Characterization of metabolism feature and potential pharmacological changes of morusin-a promising anti-tumor drug-by ultra-high-performance liquid chromatography coupled time-of-flight mass spectrometry and network pharmacology
Morusin, a prenylated flavone isolated from Morus species, was treated as a potential anti-tumor drug since it inhibited effects on numerous types of human cancer cells. In some sense, drugs-related metabolites always contribute to pharmacological changes, inducing therapy improvement, reduced effic...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-02-01
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| Series: | Arabian Journal of Chemistry |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1878535220305256 |
| _version_ | 1818449907872169984 |
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| author | Feng-xiang Zhang Yu-lin-lan Yuan Jing-yun Wang Zi-ting Li Shuang-shuang Cui Feng-cheng Zhu Di Qiu Yun Wang Rui-man Li |
| author_facet | Feng-xiang Zhang Yu-lin-lan Yuan Jing-yun Wang Zi-ting Li Shuang-shuang Cui Feng-cheng Zhu Di Qiu Yun Wang Rui-man Li |
| author_sort | Feng-xiang Zhang |
| collection | DOAJ |
| description | Morusin, a prenylated flavone isolated from Morus species, was treated as a potential anti-tumor drug since it inhibited effects on numerous types of human cancer cells. In some sense, drugs-related metabolites always contribute to pharmacological changes, inducing therapy improvement, reduced efficacy, or side-effects. Thus, the characterization of metabolites and the potential functions exerted great importance in clinical applications. Till now, the metabolism feature of morusin was still unclear, and its pharmacological changes were still unconducted, too. In this work, an integrated strategy based on metabolites profiling and network pharmacological was applied to characterize the metabolism feature and reveal pharmacological changes of morusin in vivo. As a result, a total of 31 metabolites (19 in plasma, 8 in urine, 30 in feces, 6 in heart, 17 in liver, 4 in spleen, 6 in lung, 6 in kidney, and 3 in brain) were screened out in rats, and 11 of them were characterized for the first time. Among them, metabolites M6, M18, M19, M20, and M28, were the main metabolites. Phase I metabolic reactions of hydroxylation, dehydrogenation (cyclization), isomerization and phase II reactions of glucuronidation occurred, and glucuronidation and hydroxylation were the two main metabolic reactions. Moreover, the pharmacological difference between morusin and five main metabolites was predicted by an network pharmacological method, and these 6 candidates targeted 177 targets. Meanwhile, in addition to common pathways (PI3K-Akt signaling pathway, proteoglycans in cancer, hepatitis B, cAMP signaling pathway, and viral carcinogenesis) of morusin in cancer, six metabolites’ targets were involved in prostate cancer, chemokine signaling pathway, ras signaling pathway and neuroactive ligand-receptor interaction, indicating that these functional changes might result in novel pharmacological mechanism and new indications. Our work provided the metabolism feature and functional modifications of morusin in vivo for the first time, and meaningful information for further pharmacological validations or potential indications in clinic were supplied. |
| first_indexed | 2024-12-14T20:42:52Z |
| format | Article |
| id | doaj.art-9a848e87a9aa4dac965f8094b50461d7 |
| institution | Directory Open Access Journal |
| issn | 1878-5352 |
| language | English |
| last_indexed | 2024-12-14T20:42:52Z |
| publishDate | 2021-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Arabian Journal of Chemistry |
| spelling | doaj.art-9a848e87a9aa4dac965f8094b50461d72022-12-21T22:48:11ZengElsevierArabian Journal of Chemistry1878-53522021-02-01142102964Characterization of metabolism feature and potential pharmacological changes of morusin-a promising anti-tumor drug-by ultra-high-performance liquid chromatography coupled time-of-flight mass spectrometry and network pharmacologyFeng-xiang Zhang0Yu-lin-lan Yuan1Jing-yun Wang2Zi-ting Li3Shuang-shuang Cui4Feng-cheng Zhu5Di Qiu6Yun Wang7Rui-man Li8Department of Gynaecology and Obstetrics, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou 510632, ChinaDepartment of Gynaecology and Obstetrics, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou 510632, ChinaDepartment of Gynaecology and Obstetrics, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou 510632, ChinaInstitute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou 510632, ChinaDepartment of Gynaecology and Obstetrics, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou 510632, ChinaDepartment of Gynaecology and Obstetrics, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou 510632, ChinaDepartment of Gynaecology