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Progress in Chemistry 2013, Vol. 25 Issue (09): 1553-1574 DOI: 10.7536/PC130729 Previous Articles   Next Articles

Oral Bioavailability Challenges of Natural Products Used in Cancer Chemoprevention

Song Gao1, Sumit Basu1, Guangyi Yang1,2, Arijita Deb3, Ming Hu*1   

  1. 1. Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, The University of Houston, 1441 Moursund Street, Houston, TX, 77030, USA;
    2. Taihe Hospital, Affiliated with Hubei University of Medicine, 32 Remin South Road, Shiyan 420000, China;
    3. Department of Pharmaceutical Technology, Jadavpur University, Raja S C Mullick Road, Kolkata 700032, India
  • Received: Online: Published:
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Natural products hold great promises for being developed into chemopreventive drugs due to their low toxicity and high accessibility. However, poor oral bioavailability limits the biological effects of many natural products in vivo. This paper reviews the factors that affect the bioavailability of several classes of important chemopreventive natural products including resveratrol, curcumin, berberine, genistein, quercetin, allium compound, and ginsenoside compound K. The up-to-date research data suggested that membrane permeability, solubility, and metabolism are the primary factors that limit the oral bioavailability of these natural products although chemical and microbial stability may also contribute to the problem. An important direction for future investigation is to further optimize the oral bioavailabilities of these natural products and realize their chemopreventive and chemotherapeutic effects in vivo.

Key words: oral bioavailability, natural products, chemoprevention

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[1] Sestak I, Cuzick J. Curr. Oncol. Rep., 2012, 14: 568—573
[2] Rohatgi N, Blau R, Lower E E. J. Women's Health Gend. Based Med., 2002, 11(3): 291—301
[3] FDA. http://www.drugs.com/pro/evista.html#s16, 2012
[4] Juan M E, Alfaras I, Planas J M. Pharmacol. Res., 2012, 65: 584—591
[5] Zhang Y K, Chen H. Epigenetics, 2011, 6: 888—891
[6] Cerella C, Dicato M, Jacob C, Diederich M. Anti-Cancer Agents Med. Chem., 2011, 11: 267—271
[7] Oyagbemi A A, Saba A B, Ibraheem A O. Asian Pac. J. Cancer. Prev., 2009, 10: 963—967
[8] Swamy M V, Citineni B, Patlolla J M, Mohammed A, Zhang Y, Rao C V. Nutr. Cancer, 2008, 60(Suppl 1): 81—89
[9] Wu K, Yang Q, Mu Y, Zhou L, Liu Y, Zhou Q, He B. Int. J. Oncol., 2012, 41: 292—298
[10] Spagnuolo C, Russo M, Bilotto S, Tedesco I, Laratta B, Russo G L. Ann. N. Y. Acad. Sci., 2012, 1259: 95—103
[11] Yun T K. Mutat. Res., 2003, 523/524: 63—74
[12] Sarkar F H, Adsule S, Padhye S, Kulkarni S, Li Y W. Mini. Rev. Med. Chem., 2006, 6: 401—407
[13] Khan S A, Chatterton R T, Michel N, Bryk M, Lee O, Ivancic D, Heinz R, Zalles C M, Helenowski I B, Jovanovic B D, Franke A A, Bosland M C, Wang J, Hansen N M, Bethke K P, Dew A, Coomes M, Bergan R C. Cancer Prev. Res., 2012, 5: 309—319
[14] Yang Z, Zhu W, Gao S, Xu H Y, Wu B J, Kulkarni K, Singh R, Tang L, Hu M. J. Pharm. Biomed. Anal., 2010, 53: 81—89
[15] Mimeault M, Batra S K. Chin. Med., 2011, 6: 31
[16] Mohanty C, Das M, Sahoo S K. Expert Opin. Drug Deliv., 2012, 9: 1347—1364
