Drug metabolite cluster centers-based strategy for comprehensive profiling of Neomangiferin metabolites in vivo and in vitro and network pharmacology study on anti-inflammatory mechanism
Neomangiferin (NMF) is an extremely special xanthone that could be simultaneously attributed to C-glycoside and O-glycoside with a variety of biological activities, such as anti-inflammatory, antitumor, antipyretic, and so on. So far as we know, the metabolism profiling has been insufficient until n...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-12-01
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| Series: | Arabian Journal of Chemistry |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1878535222005846 |
| _version_ | 1798015554178514944 |
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| author | Xianming Lan Yanan Li Haoran Li Shuyi Song Xiaoqing Yuan Hongyan Zhou Qimei Chen Jiayu Zhang |
| author_facet | Xianming Lan Yanan Li Haoran Li Shuyi Song Xiaoqing Yuan Hongyan Zhou Qimei Chen Jiayu Zhang |
| author_sort | Xianming Lan |
| collection | DOAJ |
| description | Neomangiferin (NMF) is an extremely special xanthone that could be simultaneously attributed to C-glycoside and O-glycoside with a variety of biological activities, such as anti-inflammatory, antitumor, antipyretic, and so on. So far as we know, the metabolism profiling has been insufficient until now. Herein, Drug Metabolite Cluster Centers (DMCCs)-based Strategy has been developed to profile the NMF metabolites in vivo and in vitro. Firstly, the DMCCs was proposed depending on literature-related and preliminary analysis results. Secondly, the specific metabolic rule was implemented to screen the metabolites of candidate DMCCs from the acquired Ultra High Performance Liquid Chromatography Quadrupole Exactive Orbitrap Mass Spectrometry (UHPLC-Q-Exactive Orbitrap MS) data by extracted ion chromatography (EIC) method. Thirdly, candidate metabolites were accurately and tentatively identified according to the pyrolysis law of mass spectrometry, literature reports, comparison of reference substances, and especially the diagnostic product ions (DPIs) deduced preliminarily. Finally, network pharmacology was adopted to elucidate the anti-inflammatory action mechanism of NMF on the basis of DMCCs. As a result, 3 critical metabolites including NMF, Mangiferin (MF) and Norathyriol (NA) were proposed as DMCCs, and a total of 61 NMF metabolites (NMF included) were finally screened and characterized coupled with 3 different biological sample preparation methods including solid phase extraction (SPE), acetonitrile precipitation and methanol precipitation. Among them, 32 metabolites were discovered in rat urine, 30 in rat plasma, 12 in rat liver, 9 metabolites in liver microsomes and 8 in rat faeces, respectively. Our results also illustrated that NMF primarily underwent deglucosylation, glucuronidation, methylation, sulfation, dihydroxylation and their composite reactions in vivo and in vitro. Additionally, network pharmacology analysis based on DMCCs revealed 85 common targets of disease-metabolites, and the key targets were TNF, EGFR, ESR1, PTGS2, HIF1A, IL-2, PRKCA and PRKCB. They exerted anti-inflammatory effects mainly through the pathways of inflammatory response, calcium-dependent protein kinase C activity, nitrogen metabolism, pathways in cancer and so on. In general, our study constructed a novel strategy to comprehensive elucidate the biotransformation pathways of NMF in vivo and in vitro, and provided vital reference for further understanding its anti-inflammatory action mechanism. Moreover, the established strategy could be generalized to the metabolism and action mechanism study of other natural products. |
| first_indexed | 2024-04-11T15:36:29Z |
| format | Article |
| id | doaj.art-077a86a3e68d4fb18988b515a36273bb |
| institution | Directory Open Access Journal |
| issn | 1878-5352 |
| language | English |
| last_indexed | 2024-04-11T15:36:29Z |
| publishDate | 2022-12-01 |
| publisher | Elsevier |
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| series | Arabian Journal of Chemistry |
| spelling | doaj.art-077a86a3e68d4fb18988b515a36273bb2022-12-22T04:15:56ZengElsevierArabian Journal of Chemistry1878-53522022-12-011512104268Drug metabolite cluster centers-based strategy for comprehensive profiling of Neomangiferin metabolites in vivo and in vitro and network pharmacology study on anti-inflammatory mechanismXianming Lan0Yanan Li1Haoran Li2Shuyi Song3Xiaoqing Yuan4Hongyan Zhou5Qimei Chen6Jiayu Zhang7School of Pharmacy, Binzhou Medical University, 264003 Yantai, Shandong, ChinaSchool of Pharmacy, Shandong University of Traditional Chinese Medicine, 250300 Jinan, Shandong, ChinaSchool of Pharmacy, Shandong University of Traditional Chinese Medicine, 250300 Jinan, Shandong, ChinaSchool of Pharmacy, Binzhou Medical University, 264003 Yantai, Shandong, ChinaSchool of Pharmacy, Binzhou Medical University, 264003 Yantai, Shandong, ChinaSchool of Pharmacy, Shandong University of Traditional Chinese Medicine, 250300 