The octanol/water distribution coefficients of ardipusilloside-I and its metabolites, and their permeation characteristics across Caco-2 cell monolayer
Tóm tắt
Ardipusilloside-I (ADS-I) is a triterpenoid saponin extracted from Chinese medicinal herb Ardisiapusill A. DC. Previous studies have demonstrated the potent anti-tumor activities of ADS-I both in vitro and in vivo, and its main metabolites (M1 and M2) from human intestinal bacteria. However, the physicochemical properties and intestinal permeation rate of ADS-I and its metabolites are not understood. In this study, the octanol/water distribution coefficients (logP) of ADS-I and metabolites were investigated using standard shake flask technique, and their permeability properties was investigated across Caco-2 cells monolayer. The logP of ADS-I, M1 and M2 was −0.01, 0.95 ± 0.04, 1.57 ± 0.11, respectively. The Papp values of ADS-I, M1 and M2 (in 10 μmol/L) across Caco-2 cell monolayers from the apical (AP) to basolateral (BL) direction were 1.88 ± 0.21 × 10−6 cm·s−1, 4.30 ± 0.43 × 10−6 cm·s−1, 4.74 ± 0.47 × 10−6 cm·s−1, respectively. Our data indicated that ADS-I has the poorer intestinal absorption than its metabolites (M1 and M2) in these experimental systems, suggesting that the metabolites of ADS-I may be the predominant products absorbed by the intestine when ADS-I is administered orally.
Tài liệu tham khảo
Zhang QH, Wang XJ, Miu ZC, Feng R (1993) Chemical research on ardipusilloside. Acta Pharm. Sin 28:673–678
Liang KM, Wang SW, Wang XJ (2001) Inhibitory effect on of ardipusilloside on human cancer cell line. J Forth Mil Med Univ 22:671–672
Xiong Jian, Cheng Guang, Tang Hai-Feng, Zhen Hai-ning, Zhang Xiang (2009) Ardipusilloside I induces apoptosis in human glioblastoma cells through a caspase-8-independent FasL/Fas-signaling pathway. J Envir Toxicol Pharmacol 27:264–270
Zhang Yan-min, You-le Qu, Zhang Jie, Xiao-juan W (2010) Ardipusilloside I purified from Ardisia pusilla competitively binds VEGFR and induces apoptosis in NCI-H460 cells. Phytomedicine 17:519–526
Lou Lian-qing, Ye Wei-wei, Chen Yong-xin, Shuang Wu, Jin Lin-zheng, He Jin-ke, Tao Xing-fei, Zhu Jing-hong, Chen Xiang-yi, Deng An-mei, Wang Jin-he (2012) Ardipusilloside inhibits survival, invasion and metastasis of human hepatocellular carcinoma cells. Phytomedicine 19:603–608
Tao XJ, Wang PX, Yang XJ, Yao HP, Liu J, Cao YS (2005) Inhibitory effect of Ardipusilloside-I on Lewis pulmonary carcinoma and hepatocarcinoma SMMC-7721. J Chin Med Mater 28:574–577
Wang XJ, Cui H, Wang R, Huan ML, Zhang BL, Zhang WD, Teng ZH, Gan HQ, Zhou SY, Gu Y (2012) Metabolism and pharmacokinetic study of Ardipusilloside I in rats. Planta Med 78:565–574
Cao Wei-Yu, Wang Ya-Nan, Wang Peng-Yuan, Lei Wan, Feng Bin, Wang Xiao-juan (2015) Ardipusilloside-I metabolites from human intestinal bacteria and their antitumor activity. Molecules 20:20569–20581
Soumyajit M, Sridhar D, Ashim KM (2004) Membrane transporter/receptor-targeted prodrug design: strategies for human and veterinary drug development. Adv Drug Delivery Rev 56:1437–1452
Odani T, Tanizawa H, Takino Y (1983) Studies on the absorption, distribution, excretion and metabolism of Ginseng saponins. IV. Decomposition of ginsenoside-Rg1 and Rb1 in the digestive tract of rats. Chem Pharm Bull 31:3691–3697
