Hypolipidemic Effects of 2-Furoic Acid in Sprague-Dawley Rats

2-Furoic acid was shown to be effective in lowering both serum cholesterol and serum triglyceride levels significantly in rats with an elevation of HDL cholesterol level at 20 mg/kg/day orally. LDL receptor activity was reduced in hepatocytes, aorta foam cells, small intestinal epithelium cells and fibroblasts. HDL receptor activity was elevated in the rat hepatocytes and small intestinal cells. These activities were correlated with inhibition of acyl CoA cholesterol acyl transferase activity. Neutral cholesterol ester hydrolase activity was elevated in rat hepatocytes and human fibroblasts. Thus, 2-furoic acid appears to interfere directly with activity of intracellular enzymes rather than affecting high affinity-mediated lipoprotein membrane receptors. In vivo treatment with 2-furoic acid led to reduction in the liver and small intestine ATP dependent citrate lyase, acetyl CoA synthetase, acyl CoA cholesterol acyl transferase, sn-glycerol 3-phosphate acyl transferase, phosphatidylate phosphohydrolase and heparin induced lipoprotein lipase activities. 2-Furoic acid reduced biliary cholesterol levels but the agent increased bile salts which are lithogenic. Acute toxicity studies in mice suggest that the agent has some hepatic toxicity effects. The LD⁵⁰ was relatively low at 250 mg/kg IP in mice.     

The Hypolipidemic Activity of Furoic Acid and Furylacrylic Acid Derivatives in Rodents

2-Furoic acid, 3-furoic acid, 3,4-furan dicarboxylic acid and furyl-acrylic acid were evaluated for hypolipidemic activity in mice and rats. 2-Furoic acid was the most potent agent of the four tested, lowering serum cholesterol levels 41 % and serum triglyceride levels 56 % at 20 mg/kg/day in mice and serum cholesterol 50 % and serum triglyceride levels 42 % in rats. 2-Furoic acid effectively suppressed liver mitochondrial citrate exchange, ATP dependent citrate lyase, acetyl CoA synthetase, acyl CoA cholesterol acyl transferase, sn-glycerol-3-phosphate acyl transferase, phosphatidate phosphohydrolase and hepatic lipoprotein lipase enzymatic activities. Lipid levels after 16 days in mice were reduced in the liver. In the rat cholesterol content of the HDL fraction was elevated and lowered in the chylomicron fraction. 2-Furoic acid administration for 14 days resulted in a large portion of ³H-cholesterol being excreted by the biliary route. The furoic acid derivatives appear to have promise as hypolipidemic agents and further studies on their ability to lower lipids are warranted.     

The Hypolipidemic Effects of l-Acetyl-4-phenyl-l,2,4-triazolidine-3,5-dione in Rodents

l-Acetyl-4-phenyl-l ,2,4-triazolidine,5-dione (APTD), a potent hypolipidemic agent, lowered both serum cholesterol and triglyceride levels in normo- and hyperlipidemic rats at 10 or 20 mg/kg/day. The agent effectively lowered VLDL-cholesterol (VLDL-C) and LDL-C content and raised HDL-C content in normal and hyperlipidemic rats treated from 4 to 8 weeks. Similar effects on the incorporation of cholesterol into the lipoprotein fractions were observed after drug treatment. Tissue lipids, e.g. cholesterol, were lowered, whereas fecal cholesterol levels were increased. APTD's primary targets were acyl CoA cholesterol acyl transferase (ACAT) for cholesterol ester synthesis and sn-glycerol-3-phosphate acyl transferase (GPAT) and phosphatidylate phosphohydrolase (PPH) for triglyceride synthesis.     

Hypolipidemic Activity of 3-Amino-1-(2,3,4-mononitro-, mono-, or dihalophenyl)propan-1-ones in Rodents

