Importance of herbal medicines have recently increased owing to rising interest in their health benefits. However, medicinal plant extracts are complex mixtures of phytochemicals that act synergistically or additively on specific and/or multiple molecular and cellular targets. Thus, it is difficult to examine the actual pharmacological roles of active compounds in plant extracts. This review describes a new strategy for isolating target compounds from plant extracts using immunoaffinity columns coupled with monoclonal antibodies (mAbs) against natural compounds. Through one-step purification using mAb-coupled immunoaffinity columns, we succeeded in preparing a knockout (KO) extract, which contains all components except the target compound. Furthermore, we investigated the pharmacological effects of the KO extract to reveal the actual effects of a bioactive compound in the crude extract. This approach may help determine the potential function of target compounds in herbal medicines.
References
[1]
Sakata, R.; Shoyama, Y.; Murakami, H. Production of monoclonal antibodies and enzyme immunoassay for typical adenylate cyclase activator, Forskolin. Cytotechnology 1994, 16, 101–108.
[2]
Xuan, L.; Tanaka, H.; Xu, Y.; Shoyama, Y. Preparation of monoclonal antibody against crocin and its characterization. Cytotechnology 1999, 29, 65–70.
[3]
Lu, Z.; Morinaga, O.; Tanaka, H.; Shoyama, Y. A quantitative ELISA using monoclonal antibody to survey paeoniflorin and albiflorin in crude drugs and traditional Chinese herbal medicines. Biol. Pharm. Bull. 2003, 26, 862–866.
[4]
Tanaka, H.; Fukuda, N.; Shoyama, Y. Formation of monoclonal antibody against a major ginseng component, ginsenoside Rb1 and its characterization. Cytotechnology 1999, 29, 115–120.
[5]
Fukuda, N.; Tanaka, H.; Shoyama, Y. Formation of monoclonal antibody against a major ginseng component, ginsenoside Rg1 and its characterization. Monoclonal antibody for a ginseng saponin. Cytotechnology 2000, 34, 197–204.
[6]
Zhu, S.; Shimokawa, S.; Tanaka, H.; Shoyama, Y. Development of an assay system for saikosaponin a using anti-saikosaponin a monoclonal antibodies. Biol. Pharm. Bull. 2004, 27, 66–71.
[7]
Shan, S.J.; Tanaka, H.; Shoyama, Y. Enzyme-linked immunosorbent assay for glycyrrhizin using anti-glycyrrhizin monoclonal antibody and an eastern blotting technique for glucuronides of glycyrrhetic acid. Anal. Chem. 2001, 73, 5784–5790.
[8]
Ishiyama, M.; Shoyama, Y.; Murakami, H.; Shinohara, H. Production of monoclonal antibodies and development of an ELISA for solamargine. Cytotechnology 1996, 18, 153–158.
[9]
Shoyama, Y.; Fukada, T.; Murakami, H. Production of monoclonal antibodies and ELISA for thebaine and codeine. Cytotechnology 1996, 19, 55–61.
[10]
Kim, J.S.; Tanaka, H.; Shoyama, Y. Immunoquantitative analysis for berberine and its related compounds using monoclonal antibodies in herbal medicines. Analyst 2004, 129, 87–91, doi:10.1039/b311304c.
[11]
Morinaga, O.; Tanaka, H.; Shoyama, Y. Production of monoclonal antibody against a major purgative component, sennoside A, its characterization and ELISA. Analyst 2000, 125, 1109–1113.
[12]
Morinaga, O.; Nakajima, S.; Tanaka, H.; Shoyama, Y. Production of monoclonal antibodies against a major purgative component, sennoside B, their characterization and use in ELISA. Analyst 2001, 126, 1372–1376.
[13]
Tanaka, H.; Goto, Y.; Shoyama, Y. Monoclonal antibody based enzyme immunoassay for marihuana (cannabinoid) compounds. Immunoassay 1996, 17, 321–342.
[14]
Loungratana, P.; Tanaka, H.; Shoyama, Y. Production of monoclonal antibody against ginkgolic acids in Ginkgo biloba Linn. Am. J. Chin. Med. 2004, 32, 33–48.
[15]
Yanagihara, H.; Sakata, R.; Minami, H.; Shoyama, Y.; Murakami, H. Immunoaffinity column chromatography against forskolin using an anti-forskolin monoclonal antibody and its application. Anal. Chim. Acta 1996, 335, 63–70.
[16]
Putalun, W.; Tanaka, H.; Yukihira, S. Rapid separation of solasodine glycosides by an immunoaffinity column using anti-solamargine monoclonal antibody. Cytotechnology 1999, 31, 151–156.
[17]
Fukuda, N.; Tanaka, H.; Shoyama, H. Isolation of the pharmacologically active saponin ginsenoside Rb1 from ginseng by immunoaffinity column chromatography. J. Nat. Prod. 2000, 63, 283–285.
[18]
Xu, J.; Tanaka, H.; Shoyama, Y. One-step immunochromatographic separation and ELISA quantification of glycyrrhizin from traditional Chinese medicines. J. Chromatogr. B 2007, 850, 53–58, doi:10.1016/j.jchromb.2006.10.062.
