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Protection of prenylated flavonoids from mori cortex radicis (Moraceae) against nitric oxide-induced cell death in neuroblastoma SH-SY5Y cells

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Abstract

Seven prenylated flavanoids, licoflavone C (1), cyclomulberrin (2), neocyclomorusin (3), sanggenon I (4), morusin (5), kuwanon U (6) and kuwanon E (7), and three 2-arylbenzofurans, moracin P (8), moracin O (9), and mulberrofuran Q (10) were isolated from the MeOH extract of Mori Cortex Radicis. Among these, compounds 27 enhanced cell viability in a dose-dependent manner against sodium nitroprusside-induced cell death in neuroblastoma SH-SY5Y cells, which was measured by MTT reduction assay (EC50 values of 4.4, 5.6, 8.0, 6.4, 8.7, and 11.9 μg/mL, respectively). Among 10 compounds, C-3 prenylated flavones (2, 3, and 5) and prenylated flavanones (4, 6, and 7) showed cell protection. However, compound 1 which lacks the prenyl group at C-3 and three 2-arylbenzofurans (810) did not show protective effect. The order of cell protection was as follow: C-3 prenylated flavones (2, 3, and 5) > prenylated flavanones (4, 6, and 7) > 2-arylbenzofurans (810) and flavone (1). From this result, we show that some prenylated flavones and flavanones might protect neuronal cells against nitrosative stress-mediated cell death. Even though further evaluations are necessary in vitro and in vivo study, we carefully suggest that some prenylated flavonoids from Mori Cortex Radicis might protect neuronal cells from neurodegenerative diseases.

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References

  • Asano, N., Yamashita, T., Yasuda, K., Ikeda, K., Kizu, H., Kameda, Y., Kato, A., Nash, R. J., Lee, H. S., and Ryu, K. S., Polyhydroxylated alkaloids isolated from mulberry trees (Morusalba L.) and silkworms (Bombyx mori L.). J. Agric. Food Chem., 49, 4208–4213 (2001).

    Article  PubMed  CAS  Google Scholar 

  • Bergendi, L., Benes, L., Durackova, Z., and Ferencik, M., Chemistry, physiology and pathology of free radicals. Life Sci., 65, 1865–1874 (1999).

    Article  PubMed  CAS  Google Scholar 

  • Calabrese, V., Colombrita, C., Guagliano, E., Sapienza, M., Ravagna, A., Cardile, V., Scapagnini, G., Santoro, A. M., Mangiameli, A., Butterfield, D. A., Giuffrida Stella, A. M., and Rizzarelli, E., Protective effect of carnosine during nitrosative stress in astroglial cell cultures. Neurochem. Res., 30, 797–807 (2005).

    Article  PubMed  CAS  Google Scholar 

  • Cardaci, S., Filomeni, G., Rotilio, G., and Ciriolo, M. R., Reactive oxygen species mediate p53 activation and apoptosis induced by sodium nitroprusside in SH-SY5Y cells. Mol. Pharmacol., 74, 1234–1245 (2008).

    Article  PubMed  CAS  Google Scholar 

  • Chen, C. C., Huang, Y. L., Ou, J. C., Lin, C. F., and Pan, T. M., Three new prenylflavones from Artocarpus altilis. J. Nat. Prod., 56, 1594–1597 (1993).

    Article  CAS  Google Scholar 

  • Chen, J., Chang, B., Williams, M., and Murad, F., Sodium nitroprusside degenerates cultured rat striatal neurons. Neuroreport, 2, 121–123 (1991).

    Article  PubMed  CAS  Google Scholar 

  • Dat, N. T., Jin, X., Lee, K., Hong, Y. S., Kim, Y. H., and Lee, J. J., Hypoxia-inducible factor-1 inhibitory benzofurans and chalcone-derived diels-alder adducts from Morus species. J. Nat. Prod., 72, 39–43 (2009).

    Article  PubMed  CAS  Google Scholar 

  • Dawson, V. L. and Dawson, T. M., Nitric oxide neurotoxicity. J. Chem. Neuroanat., 10, 179–190 (1996).

