Comprehensive Metabolite Identification of Genipin in Rats Using Ultra-High-Performance Liquid Chromatography Coupled with High Resolution Mass Spectrometry
Genipin, an aglycone of geniposide, is a rich iridoid component in the fruit of <i>Gardenia jasminoides</i> Ellis and has numerous biological activities. However, its metabolic profiles in vivo and vitro remain unclear. In this study, an effective analytical strategy based on ultra-high-...
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MDPI AG
2023-08-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/28/17/6307 |
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| author | Zhifeng Cui Zhe Li Weichao Dong Lili Qiu Jiayu Zhang Shaoping Wang |
| author_facet | Zhifeng Cui Zhe Li Weichao Dong Lili Qiu Jiayu Zhang Shaoping Wang |
| author_sort | Zhifeng Cui |
| collection | DOAJ |
| description | Genipin, an aglycone of geniposide, is a rich iridoid component in the fruit of <i>Gardenia jasminoides</i> Ellis and has numerous biological activities. However, its metabolic profiles in vivo and vitro remain unclear. In this study, an effective analytical strategy based on ultra-high-performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS) in positive and negative ion modes was developed to analyze and identify genipin metabolites in rat urine, blood, feces, and fecal fermentation in combination with many methods including post-collection data mining methods, high-resolution extracted ion chromatography (HREIC), and multiple mass defect filtering (MMDF). Simultaneously, the metabolites of genipin in vivo were verified by fecal fermentation of SD rats at different times. Finally, based on information such as reference substances, chromatographic retention behavior, and accurate mass determination, a total of 50 metabolites (including prototypes) were identified in vivo. Among them, 7, 31 and 28 metabolites in vivo were identified in blood, urine, and feces, respectively. Our results showed that genipin could generate different metabolites that underwent multiple metabolic reactions in vivo including methylation, hydroxylation, dehydroxylation, hydrogenation, sulfonation, glucuronidation, demethylation, and their superimposed reactions. Forty-six metabolites were verified in vitro. Meanwhile, 2 and 19 metabolites identified in blood and urine were also verified in fecal fermentation at different times. These results demonstrated that metabolites were produced in feces and reabsorbed into the body. In conclusion, the newly discovered metabolites of genipin can provide a new perspective for understanding its pharmacological effects and build the foundation for thee toxicity and safety evaluations of genipin. |
| first_indexed | 2024-03-10T23:17:28Z |
| format | Article |
| id | doaj.art-80526e98b3f745a6b1d0b8009a19ec7f |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T23:17:28Z |
| publishDate | 2023-08-01 |
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| record_format | Article |
| series | Molecules |
| spelling | doaj.art-80526e98b3f745a6b1d0b8009a19ec7f2023-11-19T08:34:10ZengMDPI AGMolecules1420-30492023-08-012817630710.3390/molecules28176307Comprehensive Metabolite Identification of Genipin in Rats Using Ultra-High-Performance Liquid Chromatography Coupled with High Resolution Mass SpectrometryZhifeng Cui0Zhe Li1Weichao Dong2Lili Qiu3Jiayu Zhang4Shaoping Wang5School of Pharmacy, Binzhou Medical University, Yantai 264003, ChinaCollege of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250300, ChinaCollege of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250300, ChinaSchool of Medical Technology, Binzhou Vocational College, Binzhou 256600, ChinaSchool of Pharmacy, Binzhou Medical University, Yantai 264003, ChinaSchool of Pharmacy, Binzhou Medical University, Yantai 264003, ChinaGenipin, an aglycone of geniposide, is a rich iridoid component in the fruit of <i>Gardenia jasminoides</i> Ellis and has numerous biological activities. However, its metabolic profiles in vivo and vitro remain unclear. In this study, an effective analytical strategy based on ultra-high-performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS) in positive and negative ion modes was developed to analyze and identify genipin metabolites in rat urine, blood, feces, and fecal fermentation in combination with many methods including post-collection data mining methods, high-resolution extracted ion chromatography (HREIC), and multiple mass defect filtering (MMDF). Simultaneously, the metabolites of genipin in vivo were verified by fecal fermentation of SD rats at different times. Finally, based on information such as reference substances, chromatographic retention behavior, and accurate mass determination, a total of 50 metabolites (including prototypes) were identified in vivo. Among them, 7, 31 and 28 metabolites in vivo were identified in blood, urine, and feces, respectively. Our results showed that genipin could generate different metabolites that underwent multiple metabolic reactions in vivo including methylation, hydroxylation, dehydroxylation, hydrogenation, sulfonation, glucuronidation, demethylation, and their superimposed reactions. Forty-six metabolites were verified in vitro. Meanwhile, 2 and 19 metabolites identified in blood and urine were also verified in fecal fermentation at different times. These results demonstrated that metabolites were produced in feces and reabsorbed into the body. In conclusion, the newly discovered metabolites of genipin can provide a new perspective for understanding its pharmacological effects and build the foundation for thee toxicity and safety evaluations of genipin.https://www.mdpi.com/1420-3049/28/17/6307genipinUHPLC-HRMSmetabolitesdata-mining methodfecal fermentation |
| spellingShingle | Zhifeng Cui Zhe Li Weichao Dong Lili Qiu Jiayu Zhang Shaoping Wang Comprehensive Metabolite Identification of Genipin in Rats Using Ultra-High-Performance Liquid Chromatography Coupled with High Resolution Mass Spectrometry Molecules genipin UHPLC-HRMS metabolites data-mining method fecal fermentation |
| title | Comprehensive Metabolite Identification of Genipin in Rats Using Ultra-High-Performance Liquid Chromatography Coupled with High Resolution Mass Spectrometry |
| title_full | Comprehensive Metabolite Identification of Genipin in Rats Using Ultra-High-Performance Liquid Chromatography Coupled with High Resolution Mass Spectrometry |
| title_fullStr | Comprehensive Metabolite Identification of Genipin in Rats Using Ultra-High-Performance Liquid Chromatography Coupled with High Resolution Mass Spectrometry |
| title_full_unstemmed | Comprehensive Metabolite Identification of Genipin in Rats Using Ultra-High-Performance Liquid Chromatography Coupled with High Resolution Mass Spectrometry |
| title_short | Comprehensive Metabolite Identification of Genipin in Rats Using Ultra-High-Performance Liquid Chromatography Coupled with High Resolution Mass Spectrometry |
| title_sort | comprehensive metabolite identification of genipin in rats using ultra high performance liquid chromatography coupled with high resolution mass spectrometry |
| topic | genipin UHPLC-HRMS metabolites data-mining method fecal fermentation |
| url | https://www.mdpi.com/1420-3049/28/17/6307 |
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