Qian T, Jiang ZH, Cai ZW (2006) High-performance liquid chromatograph coupled with tandem mass spectrometry applied for metabolic study of ginsenoside Rb1 on rats. Anal Biochem 352:87–96
Ruan Jian-Qing, Weng-im Leong Ru, Yan Yi-tao Wang (2010) Characterization of metabolism and in vitro permeability study of notoginsenoside R1 from Radix notoginseng. J Agric Food Chem 58:5770–5776
Tetko Igor V, Varbanov Hristo P, Galanski Markus, Talmaciu Mona, Platts James A, Ravera Mauro, Gabano Elisabetta (2016) Prediction of logP for Pt(II) and Pt(IV) complexes: comparison of statistical and quantum-chemistry based approaches. J Inorg Biochem 156:1–13
Pienko Tomasz, Grudzien Monika, Taciak Przemysław Paweł, Mazurek Aleksander Paweł (2016) Cytisine basicity, solvation, log P, and log D theoretical determinationas tool for bioavailability prediction. J Mol Graph Model 63:15–21
Pinto M, Robine-Leon S, Appay MD, Kedinger M, Triadou N, Dussaulx E, Lacroix B, Simon-Assmann P, Haffen K, Fogh J, Zweibaum A (1983) Enterocyte-like differentiation and polarization of the human colon carcinoma cell line Caco-2 in culture. Biol Cell 47:323–330
Grasset E, Pinto M, Dussaulx E, Zweibaum A, Desjeux JF (1984) Epithelial properties of human colonic carcinoma cell line Caco-2: electrical parameters. Am J Physiol 247:260–267
Borlak J, Zwadlo C (2005) Expression of drug- metabolizing enzymes, nuclear transcription factors and ABC transporters in Caco-2 cells. Xenobiotica 33:927–943
Lin JZ, Zou L, Fu CM, Zhang DK, Wang P, Qin L (2013) Octanol/water partition coefficient and absorption kinetics of salidroside and tyrosol in rat intestine. Chin Tradi Pat Med 35:483–486
Yang Yan-Fang, Wei Xu, Song Wei, Ye Min, Yang Xiu-Wei (2015) Transport of twelve coumarins from Angelicae Pubescentis Radix across a MDCK-pHaMDR cell monolayer-an in vitro model for blood-brain barrier permeability. Molecules 20:11719–11732
Yang XW, Huang X, Ma L, Wu Q, Xu W (2010) The intestinal permeability of neolignans from the seeds of Myristica fragrans in the Caco-2 cell monolayer model. Planta Med 76:1587–1591
Wahlang B, Pawar YB, Bansal AK (2011) Identification of permeability-related hurdles in oral delivery of curcumin using the Caco-2 cell model. Eur J Pharm Biopharm 77:275–282
Gao J, HuggerE D, Beck-Westermeyer MS (2000) Current protocols in pharmacology estimation of intestinal mucosal permeation of compounds using Caco-2 cell monolayers. John Wiley Sons Inc, New York
Heshmati Nasim, Wagner B, Cheng X, Schol T, Kansy M, Eisenbrand G, Fricker G (2013) Physicochemical characterization and in vitro permeation of an indirubin derivative. Europ J Pharm Sci 50:467–475
Morikawa Go, Suzuka Chihiro, Shoji Atsushi, Shibusawa Yoichi, Yanagida Akio (2016) High-throughput determination of octanol/water partition coefficients using a shake-flask method and novel two-phase solvent system. J PharmBiomed Anal 117:338–344
Zheng Mengkai, Zhou Huifen, Wan Haitong, Yu-Lin C, H Y (2015) Effects of herbal drugs in Mahuang decoction and their main components on intestinal transport characteristics of Ephedra alkaloids evaluated by a Caco-2 cell monolayer model. J Ethnopharmacol 164:22–29
Liu L, Guo L, Zhao C, Wu X, Wang R, Liu C (2015) Characterization of the intestinal absorption of seven flavonoids from the flowers of Trollius chinensis using the Caco-2 cell monolayer model. PLoS One 19(3):1–18