| Polymethoxyflavonoids (PMFs) from citrus genus have been particular of interest because of their broad spectrum of biological activities, including anti-inflammatory, anti-carcinogenic, and anti-atherogenic properties. There have been increasing interests in the exploration of health beneficial properties of PMFs in citrus fruits. Therefore, the isolation and characterization of PMFs from sweet orange (Citrus sinensis) peel has prompted the new applications of the by-products from orange juice processing.; In our study, seven hydroxylated polymethoxyflavones, two polymethoxyflavanones and two polymethoxychalcones have been isolated from sweet orange peel extract and their structures were elucidated by various MS and NMR techniques. These compounds are identified as: 5-hydroxy-6,7,4'-trimethoxyflavone (I), 5-demethyltangeretin (II), 3-hydroxy-5,6,7,4'-tetramethoxyflavone (III), 3-hydroxy-5,6,7,8,4'-pentamethoxyflavone (IV), 5-hydroxy-3,6,7,8,3',4'-hexamethoxyflavone (V), 5-hydroxy-3,7,3',4'-tetramethoxyflavone (VI), 5-hydroxy-3,7,8,3',4'-pentamethoxyflavone (VII), 5,6,7,4'-tetramethoxyflavanone (VIII), 5-hydroxy-6,7,8,3',4'-pentamethoxyflavanone (IX), 2'-hydroxy-3,4,4',5',6'-pentamethoxychalcone (X) and 2'-hydroxy-3,4,3',4',5',6'-hexamethoxychalcone (XI). These compounds are newly isolated from sweet orange peel. This result provides more resource in the exploration of biologically potent PMFs against inflammatory, cancer and cardiovascular disease etc.; Our in vivo transformation study of nobiletin in mice resulted in the demethylated nobiletin metabolites from urine and plasma. In identifying the biotransformation products and exploring the potential transformation mechanism of nobiletin with limited amount of metabolite mixtures, four hydroxylated PMFs were synthesized and their structures confirmed. By comparing the LC/MS properties and SFC profiles of the synthesized PMFs with that of the metabolite mixture, three demethylated metabolites have been identified. The investigation of other metabolites and the in vivo transformation mechanism study is in progress.; The bioavailability of 12 different PMFs was also evaluated by measuring their solubility (LYSA) and permeability (PAMPA and Caco-2) values. Conclusion has been drawn that the overall solubility of PMFs is low, but their permeability is generally high, which predicts their better bioavailability comparing to multihydroxylated flavonoids, being explained by their high lipophilicity nature of PMFs due to the existence of multiple methoxyl groups. |
