Regulation of HMGCoA Reductase Activity by Policosanol and Octacosadienol, a New Synthetic Analogue of Octacosanol

Oliaro‐Bosso, Simonetta; Gaudino, Emanuela Calcio; Mantegna, Stefano; Giraudo, Enrico; Meda, Claudia; Viola, Franca; Cravotto, Giancarlo

doi:10.1007/s11745-009-3338-y

Cited by 59 publications

(50 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since statins may exert their vasculoprotective effects through activation of AMPK (Ewart & Kennedy 2011) and can phosphorylate AMPK in vitro (Rossoni et al 2011), it is possible that AMPK signaling may also mediate some of the skeletal effects of statins. AMPK can indeed modulate the mevalonate pathway through repression of HMG-CoA reductase (Oliaro-Bosso et al 2009) and could therefore influence this pathway in bone cells. Bisphosphonates, the widely prescribed antiosteoporosis drugs, target the mevalonate pathway as well by inhibiting farnesyldisphosphate and geranylgeranyldisphosphate synthase (Russell et al 2008.…”

Section: Possible Targets and Metabolic Pathways Regulated By Ampk Inmentioning

confidence: 99%

AMP-activated protein kinase pathway and bone metabolism

Jeyabalan

Shah²,

Viollet³

et al. 2011

Journal of Endocrinology

View full text Add to dashboard Cite

There is increasing evidence that osteoporosis, similarly to obesity and diabetes, could be another disorder of energy metabolism. AMP-activated protein kinase (AMPK) has emerged over the last decade as a key sensing mechanism in the regulation of cellular energy homeostasis and is an essential mediator of the central and peripheral effects of many hormones on the metabolism of appetite, fat and glucose. Novel work demonstrates that the AMPK signaling pathway also plays a role in bone physiology. Activation of AMPK promotes bone formation in vitro and the deletion of a or b subunit of AMPK decreases bone mass in mice. Furthermore, AMPK activity in bone cells is regulated by the same hormones that regulate food intake and energy expenditure through AMPK activation in the brain and peripheral tissues. AMPK is also activated by antidiabetic drugs such as metformin and thiazolidinediones (TZDs), which also impact on skeletal metabolism. Interestingly, TZDs have detrimental skeletal side effects, causing bone loss and increasing the risk of fractures, although the role of AMPK mediation is still unclear. These data are presented in this review that also discusses the potential roles of AMPK in bone as well as the possibility for AMPK to be a future therapeutic target for intervention in osteoporosis.

show abstract

Section: Possible Targets and Metabolic Pathways Regulated By Ampk Inmentioning

confidence: 99%

AMP-activated protein kinase pathway and bone metabolism

Jeyabalan

Shah²,

Viollet³

et al. 2011

Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…The main advantage of the proposed approach is the lack of components as monakolin that sometimes (even if rarely) can have potentially dangerous pharmacological interactions [22]. Beyond the possible antihypercholesterolemic effect of octacoosanol, probably due to inhibition of the hydroxyl-methyl-glutaryl Coenzyme A reductase [23], the efficacy of the tested product could also be related to the content in polymethoxylated flavones and tocotrienols [21]. In particular, polymethoxylated flavones seems to directly inhibit the formation of apolipoprotein B containing lipoproteins, either decreasing the hepatic synthesis of cholesteryl esters and activating the peroxisome proliferator-activated receptor [24].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the short term efficacy and tolerability of a combined nutraceutical with lipid-lowering properties: a randomized clinical trial

Cicero

Bove

Gerocarni

et al. 2011

Mediterr J Nutr Metab

View full text Add to dashboard Cite

This is a double-blind, placebo-controlled clinical trial on a combined nutraceutical non containing statinlike substances in 40 patients affected by primary polygenic hypercholesterolemia. After 4 weeks of ATP III life-style improvement, patients were randomized to assume a combined nutraceutical or placebo 1 pill/day for 8 weeks. The tested nutraceutical contained octacosanols, tocotrienols and polymethoxylated flavones (offered by Ca.Di.Group Srl, Rome, Italy). When comparing the combined nutraceutical effect with the one of placebo, we observed that the combined nutraceutical assumption was associated with a significantly higher decrease in total cholesterol (p \ 0.001), LDL-cholesterol (p \ 0.001), triglycerides (p \ 0.001) and non HDL-cholesterol (p \ 0.001) than the control group. In the short term, the tested combined nutraceutical is well-tolerated and efficacious in reducing plasma lipid levels in subjects affected by primary polygenic hypercholesterolemia.

