The Mechanisms for Enhanced Oral Absorption of Hydroxysafflor Yellow A by Chuanxiong Volatile Oil

Abstract

The aims of this study were to investigate the effect of Ligusticum chuanxiong volatile oil (CVO) on the oral absorption of hydroxysafflor yellow A (HSYA). The effects were studied both in vitro and in vivo. The contents of CVO were measured by GC‐MS. The Caco-2 cell model was used to evaluate HSYA permeation with or without the presence of CVO. Transepithelial electrical resistance (TEER) of the Caco-2 cell monolayers was monitored and the alteration in the subcellular localization of claudin-1, the tight junction protein, was observed by immunofluorescence. The irritation of CVO on rat intestine was studied by paraffin slice technology. Our results demonstrated that CVO mainly contained ligustilide (47.82 %). The Papp of HSYA was improved by 5.34-fold and 4.62-fold in the presence of 0.02 mg/mL and 0.01 mg/mL of CVO, respectively. After opening of the tight junctions of the Caco-2 cell monolayer, TEER decreased, the position of claudin-1 changed, and its expression increased. CVO at different concentrations (10, 25, 100 and 200 mg/kg) caused no significant irritation on rat intestine. The bioavailability of HSYA in rats was increased by 6.48-fold and 4.91-fold when 100 and 25 mg/kg of CVO were co-administrated, respectively. CVO was an effective absorption enhancer for oral delivery of BCS III drugs. It can cause redistribution of claudin-1 proteins and open the tight junctions.

Abbreviations

Key words

Umbelliferae - Ligusticum chuanxiong Hort. - volatile oil - hydroxysafflor yellow A - oral absorption enhancer - immunofluorescence

