Potent Hypolipidemic Agent Research Articles

Effect of Parkia biglobosa seed on lipid profile of dexamethasone-treated pregnant rats

This study was aimed at evaluating the effect of Parkia biglobosa seed on dexamethasone-treated pregnant rats. Locust bean seeds were purchased from an open market in Ado Ekiti, Nigeria. It was processed and ground into powder which was subsequently used in formulating feed for experimental animals. Fifteen female pregnant rats were divided in three groups of five each. Animals in group A were exposed to standard animal feed only. This served as the control group. Those in group B were exposed to animal feed mixed with locust beans + 0.3 mg/kg body weight of dexamethasone, while those in group C were exposed to animal feed mixed with locust beans. At the end of eight days treatment, animals were sacrificed and blood sample was collected into EDTA bottles and centrifuged. Plasma was separated and used for the determination of glucose and lipid profile. Exposure of animals to dexamethasone was observed to significantly (p<0.05) increased the concentration of plasma glucose concentration when compared with the control as well as animals treated with P. biglobosa only. Animals treated with dexamethasone along with P. biglobosa were observed to have higher concentrations of triglyceride, total cholesterol, low density lipoprotein (LDL) and very low density lipoprotein (VLDL) when compared with those in animals in the control group as well as those treated with P. biglobosa only. Observations from this study revealed that dexamethasone adversely perturbed and unhinged plasma glucose and lipid profile in female pregnant rats while P. biglobosa-formulated diet was observed to be a potent hypoglycemic and hypolipidemic agent.

Structural simplification and bioisostere principle lead to Bis-benzodioxole-fibrate derivatives as potential hypolipidemic and hepatoprotective agents

The bis-benzodioxole-fibrate hybrids were designed by structural simplification and bioisostere principle. Lipids lowering activity was preliminarily screened by Triton WR 1339 induced hyperlipidemia mice model, in which T3 showed the best hypolipidemia, decreasing plasma triglyceride (TG) and total cholesterol (TC), which were better than sesamin and fenofibrate (FF). T3 was also found to significantly reduce TG, TC and low density lipoprotein cholesterin (LDL-C) both in plasma and liver tissue of high fat diet (HFD) induced hyperlipidemic mice. In addition, T3 showed hepatoprotective activity, which the noteworthy amelioration in liver aminotransferases (AST and ALT) was evaluated and the histopathological observation exhibited that T3 inhibited lipids accumulation in the hepatic and alleviated liver damage. The expression of PPAR-α receptor involved lipids metabolism in liver tissue significantly increased after T3 supplementation. Other potent activity, such as antioxidation and anti-inflammation, was also observed. The molecular docking study revealed that T3 has good affinity activity toward to the active site of PPAR-α receptor. Based on these findings, T3 may serve as an effective hypolipidemic agent with hepatoprotection.

The combination of sesamol and clofibric acid moieties leads to a novel potent hypolipidemic agent with antioxidant, anti-inflammatory and hepatoprotective activity

Oxidative stress and inflammation have been considered the main factors in the liver injury of clofibrate (CF). To obtain a novel antihyperlipidemic agent with antioxidant, anti-inflammation and hepatoprotection, the combination of sesamol and clofibric acid moieties was performed and achieved sesamol-clofibrate (CF-Sesamol). CF-Sesamol showed significant hypolipidemia effects in hyperlipidemia mice induced by Triton WR 1339, reducing TG by 38.8% (P < 0.01) and TC by 35.1% (P < 0.01). CF-Sesamol also displayed an alleviating effect on hepatotoxicity. The hepatic weight and hepatic coefficient were decreased. The amelioration of liver function was observed, such as aspartate and lactate transaminases (AST and ALT), alkaline phosphatase (ALP) and total proteins (TP) levels. Liver histopathological examination showed that hepatocyte necrosis, cytoplasmic loosening, nuclear degeneration and inflammatory cell infiltration reduced obviously by treatment with CF-Sesamol. Related molecular mechanisms on hepatoprotection showed that CF-Sesamol up-regulated Nrf2 and HO-1 expression and down-regulated p-NF-κB p65 expression in hepatic tissues. CF-Sesamol has significant antioxidant and anti-inflammatory effects. Plasma antioxidant enzymes such as SOD and CAT increased, anti-lipid peroxidation product MDA decreased. The expression of TNF-α and IL-6 inflammatory cytokines in liver was significantly lower than that in the CF group. The results indicated that CF-Sesamol exerted more potent antihyperlipidemic effects and definite hepatoprotective activity partly through the Nrf2/NF-κB-mediated signaling pathway.