and Obstetrics, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou 510632, ChinaDepartment of Gynaecology and Obstetrics, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou 510632, ChinaDepartment of Gynaecology and Obstetrics, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou 510632, China; Corresponding author.Morusin, a prenylated flavone isolated from Morus species, was treated as a potential anti-tumor drug since it inhibited effects on numerous types of human cancer cells. In some sense, drugs-related metabolites always contribute to pharmacological changes, inducing therapy improvement, reduced efficacy, or side-effects. Thus, the characterization of metabolites and the potential functions exerted great importance in clinical applications. Till now, the metabolism feature of morusin was still unclear, and its pharmacological changes were still unconducted, too. In this work, an integrated strategy based on metabolites profiling and network pharmacological was applied to characterize the metabolism feature and reveal pharmacological changes of morusin in vivo. As a result, a total of 31 metabolites (19 in plasma, 8 in urine, 30 in feces, 6 in heart, 17 in liver, 4 in spleen, 6 in lung, 6 in kidney, and 3 in brain) were screened out in rats, and 11 of them were characterized for the first time. Among them, metabolites M6, M18, M19, M20, and M28, were the main metabolites. Phase I metabolic reactions of hydroxylation, dehydrogenation (cyclization), isomerization and phase II reactions of glucuronidation occurred, and glucuronidation and hydroxylation were the two main metabolic reactions. Moreover, the pharmacological difference between morusin and five main metabolites was predicted by an network pharmacological method, and these 6 candidates targeted 177 targets. Meanwhile, in addition to common pathways (PI3K-Akt signaling pathway, proteoglycans in cancer, hepatitis B, cAMP signaling pathway, and viral carcinogenesis) of morusin in cancer, six metabolites’ targets were involved in prostate cancer, chemokine signaling pathway, ras signaling pathway and neuroactive ligand-receptor interaction, indicating that these functional changes might result in novel pharmacological mechanism and new indications. Our work provided the metabolism feature and functional modifications of morusin in vivo for the first time, and meaningful information for further pharmacological validations or potential indications in clinic were supplied.http://www.sciencedirect.com/science/article/pii/S1878535220305256MorusinMetabolism featureNetwork pharmacologyUHPLC-Q/TOF MSPharmacological changes |
| spellingShingle | Feng-xiang Zhang Yu-lin-lan Yuan Jing-yun Wang Zi-ting Li Shuang-shuang Cui Feng-cheng Zhu Di Qiu Yun Wang Rui-man Li Characterization of metabolism feature and potential pharmacological changes of morusin-a promising anti-tumor drug-by ultra-high-performance liquid chromatography coupled time-of-flight mass spectrometry and network pharmacology Arabian Journal of Chemistry Morusin Metabolism feature Network pharmacology UHPLC-Q/TOF MS Pharmacological changes |
| title | Characterization of metabolism feature and potential pharmacological changes of morusin-a promising anti-tumor drug-by ultra-high-performance liquid chromatography coupled time-of-flight mass spectrometry and network pharmacology |
| title_full | Characterization of metabolism feature and potential pharmacological changes of morusin-a promising anti-tumor drug-by ultra-high-performance liquid chromatography coupled time-of-flight mass spectrometry and network pharmacology |
| title_fullStr | Characterization of metabolism feature and potential pharmacological changes of morusin-a promising anti-tumor drug-by ultra-high-performance liquid chromatography coupled time-of-flight mass spectrometry and network pharmacology |
| title_full_unstemmed | Characterization of metabolism feature and potential pharmacological changes of morusin-a promising anti-tumor drug-by ultra-high-performance liquid chromatography coupled time-of-flight mass spectrometry and network pharmacology |
| title_short | Characterization of metabolism feature and potential pharmacological changes of morusin-a promising anti-tumor drug-by ultra-high-performance liquid chromatography coupled time-of-flight mass spectrometry and network pharmacology |
| title_sort | characterization of metabolism feature and potential pharmacological changes of morusin a promising anti tumor drug by ultra high performance liquid chromatography coupled time of flight mass spectrometry and network pharmacology |
| topic | Morusin Metabolism feature Network pharmacology UHPLC-Q/TOF MS Pharmacological changes |
| url | http://www.sciencedirect.com/science/article/pii/S1878535220305256 |
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