Identification of 20(S)-protopanaxadiol metabolites in human liver microsomes and human hepatocytes

Drug Metabolism and Disposition

Volumn 39, Issue 3, 2011, Pages 472-483

  Li, Liang ^a   Chen, Xiaoyan ^a   Li, Dan ^a   Zhong, Dafang ^a  

^a SHANGHAI INSTITUTE OF MATERIA MEDICA   (China)

Author keywords

[No Author keywords available]

Indexed keywords

3 CHLOROPERBENZOIC ACID; DRUG METABOLITE; EPOXYDAMMARANE 12,25 DIOL 3 ONE; EPOXYDAMMARANE 2,12,25 TRIOL; GLUCURONIDE; HYDROXYL GROUP; PROTOPANAXADIOL; UNCLASSIFIED DRUG;

ARTICLE; CHEMICAL BOND; CONJUGATE; DEHYDROGENATION; DRUG CONJUGATION; DRUG ELIMINATION; DRUG HYDROLYSIS; DRUG HYDROXYLATION; DRUG OXIDATION; DRUG STRUCTURE; DRUG TRANSFORMATION; ELECTROSPRAY MASS SPECTROMETRY; HUMAN; HUMAN CELL; ION TRAP MASS SPECTROMETRY; LIQUID CHROMATOGRAPHY; LIVER CELL; LIVER MICROSOME; PRIORITY JOURNAL;

ANIMALS; ANTIDEPRESSIVE AGENTS; BIOTRANSFORMATION; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; EPOXY COMPOUNDS; FECES; GINSENOSIDES; GLUCURONIDES; HEPATOCYTES; HUMANS; MALE; MICROSOMES, LIVER; MOLECULAR STRUCTURE; RATS; RATS, SPRAGUE-DAWLEY; SAPOGENINS; SPECTROMETRY, MASS, ELECTROSPRAY IONIZATION; TANDEM MASS SPECTROMETRY;

EID: 79951933277     PISSN: 00909556     EISSN: 1521009X     Source Type: Journal    
DOI: 10.1124/dmd.110.036723     Document Type: Article

References (25)

