betadex and Hyperlipidemias

Statins are the most commonly prescribed drugs to reduce cardiometabolic risk. Besides the well-known efficacy of such compounds in both preventing and treating cardiometabolic disorders, some patients experience statin-induced side effects. We hypothesize that the use of natural bergamot-derived polyphenols may allow patients undergoing statin treatment to reduce effective doses while achieving target lipid values. The aim of the present study is to investigate the occurrence of an enhanced effect of bergamot-derived polyphenolic fraction (BPF) on rosuvastatin-induced hypolipidemic and vasoprotective response in patients with mixed hyperlipidemia.. A prospective, open-label, parallel group, placebo-controlled study on 77 patients with elevated serum LDL-C and triglycerides was designed. Patients were randomly assigned to a control group receiving placebo (n=15), two groups receiving orally administered rosuvastatin (10 and 20mg/daily for 30 days; n=16 for each group), a group receiving BPF alone orally (1000 mg/daily for 30 days; n=15) and a group receiving BPF (1000 mg/daily given orally) plus rosuvastatin (10mg/daily for 30 days; n=15).. Both doses of rosuvastatin and BPF reduced total cholesterol, LDL-C, the LDL-C/HDL-C ratio and urinary mevalonate in hyperlipidemic patients, compared to control group. The cholesterol lowering effect was accompanied by reductions of malondialdehyde, oxyLDL receptor LOX-1 and phosphoPKB, which are all biomarkers of oxidative vascular damage, in peripheral polymorphonuclear cells.. Addition of BPF to rosuvastatin significantly enhanced rosuvastatin-induced effect on serum lipemic profile compared to rosuvastatin alone. This lipid-lowering effect was associated with significant reductions of biomarkers used for detecting oxidative vascular damage, suggesting a multi-action enhanced potential for BPF in patients on statin therapy.

Topics: beta-Cyclodextrins; Cholesterol, LDL; Citrus; Drug Synergism; Female; Fluorobenzenes; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Lipid Peroxidation; Male; Malondialdehyde; Phosphorylation; Placebos; Plant Extracts; Prospective Studies; Proto-Oncogene Proteins c-akt; Pyrimidines; Risk Factors; Rosuvastatin Calcium; Scavenger Receptors, Class E; Sulfonamides; Triglycerides

We examined the phytoestrogenic effects of palmiwon on breast carcinoma, lipid accumulation in methyl-β-cyclodextrin-induced HepG2 cells, and lipid-related diseases in a rat model of menopausal hyperlipidemia.. E-Screen assay was used to screen for phytoestrogens, especially those with antiestrogenic activity, in MCF-7 cells. Oil Red O staining and intracellular cholesterol analyses were used to quantify cellular cholesterol levels. 3-Hydroxy-3-methyl glutaryl coenzyme A reductase assay was used to measure enzyme activity. The levels of phosphorylated adenosine monophosphate-activated protein kinases and products of genes involved in cholesterol synthesis were measured by Western blot analysis. Thirty rats were either ovariectomized or sham-operated and randomly assigned to four groups (n = 5)-Sham, OVX, OVX-SV, or OVX-PMW (50, 150, or 450 mg/kg) group-for 8 weeks. A number of targets associated with lipid-related diseases were examined to confirm the estrogenic effects of palmiwon.. Palmiwon showed antiestrogenic activity in MCF-7 cells. Palmiwon decreased lipid accumulation, total cholesterol levels, and low-density lipoprotein/very-low-density lipoprotein levels in HepG2 cells. Moreover, palmiwon reversed the effects of methyl-β-cyclodextrin on cholesterol synthesis regulators and inhibited the activity of 3-hydroxy-3-methyl glutaryl coenzyme A reductase. Phosphorylation of adenosine monophosphate-activated protein kinase was stimulated by palmiwon. In ovariectomized rats, palmiwon reduced retroperitoneal and perirenal fat accumulation, serum lipids, atherogenic index, cardiac risk factor score, intima-media thickness, and nonalcoholic steatohepatitis scores.. These results indicate that palmiwon inhibits lipid accumulation without estrogenic activity in the breast. Therefore, palmiwon may have potential as a therapeutic agent for the treatment of hyperlipidemia in postmenopausal women.

