Cardioprotective and hepatoprotective effects of natural products in metabolic syndrome

PhD Thesis


Panchal, Sunil K.. 2012. Cardioprotective and hepatoprotective effects of natural products in metabolic syndrome. PhD Thesis Doctor of Philosophy. University of Southern Queensland.
Title

Cardioprotective and hepatoprotective effects of natural products in metabolic syndrome

TypePhD Thesis
Authors
AuthorPanchal, Sunil K.
SupervisorBrown, Lindsay
Institution of OriginUniversity of Southern Queensland
Qualification NameDoctor of Philosophy
Number of Pages322
Year2012
Abstract

The prevalence of metabolic syndrome is increasing throughout the world. Metabolic syndrome is the clustering of risk factors for cardiovascular disease and type 2 diabetes. These include obesity, hypertension, impaired
glucose tolerance, dyslipidaemia and insulin resistance, caused by oxidative stress and inflammation.

Nature has provided us with immense diversity in the form of plants and herbs, which contain a wide range of chemicals. Development of natural products as a potential treatment for metabolic syndrome requires a suitable
rodent model. To induce metabolic syndrome, young male Wistar rats were fed with a high-carbohydrate, high-fat diet for 16 weeks with corn starch serving as control diet. Treatments were given as interventions in the final 8 weeks only as a reversal protocol. These interventions included rutin (1.6 g/kg food), quercetin (0.8 g/kg food), oak bark extract (0.5 ml/kg food), ellagic acid (0.8 g/kg food), coffee extract (5% in food), caffeine (0.5 g/kg food) and ʟ-carnitine (1.2 % in food).

High-carbohydrate, high-fat diet induced hypertension, obesity, impaired glucose tolerance, dyslipidaemia, cardiovascular remodelling including ventricular dilatation, cardiomyocyte hypertrophy and cardiac
fibrosis, reduced ventricular function, hepatic steatosis, hepatic inflammation and portal fibrosis and increased plasma markers of liver function.

Rutin and quercetin ameliorated these cardiovascular and hepatic changes and attenuated impairment in glucose tolerance and hypertension whereas only rutin improved obesity and dyslipidaemia. Ellagitannins from oak
bark extract and ellagic acid attenuated cardiovascular remodelling and nonalcoholic fatty liver disease. Both ellagitannins from oak bark extract and ellagic acid reduced body weight and abdominal fat, however ellagic acid failed to reduce total body fat mass. Although coffee did not change body weight and abdominal fat, it improved the structure and function of the heart and the liver.

These effects differed from caffeine, which reduced total body fat, body weight and abdominal fat, along with the attenuation of symptoms of metabolic syndrome, cardiovascular remodelling and non-alcoholic steatohepatitis. ʟ-Carnitine, a transporter of fatty acid across mitochondrial membrane, attenuated the metabolic syndrome by increasing β-oxidation and decreasing lipogenesis in both the heart and the liver.

In humans, fatty liver is caused by the excess consumption of diets rich in ethanol, animal fats, simple carbohydrates such as fructose or a combination of all three. An initiative was taken to mimic the combined effects of highcarbohydrate, high-fat diet and ethanol in rats as in human fatty liver disease. Ethanol synergistically aggravated hepatic steatosis induced by highcarbohydrate,
high-fat diet; hepatic inflammation and fibrosis were unchanged compared to high-carbohydrate, high-fat fed rats. In contrast, ethanol feeding to high-carbohydrate, high-fat fed rats prevented cardiac fibrosis but caused minimal changes to cardiac function.

These studies clearly indicate the potential present in many natural products. The mechanisms of action of these natural products were also different as some of them reduced abdominal fat, possibly due to increased
utilisation or removal of excess fat from the body through excretion, and others redistributed the fat to other areas such as subcutaneous fat, coffee being the exception.

Keywordsmetabolic syndrome; obesity; non-alcoholic fatty liver disease; cardiovascular remodelling; natural products; high-carbohydrate, high-fat diet; polyphenols; dyslipidaemia; hypertension; impaired glucose tolerance
ANZSRC Field of Research 2020420899. Traditional, complementary and integrative medicine not elsewhere classified
320507. Metabolic medicine
321401. Basic pharmacology
320699. Medical biotechnology not elsewhere classified
Byline AffiliationsDepartment of Biological and Physical Sciences
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