1. Appendino G, Garibold P, Wollenweber E, Sironi A, and Molineri H (1992) Triterpenes from the frond exudate of the fern Notholaena greggii. Phytochemistry 31:923-927.
2. Chang SJ, Suh JS, Jeon BH, Nam KY, and Park HK (1994) Vasorelaxing effect by protopanaxatriol and protopanaxadiol of Panax ginseng in the pig coronary artery. Koryo Insam Hakhoechi 18:95-101.
3. Hasegawa H (2004) Proof of the mysterious efficacy of ginseng: basic and clinical trials: metabolic activation of ginsenoside: deglycosylation by intestinal bacteria and esterification with fatty acid. J Pharmacol Sci 95:153-157.
4. Hui YZ, Yang ZR, Yang ZQ, and Ge Q (2007) inventors; CN-KnowHow Intellectual Property Agent Limited, assignee. Antidepressant compositions containing 20(S)-protopanaxadiol extracted from ginsenoside. China Patent CN 200610027507.1. 2007 Jan 17.
5. Kasai R, Hara K, Dokan R, Suzuki N, Mizutare T, Yoshihara S, and Yamasaki K (2000) Major metabolites of ginseng sapogenins formed by rat liver microsomes. Chem Pharm Bull 48:1226-1227. (Pubitemid 30660288)
6. Kim DH, Jung JS, Moon YS, Sung JH, Suh HW, Kim YH, and Song DK (2003) Inhibition of intracerebroventricular injection stress-inducted plasma corticosterone levels by intracerebroventricularly administered compound K, a ginseng saponin metabolite, in mice. Biol Pharm Bull 26:1035-1038.
7. Lee JY, Shin JW, Chun KS, Park KK, Chung WY, Bang YJ, Sung JH, and Surh YJ (2005a) Antitumor promotional effects of a novel intestinal bacterial metabolite (IH-901) derived from the protopanaxadiol-type ginsenosides in mouse skin. Carcinogenesis 26:359-367.
8. Lee SH, Seo GS, Ko G, Kim JB, and Sohn DH (2005b) Anti-inflammatory activity of 20(S)-protopanaxadiol: enhanced heme oxygenase 1 expression in RAW 264.7 cells. Planta Med 71:1167-1170. (Pubitemid 43107066)
9. Lee WM, Kim SD, Kim KS, Song YB, Kwak YS, Cho JY, Park HJ, Oh JW, and Rhee MH (2006) Protopanaxadiol modulates LPS-induced inflammatory activity in murine macrophage RAW264.7 cells. J Ginseng Res 30:181-187.
10. Leung KW, Leung FP, Mak NK, Tombran-Tink J, Huang Y, and Wong RN (2009) Protopanaxadiol and protopanaxatriol bind to glucocorticoid and oestrogen receptors in endothelial cells. Br J Pharmacol 156:626-637.
11. Li G, Wang Z, Sun Y, Liu K, and Wang Z (2006) Ginsenoside 20(S)-protopanaxadiol inhibits the proliferation and invasion of human fibrosarcoma HT1080 cells. Basic Clin Pharmacol Toxicol 98:588-592.
12. Liu GY, Bu X, Yan H, and Jia WW (2007) 20S-Protopanaxadiol-induced programmed cell death in glioma cells through caspase-dependent and -independent pathways. J Nat Prod 70:259-264. (Pubitemid 46447640)
13. Liu Y, Li W, Li P, Deng MC, Yang SL, and Yang L (2004) The inhibitory effect of intestinal bacterial metabolite of ginsenosides on CYP3A activity. Biol Pharm Bull 27:1555-1560. (Pubitemid 41701638)
14. Liu Y, Zhang JW, Li W, Ma H, Sun J, Deng MC, and Yang L (2006) Ginsenoside metabolites, rather than naturally occurring ginsenosides, lead to inhibition of human cytochrome P450 enzymes. Toxicol Sci 91:356-364. (Pubitemid 43827288)
15. Park EK, Choo MK, Oh JK, Ryu JH, and Kim DH (2004) Ginsenoside Rh2 reduces ischemic brain injury in rats. Biol Pharm Bull 27:433-436. (Pubitemid 41685495)
16. 1 cells in two cultured intestinal cell lines, Int-407 and Caco-2. Can J Physiol Pharmacol 82:183-190.
17. Shibata S, Tanaka O, Ando T, Sado M, Tsushima S, and Ohsawa T (1966) Chemical studies on oriental plant drugs. XIV. Protopanaxadiol, a genuine sapogenin of ginseng saponins. Chem Pharm Bull 14:595-600.
18. Shin YH, Kim SC, Han JW, Kim DH, Han SS, Shin DH, and Nah SY (1997) Study on ginseng protopanaxadiol and protopanaxatriol saponins-induced antinociception. Korean J Physiol Pharmacol 1:143-149.
19. Tanaka O, Nagai M, and Shibata S (1966) Chemical studies on the oriental plant drugs. XVI. The stereochemistry of protopanaxadiol, a genuine sapogenin of ginseng. Chem Pharm Bull 14:1150-1156.
20. Usami Y, Liu YN, Lin AS, Shibano M, Akiyama T, Itokawa H, Morris-Natschke SL, Bastow K, Kasai R, and Lee KH (2008) Antitumor agents. 261. 20(S)-Protopanaxadiol and 20(S)-protopanaxatriol as antiangiogenic agents and total assignment of 1H NMR spectra. J Nat Prod 71:478-481. (Pubitemid 351549379)
21. Valverde S, Escudero J, Lopez JC, and Rabanal RM (1985) Two terpenoids from Salvia bicolor. Phytochemistry 24:111-113.
22. Yosioka I, Yamauchi H, and Kitagawa I (1972) Lichen triterpenoids. V. On the neutral triterpenoids of Pyxine endochrysina nyl. Chem Pharm Bull 20:502-513.
23. Yu Y, Zhou Q, Hang Y, Bu X, and Jia W (2007) Antiestrogenic effect of 20S-protopanaxadiol and its synergy with tamoxifen on breast cancer cells. Cancer 109:2374-2382. (Pubitemid 46801570)
24. Zhang R, Xu HL, Yu XF, Qu SC, Chen MX, and Sui DY (2008) Effect of 20(S)-protopanaxadiol on SMMC-7721 human liver cancer in vivo and in vitro. Chin Pharmacol Bull 24:1504-1508.
25. Zhou S, Chan E, Duan W, Huang M, and Chen YZ (2005) Drug bioactivation, covalent binding to target proteins and toxicity relevance. Drug Metab Rev 37:41-213. (Pubitemid 40259715)