Bioactive natural products, habitually ingested with milk or its derivative nutrients, have been studied for their bioavailability. In this study, we investigated the effects of the co-administration of bovine milk-derived lactoferrin (bLF) and bioactive products, with a focus on catechol-O-methyltransferase (COMT), an enzyme in the catechol metabolism. bLF showed inhibitory activity on COMT in vitro, and acidic pretreatment of bLF enhanced its inhibitory activity. Moreover, partially digested products of bLF by pepsin retained inhibitory activity. Based on these results, bLF was co-administered with levodopa (l-DOPA), which is a catechol compound and a precursor of dopamine, and the effect of bLF on l-DOPA absorption and metabolism was investigated in a mouse model. The co-administration of l-DOPA and bLF alone showed no effect on the concentration of l-DOPA in plasma. However, with the additional administration of carbidopa, the concentration of l-DOPA was significantly enhanced. Furthermore, the ratio of l-DOPA/3-O-methyldopa significantly increased. On the other hand, casein, which is a major milk protein, was not effective. In addition, COMT activity in the intestines was lowered with bLF administration. We concluded that the co-administration of bLF and carbidopa enhances the concentration of l-DOPA.
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