The Use of an Antioxidant Enables Accurate Evaluation of the Interaction of Curcumin on Organic Anion-Transporting Polypeptides 4C1 by Preventing Auto-Oxidation
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Published:2024-01-12
Issue:2
Volume:25
Page:991
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ISSN:1422-0067
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Container-title:International Journal of Molecular Sciences
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language:en
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Short-container-title:IJMS
Author:
Sato Toshihiro1ORCID, Yagi Ayaka2, Yamauchi Minami2, Kumondai Masaki1ORCID, Sato Yu1ORCID, Kikuchi Masafumi12ORCID, Maekawa Masamitsu12ORCID, Yamaguchi Hiroaki34ORCID, Abe Takaaki567, Mano Nariyasu12
Affiliation:
1. Department of Pharmaceutical Sciences, Tohoku University Hospital, Sendai 980-8574, Japan 2. Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan 3. Department of Pharmacy, Yamagata University Hospital, Yamagata 990-9585, Japan 4. Graduate School of Medical Science, Yamagata University, Yamagata 990-9585, Japan 5. Division of Nephrology, Endocrinology, and Vascular Medicine, Graduate School of Medicine, Tohoku University, Sendai 980-8574, Japan 6. Division of Medical Science, Graduate School of Biomedical Engineering, Tohoku University, Sendai 980-8579, Japan 7. Department of Clinical Biology and Hormonal Regulation, Graduate School of Medicine, Tohoku University, Sendai 980-8575, Japan
Abstract
Flavonoids have garnered attention because of their beneficial bioactivities. However, some flavonoids reportedly interact with drugs via transporters and may induce adverse drug reactions. This study investigated the effects of food ingredients on organic anion-transporting polypeptide (OATP) 4C1, which handles uremic toxins and some drugs, to understand the safety profile of food ingredients in renal drug excretion. Twenty-eight food ingredients, including flavonoids, were screened. We used ascorbic acid (AA) to prevent curcumin oxidative degradation in our method. Twelve compounds, including apigenin, daidzein, fisetin, genistein, isorhamnetin, kaempferol, luteolin, morin, quercetin, curcumin, resveratrol, and ellagic acid, altered OATP4C1-mediated transport. Kaempferol and curcumin strongly inhibited OATP4C1, and the Ki values of kaempferol (AA(−)), curcumin (AA(−)), and curcumin (AA(+)) were 25.1, 52.2, and 23.5 µM, respectively. The kinetic analysis revealed that these compounds affected OATP4C1 transport in a competitive manner. Antioxidant supplementation was determined to benefit transporter interaction studies investigating the effects of curcumin because the concentration-dependent curve evidently shifted in the presence of AA. In this study, we elucidated the food–drug interaction via OATP4C1 and indicated the utility of antioxidant usage. Our findings will provide essential information regarding food–drug interactions for both clinical practice and the commercial development of supplements.
Funder
Japan Society for the Promotion of Science KAKENHI Mishima Kaiun Memorial Foundation, Tokyo, Japan
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
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