Effect of Betanin, the Major Pigment of Red Beetroot (<i>Beta vulgaris</i> L.), on the Activity of Recombinant Human Cytochrome P450 Enzymes
Most of the currently available drugs are derived from natural sources, but they are used only after extensive chemical modifications to improve their safety and efficacy. Natural products are used in health supplements and cosmetic preparations and have been used as auxiliary drugs or alternative m...
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| Format: | Article |
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MDPI AG
2023-08-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/16/9/1224 |
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| author | Sung Ho Lim Seoungpyo Bae Ho Seon Lee Hyo-Kyung Han Chang-Ik Choi |
| author_facet | Sung Ho Lim Seoungpyo Bae Ho Seon Lee Hyo-Kyung Han Chang-Ik Choi |
| author_sort | Sung Ho Lim |
| collection | DOAJ |
| description | Most of the currently available drugs are derived from natural sources, but they are used only after extensive chemical modifications to improve their safety and efficacy. Natural products are used in health supplements and cosmetic preparations and have been used as auxiliary drugs or alternative medicines. When used in combination with conventional drugs, these herbal products are known to alter their pharmacokinetics and pharmacodynamics, reducing their therapeutic effects. Moreover, herb–drug interactions (HDIs) may have serious side effects, which is one of the major concerns in health practice. It is postulated that HDIs affect the pathways regulating cytochrome P450 enzymes (CYPs). Betanin, the chief pigment of red beetroot (<i>Beta vulgaris</i> L.), has various types of pharmacological activity, such as anti-inflammatory, antioxidant, and anticancer effects. However, the potential risk of HDIs for betanin has not yet been studied. Thus, we aimed to predict more specific HDIs by evaluating the effects of betanin on CYPs (CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4), the major phase I metabolic enzymes, using fluorescence-/luminescence-based assays. Our results showed that betanin inhibited CYP3A4 activity in a dose-dependent manner (IC<sub>50</sub> = 20.97 µΜ). Moreover, betanin acted as a competitive inhibitor of CYP3A4, as confirmed by evaluating Lineweaver–Burk plots (<i>Ki</i> value = 19.48 µΜ). However, no significant inhibitory effects were observed on other CYPs. Furthermore, betanin had no significant effect on CYP1A2, CYP2B6, or CYP2C9 induction in HepG2 cells. In conclusion, betanin acted as a competitive inhibitor of CYP3A4, and thus it should be used cautiously with other drugs that require metabolic enzymes as substrates. Additional in vivo studies and clinical trials are needed to further elucidate the HDIs of betanin. |
| first_indexed | 2024-03-10T22:17:02Z |
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| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T22:17:02Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-4baf1b0e26664ed69a2a8327c9eee7a12023-11-19T12:24:17ZengMDPI AGPharmaceuticals1424-82472023-08-01169122410.3390/ph16091224Effect of Betanin, the Major Pigment of Red Beetroot (<i>Beta vulgaris</i> L.), on the Activity of Recombinant Human Cytochrome P450 EnzymesSung Ho Lim0Seoungpyo Bae1Ho Seon Lee2Hyo-Kyung Han3Chang-Ik Choi4Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University-Seoul, Goyang 10326, Republic of KoreaIntegrated Research Institute for Drug Development, College of Pharmacy, Dongguk University-Seoul, Goyang 10326, Republic of KoreaIntegrated Research Institute for Drug Development, College of Pharmacy, Dongguk University-Seoul, Goyang 10326, Republic of KoreaBK21 FOUR Team and Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University-Seoul, Goyang 10326, Republic of KoreaIntegrated Research Institute for Drug Development, College of Pharmacy, Dongguk University-Seoul, Goyang 10326, Republic of KoreaMost of the currently available drugs are derived from natural sources, but they are used only after extensive chemical modifications to improve their safety and efficacy. Natural products are used in health supplements and cosmetic preparations and have been used as auxiliary drugs or alternative medicines. When used in combination with conventional drugs, these herbal products are known to alter their pharmacokinetics and pharmacodynamics, reducing their therapeutic effects. Moreover, herb–drug interactions (HDIs) may have serious side effects, which is one of the major concerns in health practice. It is postulated that HDIs affect the pathways regulating cytochrome P450 enzymes (CYPs). Betanin, the chief pigment of red beetroot (<i>Beta vulgaris</i> L.), has various types of pharmacological activity, such as anti-inflammatory, antioxidant, and anticancer effects. However, the potential risk of HDIs for betanin has not yet been studied. Thus, we aimed to predict more specific HDIs by evaluating the effects of betanin on CYPs (CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4), the major phase I metabolic enzymes, using fluorescence-/luminescence-based assays. Our results showed that betanin inhibited CYP3A4 activity in a dose-dependent manner (IC<sub>50</sub> = 20.97 µΜ). Moreover, betanin acted as a competitive inhibitor of CYP3A4, as confirmed by evaluating Lineweaver–Burk plots (<i>Ki</i> value = 19.48 µΜ). However, no significant inhibitory effects were observed on other CYPs. Furthermore, betanin had no significant effect on CYP1A2, CYP2B6, or CYP2C9 induction in HepG2 cells. In conclusion, betanin acted as a competitive inhibitor of CYP3A4, and thus it should be used cautiously with other drugs that require metabolic enzymes as substrates. Additional in vivo studies and clinical trials are needed to further elucidate the HDIs of betanin.https://www.mdpi.com/1424-8247/16/9/1224<i>Beta vulgaris</i> L.betanincytochrome P450 enzymesfluorescence-based assayHepG2 cellsherb–drug interactions |
| spellingShingle | Sung Ho Lim Seoungpyo Bae Ho Seon Lee Hyo-Kyung Han Chang-Ik Choi Effect of Betanin, the Major Pigment of Red Beetroot (<i>Beta vulgaris</i> L.), on the Activity of Recombinant Human Cytochrome P450 Enzymes Pharmaceuticals <i>Beta vulgaris</i> L. betanin cytochrome P450 enzymes fluorescence-based assay HepG2 cells herb–drug interactions |
| title | Effect of Betanin, the Major Pigment of Red Beetroot (<i>Beta vulgaris</i> L.), on the Activity of Recombinant Human Cytochrome P450 Enzymes |
| title_full | Effect of Betanin, the Major Pigment of Red Beetroot (<i>Beta vulgaris</i> L.), on the Activity of Recombinant Human Cytochrome P450 Enzymes |
| title_fullStr | Effect of Betanin, the Major Pigment of Red Beetroot (<i>Beta vulgaris</i> L.), on the Activity of Recombinant Human Cytochrome P450 Enzymes |
| title_full_unstemmed | Effect of Betanin, the Major Pigment of Red Beetroot (<i>Beta vulgaris</i> L.), on the Activity of Recombinant Human Cytochrome P450 Enzymes |
| title_short | Effect of Betanin, the Major Pigment of Red Beetroot (<i>Beta vulgaris</i> L.), on the Activity of Recombinant Human Cytochrome P450 Enzymes |
| title_sort | effect of betanin the major pigment of red beetroot i beta vulgaris i l on the activity of recombinant human cytochrome p450 enzymes |
| topic | <i>Beta vulgaris</i> L. betanin cytochrome P450 enzymes fluorescence-based assay HepG2 cells herb–drug interactions |
| url | https://www.mdpi.com/1424-8247/16/9/1224 |
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