Identification and quantitative determination of a major circulating metabolite of gambogic acid in human

Yang, Jing; Ding, Li; Shao-hong, Jin; Liu, Xiaoxue; Liu, Wenyuan; Wang, Zhenzhong

doi:10.1016/j.jchromb.2010.01.032

Cited by 15 publications

(16 citation statements)

References 24 publications

(26 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…All these results suggested that this metabolite might be 10-hydroxy-GA, an observation that was further confirmed by comparison of its retention time on LC-MS with that of the standard reference substance. This finding suggested that M11 was also the major circulating metabolite of GA in rats, which was similar to the observation in humans (Yang et al, 2010b), indicating that the safety evaluation using this species in a preclinical setting was reasonable. M4 was found in the bile.…”

Section: M13 Was Found In Rat Bile and Feces Ms Analysis Showed Its supporting

confidence: 79%

“…GA reference standard (99.3% purity) and the GA injection containing 20 mg of GA per vial were provided by Jiangsu Kanion Pharmaceutical Co., Ltd. (Lianyungang, China). 10-Hydroxygambogic acid (M11) was prepared according to our previously reported method (Yang et al, 2010b). NADPH, UDPGA, reduced glutathione, alamethicin, saccharic acid-1,4-lactone, Tris base, ␤-glucuronidase (EC 3.2.1.31, from Escherichia coli), and ␤-glucosidase (EC 3.2.1.21, from almonds) were purchased from SigmaAldrich (St. Louis, MO).…”

Section: Methodsmentioning

confidence: 99%

“…All these results suggested that M1 might contain a GSH moiety. The UV spectrum of M1 showed maximum absorptions at 275 and 320 nm, preliminarily indicating that the 9,10 double bond might be absent and that GSH was conjugated at the C-10 of GA (Feng et al, 2007;Yang et al, 2010b). Next, the GSH adduct of GA reference was synthesized using FIG.…”

Section: Identification Of the Rare Intestinal Metabolites Of Ga In Rmentioning

confidence: 99%

“…Thus, increasing demands for discovery and development of promising natural products for clinical therapy have challenged scientists to expedite the metabolic study of GA and to provide information on the metabolic soft spots of this molecule, which can be used in further medicinal chemistry efforts to optimize GA analogs. Although the pharmacokinetics of GA in rats (Hao et al, 2007a), dogs (Hao et al, 2007b;Yang et al, 2010a), and humans Yang et al, 2010b) has been reported, the ultimate fate of this natural product in all of these species was unclear. Only a few incomplete metabolic studies of GA have been reported, and no reports about the metabolism of other caged xanthones have appeared so far.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Metabolism of Gambogic Acid in Rats: A Rare Intestinal Metabolic Pathway Responsible for Its Final Disposition

Yang¹,

Ding²,

Hu³

et al. 2010

Drug Metab Dispos

Self Cite

View full text Add to dashboard Cite

ABSTRACT:Gambogic acid (GA) is a promising natural anticancer candidate. Although the anticancer activity of GA has been well demonstrated, information regarding the metabolic fate of GA is limited. Previous studies suggested that GA is mainly excreted into intestinal tract in rats through bile after intravenous administration, whereas only traces appeared in the feces, suggesting that GA is metabolized extensively in the intestine. However, there has been no report about the intestinal metabolism of GA either in animals or humans. In this study, large amounts of two sulfonic acid metabolites of GA were found in the feces samples of rats after intravenous administration, and their structures were identified as 10-␣ sulfonic acid GA and 10-␤ sulfonic acid GA by comparison of the retention times and spectral data with those of synthesized reference substances using liquid chromatography-diode array detector-tandem mass spectrometry. This rare intestinal metabolic pathway mainly involves Michael addition of the sulfite ion to the 9,10 carbon-carbon double bond of ␣,␤-unsaturated ketone. In addition, a more detailed metabolic profile in rats is proposed, according to the results of in vitro and in vivo studies. It was found that GA can be metabolized by a variety of routes, including monooxidation, hydration, glutathionylation, glucuronidation, and glucosidation in the liver of rats. These findings provide information on the major metabolic soft spot of GA in the intestine and liver of rats, which is not only useful in the future human metabolic study of this compound but also of value in the metabolic studies of GA analogs.

show abstract

Section: M13 Was Found In Rat Bile and Feces Ms Analysis Showed Its supporting

confidence: 79%

Section: Methodsmentioning

confidence: 99%

Section: Identification Of the Rare Intestinal Metabolites Of Ga In Rmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Metabolism of Gambogic Acid in Rats: A Rare Intestinal Metabolic Pathway Responsible for Its Final Disposition

Yang¹,

Ding²,

Hu³

et al. 2010

Drug Metab Dispos

Self Cite

View full text Add to dashboard Cite

show abstract

“…In metabolism studies using rat liver microsomes, compound 1 was rapidly converted to 10-hydroxygambogic acid, 9,10-epoxygambogic acid, and their glucuronyl derivatives. [85] The formation of 10-hydroxygambogic acid via cytochrome P-450 1A2 was found to be crucial for the elimination of 1 in rats. Hence, inhibitors of cytochrome P-450 1A2 can affect the metabolism of 1 and its bioactivity.…”

Section: Biological Activities Of the Caged Garcinia Xanthonesmentioning

confidence: 99%

Chemistry and Biology of the Caged Garcinia Xanthones

Chantarasriwong

Batova

Chavasiri

et al. 2010

Chemistry A European J

124

View full text Add to dashboard Cite

Natural products have been a great source of many small molecule drugs for various diseases. In spite of recent advances in biochemical engineering and fermentation technologies that allow us to explore microorganisms and the marine environment as alternative sources of drugs, more than 70% of the current small molecule therapeutics derive their structures from plants used in traditional medicine. Natural-product-based drug discovery relies heavily on advances made in the sciences of biology and chemistry. Whereas biology aims to investigate the mode of action of a natural product, chemistry aims to overcome challenges related to its supply, bioactivity, and target selectivity. This review summarizes the explorations of the caged Garcinia xanthones, a family of plant metabolites that possess a unique chemical structure, potent bioactivities, and a promising pharmacology for drug design and development.

show abstract

Gambogic Acid

Liu

2013

Handbook of Metabolic Pathways of Xenobiotics

View full text Add to dashboard Cite

Identification and quantitative determination of a major circulating metabolite of gambogic acid in human

Cited by 15 publications

References 24 publications

Metabolism of Gambogic Acid in Rats: A Rare Intestinal Metabolic Pathway Responsible for Its Final Disposition

Metabolism of Gambogic Acid in Rats: A Rare Intestinal Metabolic Pathway Responsible for Its Final Disposition

Chemistry and Biology of the Caged Garcinia Xanthones

Gambogic Acid

Contact Info

Product

Resources

About