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Isolation and Identification of an Autophagy-inducing Compound from Raphani Semen  

Gu, Ming-Yao (Natural Medicine Center, Korea Institute of Science and Technology)
Kwon, Hak Cheol (Natural Medicine Center, Korea Institute of Science and Technology)
Song, Min Ok (Natural Medicine Center, Korea Institute of Science and Technology)
Ko, Hyeonseok (Natural Medicine Center, Korea Institute of Science and Technology)
Cha, Jin-Wook (Natural Medicine Center, Korea Institute of Science and Technology)
Lee, Won Jong (Gangneung-Wonju National University)
Yang, Hyun Ok (Natural Medicine Center, Korea Institute of Science and Technology)
Publication Information
Natural Product Sciences / v.19, no.3, 2013 , pp. 242-250 More about this Journal
Abstract
The autophagy-lysosomal pathway is an important protein degradation system, and its dysfunction has been implicated in a number of neurodegenerative diseases, including Parkinson's disease. Raphani Semen, one of the herbs of Yeoldahanso-tang (YH), has neuroprotective effects via the autophagy pathway. The activity-guided method was used to isolate and identify the components of Raphani Semen. In this experiment, the total extract of Raphani Semen was partitioned to n-butanol, methylene chloride, and water fractions. Flow cytometry data showed that only the water fraction showed autophagy-inducing activity in vitro. Compounds 1 and 2 were isolated from this water fraction by preparative HPLC separation. The structures of compounds 1 and 2 were identified as stachyose and raffinose, respectively, by the analysis of various spectral data ($^1H$ NMR, $^{13}C$ NMR, and MS) and comparisons with standard stachyose and raffinose. Of these two compounds, raffinose showed autophagy-inducing activity in PC12 cells through the mTOR pathway.
Keywords
Autophagy; Raffinose; Raphani semen; Raphanus sativa L.; Cruciferae;
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1 Ariefdjohan, M.W., Martin, B.R., Lachcik, P.J., and Weaver, C.M., Acute and chronic effects of honey and its carbohydrate constituents on calcium Absorption in Rats. Journal of Agricultural and Food Chemistry. 56, 2649-2654 (2008).   DOI
2 Bae, N., Ahn, T., Chung, S.K., Oh, M.S., Ko, H., Oh, H., Park, G., and Yang, H.O., The neuroprotective effect of modified Yeoldhanso-tang via autophagy enhancement in models of Parkinson's disease. Journal of Ethnopharmacology. 134, 313-322 (2011).   DOI
3 Cho, I.H., Effects of Panax Ginseng in neurodegenerative disease. Journal of Ginseng Research. 36(4), 342-353 (2012).   DOI
4 Berger, Z., Ravikumar, B., Menzies, F.M., Oroz, L.G., Underwood, B.R., Pangalos, M.N., Schmitt, I., Wullner, U., Evert, B.O., O'Kane, C.J., and Rubinsztein, D.C., Rapamycin alleviates toxicity of different aggregate-prone proteins. Human Molecular Genetics. 15, 433-442 (2006).   DOI
5 Biederbick, A., Kern, H.F., and Elsasser, H.P., Monodansylcadaverine (MDC) is a specific in vivo marker for autophagic vacuoles. European Journal of Cell Biology. 66, 3-14 (1995).
6 Chen, H., Yan, X.J., Zhu, P., and Lin, J., Antioxidant activity and hepatoprotective potential of agaro-oligosaccharides in vitro and in vivo. Nutrition Journal. 5, 1-12 (2006).   DOI
7 Ciechanover, A., Proteolysis: from the lysosome to ubiquitin and the proteasome. Nature Reviews Molecular Cell Biology. 6, 79-86 (2005).   DOI
8 Erlich, S., Alexandrovich, A., Shohami, E., and Pinkas-Kramarski, R., Rapamycin is a neuroprotective treatment for traumatic brain injury. Neurobiololgy of Disease. 26, 86-93 (2007).   DOI
9 Kabeya, Y., Mizushima, N., Ueno, T., Yamamoto, A., Kirisako, T., Noda, T., Kominami, E., Ohsumi, Y., and Yoshimori, T., LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. The EMBO Journal. 19, 5720-5728 (2000).   DOI
10 Kim, Y.K., Ahn, J.H., and Lee, M.C., Src family kinase inhibitor PP2 induces lc3 conversion in a manner that is uncoupled from autophagy and increases apoptosis in multidrug-resistant cells. Biomolecules & Therapeutics. 20, 393-398 (2012).   DOI
