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Journal of Chinese Integrative Medicine ›› 2010, Vol. 8 ›› Issue (9): 863-869.doi: 10.3736/jcim20100910

• Original Experimental Research • Previous Articles     Next Articles

Absorption and transportation characteristics of scutellarin and scutellarein across Caco-2 monolayer model

Hai-sheng You a, Hai-feng Zhangb, Ya-lin Donga, Si-ying Chena, Mao-yi Wanga, Wei-hua Donga, Jian-Feng Xingc   

  1. a Department of Pharmacy, the First Affiliated Hospital of Medical College, Xi ’ an Jiaotong University,Xi'an 710061, Shaanxi Province, China
    b Department of Pharmacy, Tangdu Hospital, the Fourth Military Medical University, Xi'an 710038,Shaanxi Province, China
    c Department of Pharmacy,College of Medicine,Xi’an Jiaotong University,Xi’an 710061,Shaanxi Province,China;
  • Received:2010-02-05 Accepted:2010-05-28 Online:2010-09-20 Published:2010-09-15


To investigate the absorption and transepithelial transport characteristics of scutellarin and scutellarein in the human colonic adenocarcinoma cell (Caco-2) monolayer model. The influence factors on these two compounds’ absorption were investigated, such as buffer solution, duration of culture, and inhibitors of multidrug resistance-associated protein 2 (MRP2), breast cancer drug resistance protein (BCRP) and P-glycoprotein (P-gp).

By using Caco-2 monolayer as an intestinal epithelial cell model, the transport process was studied from apical (AP) side to basolateral (BL) side or from BL to AP. The two compounds were determined by high-performance liquid chromatography coupled with diode-array-detector detection. Transport parameters and apparent permeability coeffients (Papp) were calculated.

The Papp values of scutellarin and scutellarein were different in two buffer solutions, respectively. In phosphate buffered saline, scutellarin had no absorption from AP to BL, while its Papp value was 0.74×10–6 to 1.58×10–6 cm/s from BL to AP. The Papp values of scutellarein were 4.33×10–6 to 6.79×10–6 cm/s and 1.32×10–6 to 2.56×10–6 cm/s from AP to BL and from BL to AP, respectively. The Papp value gradually decreased with time. The absorption of scutellarein was better than that of scutellarin. The scutellarin absorption was improved by verapamil, MK-571 and reserpine. The scutellarein absorption was improved by verapamil whereas its excretion was improved by MK-571.

Absorption of scutellarin is difficult in Caco-2 monolayer cells, which contributes to its low bioavailability. Scutellarein absorption is better than scutellarin absorption. Scutellarein transepithelial transport is passive diffusion. The inhibitor of P-gp can improve scutellarin and scutellarein transportation. The inhibitors of MRP2 and BCRP can promote transportation of scutellarin. The inhibitor of MRP2 can promote efflux of scutellarein. The multidrug resistance-associated protein may be the second reason for low bioavailability of scutellarin.

Key words: Caco-2 monolayer cells, Scutellarin, Scutellarein, Apparent permeability coefficient

Table 1

Precisions and recovery of scutellarin and scutellarein"

Table 2

Transportation of scutellarin and scutellarein with HBSS solution in Caco-2 monolayer"

Table 3

Transportation of scutellarin and scutellarein with PBS solution in Caco-2 monolayer"

Figure 1

Transport amount from AP to BL or from BL to AP with scutellarin (100 μmol/L) and scutellarein (50 μmol/L)"

Table 4

Effects of different inhibitors of multidrug resistance-associated protein on scutellarin and scutellarein transportation"