[19]
Yun, T.K. Brief introduction of Panax ginseng C.A. Meyer. J. Korean Med. Sci. 2001, 16, S3–S5.
[20]
Park, J.D.; Rhee, D.K.; Lee, Y.H. Biological activities and chemistry of saponins from Panax ginseng C. A. Meyer. Phytochem. Rev. 2005, 4, 159–175.
[21]
Choi, K.T. Botanical characteristics, pharmacological and medicinal components of Korean Panax ginseng C.A. Meyer. Acta Pharmacol. Sin. 2008, 29, 1109–1118.
[22]
Qi, L.W.; Wang, C.Z.; Yuan, C.S. Isolation and analysis of ginseng: Advances and challenges. Nat. Prod. Rep. 2011, 28, 467–495.
[23]
Washida, D.; Kitanaka, S. Determination of polyacetylenes and ginsenosides in Panax species using high performance liquid chromatography. Chem. Pharm. Bull. 2003, 51, 1314–1317, doi:10.1248/cpb.51.1314.
[24]
Mook-Jung, I.; Hong, H.S.; Boo, J.H.; Lee, K.H.; Yun, S.H.; Cheong., M.Y.; Joo, I.; Huh, K.; Jung, M.W. Ginsenoside Rb1 and Rg1 improve spatial learning and increase hippocampal synaptophysin level in mice. J. Neurosci. Res. 2001, 63, 509–515.
[25]
Lim, J.H.; Wen, T.C.; Matsuda, S.; Tanaka, J.; Maeda, N.; Peng, H.; Aburaya, J.; Ishihara, K.; Sakanaka, M. Protection of ischemic hippocampal neurons by ginsenoside Rb1, a main ingredient of ginseng root. Neurosci. Res. 1997, 28, 191–200, doi:10.1016/S0168-0102(97)00041-2.
[26]
Liu, M.; Zhang, J. Effects of ginsenoside Rb1 and Rg1 on synaptosomal free calcium level, ATPase and calmodulin in rat hippocampus. Chin. Med. J. (Engl.) 1995, 108, 544–547.
[27]
Jiang, K.Y.; Qian, Z.N. Effects of Panax notoginseng saponins on posthypoxic cell damage of neurons in vitro. Zhongguo Yao Li Xue Bao 1995, 16, 399–402.
[28]
Fukuda, N.; Tanaka, H.; Shoyama, Y. Applications of ELISA, western blotting and immunoaffinity concentration for survey of ginsenosides in crude drugs of Panax species and traditional Chinese herbal medicines. Analyst 2000, 125, 1425–1429, doi:10.1039/b002932g.
[29]
Wengatz, I.; Schmid, R.D.; Krei？ig, S.; Wittmann, C.; Hock, B.; Ingendoh, A.; Hillenkamp, F. Determination of the hapten density of immuno-conjugates by matrix-assisted UV laser desorption/ionization mass spectrometry. Anal. Lett. 1992, 25, 1983–1997, doi:10.1080/00032719208020070.
[30]
Shoyama, Y.; Sakata, R.; Isobe, R.; Murakami, H. Direct determination of forskolin-bovine serum albumin conjugate by matrix-assisted laser desorption ionization mass spectrometry. Org. Mass Spect. 1993, 28, 987–988, doi:10.1002/oms.1210280910.
[31]
Shoyama, Y.; Fukada, T.; Tanaka, T.; Kusai, A.; Nojima, K. Direct determination of opium alkaloid-bovine serum albumin conjugate by matrix-assisted laser desorption ionization mass spectrometry. Biol. Pharm. Bull. 1993, 16, 1051–1053, doi:10.1248/bpb.16.1051.
[32]
Goto, Y.; Shima, Y.; Morimoto, S.; Shoyama, Y.; Murakami, H.; Kusai, A.; Nojima, K. Determination of tetrahydrocannabinolic acid-carrier protein conjugate by matrix-assisted laser desorption ionization mass spectrometry and antibody formation. Org. Mass Spectr. 1994, 29, 668–671, doi:10.1002/oms.1210291115.
[33]
Galfrè, G.; Milstein, C. Preparation of monoclonal antibodies: Strategies and procedures. Methods Enzymol. 1981, 73, 3–46.
[34]
Goding, J.W. Antibody production by hybridomas. J. Immunol. Methods 1980, 39, 285–308, doi:10.1016/0022-1759(80)90230-6.
[35]
Morinaga, O.; Tanaka, H.; Shoyama, Y. Detection and quantification of ginsenoside Re in ginseng samples by a chromatographic immunostaining method using monoclonal antibody against ginsenoside Re. J. Chromatogr. B 2006, 830, 100–104, doi:10.1016/j.jchromb.2005.10.040.
[36]
Tanaka, H.; Fukuda, N.; Yahara, S.; Isoda, S.; Yuan, C.S.; Shoyama, Y. Isolation of ginsenoside Rb1 from Kalopanax pictus by eastern blotting using anti-ginsenoside Rb1 monoclonal antibody. Phytother. Res. 2005, 19, 255–258, doi:10.1002/ptr.1675.