Topics: Animals; beta-Cyclodextrins; Breast Neoplasms; Carotid Intima-Media Thickness; Cholesterol; Cyclic AMP-Dependent Protein Kinases; Drugs, Chinese Herbal; Estrogens; Female; Hep G2 Cells; Humans; Hydroxymethylglutaryl CoA Reductases; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Lipid Metabolism; Lipids; Lipoproteins, LDL; MCF-7 Cells; Menopause; Models, Animal; Phosphorylation; Phytoestrogens; Rats; Rats, Sprague-Dawley

Recently, the importance of lysosomes in the context of the metabolic syndrome has received increased attention. Increased lysosomal cholesterol storage and cholesterol crystallization inside macrophages have been linked to several metabolic diseases, such as atherosclerosis and non-alcoholic fatty liver disease (NAFLD). Two-hydroxypropyl-β-cyclodextrin (HP-B-CD) is able to redirect lysosomal cholesterol to the cytoplasm in Niemann-Pick type C1 disease, a lysosomal storage disorder. We hypothesize that HP-B-CD ameliorates liver cholesterol and intracellular cholesterol levels inside Kupffer cells (KCs). Hyperlipidemic low-density lipoprotein receptor knockout (Ldlr(-/-)) mice were given weekly, subcutaneous injections with HP-B-CD or control PBS. In contrast to control injections, hyperlipidemic mice treated with HP-B-CD demonstrated a shift in intracellular cholesterol distribution towards cytoplasmic cholesteryl ester (CE) storage and a decrease in cholesterol crystallization inside KCs. Compared to untreated hyperlipidemic mice, the foamy KC appearance and liver cholesterol remained similar upon HP-B-CD administration, while hepatic campesterol and 7α-hydroxycholesterol levels were back increased. Thus, HP-B-CD could be a useful tool to improve intracellular cholesterol levels in the context of the metabolic syndrome, possibly through modulation of phyto- and oxysterols, and should be tested in the future. Additionally, these data underline the existence of a shared etiology between lysosomal storage diseases and NAFLD.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Animals; beta-Cyclodextrins; Cholesterol; Disease Models, Animal; Drug Administration Schedule; Hyperlipidemias; Injections, Subcutaneous; Kupffer Cells; Liver; Lysosomes; Mice; Mice, Knockout; Receptors, LDL

A new water-soluble inclusion complex of ilexgenin A (IGA) with β-cyclodextrin polymer (CDP) was prepared by a facile strategy and characterized by (1)H NMR , FT-IR, and UV-vis spectroscopy. Compared with IGA and the inclusion complex of IGA with β-cyclodextrin (IGA-CD), the solubility of IGA-β-cyclodextrin polymer (IGA-CDP) was greatly enhanced due to the water-soluble CDP host. The ratio of β-cyclodextrin (β-CD) units in CDP to IGA was determined as 2 : 1. KD of the inclusion complex was evaluated as 2.6 × 10(-3) mol L(-1). The effects of IGA-CDP on a hyperlipidemia mouse model were studied by intragastric administration. After 4 weeks, the IGA-CDP treatment resulted in decreased serum levels of total cholesterol and low-density lipoprotein-cholesterol. The effects of IGA-CDP on serum apolipoprotein levels were similar to its effects on lipid levels. By comparing liver area, the effects of IGA-CDP on pre-existing lesions were assessed. Furthermore, the efficacy and potency of water-soluble inclusion complex of IGA-CDP was 2-3 times higher than that of IGA. Taken together, it was possible to develop it to a novel drug candidate to regulate lipid abnormality.

Topics: Animals; beta-Cyclodextrins; Cholesterol; Disease Models, Animal; Hyperlipidemias; Hypolipidemic Agents; Mice; Mice, Inbred C57BL; Molecular Conformation; Polymers; Solubility; Triterpenes; Water