1,3-Benzodioxole-based fibrate derivatives as potential hypolipidemic and hepatoprotective agents

A series of target compounds 1,3-benzodioxole-based fibrate derivatives were designed and synthesized. All the target compounds were preliminarily evaluated by hyperlipidemia mice induced by Triton WR-1339, in which compound 12 displayed a greater anti-hyperlipidemia activity than other compounds as well as positive drug fenofibrate (FF). 12 showed a significant reduction of plasma lipids, such as triglycerides (TG), total cholesterol (TC) and low-density lipoprotein cholesterin (LDL-C), in high fat diet (HFD) induced hyperlipidemic mice. In addition, hepatic transaminases (AST and ALT) were ameliorated after administration of 12, in particular the AST, and the histopathological examination showed that 12 improved the hepatic lipid accumulation. The expression of PPAR-α involved in lipids metabolism was up-regulated in the liver tissues of 12-treated group. Other significant activity such as antioxidant, and anti-inflammation was confirmed and reinforced the effects of 12 as a potential hypolipidemia and hepatoprotective agent.

Amino acid ester-coupled caffeoylquinic acid derivatives as potential hypolipidemic agents: synthesis and biological evaluation.

Pandanus tectorius (L.) Parkins. (PTPs) is rich in caffeoylquinic acids and amino acids, especially some essential amino acids, such as valine, phenylalanine, and so forth. A series of novel amino acid ester-coupled caffeoylquinic acid derivatives have been designed and synthesized. Biological evaluation suggested that some amino acid ester-coupled derivatives exhibited varying degrees of lipid-lowering effects on oleic acid-elicited lipid accumulation in HepG2 liver cells. Particularly, derivatives 6c, 6d, 6e and 6f exhibited comparable potential lipid-lowering effect with the positive control simvastatin and chlorogenic acid. Further studies on the mechanism of 6c, 6d, 6e and 6f revealed that the lipid-lowering effects were related to their regulation of TG levels and mRNA levels of lipometabolic-modulating genes, and merit further investigation.

Sea Buckthorn and Grape Extract Might Be Helpful and Sustainable Phyto-Resources as Associated Hypolipidemic Agents—Preliminary Study

Phytotherapy can enhance the beneficial health outcomes in the prevention of obesity and is able to improve the function of the metabolic organs, like the liver and kidneys. Since sea buckthorn (SBT) and grape extracts are known as abundant sources of polyphenol, we assumed that the extracts of these two plants might have a hypolipidemic effect and an improved metabolic function in obese rats treated with atorvastatin. One hundred and twelve white Wistar rats were divided equally into seven groups (G.I–VII) and orally treated as follows: G.I, atorvastatin 20 mg × kg·bw−1; G.II, atorvastatin 20 mg × kg·bw−1 + SBT 100 mg × kg·bw−1; G.III, atorvastatin 20 mg × kg·bw−1 + grape extract 100 mg × kg·bw−1; G.IV, grape extract 100 mg × kg·bw−1; G.V, SBT 100 mg × kg·bw−1; G.VI, high-fat diet (HFD); group VII was considered the control group. After two and six months of administration, the rats were sacrificed, and blood samples were taken for biochemical analyses. The statistical results (analysis of variance (ANOVA)) showed that a combination of SBT and grape extracts with atorvastatin significantly reduced (p ˂ 0.001) the lipid parameters. After six months, the liver and kidneys improved their functioning, showing a statistically significant change (p ˂ 0.001) in the grape and sea buckthorn groups compared to the other groups. In addition, grape extract and SBT combined with atorvastatin proved to be potent hypolipidemic agents, so associations with phytodietary supplements can be considered as a valuable means of combating hypolipidemia and decreasing risk factors.

