containing spices in the diet, especially one rich in fats, could have a lipid-lowering effect.

Topics: Alanine Transaminase; Animals; Aspartate Aminotransferases; Cholesterol; Cholesterol, Dietary; Cholesterol, HDL; Cholesterol, LDL; Curcumin; Hypercholesterolemia; Hypolipidemic Agents; Liver; Male; Rats

Animal studies were carried out to examine the beneficial influence of known hypolipidemic spice principles--curcumin, capsaicin, and garlic--on the antioxidant status of red blood cells and liver under induced hypercholesterolemic conditions. Groups of experimental rats rendered hypercholesterolemic were maintained on curcumin (0.2%)/capsaicin (0.015%)/garlic (2.0% dry powder)-containing diets for eight weeks. Erythrocytes isolated at the end of the study were analyzed for intracellular antioxidant molecules and antioxidant enzymes. Intracellular thiols and glutathione content in red blood cells were significantly depleted (by about 35%) in hypercholesterolemic rats. This depletion in intracellular thiols and glutathione was effectively countered by dietary spice principles - curcumin, capsaicin, and garlic. Glutathione reductase activity that was lowered in hypercholesterolemic conditions (by 25%) was completely countered by dietary spice principles and garlic. Activities of glutathione transferase, glutathione peroxidase, and catalase in erythrocytes remained unchanged under hypercholesterolemic conditions. Although hemoglobin levels of erythrocytes were not affected, methemoglobin concentration was significantly increased in hypercholesterolemic rats. This alteration was partially countered by dietary spice principles. Significant fall in hepatic total thiols in the hypercholesterolemic situation was partially corrected by dietary spice treatment. Similarly, the lowered activities of hepatic antioxidant enzymes--glutathione reductase, glutathione-S-transferase, catalase, and superoxide dismutase--in hypercholesterolemic rats were effectively countered by the dietary spices treatment.

Topics: Animals; Antioxidants; Capsaicin; Catalase; Curcumin; Diet; Erythrocytes; Garlic; Glutathione; Glutathione Reductase; Glutathione Transferase; Hypercholesterolemia; Hypolipidemic Agents; Liver; Methemoglobin; Rats; Spices; Sulfhydryl Compounds; Superoxide Dismutase

Former studies have shown that curcumin, which can be extracted from different Curcuma species, is able to stimulate bile flow and to reduce hypercholesterolemia. We investigated in a subchronic bile fistula model the ability of curcumin to reduce cyclosporine-induced cholestasis and hypercholesterolemia. Male Wistar rats were daily treated with curcumin (100 mg/kg p. o.), cyclosporine (10 mg/kg i. p.), and a combination of curcumin with cyclosporine. After two weeks a bile fistula was installed into the rats to measure bile flow and biliary excretion of bile salts, cholesterol, bilirubin, cyclosporine and its main metabolites. Blood was taken to determine the concentration of these parameters in serum or blood. Cyclosporine reduced bile flow (-14 %) and biliary excretion of bile salts (-10 %) and cholesterol (-61 %). On the other hand, cyclosporine increased serum concentrations of cholesterol and triglycerides by 32 % and 82 %, respectively. Sole administration of curcumin led to a slight decrease of bile flow (-7 %) and biliary bile salt excretion (-12 %), but showed no effect on biliary excretion of cholesterol and serum lipid concentration. When curcumin was given simultaneously with cyclosporine, the cyclosporine-induced cholestasis was enhanced but the cyclosporine-induced hyperlipidemia was not affected. Neither the biliary excretion nor the blood concentration of cyclosporine was influenced by curcumin. The blood concentration of the main cyclosporine metabolites, however, was lowered by half while their biliary excretion was strongly increased by curcumin. From these results we conclude that curcumin is not able to prevent cyclosporine-induced cholestasis and hyperlipidemia after prolonged administration in bile fistula rats.

