지원사업
학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
커뮤니티
연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2019.10
- 수록면
- 539 - 549 (11page)
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초록· 키워드
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Background: 20(S)-Protopanaxadiol (PPD), the aglycone part of 20(S)-protopanaxadiol ginsenosides, possesses antidepressant activity among many other pharmacological activities. It is currently undergoing clinical trial in China as an antidepressant.
Methods: In this study, an ultra-performance liquid chromatography coupled with triple quadrupole time-of-flight mass tandem mass spectrometry method was established to identify the metabolites of PPD in human plasma and urine following oral administration in phase IIa clinical trial.
Results: A total of 40 metabolites in human plasma and urine were identified using this method. Four metabolites identified were isolated from rat feces, and two of them were analyzed by NMR to elucidate the exact structures. The structures of isolated compounds were confirmed as (20S,24S)-epoxydammarane- 12,23,25-triol-3-one and (20S,24S)-epoxydammarane-3,12,23,25-tetrol. Both compounds were found as metabolites in human for the first time. Upon comparing our findings with the findings of the in vitro study of PPD metabolism in human liver microsomes and human hepatocytes, metabolites with m/z 475.3783 and phase II metabolites were not found in our study whereas metabolites with m/z 505.3530, 523.3641, and 525.3788 were exclusively detected in our experiments.
Conclusion: The metabolites identified using ultra-performance liquid chromatography coupled with triple quadrupole time-of-flight mass spectrometry in our study were mostly hydroxylated metabolites. This indicated that PPD was metabolized in human body mainly through phase I hepatic metabolism. The main metabolites are in 20,24-oxide form with multiple hydroxylation sites. Finally, the metabolic pathways of PPD in vivo (human) were proposed based on structural analysis.
Methods: In this study, an ultra-performance liquid chromatography coupled with triple quadrupole time-of-flight mass tandem mass spectrometry method was established to identify the metabolites of PPD in human plasma and urine following oral administration in phase IIa clinical trial.
Results: A total of 40 metabolites in human plasma and urine were identified using this method. Four metabolites identified were isolated from rat feces, and two of them were analyzed by NMR to elucidate the exact structures. The structures of isolated compounds were confirmed as (20S,24S)-epoxydammarane- 12,23,25-triol-3-one and (20S,24S)-epoxydammarane-3,12,23,25-tetrol. Both compounds were found as metabolites in human for the first time. Upon comparing our findings with the findings of the in vitro study of PPD metabolism in human liver microsomes and human hepatocytes, metabolites with m/z 475.3783 and phase II metabolites were not found in our study whereas metabolites with m/z 505.3530, 523.3641, and 525.3788 were exclusively detected in our experiments.
Conclusion: The metabolites identified using ultra-performance liquid chromatography coupled with triple quadrupole time-of-flight mass spectrometry in our study were mostly hydroxylated metabolites. This indicated that PPD was metabolized in human body mainly through phase I hepatic metabolism. The main metabolites are in 20,24-oxide form with multiple hydroxylation sites. Finally, the metabolic pathways of PPD in vivo (human) were proposed based on structural analysis.
목차
ABSTRACT
1. Introduction
2. Materials and methods
3. Results and discussion
References
참고문헌 (17)
참고문헌 신청
Lee PS / 2006 / Physicochemical characteristics and bioavailability of a novel intestinal metabolite of ginseng saponin(IH901)complexed with beta-cyclodextrin / Int J Pharm 316:29~36
Yu Y / 2007 / Antiestrogenic effect of 20S-protopanaxadiol and its synergy with tamoxifen on breast cancer cells / Cancer 109:2374~2382
Xu C / 2010 / 20(S)-protopanaxadiol, an active ginseng metabolite, exhibits strong antidepressant-like effects in animal tests / Prog Neuropsychopharmacol Biol Psychiatry 34:1402~1411
Liu JH / 2013 / 20(S)-Protopanaxadiol(PPD)analogues chemosensitize multidrug-resistant cancer cells to clinical anticancer drugs / Bioorgan Med Chem 21:4279~4287
Xie C / 2013 / Metabolism and bioactivation of famitinib, a novel inhibitor of receptor tyrosine kinase, in cancer patients / Br J Pharmacol 168:1687~1706
Yu Y / 2007 / Antiestrogenic effect of 20S-protopanaxadiol and its synergy with tamoxifen on breast cancer cells / Cancer 109:2374~2382
Xu C / 2010 / 20(S)-protopanaxadiol, an active ginseng metabolite, exhibits strong antidepressant-like effects in animal tests / Prog Neuropsychopharmacol Biol Psychiatry 34:1402~1411
Liu JH / 2013 / 20(S)-Protopanaxadiol(PPD)analogues chemosensitize multidrug-resistant cancer cells to clinical anticancer drugs / Bioorgan Med Chem 21:4279~4287
Xie C / 2013 / Metabolism and bioactivation of famitinib, a novel inhibitor of receptor tyrosine kinase, in cancer patients / Br J Pharmacol 168:1687~1706
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UCI(KEPA) : I410-ECN-0101-2020-524-000504899