In vitro activation of peroxisome proliferator activated receptor α by some extracts from food materials

Peroxisome proliferator activated receptor α (PPARα) is a ligand-dependent transcription factor that regulates the expression of genes involved in lipid metabolism and transport. Activators of PPARα may be potential hypolipidemic agents, like the fibrate-type drugs. This study was therefore aimed at identifying potential hypolipidemic functional foods by screening activators of PPARα from food materials. CHO-K1 cells were stably transfected with vectors (pBKCMV) carrying cDNAs of a (UAS)4-tk-alkaline phosphatase reporter and a chimeric receptor Gal4-PPARα LBD successively. Clones of cells responsive to Wy-14643, a known PPARα activator were selected, characterized and used for testing the PPARα activating potency of fractions extracted from food materials. Food materials were extracted with ethyl acetate and the extract (EAE) was cold-saponified and tested for the PPARα activating ability using the selected stable transfected clone of cells. 10 µM Wy-14643 (WY) was used as the positive control. Among food materials tested, EAE of bitter gourd showed the highest activity that exceeded Wy-14643, although the activity significantly decreased after saponification. The non-saponifiable fraction of onion EAE had a high maximal fold of activation equivalent to Wy-14643, while that of peanut, lychee, ricinus seed and longan showed moderate activity. The saponifiable fraction of ricinus seed, sesame and peanut also showed moderate activity. Further investigation is needed to explore the health benefit of the PPARα activating food extracts found in this study.

Dietary Supplementation with Aqueous Extract of Talinum triangulare at Different Phases of Broiler Production and Effect on Growth, Serum Biochemistry and Carcass Quality

This study investigated at what phase of production Talinum triangulare (waterleaf) extract (TTE), a low-cost, unconventional feed ingredient and potent hypolipidemic agent will exert the optimal effect of reduced fat deposition in broilers. After one-week brooding and acclimatization period, a total of 180 broilers were separated into four treatment groups- A, B, C and D. Groups A, B and C had their diets supplemented with 1000 mg of TTE per litre of drinking water from week 2 to 12; week 2 to 7 and; week 7 to 12, of life respectively. Broilers in Group D were not treated with TTE and served as negative control. Parameters assessed include growth, serum biochemistry, carcass yield and abdominal fat deposition. Talinum triangulare extract supplementation in broilers produced very lean carcass with better cholesterol profile (enhanced HDL-C and reduced LDL-C) when administered throughout the production period (week 2 - 12) and at the finisher phase (week 7 - 12).

Design, synthesis and evaluation of 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione-Based fibrates as potential hypolipidemic and hepatoprotective agents.

Six novel target compounds 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione (ADT) based fibrates were synthesized and evaluated. All the synthesized compounds were preliminarily screened by using the Triton WR-1339-induecd hyperlipidemia model, in which T1 exhibited more potent hypolipidemic property than positive drug fenofibrate (FF). T1 also significantly decreased serum triglycerides (TG), total cholesterol (TC) and low density lipoprotein cholesterin (LDL) in methionine solution (Mets) induced hyperlipidemic mice. Moreover, hepatic transaminases (AST and ALT) were obviously ameliorated after treatment with T1 and the histological observation indicated that T1 ameliorated the injury in liver tissue and inhibited the hepatic lipid accumulation. In the livers of T1-administrated rat, the levels of PPARα related to lipids metabolism were up-regulated. Additional effects such as antioxidant, anti-inflammatory and H2S releasing action confirmed and reinforced the activity of T1 as a potential multifunctional hypolipidemic and hepatoprotective agent.