show abstract

“…Interestingly, 10 mg of this mixture had similar efficacy to an equivalent dose of statins in lowering the serum LDL concentrations Prat et al, 1999), and its supplementation caused a significant increase in the fecal excretion of neutral and acidic sterols in hamsters (Ng et al, 2005), whereas octacosanol administration to humans decreased bile acid concentration in feces (Keller and Gimmler, 2008). Various studies have suggested an inhibition of the enzyme which limits the cholesterogenic route, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA red) (Singh et al, 2006;Menendez et al, 2001;Oliaro-Bosso et al, 2009), as the mechanism of action of policosanol hypocholesterolemic activity. However, recent clinical trials failed to show significant effects.…”

Section: Introductionmentioning

confidence: 99%

The oleic acid esterification of policosanol increases its bioavailability and hypocholesterolemic action in rats

Haim¹,

Valenzuela²,

Brañes³

et al. 2012

Grasas y Aceites

View full text Add to dashboard Cite

(DH, and AV); d Naturalis S.A., Santiago, Chile (MCB, and MF) *Corresponding author: dnhaim@miuandes.cl RESUMEN La esterificación de ácido oleico en policosanoles aumenta su biodisponibilidad y el efecto hipocolesterolémico en ratasLos Policosanoles están formados por una mezcla de alcoholes alifáticos de cadena larga y se obtienen de las ceras de la caña de azúcar. Más de cincuenta estudios indican que los policosanoles reducen el colesterol sérico, mientras que otros no logran reproducir este efecto. El objetivo de esta investigación fue evaluar la biodisponibilidad de policosanoles esterificados y no esterificados (NEP), en relación con sus efectos hipocolesterolémicos. Para ello, a ratas Sprague Dawley se les administró una dosis oral diaria de 100 mg kg -1 de NEP, 117 mg kg -1 de policosanoles esterificados con ácido butírico (BAEP), ó 164 mg kg -1 de policosanoles esterificados con ácido oleico (OAEP). La absorción de los policosanoles se evaluó en el plasma entre 0 y 3 horas después de la ingestión. Para evaluar los cambios en el colesterol total, colesterol-LDL, colesterol-HDL y triglicéridos en el plasma y en la fosforilación de la hígado 3-hidroxi-3-metilglutaril coenzima A reductasa (HMG-CoA red), la ingesta de las ratas fue suplementada con policosanoles no esterificados o esterificados durante 5 semanas. Los resultados indicaron que la absorción de los policosanoles fue significativamente mayor en las ratas tratadas con los OAEP que en las sometidas a los NEP o las que se les administró BAEP. Los OAEP redujeron significativamente el colesterol plasmático total y el colesterol-LDL de las ratas, además de aumentar 5.6 veces (P < 0,05) sobre los valores control, en el contenido hepático de la HMG-CoA fosforilada red. En conclusión, la esterificación de policosanoles con ácido oleico aumenta la biodisponibilidad de los policosanoles, y mejora significativamente el perfil de lípidos séricos en ratas normocolesterolémicos en asociación con la inactivación de la colesterogénesis control HMG-CoA red. PALABRAS-CLAVE: Absorción de Policosanoles -Biodisponibilidad -Efecto reductor de colesterol -Octacosanol -Policosanol -Triacontanol -Ratas. SUMMARY The oleic acid esterification of policosanol increases its bioavailability and hypocholesterolemic action in ratsPolicosanol comprises a mixture of long-chain aliphatic alcohols from sugarcane wax. More than 50 studies indicate that policosanol decreases serum cholesterol, while others failed to reproduce this effect. The objective of this investigation was to assess the bioavailability of esterified policosanol and non-esterified policosanol (NEP), in relation to their hypocholesterolemic effects. Sprague Dawley rats were given a daily oral dose of 100 mg/kg of NEP, 117 mg kg -1 of butyric acid esterified policosanol (BAEP), or 164 mg kg -1 of oleic acid esterified policosanol (OAEP). Policosanol absorption was evaluated in plasma between 0 and 3 hours after ingestion. To assess changes in total cholesterol, LDL-cholesterol, HDLcholesterol and triacylglycerols in ...

show abstract

Regulation of HMGCoA Reductase Activity by Policosanol and Octacosadienol, a New Synthetic Analogue of Octacosanol

Cited by 59 publications

References 41 publications

AMP-activated protein kinase pathway and bone metabolism

AMP-activated protein kinase pathway and bone metabolism

Evaluation of the short term efficacy and tolerability of a combined nutraceutical with lipid-lowering properties: a randomized clinical trial

The oleic acid esterification of policosanol increases its bioavailability and hypocholesterolemic action in rats

Contact Info

Product

Resources

About