[17] Berginc K, Trontelj J, Basnet N S, Kristl A. Pharmazie, 2012, 67: 518—524
[18] Thomas V H, Bhattachar S, Hitchingham L, Zocharski P, Naath M, Surendran N, Stoner C L, El-Kattan A. Expert Opin. Drug Metab. Toxicol., 2006, 2: 591—608
[19] Gao S, Basu S, Yang Z, Deb A, Hu M. Curr. Drug Targets, 2012, 13: 1885—1899
[20] Gao S, Hu M. Mini. Rev. Med. Chem., 2010, 10: 550—567
[21] Hsieh T C, Wu J M. Biofactors, 2010, 36: 360—369
[22] Patel K R, Brown V A, Jones D J L, Britton R G, Hemingway D, Miller A S, West K P, Booth T D, Perloff M, Crowell J A, Brenner D E, Steward W P, Gescher A J, Brown K. Cancer. Res., 2010, 70: 7392—7399
[23] Miksits M, Wlcek K, Svoboda M, Thalhammer T, Ellinger I, Stefanzl G, Falany C N, Szekeres T, Jaeger W. Cancer. Lett., 2010, 289: 237—245
[24] Back J H, Zhu Y C, Calabro A, Queenan C, Kim A S, Arbesman J, Kim A L. Photochem. Photobiol., 2012, 88: 1165—1172
[25] Hu F W, Tsai L L, Yu C H, Chen P N, Chou M Y, Yu C C. Mol. Nutr. Food. Res., 2012, 56: 1247—1258
[26] Lin H C, Chen Y F, Hsu W H, Yang C W, Kao C H, Tsai T F. Cancer Prev. Res., 2012, 5: 952—962
[27] Das D K, Mukherjee S, Ray D. Heart Fail. Rev., 2011, 16: 425— 435
[28] Lopez-Lluch G, Cruz-Calvo S S, Navas P. Curr. Pharm. Des., 2012, 18: 1338—1344
[29] Muqbil I, Beck F W J, Bao B, Sarkar F H, Mohammad R M, Hadi S M, Azmi A S. Curr. Pharm. Des., 2012, 18: 1645—1654
[30] Goldberg D M, Yan J, Soleas G J. Clin. Biochem., 2003, 36: 79—87
[31] Quoc Trung L, Espinoza J L, Takami A, Nakao S. PLoS One, 2013, 8: e55183
[32] Nunes T, Almeida L, Rocha J F, Falcão A, Fernandes-Lopes C, Loureiro A I, Wright L, Vaz-da-Silva M, Soares-da-Silva P. J. Clin. Pharmacol., 2009, 49: 1477—1482
[33] Walle T, Hsieh F, DeLegge M H, Oatis J E, Jr, Walle U K. Drug Metab. Dispos., 2004, 32: 1377—1382
[34] López-Nicolás J M, García-Carmona F. J. Agric. Food Chem., 2008, 56: 7600—7605
[35] Das S, Lin H S, Ho P, Ng K Y. Pharm. Res., 2008, 25: 2593—2600
[36] Pettit G R, Anderson C R, Gapud E J, Jung M K, Knight J C, Hamel E, Pettit R K. J. Nat. Prod., 2005, 68: 1191—1197
[37] Li Y M, Shin Y G, Yu C, Kosmeder J W, Hirschelman W H, Pezzuto J M, van Breemen R B. Comb. Chem. High Throughput Screen., 2003, 6: 757—767
[38] Artursson P, Karlsson J. Biochem. Biophys. Res. Commun., 1991, 175: 880—885
[39] Henry C, Vitrac X, Decendit A, Ennamany R, Krisa S, Mérillon J M. J. Agric. Food. Chem., 2005, 53: 798—803
[40] Hu M, Chen J, Lin H M. J. Pharmacol. Exp. Ther., 2003, 307: 314—321
[41] Maier-Salamon A, Hagenauer B, Wirth M, Gabor F, Szekeres T, Jäger W. Pharm. Res., 2006, 23: 2107—2115
[42] Jensen J S, Wertz C F, O'Neill V A. J. Agric. Food Chem., 2010, 58: 1685—1690
[43] Yang N C, Lee C H, Song T Y. Biosci. Biotechnol. Biochem., 2010, 74: 63—68
[44] Long L H, Hoi A, Halliwell B. Arch. Biochem. Biophys., 2010, 501: 162—169
[45] Delmas D, Aires V, Limagne E, Dutartre P, Mazué F, Ghiringhelli F, Latruffe N. Ann. N. Y. Acad. Sci., 2011, 1215: 48—59
[46] Brill S S, Furimsky A M, Ho M N, Furniss M J, Li Y, Green A G, Green C E, Iyer L V, Bradford W W, Kapetanovic I M. J. Pharm. Pharmacol., 2006, 58: 469—479
[47] Maier-Salamon A, Böhmdorfer M, Thalhammer T, Szekeres T, Jaeger W. Drug Metab. Pharmacokinet., 2011, 26: 364—373
