Characterization, Modes of Synthesis, and Pleiotropic Effects of Hypocholesterolemic Compounds – A Review
TL;DR: Major natural sources as well as synthetic and biological routes of synthesis of these compounds are reviewed in a concise manner and various HMG-CoA analogues including statins have been reviewed specifically.
Abstract: Studies on the various cholesterol-lowering agents is one of the important areas in clinical research. Identifica- tion and characterization of potential molecules from various sources have been carried out in the past and their relation- ship with the enzymes which are involved in the cholesterol cascade is gaining interest. In this review, we have high- lighted various inhibitors involved in the cholesterol cascade as well as cholesterol-lowering agents, viz., tocotrienol, flavonoids, phytosterols, phytostanols, statins, DADS, and synthetic compounds. The mechanism of action and characteri- zation of these hypocholesterolemic compounds are discussed in this communication. Major natural sources as well as synthetic and biological routes of synthesis of these compounds are reviewed in a concise manner. Especially, various HMG-CoA analogues including statins have been reviewed specifically. In this respect, researchers have identified 2,3- oxidosqualene cyclase-lanosterol synthase (lanosterol syn- thase, oxidosqualene-lanosterol cyclase, lanosterol synthase, 2,3-oxidosqualene-lanosterol cyclase, human lanosterol syn- thase (EC 5.4.99.7)) having a molecular weight of 83 kDa, catalyzing the highly selective cyclization reaction from the substrate 2,3-oxidosqualene (squalene 2,3-epoxide, squalene 2,3-oxide, (S)-squalene-2,3-epoxide, 2,3-epoxisqualene, oxidosqualene) into lanosterol, as an appropriate step for the inhibition of cholesterol biosynthesis (3). Oxidosqualene cyclase inhibitors (OSCI) arrest the downstream of 2,3- oxidosqualene which helps to stimulate epoxysterols to
Citations
More filters
TL;DR: In this article, the authors investigated the possible mechanisms for the use of phenolic extracts from grapefruit peels in the management/prevention of cardiovascular complications and found that the phenolic contents of the extracts were investigated using HPLC-DAD.
39 citations
TL;DR: The phenolic compounds and volatile compounds which have been linked with the biological activities of the peels have been characterized and the bioactive compounds of citrus peels and the mechanisms for the biological Activities are looked at.
Abstract: Citrus peels, which are an environmental menace in many developing countries have been in use in folk medicine for the management of some degenerative conditions, though there was limited information on the mechanism of such medicinal properties. These medicinal properties also promote the peels as functional foods; since they are generally regarded as safe and are consumed in some countries in forms of candies, wines, infusions and additives. Studies on the mechanisms for the antioxidant, anti-diabetic, cardioprotective, neuroprotective and anticancer activities of the peels have established the intereaction with some key enzymes relevant to the management of such diseases. The phenolic compounds and volatile compounds which have been linked with the biological activities of the peels have been characterized. This review looks at the bioactive compounds of citrus peels and the mechanisms for the biological activities of the peels.
23 citations
Cites background from "Characterization, Modes of Synthesi..."
...The inhibition of HMG-CoA reductase by phenolic compounds is both competitive with HMG-CoA and non-competitive with NADPH (Sung et al. 2004a, b; Seenivasan et al. 2011)....
[...]
TL;DR: In this article, the authors characterized the soluble free and bound phenolic compounds from shaddock peels and investigated their effect on 3-hydroxy-methyl-3-glutaryl coenzyme A reductase (HMG-CoA) and glutathione-linked enzymes in colon (Caco-2) cells.
10 citations
TL;DR: The estimation of Lovastatin produced by Monascus purpureus and pure lovastatin was attempted by UV-visible spectrophotometer as well as HPLC, and HPLC analysis consistently gave reliable results for the estimation of lovastsatin under all the experimental conditions studied.
Abstract: Development of a novel method for the quantification of lovastatin is an interesting problem in the analytical field. In the literature, many reports use spectrophotometric method for the quantification of lovastatin. However, the analysis of fermentation broth containing lovastatin appears to be inaccurate using spectrophotometric method. Hence, the estimation of lovastatin produced by Monascus purpureus and pure lovastatin was attempted by UV-visible spectrophotometer as well as HPLC. It was observed that the analogues and/or intermediates of lovastatin synthesized in the fermentation broth and the products of fermentation caused superimposition effect on the absorption spectrum. Phosphate is a medium constituent for the production of lovastatin by the organism which contributed significantly to the superimposition of absorption spectrum. On the other hand, HPLC analysis consistently gave reliable results for the estimation of lovastatin under all the experimental conditions studied.
10 citations
TL;DR: Predicted specific substrate utilization and product excretion rates have been correlated well with the experimental observations, which validate the proposed metabolic pathway developed from metabolic footprinting data.
8 citations
References
More filters
41 citations
Journal Article•
TL;DR: In this paper, the effect of the flavonoids naringin and rutin on the metabolism lipidic of chicks hypercholesterolemic was evaluated and it was observed that naringins reduced the levels of total cholesterol significantly, LDL, HDL, VLDL, and triglycerols.
Abstract: Flavonoids are pigments fenolics of plants that possess several biological activities, and many of these are associated with prevention of chronic diseases as cancer and hyperlipidemia. This work had as objective evaluates the effect of the flavonoids naringin and rutin on the metabolism lipidic of chicks hypercholesterolemic. In agreement with the results it can be observed that naringin and rutin reduced the levels of total cholesterol significantly, cholesterol-LDL, cholesterol-VLDL and triglycerols, not presenting, however, reductions in the levels of cholesterol-HDL.
41 citations
TL;DR: The enzymatic method using the catalytic domain of Syrian hamster H MG-CoA reductase was employed for the screening of HMG- CoA reduCTase inhibitors, and the inhibitory compounds were identified as genistein, daidzein, and glycitein.
Abstract: 3-Hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase is the rate-limiting enzyme in the biosynthesis of cholesterol in mammals. Some microbial metabolites have been found to be HMG-CoA reductase inhibitors. Korean soybean paste is a unique food fermented by many microorganisms. The enzymatic method using the catalytic domain of Syrian hamster HMG-CoA reductase was employed for the screening of HMG-CoA reductase inhibitors. Soybean paste extract was fractionated by vacuum liquid chromatography. Fractions showing relatively high HMG-CoA reductase inhibition were further purified through Sephadex LH-20 column chromatography and C18 preparative HPLC, and the inhibitory compounds were identified as genistein, daidzein, and glycitein.
40 citations
"Characterization, Modes of Synthesi..." refers background in this paper
...They are genistein, glycitein, and aglycone (Table 1) [34, 35]....
[...]
TL;DR: Analogues of 3-aryl-8-isobutyl-5,6,7-trihydroxy-2-methyl-4H-chromen-4-one were synthesized with high yields via the Suzuki coupling reaction.
36 citations
"Characterization, Modes of Synthesi..." refers background in this paper
..., the Suzuki coupling reaction of 3-iodo-8-isobutyl5,6,7-trimethoxy-2-methyl-4H-chromen-4-one with different arylboronic acids [57]....
[...]
TL;DR: Treatment of HepG2 cells with a cyclase inhibitor such as 8-azadecalin does not lead to an intracellular accumulation of repressor molecules high enough to fully trigger a regulatory pathway resulting in a complete down-regulation of HMG-CoA reductase, and a synergistic mode of action of these inhibitors seems plausible.
35 citations