Characterization of osthenol metabolism <i>in vivo</i> and its pharmacokinetics

Cho, Piljoung; Choi, Sumin; Kim, Younah; Lee, Doo Hyun; Noh, Yeeun; Kim, Sujeong; Kim, Ju-Hyun; Lee, Tae‐Ho; Lee, Sangkyu

doi:10.1080/00498254.2019.1705427

Cited by 4 publications

(3 citation statements)

References 15 publications

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“…In addition to the current research, the CYPs are described as involved in the metabolites of compounds possessing a C5 isoprene (dimethylallyl) moiety in their structure and are bioactive molecules from plants that have been consumed as foods or supplements. [32][33][34] Hydroxylation of the pentane moiety has been identified as the primary phase I metabolic pathway of prenylflavonoids in HLMs, with cudratricusxanthone A (CTXA), glycyrol, and osthenol, including suberosin. Despite the hydroxylation of the same pentane moiety, the related CYPs differed for each compound.…”

Section: Discussionmentioning

confidence: 99%

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Identification of suberosin metabolites in human liver microsomes by high‐performance liquid chromatography combined with high‐resolution quadrupole–orbitrap mass spectrometer

et al. 2020

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Suberosin is a natural prenylated coumarin derivative isolated from Citropsis articulata. It has various pharmacological properties, especially as an anticoagulant, for which it has been used since antiquity. However, its metabolic pathway and metabolites have not yet been studied. Therefore, this study characterizes its metabolic pathway and metabolites in human liver microsomes (HLMs) using high-resolution quadrupole-orbitrap mass spectrometry (HRMS/MS). Eight metabolites (M1-M8) were found, including three monohydroxylated (M1-M3), one hydrated (M4), three dihydroxylated (M5-M7), and one glucuronide conjugate (M8). Furthermore, forms of cytochrome P450 (CYPs) responsible for suberosin metabolism in HLMs were characterized. CYP1A2 was identified as a major enzyme for the production of M1 and M5 metabolites. The M2, M3, and M7 metabolites were predominantly generated by CYP2B6. M8 was the only phase II metabolite, identified as a glucuronide conjugate from either M1 or M2. This glucuronide conjugate may be the only promising metabolite from phase II metabolism. Phase I metabolism, especially hydroxylation, was found to provide a predominant metabolic pathway of suberosin in HLMs. Further studies should be conducted to explore the metabolites, examining their efficacy and their toxicity in an in vivo system.

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Section: Discussionmentioning

confidence: 99%

“…32 Moreover, glycyrol, also predominantly metabolized by CYP1A2, and osthenol was hydroxylated at the pentane moiety by CYP 1A1 and CYP2D6. 33,34 Thus, it can be concluded that the enzymes involved in the metabolism of the pentane moiety of prenylflavonoids are determined by the overall flavonoid structure rather than by the pentane moiety.…”

Section: Discussionmentioning

confidence: 99%

Identification of suberosin metabolites in human liver microsomes by high‐performance liquid chromatography combined with high‐resolution quadrupole–orbitrap mass spectrometer

et al. 2020

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“…Pharmacokinetics parameters calculated for K-142 are in agreement with those determined for different coumarin derivatives bearing isoprene moieties. Thus, oral administration of osthenol to ICR mice at a dose of 5 mg/kg and 20 mg/kg resulted in the following PK parameters: C max of 66.1 ± 3.2 and 56.0 ± 29.1 ng/mL, respectively, and T max of 36.3 ± 13.8 and 6.3 ± 1.3 min, respectively, indicating the very low bioavailability of the compound as well as its non-linear pharmacokinetics [22]. Oral administration of auraptene to rats at a dose of 100 mg/kg provided the maximum concentration of the compound in blood plasma of 1719 ± 384.3 ng/mL and T max of 108.0 ± 25.3 min, and the bioavailability of auraptene was determined to be 8.5% [23].…”

Section: Pharmacokinetics Study Of K-142 After Oral Administration To...mentioning

confidence: 99%

Stability Study, Quantification Method and Pharmacokinetics Investigation of a Coumarin–Monoterpene Conjugate Possessing Antiviral Properties against Respiratory Syncytial Virus

et al. 2022

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The stability of a new coumarin derivative, agent K-142, bearing α-pinene residue and possessing antiviral activity against respiratory syncytial virus (RSV) was studied in whole mice blood in vitro, and a method for its quantification in this matrix was developed and validated. The sample preparation method was precipitation of whole blood with a mixture of 0.2 M ZnSO4 with MeOH (2:8 v/v) containing 2-adamantylamine hydrochloride as an internal standard (IS). Analysis was carried out by HPLC-MS/MS using reversed phase chromatography and a triple quadrupole mass spectrometer 6500 QTRAP (SCIEX) in multiple reaction monitoring (MRM) mode. The transitions 351.2 → 217.1 Da and 152.2 → 93.1/107.2 Da were monitored for K-142 and the IS, respectively. The method was validated in terms of selectivity, calibration curve, LLOQ, accuracy and precision, stability, recovery and carry over. The developed method was used for a pharmacokinetics study of the compound after its oral administration to mice at a dose of 20 mg/kg.

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Study of Active Phytochemicals and Mechanisms of Cnidii Fructus in Treating Osteoporosis Based on HPLC-Q-TOF-MS/MS and Network Pharmacology

Zhang

Yuan

et al. 2024

CCHTS

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Introduction: This study aimed to clarify the anti-osteoporosis mechanism of Cnidii Fructus (CF) via network pharmacology and experimental verification. Methods: HPLC fingerprints combined with HPLC-Q-TOF-MS/MS analysis confirmed common components (CCS) of CF. Then, network pharmacology was used to investigate the anti-OP mechanism of CF, including potential anti-OP phytochemicals, potential targets, and related signalling pathway. Molecular docking analysis was carried on investigating the protein-ligand interactions. Finally, in vitro experiments were performed to verify anti-OP mechanism of CF. Results: In this study, 17 compounds from CF were identified by HPLC-Q-TOF-MS/MS and HPLC fingerprints and then were further screened key compounds and potential targets by PPI analysis, ingredient-target network and hub network. The key compounds were SCZ10 (Diosmin), SCZ16 (Pabulenol), SCZ6 (Osthenol), SCZ8 (Bergaptol) and SCZ4 (Xanthotoxol). The potential targets were SRC, MAPK1, PIK3CA, AKT1 and HSP90AA1. Molecular docking further analysis indicated that the five key compounds have a good binding affinity with related proteins. CCK8 assays, TRAP staining experiments, and ALP activity assays concluded that osthenol and bergaptol inhibited osteoclast formation and promoted osteoblast bone formation to improve osteoporosis. Conclusion: Based on network pharmacology and in vitro experiments analysis, this study revealed that CF possessed an anti-OP effect, and its potential therapeutic effect may be involved with osthenol and bergaptol from CF.

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Characterization of osthenol metabolism in vivo and its pharmacokinetics

Cited by 4 publications

References 15 publications

Identification of suberosin metabolites in human liver microsomes by high‐performance liquid chromatography combined with high‐resolution quadrupole–orbitrap mass spectrometer

Identification of suberosin metabolites in human liver microsomes by high‐performance liquid chromatography combined with high‐resolution quadrupole–orbitrap mass spectrometer

Stability Study, Quantification Method and Pharmacokinetics Investigation of a Coumarin–Monoterpene Conjugate Possessing Antiviral Properties against Respiratory Syncytial Virus

Study of Active Phytochemicals and Mechanisms of Cnidii Fructus in Treating Osteoporosis Based on HPLC-Q-TOF-MS/MS and Network Pharmacology

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