[1] Li L, Liu DY, Jiang J, Hu B . Pharmacological research advances of scutellarin[J]. Zhong Cao Yao, 2006,37(8):S9-S11
李丽, 刘东阳, 江骥, 胡蓓 .灯盏乙素药理学研究进展[J].中草药, 2006, 37(8):附9-附11
[2] Ge QH, Zhou Z, Zhi XJ, Ma LL, Chen XH . Pharmacokinetics and absolute bioavailability of breviscapine in Beagle dogs[J]. Zhongguo Yi Yao Gong Ye Za Zhi, 2003,34(12):618-620
doi: 10.3969/j.issn.1001-8255.2003.12.013
葛庆华, 周臻, 支晓瑾, 马丽丽, 陈秀华 . 灯盏花素在犬体内的药动学和绝对生物利用度研究[J]. 中国医药工业杂志, 2003,34(12):618-620
doi: 10.3969/j.issn.1001-8255.2003.12.013
[3] Zheng TS, Ye LX, Xue J, Wu ZY, Zhang X, Sheng WX . Methodological discussion on determination of osteoblast alkaline phosphatase in sucking rat[J]. Zhongguo Xian Dai Yi Xue Za Zhi, 2006,16(10):1495-1497, 1500
郑铁生, 叶立新, 薛锦, 吴志勇, 张徐, 盛微翔 . 乳鼠成骨细胞碱性磷酸酶活性检测方法初探[J]. 中国现代医学杂志, 2006,16(10):1495-1497, 1500
[4] Augustijns P, Mols R . HPLC with programmed wavelength fluorescence detection for the simultaneous determination of marker compounds of integrity and P-gp functionality in the Caco-2 intestinal absorption model[J]. J Pharm Biomed Anal, 2004,34(5):971-978
doi: 10.1016/j.jpba.2003.11.016
[5] Laurent C, Besanon P, Caporiccio B .Flavonoids from a grape seed extract interact with digestive secretions and intestinal cells as assessed in an in vitro digestion/Caco-2 cell culture model[J]. Food Chem, 2007,100(4):1704-1712
doi: 10.1016/j.foodchem.2005.10.016
[6] Akao T, Hanada M, Sakashita Y, Sato K, Morita M, Imanaka T . Efflux of baicalin, a flavone glucuronide of Scutellariae Radix, on Caco-2 cells through multidrug resistance-associated protein 2[J]. J Pharm Pharmacol, 2007,59(1):87-93
doi: 10.1211/jpp.59.1.0012
[7] Qi Y, Wang M, Cai RL, Xie C, Wang XY, Li XH . Transport research of breviscapine across Caco-2 monolayer model using two assay methods[J]. Zhongguo Yao Li Xue Tong Bao, 2009,25(6):831-833
doi: 10.3321/j.issn:1001-1978.2009.06.034
齐云, 王敏, 蔡润兰, 谢忱, 王翔岩, 李晓红 . 两种方法测定灯盏花素经Caco-2细胞模型的转运[J]. 中国药理学通报, 2009,25(6):831-833
doi: 10.3321/j.issn:1001-1978.2009.06.034
[8] Yee S . In vitro permeability across Caco-2 cells(clonic) can predict in vivo(small intestina1) absorption in man — fact or myth[J]. Pharm Res, 1997,14(6):763-766
doi: 10.1023/A:1012102522787
[9] Yang XW, Yang XD, Wang Y, Ma L, Zhang Y, Yang XG, 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]. J Chin Integr Med, 2007,5(6):634-641
杨秀伟, 杨晓达, 王莹, 马莲, 张悦, 杨晓改, 王夔 . 中药化学成分肠吸收研究中Caco-2细胞模型和标准操作规程的建立[J]. 中西医结合学报, 2007,5(6):634-641
[10] You HS, Dong YL, Xing JF, Zhang CL, Wang MY . Pharmacokinetic and tissue distribution study of scutellarin in rats[J]. Zhongguo Zhong Yao Za Zhi, 2007,32(16):1688-1692
尤海生, 董亚琳, 邢建峰, 张春玲, 王茂义 . 灯盏乙素在大鼠体内药代动力学及组织分布的研究[J]. 中国中药杂志, 2007,32(16):1688-1692
[11] Zhang L, Lin G, Chang Q . Role of intestinal first-pass metabolism of baicalein in its absorption process[J]. Pharm Res, 2005,22(7):1050-1058
doi: 10.1007/s11095-005-5303-7 pmid: 16028005
[12] Che QM, Pan LY, Chen Y, He H . Study on pharmacokinetics of scutellarein in rats[J]. Zhongguo Yao Xue Za Zhi, 2007,42(18):1418-1421
车庆明, 潘丽怡, 陈颖, 何红 . 灯盏花乙素苷元的药动学研究[J]. 中国药学杂志, 2007,42(18):1418-1421
[13] Chen J, Lin H, Hu M . Metabolism of flavonoids via enteric recycling: role of intestinal disposition[J]. J Pharmacol Exp Ther, 2003,304(3):1228-1235
doi: 10.1124/jpet.102.046409 pmid: 12604700
[14] Hu M, Chen J, Lin H . Metabolism of flavonoids via enteric recycling: mechanistic studies of disposition of apigenin in the Caco-2 cell culture model[J]. J Pharmacol Exp Ther, 2003,307(1):314-321
doi: 10.1124/jpet.103.053496
[15] Huang J, Li N, Yu Y, Weng W, Huang X . Determination of aglycone conjugated metabolites of scutellarin in rat plasma by HPLC[J]. J Pharm Biomed Anal, 2006,40(2):465-471
doi: 10.1016/j.jpba.2005.07.051 pmid: 16181763
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