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Identification of metabolites from the Himalayan herbal medicine Meconopsis integrifolia total flavonoids fraction in
Enhui Ji1, Yuan Liu1, Yifan Tian1
1Qinghai-Tibetan Plateau Ethnic Medicinal Resources Protection and Utilization Key Laboratory of National Ethnic Affairs Commission of the People's Republic of China, Sichuan Provincial Qiang-Yi Medicinal Resources Protection and Utilization Technology Engineering Laboratory, Southwest Minzu University, Chengdu 610225, China.
Abstract:
Meconopsis integrifolia total flavonoids (MITF) have been identified as the hepatoprotective fraction of M. integrifolia, with its main components being flavonoid glycosides, along with lower levels of phenolic acids and alkaloids. Since flavonoid glycosides are poorly absorbed in vivo, metabolism serves as a crucial pathway for their biotransformation. However, the metabolism and material basis of pharmacological effects of MITF in vivo remain unknown. In this study, ultra-performance liquid chromatography coupled with triple quadrupole mass spectrometry was used to investigate the metabolic profiles of MITF. A total of 61 absorbed prototype compounds were identified, including 54 in feces (43 flavonoids, 8 phenolic acids, and 3 alkaloids), 8 in urine (2 flavonoids, 3 phenolic acids, 3 alkaloids), and 6 in plasma (2 flavonoids, 4 phenolic acids). Furthermore, 113 metabolites were characterized, including 64 in feces (38 flavonoids, 11 phenolic acids, 15 alkaloids), 46 in urine (17 flavonoids, 16 phenolic acids, 13 alkaloids), and 14 in plasma (5 flavonoids, 9 phenolic acids). The major metabolic pathways were dehydroxylation, hydroxylation, reduction, dehydrogenation, hydration, dehydration, methylation, sulfation, and glucuronidation. The results indicated that the biotransformation and absorption of flavonoids in vivo were limited. In contrast, phenolic acids and alkaloids were extensively absorbed. This research provides crucial insights into the metabolic fate of MITF in rats, thereby clarifying the pharmacologically active substances derived from M. integrifolia. DATA AVAILABILITY: The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.
Insights
Meconopsis integrifolia total flavonoids (MITF) are poorly absorbed, with limited biotransformation. Phenolic acids and alkaloids from MITF show extensive absorption, clarifying active compounds in this hepatoprotective fraction.
Area of Science:
- Pharmacology
- Natural Products Chemistry
- Metabolomics
Background:
- Meconopsis integrifolia total flavonoids (MITF) are identified as the hepatoprotective fraction of M. integrifolia.
- MITF primarily consists of flavonoid glycosides, with smaller amounts of phenolic acids and alkaloids.
- The in vivo metabolism and material basis of MITF's pharmacological effects are largely unknown, particularly due to poor absorption of flavonoid glycosides.
Purpose of the Study:
- To investigate the metabolic profiles and identify the absorbed prototype compounds and metabolites of MITF in rats.
- To elucidate the metabolic fate and absorption characteristics of different chemical classes within MITF.
- To clarify the pharmacologically active substances derived from M. integrifolia.
Main Methods:
- Ultra-performance liquid chromatography coupled with triple quadrupole mass spectrometry (UPLC-MS/MS) was employed for comprehensive metabolic profiling.
- Analysis of prototype compounds and metabolites in rat feces, urine, and plasma.
- Identification and characterization of metabolic pathways including dehydroxylation, hydroxylation, methylation, sulfation, and glucuronidation.
Main Results:
- A total of 61 absorbed prototype compounds were identified across excreta and plasma, with flavonoids being the most abundant.
- 113 metabolites were characterized, with significant biotransformation observed for phenolic acids and alkaloids.
- Limited in vivo biotransformation and absorption of flavonoids were observed, while phenolic acids and alkaloids demonstrated extensive absorption.
Conclusions:
- The study reveals limited absorption and biotransformation of flavonoids within MITF in vivo.
- Phenolic acids and alkaloids present in MITF are extensively absorbed, suggesting their significant contribution to pharmacological effects.
- This research provides critical insights into the metabolic fate of MITF, identifying key absorbed compounds and their metabolic pathways.
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