Statin-based therapy for primary and secondary prevention of ischemic stroke: A meta-analysis and critical overview.

To reassess the effect of statin-based lipid-lowering therapy on ischemic stroke in primary and secondary prevention trials with regard to achieved levels of low-density lipoprotein-cholesterol in view of the availability of novel potent hypolipidemic agents. English literature was searched (up to November 2018) for publications restricted to trials with a minimum enrolment of 1000 and 500 subjects for primary and secondary prevention, respectively, meeting the following criteria: adult population, randomized controlled design, and recorded outcome data on ischemic stroke events. Data were meta-analyzed and curve-estimation procedure was applied to estimate regression statistics and produce related plots. Four primary prevention trials and four secondary prevention trials fulfilled the eligibility criteria. Lipid-lowering therapy was associated with a lower risk of ischemic stroke in primary (risk ratio, RR 0.70, 95% confidence interval, CI, 0.60-0.82; p < 0.001) and in the secondary prevention setting (RR 0.80, 95% CI 0.70-0.90; p < 0.001). Curve-estimation procedure revealed a linear relationship between the absolute risk reduction of ischemic stroke and active treatment-achieved low-density lipoprotein-cholesterol levels in secondary prevention (adjusted R-square 0.90) in support of "the lower the better" hypothesis for stroke survivors. On the other hand, the cubic model followed the observed data well in primary prevention (adjusted R-square 0.98), indicating greater absolute risk reduction in high-risk cardiovascular disease-free individuals. Statin-based lipid-lowering is effective both for primary and secondary prevention of ischemic stroke. Most benefit derives from targeting disease-free individuals at high cardiovascular risk, and by achieving low treatment targets for low-density lipoprotein-cholesterol in stroke survivors.

Synthesis and In Vitro Evaluation of Caffeoylquinic Acid Derivatives as Potential Hypolipidemic Agents.

A series of novel caffeoylquinic acid derivatives of chlorogenic acid have been designed and synthesized. Biological evaluation indicated that several synthesized derivatives exhibited moderate to good lipid-lowering effects on oleic acid-elicited lipid accumulation in HepG2 liver cells. Particularly, derivatives 3d, 3g, 4c and 4d exhibited more potential lipid-lowering effect than the positive control simvastatin and chlorogenic acid. Further studies on the mechanism of 3d, 3g, 4c and 4d revealed that the lipid-lowering effects were related to their regulation of TG levels and merit further investigation.

5-(4-Hydroxyphenyl)-3H-1,2-dithiole-3-thione-based fibrates as potential hypolipidemic and hepatoprotective agents

Hypolipidemic effects of the newly synthesized 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione-based fibrates were evaluated in Triton WR-1339 and high-fat diet (HFD)-induced hyperlipidemic mice. Preliminary screening of all the synthesized compounds was done by using an acute model (Triton WR-1339 model), in which compound 6 shown more significant antidyslipidemic activity than fenofibrate (FF). The compound 6 was also found to reduce serum triglyceride (TG), total cholesterol (TC) and low density lipoprotein cholesterin (LDL) in HFD-induced hyperlipidemic mice. Moreover, compound 6 displayed hepatoprotective effect, a significant amelioration in hepatic indices (AST and ALT) toxicity was observed and the histological examination showed that compound 6 inhibited the development of hepatic lipid accumulation and ameliorated the damage in hepatic tissue compared to model mice. Additional effects such as the potent antioxidant and anti-inflammatory action confirmed and reinforced the efficacy of compound 6 as a new agent of dual-effect hypolipidemic and hepatoprotective activities.

