|ZHANG, ZHIHAO - University Of Mississippi|
|ZULFIQAR, ALI - University Of Mississippi|
|KHAN, SHABANA - University Of Mississippi|
|KHAN, IKHLAS - University Of Mississippi|
Submitted to: Journal of Natural Products
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/9/2015
Publication Date: 7/1/2016
Citation: Zhang, Z., Zulfiqar, A., Khan, S.I., Khan, I.A. 2016. Cytotoxic monacolins from red yeast rice, a Chinese medicine and food. Journal of Natural Products. 202:262-8. DOI:10.1016/j.foodchem.2015.12.039.
Interpretive Summary: Red yeast rice, which is also known as koji, anka, angkakand ben-koji, is produced from the fermentation of steamed rice using the fungus Monascus purpureus. It has been utilized for hundreds of years for coloring food, wine and preserving meat. It has also been used as a folk medicine for improving food digestion and blood circulation in East Asia for centuries. Monacolins are inhibitors of HMG-CoA reductase, the rate-limiting enzyme of cholesterol biosynthesis. Clinical observations clearly showed that red yeast rice can lower blood lipid levels. Recently, a double blind placebo controlled randomized clinical trial demonstrated that red yeast rice supplements have the ability to lower total cholesterol by 15% in 8 weeks. In United States, some physicians recommend the use of red yeast rice to patients with statin intolerance. Besides cholesterol-lowering effects, monacolins have been reported to possess protective effects against colon, liver, prostate, and breast cancer, and antioxidant activities. In this paper, we report the isolation and characterization of seven new monacolins, monacolins Q-S (1-3), a,ß-dehydromonacolin S, 3a-hydroxy-3,5-dihydromonacolin L, 3ß-hydroxy-3,5-dihydromonacolin L, and a,ß-hydromonacolin Q, and six known monacolins, a,ß-dehydrodihydromonacolin K, dehydromonacolin K, dehydromonacolin L, monacolin K, dihydromonacolin K, dihydromonacolin L. Structure elucidation of the isolates was achieved by means of NMR and mass spectroscopic data analyses. Compounds were evaluated for their cytotoxic activity against four cancer cell lines and two noncancerous kidney cell lines. Monacolin Q, monocolin R a,ß-dehydrodihydromonacolin K, dehydromonacolin K, and monocolin K showed cytotoxicity to most of these cell lines. Monacolin K was the most potent among all tested compounds.
Technical Abstract: Seven new monacolins, monacolins Q-S (1-3), a,ß-dehydromonacolin S (4), 3a-hydroxy-3,5-dihydromonacolin L (5), 3ß-hydroxy-3,5-dihydromonacolin L (6), and a,ß-hydromonacolin Q (7) were isolated and characterized from the methanol extract of red yeast rice. In addition, six known monacolins, a,ß-dehydrodihydromonacolin K (8), dehydromonacolin K (9), dehydromonacolin L (10), monacolin K (11), dihydromonacolin K (12), dihydromonacolin L (13) and two compounds other than monacolins were also isolated. Structure elucidation of the isolates was achieved by means of NMR and mass spectroscopic data analyses. Compounds 1-5, 8, 9, 11, 13, and 14 were evaluated for their cytotoxic activity against four cancer cell lines (SK-MEL, KB, BT-549, SK-OV-3) and two noncancerous kidney cell lines ( LLC-PK1 and Vero). Monacolin Q (1), monocolin R (2) a,ß-dehydrodihydromonacolin K (8), dehydromonacolin K (9), and monocolin K (11) showed cytotoxicity to most of these cell lines. Monacolin K (11) was the most potent among all tested compounds.