Monacoline

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Structure of Monacolin K ( Lovastatin )
Structure of compactin ( mevastatin )

Monacolines are a group of naturally occurring chemical compounds in various mold strains that are derived from decalin or hexahydronaphthalene .

Monacolines inhibit the body's own production of cholesterol in the liver . The lipid-lowering properties is based on the dose-dependent inhibition ( inhibition ) of the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase (short: HMG-CoA reductase ).

history

The Japanese biochemist Akira Endo recognized the cholesterol-lowering effect of the compactin isolated from Penicillium citrinum by him in 1976, and in 1979 that of Monacolin K isolated from Monascus ruber . They were the basis for the development of statins ( CSE inhibitors ). Monacolin K carries since 1987 the generic name lovastatin and came in the same year as the first statin drug under the trade name Mevacor in the US market. Monacolin K comes along with a number of other monacolins naturally in the "Rotschimmelreis" ( red yeast rice (RYR), red fermented rice ) before, a Chinese traditional foods.

properties

Monacolines act as HMG-CoA reductase inhibitors , whose effect in the liver is directly related to cholesterol synthesis . By inhibiting HMG-CoA reductase, they prevent the conversion of β-hydroxy-β-methylglutaryl-CoA (HMG-CoA) into mevalonic acid . This interrupts a preliminary stage of cholesterol synthesis and, as a result, dose-dependently inhibits cholesterol synthesis.

In a study with 25 otherwise healthy volunteers and elevated blood lipids , a relevant drop in total and LDL cholesterol (−12.45%, −21.99%) was observed after four weeks with a daily dose of 10 mg monacoline, an influence on the HDL cholesterol was undetectable. A meta-analysis including placebo-controlled studies came to similar results. In a Chinese double-blind, placebo-controlled secondary prophylaxis study (n = 2704), taking 5 mg twice daily reduced coronary events by 43.0% (P = 0.02) and death from heart disease by 30.0% (P <0, 01) as well as a reduction in total mortality of 35.8% (P = 0.001).

Monacolines also have anti- inflammatory , antioxidant and anti- tumor effects.

Occurrence and extraction

Monacolins arise biogenically by the polyketide route in fungal species such as Aspergillus spp. , Penicillium spp. and Monascus spp. In Rotschimmelreis , a means of Monascus strains rice produced fermentation product , a series of Monaco Linen has been demonstrated, for example:

  • Monacolin K (Mevinolin, Lovastatin )
  • Compactin ( mevastatin )
  • Monacolin J.
  • Monacolin L.
  • Monacolin M.
  • Monacolin X
  • Dihydromonacolin L.
  • Dehydromonacolin K

Monacolin- forming Monascus species (from the order of the Eurotiales ) that are used in the production of red fermented rice are:

The drug lovastatin is obtained from cultures of Aspergillus terreus and Monascus ruber in a multi-stage fermentation process.

Web links

Individual evidence

  1. ↑ a b Theodor Dingermann (Ed.), Rudolf Hänsel (Ed.), Ilse Zündorf (Ed.): Pharmaceutical Biology: Molecular Basics and Clinical Application. Springer 2002, ISBN 978-3-642-55943-3 , pp. 59-60.
  2. ^ Cholesterol-lowering effects of a proprietary Chinese red-yeast-rice dietary supplement . ajcn.org
  3. ↑ A. Endo et al .: ML-236A, ML-236B, and ML-236C, new inhibitors of cholesterogenesis produced by Penicillium citrinium. In: J Antibiot , 1976 Dec, 29 (12), pp. 1346-1348, PMID 1010803
  4. ↑ A. Endo et al .: Monacolin K, a new hypocholesterolemic agent produced by a Monascus species. In: J Antibiot , 1979 Aug, 32 (8), pp. 852-854, PMID 500505 .
  5. ^ A b C. W. Yang, SA Mousa: The effect of red yeast rice (Monascus purpureus) in dyslipidemia and other disorders. In: Complementary therapies in medicine. Volume 20, Number 6, December 2012, pp. 466-474, doi: 10.1016 / j.ctim.2012.07.004 , PMID 23131380 (review).
  6. ↑ P. Patakova: Monascus secondary metabolites: production and biological activity. In: Journal of industrial microbiology & biotechnology. Volume 40, Number 2, February 2013, pp. 169-181, doi: 10.1007 / s10295-012-1216-8 . PMID 23179468 .
  7. ↑ Red Yeast Rice: Cholesterol Lowering Supplement . MedicineNet.com
  8. ↑ a b A. F. Cicero, G. Derosa and a .: Red yeast rice improves lipid pattern, high-sensitivity C-reactive protein, and vascular remodeling parameters in moderately hypercholesterolemic Italian subjects. In: Nutrition research. Volume 33, Number 8, August 2013, pp. 622-628, doi: 10.1016 / j.nutres.2013.05.015 , PMID 23890351 .
  9. ↑ JJ Li, ZL Lu u. a .: Impact of Xuezhikang on coronary events in hypertensive patients with previous myocardial infarction from the China Coronary Secondary Prevention Study (CCSPS). In: Annals of medicine. Volume 42, Number 3, April 2010, pp. 231-240, doi: 10.3109 / 07853891003652534 , PMID 20350253 .
  10. ^ WH Hsu, TM Pan: Monascus purpureus-fermented products and oral cancer: a review. In: Applied Microbiology and Biotechnology . Volume 93, Number 5, March 2012, pp. 1831-1842, doi: 10.1007 / s00253-012-3891-9 . PMID 22290648 .
  11. ↑ A. Seenivasan et al .: Microbial Production and Biomedical Applications of Lovastatin. In: Indian J Pharm Sci. 2008 Nov-Dec; 70 (6), pp. 701-709, PMC 3040861 (free full text).
  12. ↑ K. Hardtke et al. (Ed.): Commentary on the European Pharmacopoeia Ph. Eur. 7.4 , Lovastatin. Loose-leaf collection, 40th delivery 2012, Wissenschaftliche Verlagsgesellschaft Stuttgart