A series of 3-amino-1-(2,3,4-mononitro-, mono-, or dihalophenyl)propan-1-ones were synthesized and shown to be effective in lowering both serum cholesterol and triglyceride levels significantly in CF₁ mice and Sprague-Dawley rats. All analogs showed better activity than the standard drugs, lovastatin and clofibrate, in reducing the serum cholesterol and triglyceride levels in mice at 8 mg/kg/day intraperitoneally. The best active analogs, 3-morpholino-1-(3-nitrophenyl)propan-1-one ( 4 ) and 3-piperidino-1-(3-nitrophenyl)propan-1-one ( 5 ), exhibited 58% and 67% reduction of serum cholesterol levels, respectively, and 42% and 46% reduction of serum triglyceride levels, respectively, after 16 days of administration at 8 mg/kg/day intraperitoneally in CF₁ mice. In Sprague-Dawley rats at 8 mg/kg/day oral administration, both compounds ( 4 and 5 ) significantly decreased the serum cholesterol and triglyceride levels. Rat tissue lipid levels were reduced significantly by compound 4, while less effects resulted from compound 5. The cholesterol and triglyceride levels in chylomicrons, VLDL, and LDL fractions were reduced by both analogs while the HDL cholesterol levels were significantly increased. Compound 5 was also effective in lowering serum cholesterol and triglyceride levels in hyperlipidemic mice, at 8 mg/kg/day intraperitoneally, but not effective in hyperlipidemic rats at 8 mg/kg/day intraperitoneally, but not effective in hyperlipidemic rats at 8 mg/kg/day orally. Cholesterol and triglyceride lowering effects of the agents were correlated with inhibition of the activities of liver acetyl CoA synthetase, HMG CoA reductase, phosphatidylate phosphohydrolase, and lipoprotein lipase, and with elevation of the activity of cholesterol ester hydrolase.     

Synthesis and Hypolipidemic Activity of 3-Imino-l-oxoisoindolines in Rodents

A series of substituted 3-imino-l-oxoisoindolines derivatives demonstrated significant hypolipidemic activity, lowering both serum cholesterol and triglycerides levels after 16 days of dosing at 20 mg/kg/ day ip in CF₁ mice. 2-Butyl-3-butylimino-l-oxoisoindoline lowered serum cholesterol levels 52% and serum triglyceride 42%. 2-Pentyl-3-imino-l-oxoisoindoline lowered serum cholesterol levels 42% and serum triglyceride 61%. These derivatives resulted in better activity than the parent compound, 3-imino-1-oxoisoindoline. These studies showed that compounds with N-alkyl substitution of nitrogen atoms in the ring and outside the ring possessed potent hypolipidemic activity at the low dose of 20 mg/kg/day ip in normolipidemic CF₁ mice. Studies with 2-butyl-3-butylimino-l-oxoisoinodine in rats showed that serum cholesterol was reduced 60% and serum triglyceride 43% after 14 days of dosing at 20 mg/kg/day, orally. Treatment with this agent lowered lipid levels in the liver and aorta tissue, with increases in lipid levels in the small intestine tissue. Higher levels of cholesterol and phospholipids were excreted in the feces of treated animals compared to the control. Cholesterol levels of the very low-density lipoprotein (VLDL) and high-density lipoprotein (HDL) fractions were reduced, whereas the HDL cholesterol levels were elevated significantly. This ratio of low-density lipoprotein (LDL) cholesterol:HDL cholesterol levels suggests that the agent may be effective in treating hyperlipidemic states in humans.     

Terephthalic Acid in Sprague-Dawley Rats as a Hypolipidemic Agent

Terephthalic acid at 20 mg/kg/day in lowered serum cholesterol and triglyceride levels in rats. The cholesterol content was lowered in the lipoprotein fractions. The effects of the agents on de novo lipid synthesis showed that similar enzymes were affected in rat liver and small intestinal mucosa cells as when compared to in vitro tissue culture cells from rats and humans, e.g. reduction of acyl CoA cholesterol acyl transferase and elevation of neutral cholesterol ester hydrolase activities suggest that net cholesterol esters deposition in foam cells should be reduced and plaque growth should be slowed. The suppression of LDL receptor binding and degradation by the drug suggest that less apoB lipoproteins are taken up by peripheral tissues. The elevated HDL receptor binding and internalization in the liver suggest that the drug accelerates cholesterol return to the liver. Additional studies show that cholesterol and bile acid secretion in the bile is elevated. However, the bile acids secreted are not lithogenic. Acute toxicity studies show that the agent appears to be safe in rodents. Two observations of increased serum alkaline phosphophatase levels and increased liver vacuolation suggest some alteration of hepatic cell morphology, which requires further investigation.     