NEW SLANT ON HYPERLIPIDEMIA: PREVENTION BY VITAMIN B-3 AND COMMON FRUIT ZIZIPHUS JUJUBA

Coronary artery disease (CAD) is complication of primary or secondary hyperlipidemia. Etiological factors for hyperlipidemia include inherited genetic defects in low density lipoproteins (LDLs), persons accustomed to sit for prolong time, cigarette smoking, diabetes mellitus, and hypertension. This research work’s aim was to compare hypolipidemic features of an allopathic agent vitamin B-3 and another medicinal plant Z. Jujuba. Study was conducted from January 2016 to June 2016 at Jinnah Hospital Lahore, Pakistan. 60 male and female hyperlipidemic patients age range from 20 to 70 years were selected from the hospital. Written and explained consent was taken from all patients. They were divided in two groups. Group-I was advised to take two grams vitamin B-3 in divided doses for the period of two months. Group-II was advised to take 500 grams of fruit Z. Jujuba daily for 60 days per their convenience. Their initial LDL and HDL cholesterol was determined by Friedwald’s formula. After 60 days therapy, their post treatment lipid profile was measured and mean values with ± SD were analyzed biostatistically by using SPSS version 2; 2010. Group-I which was on vitamin B-3 their LDL cholesterol decreased significantly and HDL cholesterol was increased significantly. In group-II patients LDL cholesterol was decreased significantly but HDL increase was not significant with p-value of >0.05. It was concluded from the research study that vitamin B-3 is potent hypolipidemic agent as compared to medicinal plant Z. Jujuba.

Hypolipidemic Activities of a Series of Pyrazoles of Curcumin

A series of curcumin pyrazole derivatives (3a-3e) were investigated for in-vitro hypolipidemic activity. The compounds were screened for the inhibition studies of the enzymes such as pancreatic lipase, glucose 6 phosphate dehydrogenase and malate dehydrogenase which are actively involved in lipid metabolism. Curcumin and all the other compounds in the series showed differential enzyme inhibitory activity. Curcumin and compound 3b showed prominent pancreatic lipase inhibitory activity showing IC50 17.39 and 16 µM respectively. Curcumin, compound 3a and compound 3b exhibited considerable malic dehydrogenase inhibitory activity and the IC50 was found to be 23.42, 18.54 and 22.82 µM respectively. Glucose 6 phosphate dehydrogenase activity was inhibited significantly by curcumin, compounds 3a, 3b and 3e and IC50 was 17.41, 17.11, 14.02 and 18.7 µM respectively. Our results suggest that among the curcumin pyrazole derivatives (3a- 3e), compound 3a and 3b could be potential hypolipidemic agents and can be promoted for further in-vitro and in vivo investigations. Keywords: Pancreatic lipase, enzyme inhibition, glucose 6 phosphate dehydrogenase, malate dehydrogenase, in-vitro.

Synthesis and highly potent hypolipidemic activity of alpha-asarone- and fibrate-based 2-acyl and 2-alkyl phenols as HMG-CoA reductase inhibitors

In the search for new potential hypolipidemic agents, the present study focused on the synthesis of 2-acyl phenols (6a–c and 7a–c) and their saturated side-chain alkyl phenols (4a–c and 5a–c), and on the evaluation of their hypolipidemic activity using a murine Tyloxapol-induced hyperlipidemic protocol. The whole series of compounds 4–7 greatly and significantly reduced elevated serum levels of total cholesterol, LDL-cholesterol, and triglycerides, with series 6 and 7 showing the greatest potency ever found in our laboratory. At the minimum dose (25mg/kg/day), the latter compounds lowered cholesterol by 68–81%, LDL by 72–86%, and triglycerides by 59–80%. This represents a comparable performance than that shown by simvastatin. Experimental evidence and docking studies suggest that the activity of these derivatives is associated with the inhibition of HMG-CoA reductase.