Jinan, Shandong, ChinaSchool of Pharmacy, Binzhou Medical University, 264003 Yantai, Shandong, ChinaSchool of Pharmacy, Binzhou Medical University, 264003 Yantai, Shandong, China; Corresponding author at: School of Pharmacy, Binzhou Medical University, 264003 Yantai, Shandong, China.Neomangiferin (NMF) is an extremely special xanthone that could be simultaneously attributed to C-glycoside and O-glycoside with a variety of biological activities, such as anti-inflammatory, antitumor, antipyretic, and so on. So far as we know, the metabolism profiling has been insufficient until now. Herein, Drug Metabolite Cluster Centers (DMCCs)-based Strategy has been developed to profile the NMF metabolites in vivo and in vitro. Firstly, the DMCCs was proposed depending on literature-related and preliminary analysis results. Secondly, the specific metabolic rule was implemented to screen the metabolites of candidate DMCCs from the acquired Ultra High Performance Liquid Chromatography Quadrupole Exactive Orbitrap Mass Spectrometry (UHPLC-Q-Exactive Orbitrap MS) data by extracted ion chromatography (EIC) method. Thirdly, candidate metabolites were accurately and tentatively identified according to the pyrolysis law of mass spectrometry, literature reports, comparison of reference substances, and especially the diagnostic product ions (DPIs) deduced preliminarily. Finally, network pharmacology was adopted to elucidate the anti-inflammatory action mechanism of NMF on the basis of DMCCs. As a result, 3 critical metabolites including NMF, Mangiferin (MF) and Norathyriol (NA) were proposed as DMCCs, and a total of 61 NMF metabolites (NMF included) were finally screened and characterized coupled with 3 different biological sample preparation methods including solid phase extraction (SPE), acetonitrile precipitation and methanol precipitation. Among them, 32 metabolites were discovered in rat urine, 30 in rat plasma, 12 in rat liver, 9 metabolites in liver microsomes and 8 in rat faeces, respectively. Our results also illustrated that NMF primarily underwent deglucosylation, glucuronidation, methylation, sulfation, dihydroxylation and their composite reactions in vivo and in vitro. Additionally, network pharmacology analysis based on DMCCs revealed 85 common targets of disease-metabolites, and the key targets were TNF, EGFR, ESR1, PTGS2, HIF1A, IL-2, PRKCA and PRKCB. They exerted anti-inflammatory effects mainly through the pathways of inflammatory response, calcium-dependent protein kinase C activity, nitrogen metabolism, pathways in cancer and so on. In general, our study constructed a novel strategy to comprehensive elucidate the biotransformation pathways of NMF in vivo and in vitro, and provided vital reference for further understanding its anti-inflammatory action mechanism. Moreover, the established strategy could be generalized to the metabolism and action mechanism study of other natural products.http://www.sciencedirect.com/science/article/pii/S1878535222005846Drug Metabolism Cluster Centers-based strategyNeomangiferinUHPLC-Q-Exactive Orbitrap MSAnti-inflammatoryNetwork pharmacology |
| spellingShingle | Xianming Lan Yanan Li Haoran Li Shuyi Song Xiaoqing Yuan Hongyan Zhou Qimei Chen Jiayu Zhang Drug metabolite cluster centers-based strategy for comprehensive profiling of Neomangiferin metabolites in vivo and in vitro and network pharmacology study on anti-inflammatory mechanism Arabian Journal of Chemistry Drug Metabolism Cluster Centers-based strategy Neomangiferin UHPLC-Q-Exactive Orbitrap MS Anti-inflammatory Network pharmacology |
| title | Drug metabolite cluster centers-based strategy for comprehensive profiling of Neomangiferin metabolites in vivo and in vitro and network pharmacology study on anti-inflammatory mechanism |
| title_full | Drug metabolite cluster centers-based strategy for comprehensive profiling of Neomangiferin metabolites in vivo and in vitro and network pharmacology study on anti-inflammatory mechanism |
| title_fullStr | Drug metabolite cluster centers-based strategy for comprehensive profiling of Neomangiferin metabolites in vivo and in vitro and network pharmacology study on anti-inflammatory mechanism |
| title_full_unstemmed | Drug metabolite cluster centers-based strategy for comprehensive profiling of Neomangiferin metabolites in vivo and in vitro and network pharmacology study on anti-inflammatory mechanism |
| title_short | Drug metabolite cluster centers-based strategy for comprehensive profiling of Neomangiferin metabolites in vivo and in vitro and network pharmacology study on anti-inflammatory mechanism |
| title_sort | drug metabolite cluster centers based strategy for comprehensive profiling of neomangiferin metabolites in vivo and in vitro and network pharmacology study on anti inflammatory mechanism |
| topic | Drug Metabolism Cluster Centers-based strategy Neomangiferin UHPLC-Q-Exactive Orbitrap MS Anti-inflammatory Network pharmacology |
| url | http://www.sciencedirect.com/science/article/pii/S1878535222005846 |
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