References

• 1 Gao D, Song J, Hu J, Lin J, Zheng L, Cai J, Du J, Chen K. Angiogenesis promoting effects of Chinese herbal medicine for activating blood circulation to remove stasis on chick embryo chorio-allantoic membrane.  Chin J Integrated Tradit Western Med. 2005;  25 912-915
• 2 Liang M J, He L C, Yang G D. Screening, analysis and in vitro vasodilatation of effective components from Ligusticum chuanxiong.  Life Sci. 2005;  78 128-133
• 3 Li X R, Liang Y Z, Guo F Q. Analysis of volatile oil in Rhizoma Ligustici chuanxiong-Radix Paeoniae rubra by gas chromatography-mass spectrometry and chemometric resolution.  Acta Pharmacol Sin. 2006;  27 491-498
• 4 Xie X Q, Zhan K, Yin R L, Yang L H. The progress of studies on volatile oil from Rhizome Ligustici Chuanxiong Lishizhen.  Med Mater Med Res. 2007;  18 1508-1510
• 5 Fang J Y, Leu Y L, Hwang T L, Cheng H C. Essential oils from sweet basil (Ocimum basilicum) as novel enhancers to accelerate transdermal drug delivery.  Biol Pharm Bull. 2004;  27 1819-1825
• 6 Fang J Y, Tsai T H, Hung C F, Wong W W. Development and evaluation of the essential oil from Magnolia fargesii for enhancing the transdermal absorption of theophylline and cianidanol.  J Pharm Pharmacol. 2004;  56 1493-1500
• 7 Xiao Y Y, Ping Q N, Chen Z P. The enhancing effect of synthetical borneol on the absorption of tetramethylpyrazine phosphate in mouse.  Int J Pharm. 2007;  337 74-79
• 8 Liu Y D, Sun H J, Li R, Wu W, Chen H G. Influence of borneol on nasal absorption of Ligustrazinee.  Chin J Tradit Mater Med. 2008;  33 259-261
• 9 Wu C J, Huang Q W, Qi H Y, Guo P, Hou S X. Promoting effect of borneol on the permeability of puerarin eye drops and timolol maleate eye drops through the cornea in vitro.  Pharmazie. 2006;  61 783-788
• 10 Chen Y M, Wang N S. Effect of borneol on the intercellular tight junction and pinocytosis vesicles in vitro blood-brain barrier model.  Chin J Integrated Tradit Western Med. 2004;  24 632-634
• 11 Zhang L C, Gao L H, Hu J H, Yan C X, Zhu Q G. Enhancing effect of essential oils from Ligusticum chuanxiong on permeation of flurbiprofen through isolated rat skin.  Pharm Care Res. 2006;  6 413-416
• 12 Zhang L C, Hu J H, Li L, Gao L H, Zhu Q G, Li Z, Wang Z Z, Su D F. In vivo and in vitro evaluation of essential oils from Ligusticum chuanxiong Hort. on the transdermal delivery of flurbiprofen in rabbits.  Biol Pharm Bull. 2006;  29 1217-1222
• 13 Liu Y N, Zhou Z M, Chen P. Evidence that hydroxysafflor yellow A protects the heart against ischaemia-reperfusion injury by inhibiting mitochondrial permeability transition pore opening.  Clin Exp Pharmacol Physiol. 2008;  35 211-216
• 14 Zhu H, Wang Z, Ma C, Tian J, Fu F, Li C, Guo D, Roeder E, Liu K. Neuroprotective effects of hydroxysafflor yellow A: in vivo and in vitro studies.  Planta Med. 2003;  69 429-433
• 15 Zhu H B, Wang Z H, Tian J W, Fu F H, Liu K, Li C L. Protective effect of hydroxysafflor yellow A on experimental cerebral ischemia in rats.  Acta Pharm Sin. 2005;  40 1144-1146
• 16 Wang S, Sun M, Ping Q. Enhancing effect of Labrafac Lipophile WL 1349 on oral bioavailability of hydroxysafflor yellow A in rats.  Int J Pharm. 2008;  358 198-204
• 17 Chu D, Liu W, Huang Z, Liu S, Fu X, Liu K. Pharmacokinetics and excretion of hydroxysafflor yellow A, a potent neuroprotective agent from safflower, in rats and dogs.  Planta Med. 2006;  72 418-423
• 18 Tsukita S, Furuse M, Itoh M. Structural and signalling molecules come together at tight junctions.  Curr Opin Cell Biol. 1999;  11 628-633
• 19 Dorkoosh F A, Broekhuizen C A, Borchard G, Rafiee-Tehrani M, Verhoef J C, Junginger H E. Transport of octreotide and evaluation of mechanism of opening the paracellular tight junctions using superporous hydrogel polymers in Caco-2 cell monolayers.  J Pharm Sci. 2004;  93 743-752
• 20 Furuse M, Fujita K, Hiiragi T, Fujimoto K, Tsukita S. Claudin-1 and − 2: novel integral membrane proteins localizing at tight junctions with no sequence similarity to occludin.  J Cell Biol. 1998;  141 1539-1550
• 21 Salama N N, Eddington N D, Fasano A. Tight junction modulation and its relationship to drug delivery.  Adv Drug Deliv Rev. 2006;  58 15-28
• 22 Sha X, Yan G, Wu Y, Li J, Fang X. Effect of self-microemulsifying drug delivery systems containing Labrasol on tight junctions in Caco-2 cells.  Eur J Pharm Sci. 2005;  24 477-486
• 23 Qi J, Jin X, Huang L, Ping Q. Simultaneous determination of hydroxysafflor yellow A and ferulic acid in rat plasma after oral administration of the co-extractum of Rhizoma chuanxiong and Flos Carthami by HPLC-diode array detector.  Biomed Chromatogr. 2007;  21 816-822
• 24 Hidalgo I J. Assessing the absorption of new pharmaceuticals.  Curr Top Med Chem. 2001;  1 385-401
• 25 Balda M S, Whitney J A, Flores C, Gonzalez S, Cereijido M, Matter K. Functional dissociation of paracellular permeability and transepithelial electrical resistance and disruption of the apical-basolateral intramembrane diffusion barrier by expression of a mutant tight junction membrane protein.  J Cell Biol. 1996;  134 1031-1049
• 26 Zhuo Y H, Huang Y L, Wei Y T, Ling Y L, Lin M K, Ge J. Glucocorticoids upregulate transepithelial electrical resistance and expression of tight junction-related protein in human trabecular meshwork cells.  Chin Med J. 2005;  118 1742-1745
• 27 Zhang H F. Study on absorption mechanism of hydroxysafflor yellow A in gastrointestinal tract [dissertation]. Beijing; Chin Pharmaceutical University 2006: 29-44
• 28 Zhang H F, Guo J X, Huang L S, Ping Q N. Absorption mechanism of hydroxysafflor yellow A in rats.  J Chin Pharm Univ. 2006;  37 312-317
• 29 Chiba H, Osanai M, Murata M, Kojima T, Sawada N. Transmembrane proteins of tight junctions.  Biochim Biophys Acta. 2008;  1778 588-600

1 Both authors contributed equally to this work