Synthesis and Pharmacological Studies of 3-Amino-2-methyl-1-phenylpropanones as Hypolipidemic Agents in Rodents

A series of 3-amino-2-methyl-1-phenylpropanones were synthesized and proven to have potent hypolipidemic activity in rodents by lowering both serum cholesterol and triglyceride levels at 8 mg/kg/day, i.p. and orally. Many of these analogs showed significantly higher activity than standard drugs, lovastatin and clofibrate at their therapeutic doses. 2-Methyl-3-(perhydroazepin-1-yl)-1-phenylpropanone (@!4), 3-(4-methylpiperazin-1-yl)-1-phenylpropanone ( 5 ), and 2-methyl-3-(4-pyrrolidinocarbonyl-methylpiperazin-1-yl)-1-(4-fluorophenyl) propanone ( 17 ) showed the best overall activities in lowering both serum cholesterol and triglyceride levels in CF₁ mice at 8 mg/kg/day after 16 days of treatment. Compounds 4, 5 , and 17 lowered serum cholesterol levels 63%, 58%, and 42%, respectively, after 16 days at 8 mg/kg/day i.p. These agents reduced the serum triglyceride levels by 33%, 37%, and 54%, respectively. In Sprague-Dawley rats these compounds also demonstrated significant serum lipid lowering effects by decreasing both serum cholesterol and triglyceride levels after 14 days of oral drug administration at 8 mg/kg/day. Compound 17 reduced the rat aorta cholesterol levels by 37%, triglyceride levels by 50%, and neutral lipid levels by 34% after 14 days of oral administration. These compounds lowered the chylomicron, VLDL, and LDL cholesterol and triglyceride levels while elevating the HDL cholesterol levels significantly. In hyperlipidemic rodents, these analogs also demonstrated significant serum lipid lowering effects but were less active than in normalipidemic rodents. The activities of some enzymes, such as mouse hepatic acetyl CoA synthetase, HMG CoA reductase, phosphatidylate phosphohydrolase, and hepatic lipoprotein lipase, were significantly reduced by these compounds.     

The Hypolipidemic Activity of 3-Iminophthalimidine in Rodents

3-Immophthalimidine (3-imino-2,3-dihydroisoindol-l-one) was examined for its hypolipidemic activity in rodents as a chemical modification of the phthalimide nucleus. Administration of 3-iminophthalimidine for 16 days, at 20 mg/kg/day, demonstrated potent hypolipidemic activity, decreasing serum cholesterol and triglyceride levels by 44 % and 41 %, respectively. No effects on organ or body weight, or food consumption were noted as a result of administration of this agent to rats. However, reductions of liver lipid levels, i. e., triglycerides and neutral lipids, as well as lipid content of serum lipoprotein fractions, i. e., cholesterol, triglyceride and neutral lipids, were observed following administration of this agent. An increase was noted in fecal excretion of cholesterol and/or its metabolites. This effect was not correlated with an increase in bile acid synthesis, but may due in part to increased biliary excretion of cholesterol. Significant inhibitory effects of 3-iminophthalimidine on liver enzyme activities were noted, including acetyl CoA carboxylase and sn-glycerol-3-phosphate acyl transferase. Mitochondrial citrate exchange was also greatly reduced at low concentrations of the agent. Inhibition at these sites could account for the reduction in serum triglyceride levels observed after treatment in rodents.     

The Hypolipidemic Activity of N-(p-Chlorobenzoyl)-sulfamate in Rodents and its Effect on Lipid Metabolism

N-(p-Chlorobenzoyl)-sulfamate was observed to produce potent hypolipidemic activity in rodents at 10 to 60 mg/kg/day. Liver phosphatidate phosphohydrolase and sn-glycerol-3-phosphate acyl transferase activities were suppressed by the agent in vitro and in vivo, and ATP dependent citrate lyase and acetyl CoA carboxylase activities were reduced in vivo. N-(p-Chlorobenzoyl)-sulfamate reduced cholesterol, neutral lipids, and triglycerides in the liver and increased excretion of cholesterol and neutral lipids in the bile and feces. Drug treatment reduced the neutral lipid and triglyceride content of serum chylomicrons, VLDL and LDL, and cholesterol content was reduced in the chylomicron and HDL fractions.     

Efficacy and safety of coenzyme A versus fenofibrate in patients with hyperlipidemia: a multicenter,double-blind,double-mimic,randomized clinical trial

Abstract

Background: We investigated the lipid-lowering efficacy and safety of coenzyme A (CoA) versus fenofibrate in Chinese patients with moderate dyslipidemia.