[48] Miksits M, Maier-Salamon A, Aust S, Thalhammer T, Reznicek G, Kunert O, Haslinger E, Szekeres T, Jaeger W. Xenobiotica, 2005, 35: 1101—1119
[49] Miksits M, Wlcek K, Svoboda M, Kunert O, Haslinger E, Thalhammer T, Szekeres T, Jäger W. Planta Med., 2009, 75: 1227—1230
[50] Maier-Salamon A, Hagenauer B, Reznicek G, Szekeres T, Thalhammer T, Jäger W. J. Pharm. Sci., 2008, 97: 1615—1628
[51] McGhie T K, Walton M C. Mol. Nutr. Food Res., 2007, 51: 702—713
[52] Zhang L, Zuo Z, Lin G. Mol. Pharm., 2007, 4: 833—845
[53] Ammon H P T, Wahl M A. Planta Med., 1991, 57: 1—7
[54] Bansal S S, Goel M, Aqil F, Vadhanam M V, Gupta R C. Cancer Prev. Res., 2011, 4: 1158—1171
[55] Lao C D, Ruffin M T, Normolle D, Heath D D, Murray S I, Bailey J M, Boggs M E, Crowell J, Rock C L, Brenner D E. BMC Complement. Altern. Med., 2006, 6: 10
[56] Cheng A L, Hsu C H, Lin J K, Hsu M M, Ho Y F, Shen T S, Ko J Y, Lin J T, Lin B R, Ming-Shiang W, Yu H S, Jee S H, Chen G S, Chen T M, Chen C A, Lai M K, Pu Y S, Pan M H, Wang Y J, Tsai C C, Hsieh C Y. Anticancer Res., 2001, 21: 2895—2900
[57] Anand P, Thomas S G, Kunnumakkara A B, Sundaram C, Harikumar K B, Sung B, Tharakan S T, Misra K, Priyadarsini I K, Rajasekharan K N, Aggarwal B B. Biochem. Pharmacol., 2008, 76: 1590—1611
[58] Aggarwal B B, Harikumar K B. Int. J. Biochem. Cell Biol., 2009, 41: 40—59
[59] Aggarwal B B, Kumar A, Bharti A C. Anticancer Res., 2003, 23: 363—398
[60] Anand P, Kunnumakkara A B, Newman R A, Aggarwal B B. Mol. Pharm., 2007, 4: 807—818
[61] Yang K Y, Lin L C, Tseng T Y, Wang S C, Tsai T H. J. Chromatogr. B: Analyt. Technol. Biomed. Life Sci., 2007, 853: 183—189
[62] Pan M H, Huang T M, Lin J K. Drug Metab. Dispos., 1999, 27: 486—494
[63] Dhillon N, Aggarwal B B, Newman R A, Wolff R A, Kunnumakkara A B, Abbruzzese J L, Ng C S, Badmaev V, Kurzrock R. Clin. Cancer Res., 2008, 14: 4491—4499
[64] Carroll R E, Benya R V, Turgeon D K, Vareed S, Neuman M, Rodriguez L, Kakarala M, Carpenter P M, McLaren C, Meyskens F L, Jr, Brenner D E. Cancer Prev. Res., 2011, 4: 354—364
[65] Tønnesen H H. Pharmazie, 2002, 57: 820—824
[66] Hu L D, Jia Y H, Niu F, Jia Z, Yang X, Jiao K L. J. Agric. Food Chem., 2012, 60: 7137—7141
[67] Michel D, Chitanda J M, Balogh R, Yang P, Singh J, Das U, El-Aneed A, Dimmock J, Verrall R, Badea I. Eur. J. Pharm. Biopharm., 2012, 81: 548—556
[68] Lu Y, Ding N, Yang C, Huang L, Liu J, Xiang G. J. Liposome Res., 2012, 22: 110—119
[69] Tønnesen H H, Karlsen J, van Henegouwen G B. Z. Lebensm. Unters. Forsch., 1986, 183: 116—122
[70] Cañamares M V, Garcia-Ramos J V, Sanchez-Cortes S. Appl. Spectrosc., 2006, 60: 1386—1391
[71] Wang Y J, Pan M H, Cheng A L, Lin L I, Ho Y S, Hsieh C Y, Lin J K. J. Pharm. Biomed. Anal., 1997, 15: 1867—1876
[72] Wahlang B, Pawar Y B, Bansal A K. Eur. J. Pharm. Biopharm., 2011, 77: 275—282
[73] Dempe J S, Scheerle R K, Pfeiffer E, Metzler M. Mol. Nutr. Food Res., 2012, doi: 10.1002/mnfr.201200113
[74] Yu H L, Huang Q R. J. Agric. Food Chem., 2011, 59: 9120—9126
[75] Ravindranath V, Chandrasekhara N. Toxicology, 1980, 16: 259—265
[76] Cui J, Yu B, Zhao Y, Zhu W W, Li H L, Lou H X, Zhai G X. Int. J.Pharm., 2009, 371: 148—155
[77] Setthacheewakul S, Mahattanadul S, Phadoongsombut N, Pichayakorn W, Wiwattanapatapee R. Eur. J. Pharm. Biopharm., 2010, 76: 475—485
