Anti-hyperlipidemic activities of Ilex latifolia and other selected herbs

Saleh, Ali (2016) Anti-hyperlipidemic activities of Ilex latifolia and other selected herbs. Doctoral thesis, London Metropolitan University.


Hyperlipidemia is defined by abnormally elevated levels of one or more lipids such as cholesterol or triglycerides in the bloodstream. It also involves elevated levels of lipoproteins especially LDL-cholesterol and this is the most common form of dyslipidemia. Hyperlipidemia is the result of complex interactions between environmental and genetic factors. Hyperlipidemia is the main cause of congestive heart diseases in adulthood. It is also the main cause of atherosclerosis which is the pathophysiological cause of vascular diseases such as angina pectoris, myocardial infarction, and stroke. It occurs due to disorders in lipid metabolism including elevation in cholesterol, low density lipoprotein, or triglyceride, or due to low levels of high density lipoprotein. Lifestyle is the main factor in prevention of hyperlipidemia. If lifestyle is not beneficial in the treatment or prevention of hyperlipidemia, drug therapy is required. Statins, fibrates, nicotinic acid bile acid sequestrants, and ezetimibe are approved drugs for the treatment of hyperlipidemia. Because of the tolerability problems, side effects, and low effectiveness of some of these drugs, discovery of new drugs is explored and investigated. Herbal products are not well explored as an alternative treatment for the treatment of hyperlipidemia. Ilex latifolia is a traditional Chinese medicine which has been used for decades for the treatment of hyperlipidemia and for weight loss. Prunella vulgaris, Rheum palmatum, and Panax notoginseng have been also used in traditional Chinese medicine. Very little work has been published about the effect of Ilex latifolia on hyperlipidemia. In this research project, Ilex latifolia hypolipidemic effect was compared to several herbs effects by assaying the effect of the extracts on pancreatic lipase. Ilex latifolia was the most active, and the other parts of the project focused on its effect on HMG-CoA reductase expression, and on LDL receptor expression in HepG2 and AML-12 hepatocytes. Ilex latifolia effect on mitochondrial metabolism, and glucose uptake was assayed in HepG2 and AML-12 hepatocytes.

Chapter I is an introduction to hyperlipidemia, its types, causes, and treatment. A review of the literature relating to Ilex latifolia and other herbs and herbal compounds is given.

Chapter II describes the assay of extracts from several herbs, and herbal compounds, for their inhibitory effect on pancreatic lipase, using orlistat as a positive control. It also shows that HPLC is more sensitive and accurate than a spectrophotometric assay of lipase. Ilex latifolia showed the most inhibition activity on pancreatic lipase compared to other herbs.

Chapter III describes the fractionation of Ilex latifolia and pancreatic lipase inhibition activity of each fraction.

Chapter IV describes the effect of Ilex latifolia extract on HMG-CoA reductase expression in HepG2 cells and the effect of Ilex latifolia extract on LDL receptors expression in HepG2 and AML-12 cells.

Chapter V describes the effect of Ilex latifolia extracts on cell growth, mitochondrial toxicity, and glucose uptake in HepG2 and AML-12 cells. It also describes the effect of Ilex latifolia extract on ATP production in HepG2 cells.

This study has demonstrated for the first time that Ilex latifolia can play a role in the treatment of hyperlipidemia through pancreatic lipase inhibition. Effects on HMG-CoA reductase inhibition and mitochondrial inhibition were not marked, but under some circumstances glucose uptake can be significantly affected. It remains to be seen, using animal studies and other cell culture models, whether inhibition of pancreatic lipase can wholly account for the hypolipidemic activity of Ilex latifolia, or whether other mechanisms may be involved.

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