OpenLB
Open Library of Bioscience
Advanced Search
Molecules (Basel, Switzerland)
Mar 28, 2019;24 (7):

In Vitro and In Situ Characterization of the Intestinal Absorption of Capilliposide B and Capilliposide C from Hemsl.

Xu Zhang, Xiao Cheng, Yali Wu, Di Feng, Yifan Qian, Liping Chen, Bo Yang, Mancang Gu
Author Information
  1. Xu Zhang: College of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 311402, China. zhangxu@zcmu.edu.cn.
  2. Xiao Cheng: Huzhou Institute for Food and Drug Control, Huzhou, Zhejiang 313000, China. cheng_xiao1981@163.com.
  3. Yali Wu: College of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 311402, China. wuyali@zcmu.edu.cn.
  4. Di Feng: College of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 311402, China. fengdi@zcmu.edu.cn.
  5. Yifan Qian: College of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 311402, China. qianyifan@zcmu.edu.cn.
  6. Liping Chen: College of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 311402, China. LipingChen@zcmu.edu.cn.
  7. Bo Yang: College of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 311402, China. Yangbo@zcmu.edu.cn.
  8. Mancang Gu: College of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 311402, China. gmancang@zcmu.edu.cn.
PMID: 30925820 DOI: 10.3390/molecules24071227

Abstract

The goal of this investigation was to determine the processes and mechanism of intestinal absorption for capilliposide B (CAPB) and capilliposide C (CAPC) from the Chinese herb, Hemsl. An analysis of basic parameters, such as drug concentrations, time, and behavior in different intestinal segments was analyzed by liquid chromatography-tandem mass spectrometry (LC-MS). The susceptibility of CAPB and CAPC to various inhibitors such as P-glycoprotein (P-gp) inhibitor (verapamil); multidrug resistance-associated protein 2 (MRP2) inhibitor (indomethacin); cytochrome P450 protein 3A4 (CYP3A4) inhibitor (ketoconazole); and the co-inhibitor of P-gp, MRP2 and CYP3A4 (cyclosporine A) were assessed using both caco-2 cell monolayer and single-pass intestinal perfusion (SPIP) models. As a result, CAPB and CAPC are both poorly absorbed in the intestines and exhibited segment-dependent permeability. The intestinal permeability of CAPB and CAPC were significantly increased by the co-treatment of verapamil, indomethacin. In addition, the intestinal permeability of CAPB was also enhanced by ketoconazole and cyclosporine A. It can be concluded that the intestinal absorption mechanisms of CAPB and CAPC involve processes such as facilitated passive diffusion, efflux transporters, and enzyme-mediated metabolism. Both CAPB and CAPC are suggested to be substrates of P-gp and MRP2. However, CAPB may interact with the CYP3A4 system.

Keywords

caco-2 cell capilliposide B capilliposide C intestinal absorption liquid chromatography-tandem mass spectrometry single-pass intestinal perfusion

