Regioselective Hydroxylation of Oleanolic Acid Catalyzed by Human CYP3A4 to Produce Hederagenenin, a Chiral Metabolite
Oleanolic acid (OA) is a pentacyclic triterpenoid widely found in plants and foods as an aglycone of triterpenoid saponins or as a free acid. OA exhibits beneficial activities for humans, including antitumor, antivirus, and hepatoprotection properties without apparent toxicity. The metabolites produ...
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MDPI AG
2021-02-01
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| Series: | Catalysts |
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| Online Access: | https://www.mdpi.com/2073-4344/11/2/267 |
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| author | Ngoc Tan Cao Ngoc Anh Nguyen Thien-Kim Le Gun Su Cha Ki Deok Park Chul-Ho Yun |
| author_facet | Ngoc Tan Cao Ngoc Anh Nguyen Thien-Kim Le Gun Su Cha Ki Deok Park Chul-Ho Yun |
| author_sort | Ngoc Tan Cao |
| collection | DOAJ |
| description | Oleanolic acid (OA) is a pentacyclic triterpenoid widely found in plants and foods as an aglycone of triterpenoid saponins or as a free acid. OA exhibits beneficial activities for humans, including antitumor, antivirus, and hepatoprotection properties without apparent toxicity. The metabolites produced by the cytochrome P450 (P450) enzymes are critical for the evaluation of the efficacy and safety of drugs. In this study, the potential metabolites of OA were investigated by P450-catalyzed oxidation reactions. Among the various tested human P450s, only human CYP3A4 was active for the hydroxylation of OA. The major metabolite was characterized by a set of analyses using HPLC, LC–MS, and NMR. It was found to be 4-epi-hederagenenin, a chiral product, by regioselective hydroxylation of the methyl group at the C-23 position. These results indicated that CYP3A4 can hydroxylate an OA substrate to make 4-epi-hederagenenin. Possible drug–food interactions are discussed. |
| first_indexed | 2024-03-09T00:48:47Z |
| format | Article |
| id | doaj.art-95b442ea98714e4c8cecca0a56f76e17 |
| institution | Directory Open Access Journal |
| issn | 2073-4344 |
| language | English |
| last_indexed | 2024-03-09T00:48:47Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Catalysts |
| spelling | doaj.art-95b442ea98714e4c8cecca0a56f76e172023-12-11T17:22:15ZengMDPI AGCatalysts2073-43442021-02-0111226710.3390/catal11020267Regioselective Hydroxylation of Oleanolic Acid Catalyzed by Human CYP3A4 to Produce Hederagenenin, a Chiral MetaboliteNgoc Tan Cao0Ngoc Anh Nguyen1Thien-Kim Le2Gun Su Cha3Ki Deok Park4Chul-Ho Yun5School of Biological Sciences and Technology, Chonnam National University, 77 Yongbongro, Gwangju 61186, KoreaSchool of Biological Sciences and Technology, Chonnam National University, 77 Yongbongro, Gwangju 61186, KoreaSchool of Biological Sciences and Technology, Chonnam National University, 77 Yongbongro, Gwangju 61186, KoreaNamhae Garlic Research Institute, 2465-8 Namhaedaero, Gyeongsangnamdo 52430, KoreaGwangju Center, Korea Basic Science Institute, Gwangju 61186, KoreaSchool of Biological Sciences and Technology, Chonnam National University, 77 Yongbongro, Gwangju 61186, KoreaOleanolic acid (OA) is a pentacyclic triterpenoid widely found in plants and foods as an aglycone of triterpenoid saponins or as a free acid. OA exhibits beneficial activities for humans, including antitumor, antivirus, and hepatoprotection properties without apparent toxicity. The metabolites produced by the cytochrome P450 (P450) enzymes are critical for the evaluation of the efficacy and safety of drugs. In this study, the potential metabolites of OA were investigated by P450-catalyzed oxidation reactions. Among the various tested human P450s, only human CYP3A4 was active for the hydroxylation of OA. The major metabolite was characterized by a set of analyses using HPLC, LC–MS, and NMR. It was found to be 4-epi-hederagenenin, a chiral product, by regioselective hydroxylation of the methyl group at the C-23 position. These results indicated that CYP3A4 can hydroxylate an OA substrate to make 4-epi-hederagenenin. Possible drug–food interactions are discussed.https://www.mdpi.com/2073-4344/11/2/267biocatalystC-H hydroxylationhederageninhuman CYP3A4regioselective hydroxylationoleanolic acid |
| spellingShingle | Ngoc Tan Cao Ngoc Anh Nguyen Thien-Kim Le Gun Su Cha Ki Deok Park Chul-Ho Yun Regioselective Hydroxylation of Oleanolic Acid Catalyzed by Human CYP3A4 to Produce Hederagenenin, a Chiral Metabolite Catalysts biocatalyst C-H hydroxylation hederagenin human CYP3A4 regioselective hydroxylation oleanolic acid |
| title | Regioselective Hydroxylation of Oleanolic Acid Catalyzed by Human CYP3A4 to Produce Hederagenenin, a Chiral Metabolite |
| title_full | Regioselective Hydroxylation of Oleanolic Acid Catalyzed by Human CYP3A4 to Produce Hederagenenin, a Chiral Metabolite |
| title_fullStr | Regioselective Hydroxylation of Oleanolic Acid Catalyzed by Human CYP3A4 to Produce Hederagenenin, a Chiral Metabolite |
| title_full_unstemmed | Regioselective Hydroxylation of Oleanolic Acid Catalyzed by Human CYP3A4 to Produce Hederagenenin, a Chiral Metabolite |
| title_short | Regioselective Hydroxylation of Oleanolic Acid Catalyzed by Human CYP3A4 to Produce Hederagenenin, a Chiral Metabolite |
| title_sort | regioselective hydroxylation of oleanolic acid catalyzed by human cyp3a4 to produce hederagenenin a chiral metabolite |
| topic | biocatalyst C-H hydroxylation hederagenin human CYP3A4 regioselective hydroxylation oleanolic acid |
| url | https://www.mdpi.com/2073-4344/11/2/267 |
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