Intestinal Permeability of Sesquiterpenes in the Caco-2 Cell Monolayer Model

 

 Buy Article Permissions and Reprints

Abstract

The intestinal permeability of eight sesquiterpenes which are active constituents of some traditional Chinese medicines, were studied by using the Caco-2 cell monolayer; they include tanacetin, artesin, magnolialide, crossostephin, atractylon, isocalamenediol (ICL), bisabolangelone (BSE) and (3R)-des-O-methyllasiodiplodin (DML). The bidirectional permeability of the eight sesquiterpenes was studied from the apical (AP) side to the basolateral (BL) side or from the BL side to the AP side. The eight compounds were assayed by HPLC. Transport parameters and apparent permeability coefficients (P _app) were then calculated. The bidirectional P _app values of the eight compounds were compared with those of propranolol, a marker of high permeability and transcellular transport. The transport of the eight sesquiterpenes was concentration-dependent in the range of 10–200 µM. Lower recoveries of ICL, BSE and DML than other sesquiterpenes were found during transport. The results indicated that all the sesquiterpenes are well absorbed mainly by the passive diffusion via the transcellular pathway and metabolism may be involved during the absorption of ICL, BSE and DML.

References

• 1 Guo Q L, Yang J S. Sesquiterpenes in Inula L. plants and their pharmacological activities.  Nat Prod Res Dev. 2005;  17 804-808
  PubMedGoogle Scholar
• 2 Suo M R, Yang J S. Survey in studies on chemical constituents of sesquiterpene and their physiological activities in plants of Helianthus L.  Chin Tradit Herb Drugs. 2006;  37 135-140
  PubMedGoogle Scholar
• 3 Ding Z H, Liu J K, Ding J K, Gu K. Sesquiterpene components from Eupatorium genus.  Nat Prod Res Dev. 2001;  13 76-83
  PubMedGoogle Scholar
• 4 Wang L, Zhao F, He E Q, Wang S, Liu K. Effects of eighteen sesquiterpenes from Saussurea lappa on the proliferation of six human cancer cell lines.  Nat Prod Res Dev. 2008;  20 808-812
  PubMedGoogle Scholar
• 5 Dornelles Vieira C M, De Paris F, Fiegenbaum M, Lino von Poser G. The use of Tanacetum parthenium in treatment of migraine and rheumatoid arthritis.  Rev Bras Farm. 1998;  79 42-44
  PubMedGoogle Scholar
• 6 Villar A, Zafra-Polo Maria C. Sesquiterpene lactones of Artemisia barrelieri. Part I. Study on their relaxant effect.  Plant Med Phytother. 1981;  15 144-148
  PubMedGoogle Scholar
• 7 Matsuda H, Kagerura T, Toguchida I, Ueda H, Morikawa T, Yoshikawa M. Inhibitory effects of sesquiterpenes from bay leaf on nitric oxide production in lipopolysaccharide-activated macrophages: structure requirement and role of heat shock protein induction.  Life Sci. 2000;  66 2151-2157
  CrossrefPubMedGoogle Scholar
• 8 Satoh K, Nagai F, Ushiyama K, Kano I. Specific inhibition of Na⁺/K⁺-ATPase activity by atractylon, a major component of Byaku-jutsu, by interaction with enzyme in the E₂ state.  Biochem Pharmacol. 1996;  51 339-343
  CrossrefPubMedGoogle Scholar
• 9 Pan J H, Gareth Jones E B, She Z G, Pang J Y, Lin Y C. Review of bioactive compounds from fungi in the South China Sea.  Botanica Marina. 2008;  51 179-190
  CrossrefPubMedGoogle Scholar
• 10 Seo E K, Kim K H, Kim M K, Cho M H, Choi E, Kim K, Mar W. Inhibitors of 5alpha-reductase type I in LNCaP cells from the roots of Angelica koreana.  Planta Med. 2002;  68 162-163
  Article in Thieme ConnectPubMedGoogle Scholar
• 11 Muckensturm B, Duplay D, Robert P C, Simonis M T, Kienlen J C. Substances antiappétantes pour insectes phytophages présentes dans Angelica silvestris et Heracleum sphondylium.  Biochem Syst Ecol. 1981;  9 289-292
  CrossrefPubMedGoogle Scholar
• 12 Navrot J, Harmatha J, Novotny L. Insect feeding deterrent activity of bisabolangelone and of some sesquiterpenes of eremophilanolide type.  Biochem Syst Ecol. 1984;  12 99-101