References

  1. Drug Metab Dispos. 2003 Dec;31(12):1507-19 [PMID: 14625347]
  2. Chem Pharm Bull (Tokyo). 2006 Apr;54(4):567-9 [PMID: 16595968]
  3. J Asian Nat Prod Res. 2006 Jul-Aug;8(5):439-44 [PMID: 16864460]
  4. Drug Metab Dispos. 2008 Jan;36(1):102-23 [PMID: 17932224]
  5. Bioorg Med Chem. 2010 Sep 15;18(18):6725-33 [PMID: 20724170]
  6. Toxicol Lett. 2011 Apr 10;202(1):47-54 [PMID: 21277363]
  7. Drug Metab Dispos. 2011 Oct;39(10):1866-72 [PMID: 21757611]
  8. Environ Toxicol Pharmacol. 2010 May;29(3):229-34 [PMID: 21787607]
  9. Drug Metab Dispos. 2012 Aug;40(8):1538-44 [PMID: 22584255]
  10. Acta Pharmacol Sin. 2012 Aug;33(8):1069-79 [PMID: 22773077]
  11. Drug Metab Dispos. 2012 Oct;40(10):2041-53 [PMID: 22829543]
  12. Adv Drug Deliv Rev. 2013 Oct;65(10):1340-56 [PMID: 23041352]
  13. Adv Drug Deliv Rev. 2013 Jun 15;65(6):822-32 [PMID: 23123292]
  14. Bioanalysis. 2014 Apr;6(7):935-45 [PMID: 24313264]
  15. Eur J Pharm Sci. 2014 Mar 12;53:69-76 [PMID: 24365259]
  16. Molecules. 2014 Jan 07;19(1):686-98 [PMID: 24402200]
  17. Evid Based Complement Alternat Med. 2014;2014:497456 [PMID: 24523821]
  18. J Agric Food Chem. 2014 Mar 5;62(9):2096-103 [PMID: 24524563]
  19. Int Urol Nephrol. 2014 Jul;46(7):1335-44 [PMID: 24554216]
  20. Expert Opin Drug Metab Toxicol. 2014 Jun;10(6):859-71 [PMID: 24708201]
  21. Saudi Pharm J. 2014 Jul;22(3):246-57 [PMID: 25067902]
  22. Int J Pharm. 2015 Jan 30;478(2):665-81 [PMID: 25448559]
  23. Expert Opin Drug Metab Toxicol. 2015 Jun;11(6):857-68 [PMID: 25850339]
  24. J Cancer Res Ther. 2015 Nov;11 Suppl:C239-43 [PMID: 26612445]
  25. J Ethnopharmacol. 2016 Feb 3;178:34-9 [PMID: 26657265]
  26. J Pharm Biomed Anal. 2016 Feb 5;119:130-8 [PMID: 26678180]
  27. J Pharm Biomed Anal. 2016 Nov 30;131:6-12 [PMID: 27521984]
  28. Acta Pharmacol Sin. 2017 Jan;38(1):100-109 [PMID: 27840409]
  29. Biomed Chromatogr. 2017 Jun;31(6):null [PMID: 27859436]
  30. Toxicol In Vitro. 2017 Apr;40:26-33 [PMID: 27939799]
  31. J Chromatogr B Analyt Technol Biomed Life Sci. 2017 Feb 15;1044-1045:54-62 [PMID: 28081477]
  32. Exp Ther Med. 2016 Dec;12(6):3716-3722 [PMID: 28105103]
  33. Drug Metab Dispos. 2017 Apr;45(4):353-360 [PMID: 28153842]
  34. Med Sci Monit. 2017 May 02;23:2096-2103 [PMID: 28463955]
  35. Eur J Pharm Sci. 2017 Aug 30;106:212-219 [PMID: 28591563]
  36. Pharmacol Rep. 2017 Oct;69(5):1044-1048 [PMID: 28939344]
  37. Molecules. 2017 Sep 29;22(10):null [PMID: 28961192]
  38. Int J Pharm. 2018 Feb 15;537(1-2):84-93 [PMID: 29102702]
  39. Molecules. 2017 Nov 01;22(11):null [PMID: 29104273]
  40. J Asian Nat Prod Res. 2019 Jan;21(1):62-75 [PMID: 29126363]
  41. Chin J Nat Med. 2018 Feb;16(2):143-149 [PMID: 29455730]
  42. Drug Deliv. 2018 Jan 1;25(1):862-871 [PMID: 29608116]
  43. Biomed Pharmacother. 2018 Oct;106:1563-1569 [PMID: 30119231]
  44. J Ethnopharmacol. 2018 Dec 5;227:300-315 [PMID: 30205181]
  45. Pharmaceutics. 2018 Oct 08;10(4):null [PMID: 30297638]

MeSH Term

ATP Binding Cassette Transporter, Subfamily B, Member 1
Biological Transport
Caco-2 Cells
Chromatography, Liquid
Cytochrome P-450 CYP3A
Humans
Intestinal Absorption
Multidrug Resistance-Associated Protein 2
Multidrug Resistance-Associated Proteins
Permeability
Primulaceae
Reproducibility of Results
Saponins
Tandem Mass Spectrometry
Triterpenes

Chemicals

ABCC2 protein, human
ATP Binding Cassette Transporter, Subfamily B, Member 1
Multidrug Resistance-Associated Protein 2
Multidrug Resistance-Associated Proteins
Saponins
Triterpenes
capilliposide B
capilliposide C
Cytochrome P-450 CYP3A
Journal Article
Article has an altmetric score of 1

Word Cloud

Created with Highcharts 10.0.0intestinalCAPBCAPCcapilliposideabsorptionBCP-gpinhibitorMRP2CYP3A4permeabilityprocessesHemslliquidchromatography-tandemmassspectrometryverapamilproteinindomethacinketoconazolecyclosporinecaco-2cellsingle-passperfusionCapilliposidegoalinvestigationdeterminemechanismChineseherbanalysisbasicparametersdrugconcentrationstimebehaviordifferentsegmentsanalyzedLC-MSsusceptibilityvariousinhibitorsP-glycoproteinmultidrugresistance-associated2cytochromeP4503A4co-inhibitorassessedusingmonolayerSPIPmodelsresultpoorlyabsorbedintestinesexhibitedsegment-dependentsignificantlyincreasedco-treatmentadditionalsoenhancedcanconcludedmechanismsinvolvefacilitatedpassivediffusioneffluxtransportersenzyme-mediatedmetabolismsuggestedsubstratesHowevermayinteractsystemVitroSituCharacterizationIntestinalAbsorption

Similar Articles

Cited By (3)