Topics: Administration, Oral; Animals; Bile; Bile Acids and Salts; Biliary Fistula; Cholagogues and Choleretics; Cholestasis; Cholesterol; Curcuma; Curcumin; Cyclosporine; Disease Models, Animal; Hypercholesterolemia; Hypolipidemic Agents; Immunosuppressive Agents; Injections, Intraperitoneal; Male; Phytotherapy; Plant Extracts; Rats; Rats, Wistar; Triglycerides

Our previous observation that induction of low density lipoprotein (LDL) receptor expression by a variety of extracellular signals is blocked by PD98059, a specific mitogen-activated protein kinase kinase inhibitor, led to the suggestion that the growth-responsive p42/44(MAPK) cascade plays a critical role in regulating LDL receptor transcription. To analyze the specific contribution of the p42/44(MAPK) cascade in regulating cell growth and LDL receptor induction, we established a HepG2-derived cell line that stably expresses an inducible form of oncogenic human Raf-1 kinase. Using this system, we provide direct evidence that specific activation of this cascade alone is not only required but is sufficient to fully induce LDL receptor expression. Interestingly, degree of p42/44(MAPK) activation determines the extent of LDL receptor induction. However, activation of p42/44(MAPK) in the above cells led to the inhibition of DNA synthesis, caused growth arrest, decrease in cyclin A and upregulation of p21(Cip) expression in a time-dependent manner. These results suggest that each of these two processes can be regulated independently of each other in response to p42/44(MAPK) activation. Thus, extent of p42/44(MAPK) activation may be important in transducing divergent cellular responses in human cells with implications for altered signaling resulting in hypercholesterolemia.

Topics: Blotting, Northern; Cell Cycle; Cell Division; Curcumin; Cyclin A; DNA; Dose-Response Relationship, Drug; Enzyme Activation; Enzyme Inhibitors; Flavonoids; Humans; Hypercholesterolemia; Immunoblotting; Luciferases; MAP Kinase Kinase 1; MAP Kinase Kinase 2; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinase Kinases; Mitogen-Activated Protein Kinases; Promoter Regions, Genetic; Protein Serine-Threonine Kinases; Protein-Tyrosine Kinases; Proto-Oncogene Proteins c-raf; Receptors, LDL; Signal Transduction; Staurosporine; Subcellular Fractions; Time Factors; Transcription, Genetic; Transfection; Tumor Cells, Cultured; Up-Regulation

The oxidation of low-density lipoproteins (LDL) plays an important role in the development of atherosclerosis. Curcumin is a yellow pigment obtained from rhizomes of Curcuma longa and is commonly used as a spice and food colouring. Curcumin and turmeric extracts have several pharmacological effects including antitumour, anti-inflammatory, antioxidant and antiinfectious activities although the precise mechanisms involved remain to be elicited. We evaluated the effect of an ethanol-aqueous extract obtained from rhizomes of C. longa on LDL oxidation susceptibility and plasma lipids in atherosclerotic rabbits. A total of 18 rabbits were fed for 7 weeks on a diet containing 95.7% standard chow, 3% lard and 1. 3% cholesterol, to induce atherosclerosis. The rabbits were divided into groups, two of which were also orally treated with turmeric extract at doses of 1.66 (group A) and 3.2 (group B) mg/kg body weight, respectively. A third group (group C) acted as a control. Plasma and LDL lipid composition, plasma alpha-tocopherol, plasma retinol, LDL TBARS, LDL lipid hydroperoxides and analysis of aortic atherosclerotic lesions were assayed. The low but not the high dosage decreased the susceptibility of LDL to lipid peroxidation. Both doses had lower levels of total plasma cholesterol than the control group. Moreover, the lower dosage had lower levels of cholesterol, phospholipids and triglycerides in LDL than the 3.2-mg dosage. In conclusion, the use of this extract could be useful in the management of cardiovascular disease in which atherosclerosis is important.

Topics: Administration, Oral; Animals; Anticholesteremic Agents; Antioxidants; Arteriosclerosis; Curcuma; Disease Models, Animal; Dose-Response Relationship, Drug; Hypercholesterolemia; Lipid Peroxidation; Lipoproteins, LDL; Male; Plant Extracts; Rabbits; Random Allocation; Reference Values