An integrated strategy by chemical characterization, in vivo metabolism, chemical isolation, and activity evaluation to target discovery of potential active substances in traditional Chinese medicine: Mori Fructus as an example
Mori Fructus (MF) is a famous edible fruit of Morus alba L. as well as traditional Chinese medicine (TCM). Moreover, exposure behavior of complex components in vivo is a necessary way to elucidate active substances in TCMs. However, the effective discovery of active ingredients from MF in vivo is st...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-07-01
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| Series: | Arabian Journal of Chemistry |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1878535223003209 |
| _version_ | 1797837081648562176 |
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| author | Xi-yang Tang Peng-cheng Zhao Ming-hao Chen Xiao-xing Wang Cai-lian Fan Zhi-hong Yao Xin-sheng Yao Yi Dai |
| author_facet | Xi-yang Tang Peng-cheng Zhao Ming-hao Chen Xiao-xing Wang Cai-lian Fan Zhi-hong Yao Xin-sheng Yao Yi Dai |
| author_sort | Xi-yang Tang |
| collection | DOAJ |
| description | Mori Fructus (MF) is a famous edible fruit of Morus alba L. as well as traditional Chinese medicine (TCM). Moreover, exposure behavior of complex components in vivo is a necessary way to elucidate active substances in TCMs. However, the effective discovery of active ingredients from MF in vivo is still a challenge for researchers. In this study, an integrated strategy with chemical characterization, in vivo metabolism, chemical isolation, and activity evaluation was established and applied in targeted discovery of potential lipid-lowering substances in MF. First, an ultra-performance liquid chromatography with quadrupole time-of-flight mass spectrometry method was established to characterize various chemical components in MF extract. Second, with the automatic matching (in-house database), discriminant ions analysis and metabolite software prediction, the metabolic profiling of different types of MF was elucidated in vivo. And the compounds from MF with high MS response in vivo were discovered. Third, according to LC-MS information of fractions, these compounds were isolated and identified by NMR. Finally, the isolated compounds were evaluated for the lipid-lowering activity on determination of triglyceride levels in high fructose-induced HepG2 cells at different concentrations. And PCSK9 inhibitory and LDL-R promoting activity were measured by western blot experiment. As a result, a total of 72 constituents were characterized in MF. After oral administration of MF extract, 16 prototypes and 33 metabolites were rapidly screened out. And the metabolism features of alkaloids, flavonols and organic acids were further revealed. Six alkaloids (morusimic acid A-D, G, F), with high MS response in vivo and no reference standards on the market, were isolated guided by LC-MS and identified by NMR. Among them, morusimic acid A, B, G and F could reduce triglyceride levels in fructose-induced HepG2 cells. Moreover, with western blot experiment, morusimic acid A, B, G and F could inhibit the expression of PCSK9 protein. And morusimic acid A, B and F could increase the expression of LDL-R protein. This work provides meaningful information for the discovery of potential compounds in MF for the treatment of obesity and hyperlipidemia, along with a new approach for exploring effective compounds from complex systems. |
| first_indexed | 2024-04-09T15:20:11Z |
| format | Article |
| id | doaj.art-3a32e17c44ea4932903cc120a7eae737 |
| institution | Directory Open Access Journal |
| issn | 1878-5352 |
| language | English |
| last_indexed | 2024-04-09T15:20:11Z |
| publishDate | 2023-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Arabian Journal of Chemistry |
| spelling | doaj.art-3a32e17c44ea4932903cc120a7eae7372023-04-29T14:49:26ZengElsevierArabian Journal of Chemistry1878-53522023-07-01167104858An integrated strategy by chemical characterization, in vivo metabolism, chemical isolation, and activity evaluation to target discovery of potential active substances in traditional Chinese medicine: Mori Fructus as an exampleXi-yang Tang0Peng-cheng Zhao1Ming-hao Chen2Xiao-xing Wang3Cai-lian Fan4Zhi-hong Yao5Xin-sheng Yao6Yi Dai7Institute of Traditional Chinese Medicine & Natural Products, College of Pharmacy, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, and International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education (MOE) of China, Jinan University, Guangzhou 510632, PR ChinaInstitute of Traditional Chinese Medicine & Natural Products, College of Pharmacy, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, and International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education (MOE) of China, Jinan University, Guangzhou 510632, PR ChinaInstitute of Traditional Chinese Medicine & Natural Products, College of Pharmacy, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, and International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education (MOE) of China, Jinan University, Guangzhou 510632, PR ChinaInstitute of Traditional Chinese Medicine & Natural Products, College of Pharmacy, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, and International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education (MOE) of China, Jinan University, Guangzhou 510632, PR ChinaCollege of Medicine, Henan Engineering Research Center of Funiu Mountain's Medicinal Resources Utilization and Molecular Medicine, Pingdingshan University, Pingdingshan, Henan 467000, PR China; Corresponding authors at: College of Medicine, Henan Engineering Research Center of