γ-sitosterol a potent hypolipidemic agent: In silico docking analysis

A molecular docking analysis has been carried out to examine the hypolipidemic property of γ-sitosterol against five target proteins [acetoacetyl thiolase (PDB ID: 2 F2S), 3-(HMG-CoA) reductase (1DQ8), HMG-CoA synthase (PDB ID: 2P8U), squalene synthase (PDB ID: 3 V66, Oxido squalene cyclase (PDB ID: 1W6J)] which involved in cholesterol biosynthesis. The crystallographic structures of these target proteins were retrieved from PDB data base, and their active sites were identified by CastP server. The target proteins were subjected to docking analysis using Autodock tool v 4.2 and ADT v 1.5.6 programs. The docking studies showed that γ-sitosterol is a good and significant molecule which docks well with least lowest binding energy and inhibition constant values. Hence, γ-sitosterol can be considered for developing into a potent hypolipidemic agent.

Rice Bran Oil Compared to Atorvastatin for Treatment of Dyslipidemia in Patients with Type 2 Diabetes

Objective: To compare the effect of rice bran oil versus statins (atorvastatin drug) on blood glucose, glycosylated hemoglobin (HbA1C) and serum lipid profiles in patients with type 2 diabetes. The safety of the tested rice bran oil and atorvastatin were investigated. Fatty acids contents of RBO, olive and sesame oil were also assessed.Materials and Methods: Forty four eligible patients with type 2 diabetes and moderately hyperlipidemic were randomly and equally allocated into two groups, rice bran oil (RBO) group and atorvastatin group. The RBO group received a low-calorie diet and consumed 30Â g / day RBO oil as salad dressing and for use as main cooking oil for 6 months. The Atorvastatin group received a low-calorie diet and 40 mg/day of atorvastatin drug for 6 months. At baseline and after 6 months of study intervention, blood glucose, glycosylated hemoglobin (HbA1c), serum lipid profiles; hepatic, renal and inflammatory biomarkers were estimated.Results: Results showed significant increase in fasting and postprandial blood glucose, HbA1C and liver transaminases (alanine transaminase ALT and aspartate transaminase AST) in the atorvastatin group while a significant reduction was shown in RBO group. Moreover, significant reductions in lipid profile levels, blood urea, serum uric acid and erythrocyte sedimentation rate (ESR) were observed in both RBO and atorvastatin groups after 6 months of the study intervention.Conclusion: The use of rice bran oil together with dietary modifications may have implications in lowering fasting and postprandial blood glucose, suppressing serum lipid levels, reduce the TC/HDL-C ratio and therefore reducing the risk of cardiovascular disease. Moreover, RBO exerts a hypouricemic action and anti-inflammatory effects. The findings obtained from the current study reinforce the use of RBO as an alternative natural potent hypolipidemic agent safer than atorvastatin drug that may induce side effects in some cases in patients intolerant to statins.

Rice Bran Oil Compared to Atorvastatin for Treatment of Dyslipidemia in Patients with Type 2 Diabetes

Objective: To compare the effect of rice bran oil versus statins (atorvastatin drug) on blood glucose, glycosylated hemoglobin (HbA1C) and serum lipid profiles in patients with type 2 diabetes. The safety of the tested rice bran oil and atorvastatin were investigated. Fatty acids contents of RBO, olive and sesame oil were also assessed.Materials and Methods: Forty four eligible patients with type 2 diabetes and moderately hyperlipidemic were randomly and equally allocated into two groups, rice bran oil (RBO) group and atorvastatin group. The RBO group received a low-calorie diet and consumed 30Â g / day RBO oil as salad dressing and for use as main cooking oil for 6 months. The Atorvastatin group received a low-calorie diet and 40 mg/day of atorvastatin drug for 6 months. At baseline and after 6 months of study intervention, blood glucose, glycosylated hemoglobin (HbA1c), serum lipid profiles; hepatic, renal and inflammatory biomarkers were estimated.Results: Results showed significant increase in fasting and postprandial blood glucose, HbA1C and liver transaminases (alanine transaminase ALT and aspartate transaminase AST) in the atorvastatin group while a significant reduction was shown in RBO group. Moreover, significant reductions in lipid profile levels, blood urea, serum uric acid and erythrocyte sedimentation rate (ESR) were observed in both RBO and atorvastatin groups after 6 months of the study intervention.Conclusion: The use of rice bran oil together with dietary modifications may have implications in lowering fasting and postprandial blood glucose, suppressing serum lipid levels, reduce the TC/HDL-C ratio and therefore reducing the risk of cardiovascular disease. Moreover, RBO exerts a hypouricemic action and anti-inflammatory effects. The findings obtained from the current study reinforce the use of RBO as an alternative natural potent hypolipidemic agent safer than atorvastatin drug that may induce side effects in some cases in patients intolerant to statins.

