Abstract
BackgroundHypercholesterolemia is a serious diseases associated with type-2 diabetes, atherosclerosis, cardiovascular disorders and liver diseases. Humans seek for safe herbal medication such as karela (Momordica charantia/bitter melon) to treat such disorders to avoid side effect of pharmacotherapies widely used.MethodsForty male Wistar rats were divided into four equal groups; control group with free access to food and water, cholesterol administered group (40 mg/kg BW orally); karela administered group (5 g /kg BW orally) and mixture of cholesterol and karela. The treatments continued for 10 weeks. Karela was given for hypercholesterolemic rats after 6 weeks of cholesterol administration. Serum, liver and epididymal adipose tissues were taken for biochemical, histopathological and genetic assessments.ResultsHypercholesterolemia induced a decrease in serum superoxide dismutase (SOD), catalase, reduced glutathione (GSH) and an increase in malondialdehyde (MDA) levels that were ameliorated by karela administration. Hypercholesterolemia up regulated antioxidants mRNA expression and altered the expression of carbohydrate metabolism genes. In parallel, hypercholesterolemic groups showed significant changes in the expression of PPAR-alpha and gamma, lipolysis, lipogenesis and cholesterol metabolism such as carnitine palmitoyltransferase-1 (CPT-1). Acyl CoA oxidase (ACO), fatty acids synthase (FAS), sterol responsible element binding protein-1c (SREBP1c), 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoAR) and cholesterol 7α-hydroxylase (CYP7A1) at hepatic and adipose tissue levels. Interestingly, Karela ameliorated all altered genes confirming its hypocholesterolemic effect. Histopathological and immunohistochemical findings revealed that hypercholesterolemia induced hepatic tissue changes compared with control. These changes include cholesterol clefts, necrosis, karyolysis and sever congestion of portal blood vessel. Caspase-3 immunoreactivity showed positive expression in hepatic cells of hypercholesterolemic rats compared to control. All were counteracted and normalized after Karela administration to hypercholesterolemic group.ConclusionCurrent findings confirmed that karela is a potential supplement useful in treatment of hypercholesterolemia and its associated disorders and is good for human health.
Highlights
Hypercholesterolemia is a serious diseases associated with type-2 diabetes, atherosclerosis, cardiovascular disorders and liver diseases
Effects of karela on genes regulate cholesterol metabolism expression we examined the effect of karela on genes associated with cholesterol metabolism such as sterol responsible element binding protein-1c (SREBP-1c), 3-hydroxy-3methylglutaryl coenzyme A reductase (HMG-CoAR) and cholesterol 7α-hydroxylase (CYP7A1)
Total Ribonucleic acid (RNA) was extracted from liver tissues and the expressions of carnitine palmitoyltransferase-1 (CPT-1), Acyl CoA oxidase (ACO) and fatty acids synthase (FAS) were analyzed by semi-quantitative Reverse transcription polymerase chain reaction (RT-PCR) analysis
Summary
Hypercholesterolemia is a serious diseases associated with type-2 diabetes, atherosclerosis, cardiovascular disorders and liver diseases. Hypertriglyceridemia, and/or hypercholesterolemia are the common causes for many diseases such as cardiovascular [6] and liver diseases [7]. Rat fed with high cholesterol diet can be used as model of the human obesity syndrome [8]. The liver is the first organ to metabolize the ingested cholesterol and it is affected by oxidative stress that results from an imbalance between the production of free radicals and effectiveness of antioxidant systems [9]. Rats fed high cholesterol diet showed several abnormalities in liver sections such as cholesterol clefts, hepatotoxicity and fatty liver [10, 11]
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