Methods: A total of 417 subjects (aged 18–75?years) diagnosed with moderate dyslipidemia (triglyceride 2.3–6.5?mmol/L) from 13 large cardiovascular centers in China were recruited and randomly divided into a fenofibrate group (n?=?207), which received 200?mg of fenofibrate orally once daily, and a CoA group (n?=?210), which received 400?mg of CoA orally once a day. Blood lipoproteins, liver and renal function, creatine kinase, and blood glucose were measured at baseline, and after 4 and 8?weeks of treatment.

Results: The baseline triglyceride (TG) level in the fenofibrate group and the CoA group was 3.39?±?0.99?mmol/L and 3.60?±?1.11?mmol/L, respectively. After treatment for 4 and 8?weeks with fenofibrate, TG was reduced by 31.62% and 33.13%. In the CoA group, TG was reduced by 17.29% and 23.80%. Compared with baseline, total cholesterol (TC) was significantly decreased in both groups after either 4 or 8?weeks of treatment (p?<?.05). CoA increased high-density lipoprotein cholesterol (HDL-C) after 4?weeks of treatment, whereas it had no significant effect on HDL-C after 8?weeks of treatment. Low-density lipoprotein cholesterol (LDL-C) was not modified in either group. The incidence of side effects was significantly lower in the CoA group compared with the fenofibrate group (p?<?.05).

Conclusions: Compared with fenofibrate, CoA has less effect on reducing plasma TG levels in subjects with moderate dyslipidemia. However, it has fewer adverse effects.     

The Effects of N(4-Methylphenyl)diphenimide on Lipid Metabolism of Sprague Dawley Rats

N(4-Methylphenyl)diphenimide proved to be an effective hypolipidemic agent in rats at 10 and 20 mg/kg/day. Both serum cholesterol and triglyceride levels were reduced significantly. Decreases in tissue lipids as well as VLDL cholesterol levels were observed. HDL-cholesterol was elevated even at 10 mg/kg/day. The agent was equally effective in hyperlipidemic diet-induced rats, lowering serum lipids and VLDL- and LDL-cholesterol while elevating HDL-cholesterol levels. The drug interfered with the incorporation of ³H-cholesterol and ³H-palmitic acid into chylomicrons, VLDL, and LDL. The two precursors were incorporated at a higher rate into HDL.³H-Leucine was incorporated into chylomicrons, VLDL, and LDL at a higher rate, but not into HDL. Reduced uptake of the precursor for lipid synthesis was noted in tissues after treatment with the drug.     

Hypolipidemic Activity of o-(N-Phthalimido)acetophenone in Sprague Dawley Rats

o-(N-Phthalimido)acetophenone has proven to be an effective hypolipidemic agent in rats at 20 mg/kg/ day orally. The agent suppressed the activity of the rate-limiting enzyme of the liver involved in de novo synthesis of triglycerides. The synthetic rate-limiting enzyme for cholesterol esters was also inhibited by the drug in vivo. o-(N-Phthalimido)acetophenone lowered cholesterol in the liver and the aorta wall and generally caused an increase in phospholipids in body tissues. Serum lipoproteins were modulated by the drug with a decrease in cholesterol and triglycerides in the chylomicron, very low-density lipoproteins (VLDL), and low-density lipoproteins (LDL) and an increase in high-density lipoprotein (HDL) cholesterol. The phospholipid content was increased in the chylomicron, VLDL, and LDL fractions. In hyperlipidemic rats, o-(N-phthalimido)acetophenone lowered elevated blood lipid levels at 20 mg/kg/day orally after 3 weeks of administration. The hypolipidemic rat after drug treatment had a lower LDL cholesterol and a higher HDL cholesterol content, which is therapeutically desirable to protect against cardiovascular disease.     