  CrossrefPubMedGoogle Scholar
• 13 Yang X W, Wu Q, Zou L, Fu D X, Chang Y, Lu Y, Zheng Q T. Characterization of NMR signals of tanacetin and artesin isolated from the whole herbs of Crossostephium chinense.  Chin J Magn Reson. 2008;  25 117-127
  PubMedGoogle Scholar
• 14 Wu Q, Zou L, Yang X W, Fu D X. Novel sesquiterpene and coumarin constituents from the whole herbs of Crossostephium chinense.  J Asian Nat Prod Res. 2009;  11 85-90
  CrossrefPubMedGoogle Scholar
• 15 Zhang P, Yang X W. Studies on chemical constituents in roots and rhizomes of Notopterygium incisum.  China J Chin Mater Med. 2008;  33 2918-2921
  PubMedGoogle Scholar
• 16 Zhang C Y, Zhang B G, Yang X W. Studies on the chemical constituents of the root of Angelica pubescens f. biserrata.  Pharm J Chin PLA. 2007;  23 241-245
  PubMedGoogle Scholar
• 17 Wu Q, Yang X W, Yang S H, Zou L, Yan J. Chemical constituents of Cibotium barometz.  Nat Prod Res Dev. 2007;  19 240-243
  PubMedGoogle Scholar
• 18 Yang X W, Yang X D, Wang Y, Ma L, Zhang Y, Yang X G, Wang K. Establishment of Caco-2 cell monolayer model and standard operation procedure for assessing intestinal absorption of chemical components of traditional Chinese medicine.  J Chin Integr Med. 2007;  5 634-641
  CrossrefPubMedGoogle Scholar
• 19 Ma L, Yang X W. Absorption of papaverine, laudanosine and cepharanthine across human intestine by using human Caco-2 cells monolayers model.  Acta Pharm Sin. 2008;  43 202-207
  PubMedGoogle Scholar
• 20 Artursson P, Palm K, Luthman K. Caco-2 monolayers in experimental and theoretical predictions of drug transport.  Adv Drug Deliv Rev. 2001;  46 27-43
  CrossrefPubMedGoogle Scholar
• 21 Artursson P, Karlsson J. Correlation between oral drug absorption in humans and apparent drug permeability coefficients in human intestinal epithelial (Caco-2) cells.  Biochem Biophys Res Commun. 1991;  175 880-885
  CrossrefPubMedGoogle Scholar
• 22 Alemdaroglu N C, Wolffram S, Boissel J P, Closs E, Spahn-Langguth H, Langguth P. Inhibition of folic acid uptake by catechins and tea extracts in Caco-2 cells.  Planta Med. 2007;  73 27-32
  Article in Thieme ConnectPubMedGoogle Scholar
• 23 Yee S. In vitro permeability across Caco-2 cells (colonic) can predict in vivo (small intestinal) absorption in man – fact or myth.  Pharm Res. 1997;  14 763-766
  CrossrefPubMedGoogle Scholar
• 24 Wu Q, Yang X W. The constituents of Cibotium barometz and their permeability in the human Caco-2 monolayer cell model.  J Ethnopharmacol. 2009;  125 417-422
  CrossrefPubMedGoogle Scholar
• 25 Chaves J S, Leal P C, Pianowisky L, Calixto J B. Pharmacokinetics and tissue distribution of the sesquiterpene α-humulene in mice.  Planta Med. 2008;  74 1678-1683
  Article in Thieme ConnectPubMedGoogle Scholar
• 26 Augustijnsx P, D'Hulst A, Van Daele J, Kinget R. Transport of artemisinin and sodium artesunate in Caco-2 intestinal epithelial cells.  J Pharm Sci. 1996;  85 577-579
  CrossrefPubMedGoogle Scholar
• 27 Khan S I, Abourashed E A, Khan I A, Walker L A. Transport of parthenolide across human intestinal cells (Caco-2).  Planta Med. 2003;  69 1009-1012
  Article in Thieme ConnectPubMedGoogle Scholar
• 28 Anderle P, Niederer E, Rubas W, Hilgendorf C, Spahn-Langguth H, Wunderli-Allenspach H, Merkle H P, Langguth P. P-glycoprotein (P-gp) mediated efflux in Caco-2 cell monolayers: the influence of culturing conditions and drug exposure on P-gp expression levels.  J Pharm Sci. 2000;  87 757-762
  PubMedGoogle Scholar

Prof. Dr. Xiu-Wei Yang

State Key Laboratory of Natural and Biomimetic Drugs
School of Pharmaceutical Sciences
Peking University

38 Xueyuan Road

Haidian District

100191 Beijing

People's Republic of China

Phone: + 86 10 82 80 51 06

Fax: + 86 10 82 80 27 24

Email: xwyang@bjmu.edu.cn

• Supplementary Material