11 Laidlaw, R.A., and Wylam, C.B., The structure of stachyose. Journal of the Chemical Society. 114, 567-571 (1953).
12 Mizushima, N., Methods for monitoring autophagy. The International Journal of Biochemistry & Cell Biology. 36, 2491-2502 (2004).   DOI
13 Lim, Y., Son, D.J., Kim, Y.B., Hwang, B.Y., Yun, Y.P., and Hwang, S.Y., Effect of Yacon on platelet function in hypercholesterolemic rabbits. Biomolecules & Therapeutics. 19, 472-476 (2011).   DOI
14 Nedelsky, N.B., Todd, P.K., and Taylor, J.P., Autophagy and the ubiquitinproteasome system: Collaborators in neuroprotection. Biochimica et Biophysica Acta. 1782, 691-699 (2008).   DOI
15 Lucchesi, K.J. and Gosselin, R.E., Mechanism of L-glucose, raffinose, and inulin transport across intact blood-brain barriers. American Journal of Physiology. 258, H695-705 (1990).
16 Matsukawa, N., Matsumoto, M., Chiji, H., and Hara, H., Oligosaccharide promotes bioavailability of a water-soluble flavonoid glycoside, aGrutin, in rats. Journal of Agricultural and Food Chemistry. 57, 1498- 1505 (2009).   DOI
17 MunafO, D.B. and Colomb, M.I., A novel assay to study autophagy: regulation of autophagosome vacuole size by amino acid deprivation. Journal of Cell Science. 114, 3619-3629 (2001).
18 Neubauer, H., Meiler, J., Peti, W., and Griesinger, C., NMR structure determination of saccharose and raffinose by means of homo- and heteronuclear dipolar couplings. Helvetica Chimica Acta. 84, 243-258 (2001).   DOI
19 Pan, T., Kondo, S., Le, W., and Jankovic, J., The role of autophagylysosome pathway in neurodegeneration associated with Parkinson's disease. Brain. 131, 1969-1978 (2008).   DOI
20 Pan, T., Kondo, S., Zhu, W., Xie, W., Jankovic, J., and Le, W., Neuroprotection of rapamycin in lactacystin-induced neurodegeneration via autophagy enhancement. Neurobiology of Disease. 32, 16-25 (2008).   DOI
21 Pangestui, R. and Kim, S.K., Neuroprotective properties of chitosan and its derivatives. Marine Drugs. 8, 2117-2128 (2010).   DOI
22 Taylor, J.P., Hardy, J., and Fischbeck, K.H., Toxic proteins in neurodegenerative disease. Science. 296, 1991-1995 (2002).   DOI
23 Parker, E.M., Monopoli, A., Ongini, E., Lozza, G., and Babij, C.M., Rapamycin, but not FK506 and GPI-1046, increases neurite outgrowth in PC12 cells by inhibiting cell cycle progression. Neuropharmacology. 39, 1913-1919 (2000).   DOI
24 Wu, Y.T., Tan, H.L., Huang, Q., Kim, Y.S., Pan, N., Ong, W.Y., Liu, Z.G., Ong, C.N., and Shen, H.M., Autophagy plays a protective role during zVAD-induced necrotic cell death. Landes Bioscience. 4, 457-66 (2008).
25 Qiao, Y., Bai, X.F., and Du, Y.G., Chitosan oligosaccharides protect mice from LPS challenge by attenuation of inflammation and oxidative stress. International Immunopharmacology. 11, 121-127 (2011).   DOI
26 Rubinsztein, D.C., The roles of intracellular protein-degradation pathways in neurodegeneration. Nature. 443, 780-786 (2006).   DOI
27 Webb, J.S., Thompson, L.S., James, S., Charlton, T., Tolker-Nielsen, T., Koch, B., Giveskov, M., and Kjelleberg, S., Cell death in Pseudomonas aeruginosa biofilm development. Journal of Bacteriology. 185, 4585-4592 (2003).   DOI
28 Zemke, D., Azhar, S., and Majid, A., The mTOR pathway as a potential target for the development of therapies against neurological disease. Drug News Perspect. 20, 495-499 (2007).   DOI
29 Wakao, N., Imagama, S., Zhang, H., Tauchi, R., Muramoto, A., Natori, T., Takeshita, S., Ishiguro, N., Matsuyama, Y., and Kadomatsu, K., Hyaluronan oligosaccharides promote functional recovery after spinal cord injury in rats. 488, 299-304 (2011).   DOI