The Hypolipidemic Activity of a Series of 2,3-Dihydrophthalazine-l,4-dione Derivatives in Rodents

A series of substituted 2,3-dihydrophthalazine-l,4-dione derivatives as well as the corresponding N,N-diaminophthalamides were prepared and were demonstrated to have potent hypolipidemic activity, lowering both serum triglyceride and cholesterol levels significantly at 20 mg/kg/day after 16 days of dosing in CF₁ male mice. The parent compound, 2,3-dihydrophthalazine-l,4-dione, lowered serum cholesterol 51% and serum triglyceride 43%. 2-(2-Carboxyethyl)-2,3-dihydrophthalazine-l,4-dione demonstrated the best hypocholesterolemic activity, with a 66% reduction after 16 days. The 2-(p-chlorophenyl) derivative demonstrated good activity (>40% reduction) in both screens, as did the 6-methyl-2,3-dihydrophthalazine-l,4-dione derivative. Of the amides, 4-methyk N,N-diaminophthalamide demonstrated the best hypolipidemic activity, affording a greater than 40% reduction. 2,3-Dihydrophthalazine-l,4-dione was found to inhibit the enzyme activity of acetyl CoA synthetase, ATP-dependent citrate lyase, sn-glycerol-3-phosphate acyl transferase, phosphatidylate phosphohydrolase, and mitochondrial citrate exchange of liver. In mice after 16 days of dosing, there was a reduction of cholesterol, triglycerides, neutral lipids, and phospholipids in the liver. Cholesterol and neutral lipids were reduced in rat chylomicrons, very low-density lipoproteins, and low-density lipoproteins. The cholesterol content of the high-density lipoprotein fraction was slightly elevated, but reductions in the triglycerides and phospholipids were observed in this lipoprotein fraction. ³H-Cholesterol distribution studies showed a lower concentration in the major organs and plasma, with a higher ³H-cholesterol content in the stomach and large intestine.     

Effects of Red ginseng-crude saponin on plasma lipid levels in rats fed on a diet high in cholesterol and triglyceride

The effect of Red ginseng saponin on plasma lipid levels in Wistar rats fed on a diet high in cholesterol and triglyceride was determined. A dose of Red ginseng-crude saponin (150 mg/kg/day) was administered orally for 4 weeks to Wistar rats fed on a diet containing 2% cholesterol and 10% olive oil. Plasma levels of total cholesterol, HDL-cholesterol and triglyceride were measured and lipoproteins were analyzed by using electrophoretic technique. Red ginseng saponin showed no significant changes of HDL-cholesterol level but it lowered plasma levels of total cholesterol and elevate those of triglyceride intensively.     

The hypolipidemic activity of N(4-methyl-phenyl)diphenimide in rodents

N(4-Methyl-phenyl)diphenimide afforded potent hypolipidemic activity in rodents. Serum cholesterol levels were reduced 67% and serum triglyceride were lowered 66% in rats by the drug after two weeks administration orally at 20 mg/kg/day. Rate limiting enzymes in the de novo synthesis of lipids in the liver were suppressed by the drug. Cholesterol was also removed from the body due to the drug accelerating bile excretion. Lipids removed from the blood compartment were not deposited in the organs of the body. VLDL and LDL cholesterol content was significantly reduced in rats treated with the drug with marked increase in HDL cholesterol after two weeks of administration. These data suggest that the drug may be useful in hyperlipidemic states and atherosclerosis in man, thus, further investigation of this class of chemicals is warranted.     

Antilipidemic activity of organic solvent extract from Sorghum bicolor on rats with diet-induced obesity

The present study evaluated the antiobesity and lipid-lowering effects from dichloromethane and ethyl acetate extracts of Hwanggeumchal Sorghum varieties on Sorghum bicolor. The Hwanggeumchal Sorghum ethyl acetate extracts significantly reduced the plasma total cholesterol and triglyceride levels significantly when given orally at a dose of 50 and 300 mg/kg/day to the high-fat diet-induced obese rats for 2 weeks. These findings demonstrate the excellent pharmacological potential of Hwanggeumchal Sorghum varieties to prevent obesity.     

Hypolipidemic Activity and Toxicity of 3-Methoxy-N,N′-diaminophthalamide in Rodents

3-Methoxy-N,N′-diaminophthalamide was observed to be a potent hypolipidemic agent in rodents. Serum cholesterol and triglyceride levels in rats were significantly reduced as were lipid contents of the liver, small intestine, and aorta wall. VLDL and LDL cholesterol levels were significantly reduced. Unfortunately, HDL cholesterol levels were also markedly reduced. Furthermore, acute toxicity studies showed that the compound caused marked increases in serum CP kinase activity with doses of 40 and 100 mg/kg/day in mice. This is not a property of the 2,3-dihydrophthalazine-1,4-dione, the resultant product of the N,N′-diaminophthalamides. Apparently, closing the ring results in a safer compound with elevations in HDL cholesterol levels, a desirable characteristic in effective hypolipidemic agents.     