[37]
Tanaka, H.; Fukuda, N.; Shoyama, Y. Eastern blotting and immunoaffinity concentration using monoclonal antibody for ginseng saponins in the field of traditional Chinese medicines. J. Agric. Food Chem. 2007, 55, 3783–3787, doi:10.1021/jf063457m.
[38]
Wang, C.A.; Shoyama, Y. Herbal medicine: Identification, analysis, and evaluationstrategies. In Textbook of Complementary and Alternative Medicine, 2nd; Yuan, C.S., Bieber, E.J., Bauer, B.A., Eds.; Informa Healthcare: London, UK, 2006; pp. 51–70.
[39]
Kim, S.C.; Byun, S.H.; Yang, C.H.; Kim, C.Y.; Kim, J.W.; Kim, S.G. Cytoprotective effects of Glycyrrhizae radix extract and its active component liquiritigenin against cadmium-induced toxicity (effects on bad translocation and cytochrome c-mediated PARP cleavage). Toxicology 2004, 197, 239–251, doi:10.1016/j.tox.2004.01.010.
[40]
Fuchikami, J.; Isohama, Y.; Sakaguchi, M.; Matsuda, M.; Kucota, T.; Akie, Y.; Fujino, A.; Miyata, T. Effect of glycyrrhizin on late asthmatic responses induced by antigen inhalation in guinea pigs. J. Pharmacol. Sci. 2004, 94, 251.
[41]
Asl, M.N.; Hosseinzadeh, H. Review of pharmacological effects of Glycyrrhiza sp. and its bioactive compounds. Phytother. Res. 2008, 22, 709–724, doi:10.1002/ptr.2362.
[42]
Zhang, Q.; Ye, M. Chemical analysis of the Chinese herbal medicine Gan-Cao (licorice). J. Chromatogr. A 2009, 1216, 1954–1969, doi:10.1016/j.chroma.2008.07.072.
[43]
Wang, Z.Y.; Nixon, D.W. Licorice and cancer. Nutr. Cancer 2001, 39, 1–11.
[44]
Chin, Y.W.; Jung, H.A.; Liu, Y.; Su, B.N.; Castoro, J.A.; Keller, W.J.; Pereira, M.A.; Kinghorn, A.D. Anti-oxidant constituents of the roots and stolons of licorice (Glycyrrhiza glabra). J. Agric. Food Chem. 2007, 55, 4691–4697, doi:10.1021/jf0703553.
[45]
Morinaga, O.; Fujino, A.; Tanaka, H.; Shoyama, Y. An on-membrane quantitative analysis system for glycyrrhizin in licorice roots and traditional Chinese medicines. Anal. Bioanal. Chem. 2005, 383, 668–672, doi:10.1007/s00216-005-0054-1.
[46]
Uto, T.; Morinaga, O.; Tanaka, H.; Shoyama, Y. Analysis of the synergistic effect of glycyrrhizin and other constituents in licorice extract onlipopolysaccharide-induced nitric oxide production using knock-out extract. Biochem. Biophys. Res. Commun. 2012, 417, 473–478, doi:10.1016/j.bbrc.2011.11.143.
[47]
Bogdan, C. Nitric oxide and the immune response. Nat. Immunol. 2001, 2, 907–916, doi:10.1038/ni1001-907.
[48]
Bogdan, C. Nitric oxide and the regulation of gene expression. Trends Cell Biol. 2001, 11, 66–75, doi:10.1016/S0962-8924(00)01900-0.
Abramson, S.B.; Amin, A.R.; Clancy, R.M.; Attur, M. The role of nitric oxide in tissue destruction. Best Pract. Res. Clin. Rheumatol. 2001, 15, 831–845, doi:10.1053/berh.2001.0196.
[51]
Gassull, M.A. The role of nutrition in the treatment of inflammatory bowel disease. Aliment. Pharmacol. Ther. 2004, 20, 79–83, doi:10.1111/j.1365-2036.2004.02050.x.
[52]
Blantz, R.C.; Munger, K. Role of nitric oxide in inflammatory conditions. Nephron 2002, 90, 373–378, doi:10.1159/000054723.
[53]
Kr？ncke, K.D.; Fehsel, K.; Kolb-Bachofen, V. Inducible nitric oxide synthase in human diseases. Clin. Exp. Immunol. 1998, 113, 147–156, doi:10.1046/j.1365-2249.1998.00648.x.
[54]
Fukuda, N.; Tanaka, H.; Shoyama, Y. Western blotting for ginseng saponins, ginsenosides using anti-ginsenoside Rb1 monoclonal antibody. Biol. Pharm. Bull. 1999, 22, 219–220, doi:10.1248/bpb.22.219.
[55]
Sritularak, B.; Morinaga, O.; Yuan, C.S.; Shoyama, Y.; Tanaka, H. Quantitative analysis of ginsenosides Rb1, Rg1, and Re in American ginseng berry and flower samples by ELISA using monoclonal antibodies. J. Nat. Med. 2009, 63, 360–363.
