The Use of an Antioxidant Enables Accurate Evaluation of the Interaction of Curcumin on Organic Anion-Transporting Polypeptides 4C1 by Preventing Auto-Oxidation
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,...
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| Format: | Article |
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MDPI AG
2024-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/2/991 |
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| author | Toshihiro Sato Ayaka Yagi Minami Yamauchi Masaki Kumondai Yu Sato Masafumi Kikuchi Masamitsu Maekawa Hiroaki Yamaguchi Takaaki Abe Nariyasu Mano |
| author_facet | Toshihiro Sato Ayaka Yagi Minami Yamauchi Masaki Kumondai Yu Sato Masafumi Kikuchi Masamitsu Maekawa Hiroaki Yamaguchi Takaaki Abe Nariyasu Mano |
| author_sort | Toshihiro Sato |
| collection | DOAJ |
| description | 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 <i>K</i><sub>i</sub> 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. |
| first_indexed | 2024-03-08T09:53:27Z |
| format | Article |
| id | doaj.art-0497556de20d400491c0339bc4826882 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-08T09:53:27Z |
| publishDate | 2024-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-0497556de20d400491c0339bc48268822024-01-29T13:56:04ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-01-0125299110.3390/ijms25020991The Use of an Antioxidant Enables Accurate Evaluation of the Interaction of Curcumin on Organic Anion-Transporting Polypeptides 4C1 by Preventing Auto-OxidationToshihiro Sato0Ayaka Yagi1Minami Yamauchi2Masaki Kumondai3Yu Sato4Masafumi Kikuchi5Masamitsu Maekawa6Hiroaki Yamaguchi7Takaaki Abe8Nariyasu Mano9Department of Pharmaceutical Sciences, Tohoku University Hospital, Sendai 980-8574, JapanGraduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, JapanGraduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, JapanDepartment of Pharmaceutical Sciences, Tohoku University Hospital, Sendai 980-8574, JapanDepartment of Pharmaceutical Sciences, Tohoku University Hospital, Sendai 980-8574, JapanDepartment of Pharmaceutical Sciences, Tohoku University Hospital, Sendai 980-8574, JapanDepartment of Pharmaceutical Sciences, Tohoku University Hospital, Sendai 980-8574, JapanDepartment of Pharmacy, Yamagata University Hospital, Yamagata 990-9585, JapanDivision of Nephrology, Endocrinology, and Vascular Medicine, Graduate School of Medicine, Tohoku University, Sendai 980-8574, JapanDepartment of Pharmaceutical Sciences, Tohoku University Hospital, Sendai 980-8574, JapanFlavonoids 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 <i>K</i><sub>i</sub> 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.https://www.mdpi.com/1422-0067/25/2/991OATP4C1renal transporterfood–drug interactionflavonoidscurcuminkaempferol |
| spellingShingle | Toshihiro Sato Ayaka Yagi Minami Yamauchi Masaki Kumondai Yu Sato Masafumi Kikuchi Masamitsu Maekawa Hiroaki Yamaguchi Takaaki Abe Nariyasu Mano The Use of an Antioxidant Enables Accurate Evaluation of the Interaction of Curcumin on Organic Anion-Transporting Polypeptides 4C1 by Preventing Auto-Oxidation International Journal of Molecular Sciences OATP4C1 renal transporter food–drug interaction flavonoids curcumin kaempferol |
| title | The Use of an Antioxidant Enables Accurate Evaluation of the Interaction of Curcumin on Organic Anion-Transporting Polypeptides 4C1 by Preventing Auto-Oxidation |
| title_full | The Use of an Antioxidant Enables Accurate Evaluation of the Interaction of Curcumin on Organic Anion-Transporting Polypeptides 4C1 by Preventing Auto-Oxidation |
| title_fullStr | The Use of an Antioxidant Enables Accurate Evaluation of the Interaction of Curcumin on Organic Anion-Transporting Polypeptides 4C1 by Preventing Auto-Oxidation |
| title_full_unstemmed | The Use of an Antioxidant Enables Accurate Evaluation of the Interaction of Curcumin on Organic Anion-Transporting Polypeptides 4C1 by Preventing Auto-Oxidation |
| title_short | The Use of an Antioxidant Enables Accurate Evaluation of the Interaction of Curcumin on Organic Anion-Transporting Polypeptides 4C1 by Preventing Auto-Oxidation |
| title_sort | use of an antioxidant enables accurate evaluation of the interaction of curcumin on organic anion transporting polypeptides 4c1 by preventing auto oxidation |
| topic | OATP4C1 renal transporter food–drug interaction flavonoids curcumin kaempferol |
| url | https://www.mdpi.com/1422-0067/25/2/991 |
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