The Safety Evaluation of Fluvastatin,an HMG–CoA Reductase Inhibitor,in Beagle Dogs and Rhesus Monkeys

Fluvastatin is a potent synthetic competitive inhibitor of β-hydroxy-β-methyl-glutaryl-coenzyme A (HMG–CoA) reductase, the rate-limiting enzyme in the biosynthetic pathway for hepatic cholesterol synthesis. The therapeutic indication is reduction of elevated total and low-density lipoprotein cholesterol levels. Results from four toxicity studies in beagle dogs and one study in rhesus monkeys following oral administration of fluvastatin are reported. In two 26-week dog studies, doses were 0, 1, 8, or 48 mg/kg/day (reduced to 36 mg/kg/day in Week 7) and 0, 6, 24, or 36 mg/kg/day (reduced to 30 mg/kg/day in Week 2). In a 2-year dog study, doses were 0, 1, 8, or 16 mg/kg/day. Dose levels in the 26-week monkey study were 0, 0.6, 12, and 48 mg/kg/day (raised to 84 mg/kg/day in Week 17 and to 108 mg/kg/day in Week 22). In these studies, evaluations included clinical and physical examinations, body weight and food consumption, electrocardiography, ophthalmoscopy, hematology and clinical chemistries, urinalysis, blood drug concentration, and macroscopic and microscopic examinations of observed lesions and representative tissues. In the 26- and 52-week dog studies and the monkey study, lenticular biochemistry, the HMG–CoA reductase activity of liver microsomes, and serum lipid concentrations were investigated. The fourth dog study was a single-dose toxicokinetic study in which 48 mg/kg [³H]fluvastatin was monitored for up to 2 weeks. Sampling was limited to ocular tissues for enzyme analysis. Doses of ≥24 mg/kg/day were lethal in dogs. At lethal doses, ataxia, convulsions, fecal blood, multifocal congestion and hemorrhage, isolated foci of malacia in the medulla oblongata, and liver necrosis were observed. Reduced weight gain, emesis, cataracts, elevated liver enzymes, reduced cholesterol, and gallbladder inflammation with mucosal hyperplasia occurred at ≥8 mg/kg/day. In contrast to other HMG–CoA reductase inhibitors, fluvastatin did not cause significant central nervous system hemorrhage or testicular changes in dogs. Monkeys tolerated exposure to fluvastatin well with only mild gallbladder changes observed. Reduced serum cholesterol and slight hyperplasia of the gallbladder mucosa occurred in the 12 and 48/84/108 mg/kg/day groups.     

Kaempferol regulates the lipid-profile in high-fat diet-fed rats through an increase in hepatic PPARα levels

The aim of this study was to investigate the antiobesity and antihyperlipidemic effects of the flavonoid kaempferol (3,5,7,4'-tetrahydroxyflavone). After being fed a high-fat diet (HFD) for two weeks, rats were dosed orally with kaempferol (75, 150, or 300 mg/kg) or fenofibrate (100?mg/kg) once daily for eight weeks. Fenofibrate is an antilipemic agent that exerts its therapeutic effects through activation of peroxisome proliferator-activated receptor α (PPAR α). Kaempferol (300?mg/kg/day) produced effects similar to fenofibrate in reducing body weight gain, visceral fat-pad weights, plasma lipid levels, as well as the coronary artery risk and atherogenic indices of HFD-fed rats. Kaempferol also caused dose-related reductions in hepatic triglyceride and cholesterol content and lowered hepatic lipid droplet accumulation and the size of epididymal adipocytes in HFD-fed rats. Kaempferol and fenofibrate reversed the HFD-induced downregulation of hepatic PPAR α. HFD-induced reductions in the hepatic levels of acyl-CoA oxidase (ACO), and cytochrome P450 isoform 4A1 (CYP4A1) proteins were reversed by kaempferol and fenofibrate. The elevated expression of hepatic sterol regulatory element binding proteins (SREBPs) in HFD-fed rats were lowered by kaempferol and fenofibrate. These results suggest that kaempferol reduced the accumulation of visceral fat and improved hyperlipidemia in HFD-fed obese rats by increasing lipid metabolism through the downregulation of SREBPs and promoting the hepatic expression of ACO and CYP4A1, secondary to a direct upregulation hepatic PPAR α expression.