[78] Kunwar A, Barik A, Pandey R, Priyadarsini K I. Biochim. Biophys. Acta, 2006, 1760: 1513—1520
[79] Ireson C R, Jones D J, Orr S, Coughtrie M W, Boocock D J, Williams M L, Farmer P B, Steward W P, Gescher A J. Cancer Epidemiol. Biomarkers. Prev., 2002, 11: 105—111
[80] Holder G M, Plummer J L, Ryan A J. Xenobiotica, 1978, 8: 761—768
[81] Sandur S K, Pandey M K, Sung B, Ahn K S, Murakami A, Sethi G, Limtrakul P, Badmaev V, Aggarwal B B. Carcinogenesis, 2007, 28: 1765—1773
[82] Pfeiffer E, Hoehle S I, Walch S G, Riess A, Sólyom A M, Metzler M. J. Agric. Food Chem., 2007, 55: 538—544
[83] Kim J B, Yu J H, Ko E, Lee K W, Song A K, Park S Y, Shin I, Han W, Noh D Y. Phytomedicine, 2010, 17: 436—440
[84] Serafim T L, Oliveira P J, Sardao V A, Perkins E, Parke D, Holy J. Cancer Chemother. Pharmacol., 2008, 61: 1007—1018
[85] Pinto-Garcia L, Efferth T, Torres A, Hoheisel J D, Youns M. Planta Med., 2010, 76: 1155—1161
[86] Ho Y T, Lu C C, Yang J S, Chiang J H, Li T C, Ip S W, Hsia T C, Liao C L, Lin J G, Wood W G, Chung J G. Anticancer Res., 2009, 29: 4063—4070
[87] Sindhu G, Manoharan S. Basic Clin. Pharmacol. Toxicol., 2010, 107: 818—824
[88] Vuddanda P R, Chakraborty S, Singh S. Expert Opin. Investig. Drugs, 2010, 19: 1297—1307
[89] Sun Y Y, Xun K L, Wang Y T, Chen X P. Anticancer Drugs., 2009, 20: 757—769
[90] Uglyanitsa K N, Nechiporenko N A, Nefyodov L I, Doroshenko Y M, Brzosko W, Nowicky W. Drugs Exp. Clin. Res., 2000, 26: 191—193
[91] Zemskov V S, Procopchuk O L, Susak Y M, Zemskov S V, Hodysh Y Y, Zemskova M V. Drugs Exp. Clin. Res., 2000, 26: 179—190
[92] Nefyodov L I, Uglyanitsa K N, Nechiporenko N A, Smirnov V Y, Brzosko W, Karavay N L. Drugs Exp. Clin. Res., 2000, 26: 195—199
[93] Uglyanitsa K N, Nefyodov L I, Doroshenko Y M, Brzosko W J. Drugs Exp. Clin. Res., 2000, 26: 201—221
[94] Tan W, Li Y, Chen M, Wang Y. Int. J. Nanomedicine, 2011, 6: 1773—1777
[95] Diogo C V, Machado N G, Barbosa I A, Serafim T L, Burgeiro A, Oliveira P J. Curr. Drug Targets, 2011, 12: 850—859
[96] Chen W, Miao Y Q, Fan D J, Yang S S, Lin X, Meng L K, Tang X. AAPS PharmSciTech, 2011, 12: 705—711
[97] Liu Y T, Hao H P, Xie H G, Lv H, Liu C X, Wang G J. J. Pharm. Sci., 2009, 98: 4391—4401
[98] Hua W Y, Ding L, Chen Y, Gong B, He J C, Xu G L. J. Pharm. Biomed. Anal., 2007, 44: 931—937
[99] Li J, Cao B, Liu X C, Fu X Q, Xiong Z G, Chen L, Sartor O, Dong Y, Zhang H T. Mol. Cancer Ther., 2011, 10: 1346—1356
[100] Brand W, van der Wel P A I, Rein M J, Barron D, Williamson G, van Bladeren P J, Rietjens I M C M. Drug Metab. Dispos., 2008, 36: 1794—1802
[101] Maeng H J, Yoo H J, Kim I W, Song I S, Chung S J, Shim C K. J. Pharm. Sci., 2002, 91: 2614—2621
[102] Pan J F, Yu C, Zhu D Y, Zhang H, Zeng J F, Jiang S H, Ren J Y. Acta Pharmacol. Sin., 2002, 23: 77—82
[103] Sarkar F H, Li Y W. Cancer Metastasis Rev., 2002, 21: 265—280
[104] Iwasaki M, Inoue M, Otani T, Sasazuki S, Kurahashi N, Miura T, Yamamoto S, Tsugane S. J. Clin. Oncol., 2008, 26: 1677—1683
[105] Bitto A, Minutoli L, Squadrito F, D'Anna R, Polito F, Altavilla D. Indian J. Med. Res., 2007, 125: 508—509
[106] Pugalendhi P, Manoharan S, Suresh K, Baskaran N. Afr. J. Tradit. Complement. Altern. Med., 2011, 8: 91—97
[107] Chen J, Lin H, Hu M. J. Pharmacol. Exp. Ther., 2003, 304: 1228—1235
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