Dihydromevinolin,a potent hypocholesterolemic metabolite produced by Aspergillus terreus.

Albers-Schönberg, Georg; Joshua, H; López, Maribel Sánchez; Hensens, Otto D.; Springer, James P.; Chen, J.; Ostrove, S. A.; Hoffman, Cecilia; Alberts, Alfred W.; Patchett, Arthur A.

doi:10.7164/antibiotics.34.507

Cited by 69 publications

(33 citation statements)

References 7 publications

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“…Lovastatin and simvastatin have been shown to potently inhibit cho lesterol synthesis in cultured animal cells [16,17]. whereas pravastatin is relatively ineffective.…”

Section: Inhibition Of Cholesterol Synthesis In Vitromentioning

confidence: 99%

Lovastatin and Simvastatin - Inhibitors of HMG CoA Reductase and Cholesterol Biosynthesis

Alberts¹

1990

Cardiology

106

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The microsomal enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase is a key rate-controlling step early in the cholesterol biosynthetic pathway that catalyzes the conversion of HMG CoA to mevalonic acid. Since this enzyme plays a significant role in regulating cholesterol synthesis, it is a rational target for pharmacologic intervention. The first potent, specific inhibitor of HMG CoA was mevastatin (compactin, ML-236B) which was discovered in 1976 by Endo et al. [J Antibiot 1976;29:1346-1348]. Subsequently, lovastatin, a novel, more active fungal metabolite was isolated from a strain of Aspergillus terreus.Lovastatin, the first of this class of agents to be approved for clinical use, was chemically modified to form simvastatin. Simvastatin is superior to lovastatin in intrinsic inhibitory potency. Both are inactive lactone prodrugs that must be converted to their respective dihy-droxy open-acid forms to elicit inhibitory activity. Pharmacologic characterization of lovastatin and simvastatin has demonstrated that these potent inhibitors of HMG CoA reductase specifically inhibit cholesterol synthesis in animal cells, as well as in vivo after oral administration of the agents. Oral administration of either lovastatin or simvastatin to dogs in the presence or absence of the bile acid sequestrant cholestyramine results in a marked, sustained lowering of plasma cholesterol. Associated with the cholesterol lowering is a decrease in urinary and plasma levels of mevalonic acid, the end product of the HMG CoA reductase reaction. The target organ for inhibitors of HMG CoA reductase is the liver, the primary site of cholesterol biosynthesis. Both lovastatin and simvastatin are preferentially extracted by this organ. In studies in the rat in which direct measurements of drug levels have been carried out, much more inhibitory activity derived from the prodrugs lovastatin and simvastatin is found in the liver than in spleen, testes, and kidney. This is reflected in a much greater in vivo inhibition of cholesterol synthesis in the liver by these agents than in the periphery. In summary, the HMG CoA reductase inhibitors lovastatin and simvastatin are potent inhibitors of mevalonic acid synthesis in vitro and in vivo. They are preferentially concentrated in the liver, the target organ. This results in inhibition of cholesterol synthesis and a concomitant decrease in plasma low-density lipoprotein cholesterol in experimental animals and humans.

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“…Lovastatin and simvastatin have been shown to potently inhibit cho lesterol synthesis in cultured animal cells [16,17]. whereas pravastatin is relatively ineffective.…”

Section: Inhibition Of Cholesterol Synthesis In Vitromentioning

confidence: 99%

Lovastatin and Simvastatin - Inhibitors of HMG CoA Reductase and Cholesterol Biosynthesis

Alberts¹

1990

Cardiology

106

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“…연구보고에 의하면, Asp. terreus균주는 세포에서 HMG-CoA 환 원효소를 억제하고, 동물에서 콜레스테롤 생합성을 억제하여 콜 레스테롤을 조절한다고 알려져 있다 (18). 최근에는 Asp.…”

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The Effect of Rice with Aspergillus terreus on Lipid Metabolism in Rats

장지은¹,

최혜란²,

이정현³

et al. 2015

Korean Journal of Food Science and Technology

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The aim of this study was to investigate the effects of rice contatining Aspergillus terreus (Hwangkuk, HK) on lipid metabolism in male Sprague-Dawley (SD) rats fed a high-cholesterol diet (HCD) for 8 weeks. SD rats were divided into five groups: Normal, [Negative Control (HCD), Positive Control (lovastatin)], [HK 0.5 g/kg and HK 2 g/kg]. Hepatic total lipids significantly decreased following treatment with rice contatining Asp. terreus. Furthermore, this treatment led to higher expression levels of HMG-CoA reductase, LDL receptor and SREBP2 mRNA in the liver compared with the HCD group. In addition, histopathologic evaluation showed that feeding rats with rice containing Asp. terreus suppressed hepatic steatosis. These results suggest that rice containing Asp. terreus may be able to regulate of cholesterol synthesis and prevent hyperlipidemia.

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“…Lovastatin (30), an interesting polyketide, was delivered from Aspergillus terreus [53] . Lovastatin (30) experienced a wide use as a cholesterol lowering agent (Mevacor ® ).…”

mentioning

confidence: 99%

A new 16-membered tetraene macrolide JBIR-100 from a newly identified Streptomyces species

Ueda¹,

Hashimoto²,

Yamamura³

et al. 2011

J Antibiot

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Dihydromevinolin,a potent hypocholesterolemic metabolite produced by Aspergillus terreus.

Abstract: A new, potent hypocholesterolemic agent is produced by cultures of Aspergillus terreus.

Cited by 69 publications

References 7 publications

Lovastatin and Simvastatin - Inhibitors of HMG CoA Reductase and Cholesterol Biosynthesis

Lovastatin and Simvastatin - Inhibitors of HMG CoA Reductase and Cholesterol Biosynthesis

The Effect of Rice with Aspergillus terreus on Lipid Metabolism in Rats

A new 16-membered tetraene macrolide JBIR-100 from a newly identified Streptomyces species

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