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Isolation of gentiopicroside from Gentianae Radix and its pharmacokinetics on liver ischemia/reperfusion rats.
J Ethnopharmacol. 2012 Jun 01; 141(2):668-73.JE

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Gentiopicroside (GPS) is a secoiridoid glucoside isolated from the ethanol extract of Gentianae Radix with a content of 13%, which has been used for centuries in Chinese as a digestive aid.

AIM OF THE STUDY

This study investigates the pharmacokinetics of GPS and its metabolic pathway for the liver ischemia/reperfusion (I/R) in rats.

MATERIALS AND METHODS

The experimental animals were anesthetized intraperitoneally (i.p.) with a mixture of urethane (1.0 g/kg) and α-chloralose (0.1 g/kg). A midline laparatomy was performed and the liver hilum was gently exposed. All structures in the portal triad (hepatic artery, portal vein, and bile duct) to the left and median liver lobes were occluded with silk thread for 30 min. Ischemia was followed by a sudden reperfusion after removing the occluding threads. After 60 min reperfusion, the rats received a single intravenous 5 mg/kg dose of GPS.

RESULTS

The area under concentration curve (AUC) was significantly increased; however, the clearance (Cl) was significantly decreased in the liver I/R rats. Furthermore, after pretreated with SKF-525A (50 mg/kg, i.p.), a cytochrome P450 (CYP) inhibitor, AUC, elimination half-life (t(1/2)) and the mean residence time (MRT) of GPS in rat blood were significantly increased, suggesting that CYP was involved in the metabolism of GPS. For the group without liver I/R, GPS was administered at doses of 5 mg/kg and 100 mg/kg intravenously and orally, respectively. The pharmacokinetic results indicated that the AUC was 565±95.1 and 1163±273 min μg/mL and the t(1/2) of GPS was 71±9 and 106±17 min after intravenous and oral administration, respectively. The oral bioavailability of GPS was 10.3±2.4% in the rats.

CONCLUSIONS

The status of I/R might prolong the disposition of GPS, and the plasma concentration of GPS in the liver I/R injury rats was significantly increased. The increased body exposure of GPS in the treatment of liver I/R may result from the decreased metabolism of GPS mediated by CYP in the liver.

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Publisher Full Text

Authors+Show Affiliations

Chang-Liao WL
Institute of Traditional Medicine, National Yang-Ming University, Taipei 112, Taiwan.
Chien CF
No affiliation info available
Lin LC
No affiliation info available
Tsai TH
No affiliation info available

MeSH

Administration, OralAnimalsArea Under CurveBiological AvailabilityBiotransformationChromatography, High Pressure LiquidCytochrome P-450 Enzyme InhibitorsCytochrome P-450 Enzyme SystemDisease Models, AnimalDrugs, Chinese HerbalEnzyme InhibitorsGentianaHalf-LifeInjections, IntravenousIridoid GlucosidesLiverMaleMedicine, Chinese TraditionalMetabolic Clearance RatePlants, MedicinalProadifenRatsRats, Sprague-DawleyReperfusion InjuryReproducibility of ResultsSpectrophotometry, Ultraviolet

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21855624

Citation

Chang-Liao, Wan-Ling, et al. "Isolation of Gentiopicroside From Gentianae Radix and Its Pharmacokinetics On Liver Ischemia/reperfusion Rats." Journal of Ethnopharmacology, vol. 141, no. 2, 2012, pp. 668-73.
Chang-Liao WL, Chien CF, Lin LC, et al. Isolation of gentiopicroside from Gentianae Radix and its pharmacokinetics on liver ischemia/reperfusion rats. J Ethnopharmacol. 2012;141(2):668-73.
Chang-Liao, W. L., Chien, C. F., Lin, L. C., & Tsai, T. H. (2012). Isolation of gentiopicroside from Gentianae Radix and its pharmacokinetics on liver ischemia/reperfusion rats. Journal of Ethnopharmacology, 141(2), 668-73. https://doi.org/10.1016/j.jep.2011.08.001
Chang-Liao WL, et al. Isolation of Gentiopicroside From Gentianae Radix and Its Pharmacokinetics On Liver Ischemia/reperfusion Rats. J Ethnopharmacol. 2012 Jun 1;141(2):668-73. PubMed PMID: 21855624.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Isolation of gentiopicroside from Gentianae Radix and its pharmacokinetics on liver ischemia/reperfusion rats. AU - Chang-Liao,Wan-Ling, AU - Chien,Chao-Feng, AU - Lin,Lie-Chwen, AU - Tsai,Tung-Hu, Y1 - 2011/08/06/ PY - 2011/03/11/received PY - 2011/08/02/revised PY - 2011/08/02/accepted PY - 2011/8/23/entrez PY - 2011/8/23/pubmed PY - 2012/9/29/medline SP - 668 EP - 73 JF - Journal of ethnopharmacology JO - J Ethnopharmacol VL - 141 IS - 2 N2 - ETHNOPHARMACOLOGICAL RELEVANCE: Gentiopicroside (GPS) is a secoiridoid glucoside isolated from the ethanol extract of Gentianae Radix with a content of 13%, which has been used for centuries in Chinese as a digestive aid. AIM OF THE STUDY: This study investigates the pharmacokinetics of GPS and its metabolic pathway for the liver ischemia/reperfusion (I/R) in rats. MATERIALS AND METHODS: The experimental animals were anesthetized intraperitoneally (i.p.) with a mixture of urethane (1.0 g/kg) and α-chloralose (0.1 g/kg). A midline laparatomy was performed and the liver hilum was gently exposed. All structures in the portal triad (hepatic artery, portal vein, and bile duct) to the left and median liver lobes were occluded with silk thread for 30 min. Ischemia was followed by a sudden reperfusion after removing the occluding threads. After 60 min reperfusion, the rats received a single intravenous 5 mg/kg dose of GPS. RESULTS: The area under concentration curve (AUC) was significantly increased; however, the clearance (Cl) was significantly decreased in the liver I/R rats. Furthermore, after pretreated with SKF-525A (50 mg/kg, i.p.), a cytochrome P450 (CYP) inhibitor, AUC, elimination half-life (t(1/2)) and the mean residence time (MRT) of GPS in rat blood were significantly increased, suggesting that CYP was involved in the metabolism of GPS. For the group without liver I/R, GPS was administered at doses of 5 mg/kg and 100 mg/kg intravenously and orally, respectively. The pharmacokinetic results indicated that the AUC was 565±95.1 and 1163±273 min μg/mL and the t(1/2) of GPS was 71±9 and 106±17 min after intravenous and oral administration, respectively. The oral bioavailability of GPS was 10.3±2.4% in the rats. CONCLUSIONS: The status of I/R might prolong the disposition of GPS, and the plasma concentration of GPS in the liver I/R injury rats was significantly increased. The increased body exposure of GPS in the treatment of liver I/R may result from the decreased metabolism of GPS mediated by CYP in the liver. SN - 1872-7573 UR - https://www.unboundmedicine.com/medline/citation/21855624/Isolation_of_gentiopicroside_from_Gentianae_Radix_and_its_pharmacokinetics_on_liver_ischemia/reperfusion_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-8741(11)00565-4 DB - PRIME DP - Unbound Medicine ER -