Funiu Mountain's Medicinal Resources Utilization and Molecular Medicine, Pingdingshan University, China.Institute of Traditional Chinese Medicine & Natural Products, College of Pharmacy, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, and International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education (MOE) of China, Jinan University, Guangzhou 510632, PR ChinaInstitute of Traditional Chinese Medicine & Natural Products, College of Pharmacy, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, and International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education (MOE) of China, Jinan University, Guangzhou 510632, PR ChinaInstitute of Traditional Chinese Medicine & Natural Products, College of Pharmacy, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, and International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education (MOE) of China, Jinan University, Guangzhou 510632, PR China; Corresponding authors at: Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, China.Mori Fructus (MF) is a famous edible fruit of Morus alba L. as well as traditional Chinese medicine (TCM). Moreover, exposure behavior of complex components in vivo is a necessary way to elucidate active substances in TCMs. However, the effective discovery of active ingredients from MF in vivo is still a challenge for researchers. In this study, an integrated strategy with chemical characterization, in vivo metabolism, chemical isolation, and activity evaluation was established and applied in targeted discovery of potential lipid-lowering substances in MF. First, an ultra-performance liquid chromatography with quadrupole time-of-flight mass spectrometry method was established to characterize various chemical components in MF extract. Second, with the automatic matching (in-house database), discriminant ions analysis and metabolite software prediction, the metabolic profiling of different types of MF was elucidated in vivo. And the compounds from MF with high MS response in vivo were discovered. Third, according to LC-MS information of fractions, these compounds were isolated and identified by NMR. Finally, the isolated compounds were evaluated for the lipid-lowering activity on determination of triglyceride levels in high fructose-induced HepG2 cells at different concentrations. And PCSK9 inhibitory and LDL-R promoting activity were measured by western blot experiment. As a result, a total of 72 constituents were characterized in MF. After oral administration of MF extract, 16 prototypes and 33 metabolites were rapidly screened out. And the metabolism features of alkaloids, flavonols and organic acids were further revealed. Six alkaloids (morusimic acid A-D, G, F), with high MS response in vivo and no reference standards on the market, were isolated guided by LC-MS and identified by NMR. Among them, morusimic acid A, B, G and F could reduce triglyceride levels in fructose-induced HepG2 cells. Moreover, with western blot experiment, morusimic acid A, B, G and F could inhibit the expression of PCSK9 protein. And morusimic acid A, B and F could increase the expression of LDL-R protein. This work provides meaningful information for the discovery of potential compounds in MF for the treatment of obesity and hyperlipidemia, along with a new approach for exploring effective compounds from complex systems.http://www.sciencedirect.com/science/article/pii/S1878535223003209Mori FructusIn vivo metabolismLC-MS guided isolationAlkaloidsLipid-lowering activityPCSK9 |
| spellingShingle | Xi-yang Tang Peng-cheng Zhao Ming-hao Chen Xiao-xing Wang Cai-lian Fan Zhi-hong Yao Xin-sheng Yao Yi Dai An integrated strategy by chemical characterization, in vivo metabolism, chemical isolation, and activity evaluation to target discovery of potential active substances in traditional Chinese medicine: Mori Fructus as an example Arabian Journal of Chemistry Mori Fructus In vivo metabolism LC-MS guided isolation Alkaloids Lipid-lowering activity PCSK9 |
| title | An integrated strategy by chemical characterization, in vivo metabolism, chemical isolation, and activity evaluation to target discovery of potential active substances in traditional Chinese medicine: Mori Fructus as an example |
| title_full | An integrated strategy by chemical characterization, in vivo metabolism, chemical isolation, and activity evaluation to target discovery of potential active substances in traditional Chinese medicine: Mori Fructus as an example |
| title_fullStr | An integrated strategy by chemical characterization, in vivo metabolism, chemical isolation, and activity evaluation to target discovery of potential active substances in traditional Chinese medicine: Mori Fructus as an example |
| title_full_unstemmed | An integrated strategy by chemical characterization, in vivo metabolism, chemical isolation, and activity evaluation to target discovery of potential active substances in traditional Chinese medicine: Mori Fructus as an example |
| title_short | An integrated strategy by chemical characterization, in vivo metabolism, chemical isolation, and activity evaluation to target discovery of potential active substances in traditional Chinese medicine: Mori Fructus as an example |
| title_sort | integrated strategy by chemical characterization in vivo metabolism chemical isolation and activity evaluation to target discovery of potential active substances in traditional chinese medicine mori fructus as an example |
| topic | Mori Fructus In vivo metabolism LC-MS guided isolation Alkaloids Lipid-lowering activity PCSK9 |
| url | http://www.sciencedirect.com/science/article/pii/S1878535223003209 |
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