Synthesis, hypolipidemic, and anti-inflammatory activities of arylphthalimides

Phthalimide and some N-substituted cyclic imides may be potent hypolipidemic agents, capable of reducing plasma cholesterol, and triglyceride levels. In this work, N-phenylphthalimide (5a), N-(2-nitrophenyl)phthalimide (5b), N-(3-nitrophenyl)phthalimide (5c), N-(4-nitrophenyl)phthalimide (5d), N-(4-bromophenyl)phthalimide (5e), N-(4-amidaphenyl)phthalimide (5f), N-(4-methylthiophenyl)phthalimide (5g), and N-(4-chlorophenyl)phthalimide (5h) were synthesized, and their effects on reducing lipid levels and as acute antiinflammatory agents in 3-month-old male Swiss mice were compared with phthalimide. To access their safety, the drugs were administered to determine the acute toxicity (LD50 value). In addition, the acute anti-inflammatory activity was evaluated via carrageenan-induced edema; and the effective dose was determined for compounds that showed the best anti-inflammatory activity in comparison with ibuprofen. The compound (5g) proved to be a more active hypolipidemic compound than phthalimide, at a dose level of 20 mg kg−1 day−1. The derivative (5g) reduced the plasmatic triglycerides and cholesterol levels by 54 and 41 %, respectively, while the percentages of reduction were 43 and 30 %, respectively, with phthalimide. The hypocholesterolemic and hypotriglyceridemic activities of the (5g) derivative were similar to that obtained with the commercially available drug, pravastatin. The anti-inflammatory activity of compound (5b) was similar to ibuprofen and aspirin at 250 mg kg−1. Taken together, it was demonstrated that the new phthalimide derivatives were able to increase HDL-cholesterol levels, along with reducing the cholesterol and triglyceride levels and carrageenan-induced edema in mice. Therefore, they may offer promise in the future as new hypolipidemic and anti-inflammatory agents.

Grape seed proanthocyanidins repress the hepatic lipid regulators miR‐33 and miR‐122 in rats

One major health problem in westernized countries is dysregulated fatty acid and cholesterol metabolism that causes pathologies such as metabolic syndrome. Previous studies from our group have shown that proanthocyanidins, which are the most abundant polyphenols in the human diet, regulate lipid metabolism and are potent hypolipidemic agents. The noncoding RNAs, miR-33 and miR-122, regulate genes that are involved in lipid metabolism. Here, we show that grape seed proanthocyanidins rapidly and transiently repressed the expression of miR-33 and miR-122 in rat hepatocytes in vivo and in vitro. Furthermore, the miR-33 target gene ATP-binding cassette A1 and the miR-122 target gene fatty acid synthase were also modulated by proanthocyanidins. Specifically, ATP-binding cassette A1 mRNA and protein levels were increased, and fatty acid synthase mRNA and protein levels were reduced after the miRNA levels were altered. These results suggest that proanthocyanidin treatment increased hepatic cholesterol efflux to produce new HDL particles by repressing miR-33, and it reduced lipogenesis by repressing miR-122. These results highlight a new mechanism by which grape seed proanthocyanidins produce hypolipidemia through their effects on miRNA modulators of lipid metabolism.