TITLE:
Towards Application of Bioactive Natural Products Containing Isoprenoids for the Regulation of HMG-CoA Reductase—A Review
AUTHORS:
Sepideh Pakpour
KEYWORDS:
Isoprenoids; HMG-CoA Reductase; Mevalonate Pathway; Hypercholesterolemia
JOURNAL NAME:
American Journal of Plant Sciences,
Vol.4 No.5,
May
29,
2013
ABSTRACT: Recognition of the
biological properties of numerous “natural products” has fueled the current
focus of this field, namely, the search for new drugs, antibiotics, insecticides,
and herbicides. Based on their biosynthetic origins, natural products can be
divided into three major groups: the isoprenoids, alkaloids, and phenolic
compounds. Isoprenoids are structurally the most diverse group of secondary
natural metabolites with different roles in the growth, development, and
reproduction of a diverse range of prokaryotic and eukaryotes cells. Mevalonate
and 2-C-methyl-D-erythritol 4-phosphate
(MEP) pathways are known to be responsible for biosynthesis of numerous isoprenoids.
HMG-CoA reductase is a
rate-determining enzyme in mevalonate pathway, producing intermediates such as
farnesyl and geranylgeranyl pyrophosphates, which lead to by-products such as
cholesterol. Earlier studies have demonstrated that the inhibition of HMG-CoA
reductase is one of the most effective approaches for treating
hypercholesterolemia and eventually cardiovascular disease (CVD). Statins are HMG-CoA reductase inhibitors
and the most prescribed group of drugs worldwide in treating hypercholesterolemia;
however the application of this group of drugs may be expensive and has side
effects including rashes and gastrointestinal symptoms. For these reasons,
there is an important need to examine the viability of natural products as an
alternative to statin treatment. This article is a review of different aforementioned areas with a focus on isoprenoids that can be used for the regulation of
HMG-CoA reductase.