    Article  PubMed  CAS  Google Scholar 

  • Dobrota, D., Fedorova, T., Stvolinsky, S., Babusikova, E., Likavcanova, K., Drgova, A., Strapkova, A., and Boldyrev, A., Carnosine protects the brain of rats and Mongolian gerbils against ischemic injury: after-stroke-effect. Neurochem. Res., 30, 1283–1288 (2005).

    Article  PubMed  CAS  Google Scholar 

  • Fordel, E., Thijs, L., Martinet, W., Schrijvers, D., Moens, L., and Dewilde, S., Anoxia or oxygen and glucose deprivation in SH-SY5Y cells: a step closer to the unraveling of neuroglobin and cytoglobin functions. Gene, 398, 114–122 (2007).

    Article  PubMed  CAS  Google Scholar 

  • Friederich, J. A. and Butterworth, J. F., Sodium nitroprusside: twenty years and counting. Anesth. Analg., 81, 152–162 (1995).

    PubMed  CAS  Google Scholar 

  • Goldberg, M. P. and Choi, D. W., Combined oxygen and glucose deprivation in cortical cell culture: calcium-dependent and calcium-independent mechanisms of neuronal injury. J. Neurosci., 13, 3510–3524 (1993).

    PubMed  CAS  Google Scholar 

  • Hano, Y. and Nomura, T., Constituents of the chinese crude drug “Sang-Bai-Pi” (Morus Root Barks) IV. Structures of four new flavonoids, sanggenon H, I, J and K. Heterocycles, 20, 1071–1076 (1983).

    Article  CAS  Google Scholar 

  • Hano, Y. and Nomura, T., Structure of mulberrofuran P, a novel 2-arylbenzofuran derivative from the cultivated mulberry tree (Morus alba L.). Heterocycles, 24, 1381–1386 (1986).

    Article  CAS  Google Scholar 

  • Hano, Y., Hirakura, T., Someya, T., and Nomura, T., Structure of mulberrofuran M, a novel 2-arylbenzofuran derivative from the cultivated mulberry tree (Morus alba L). Heterocycles, 24, 1251–1256 (1986).

    Article  CAS  Google Scholar 

  • Hano, Y., Nomura, T., and Ueda, S., Two new diels-alder type adducts, mulberrofuran T and kuwanol E, from callus tissues of Morus alba L. Heterocycles, 29, 2035–2041 (1989a).

    Article  CAS  Google Scholar 

  • Hano, Y., Suzuki, S., Nomura, T., and Ueda, S., Two new phenolic compounds, kuwanols C and D, from the root bark of a mulberry tree redifferentiated from the callus tissues. Heterocycles, 29, 807–813 (1989b).

    Article  CAS  Google Scholar 

  • Hantraye, P., Brouillet, E., Ferrante, R., Palfi, S., Dolan, R., Matthews, R. T., and Beal, M. F., Inhibition of neuronal nitric oxide synthase prevents MPTP-induced parkinsonism in baboons. Nat. Med., 2, 1017–1021 (1996).

    Article  PubMed  CAS  Google Scholar 

  • Heales, S. J., Bolanos, J. P., Stewart, V. C., Brookes, P. S., Land, J. M., and Clark, J. B., Nitric oxide, mitochondria and neurological disease. Biochim. Biophys. Acta, 1410, 215–228 (1999).

    Article  PubMed  CAS  Google Scholar 

  • Hirakura, K., Fujimoto, Y., Fukai, T., and Nomura T., Two phenolic glycosides from the root bark of the cultivated mulberry tree (Morus lhou). J. Nat. Prod., 49, 218–224 (1986).

    Article  CAS  Google Scholar 

  • Huang, Z., Huang, P. L., Panahian, N., Dalkara, T., Fishman, M. C., and Moskowitz, M. A., Effects of cerebral ischemia in mice deficient in neuronal nitric oxide synthase. Science, 265, 1883–1885 (1994).

    Article  PubMed  CAS  Google Scholar 

  • Kajiyama, K., Demizu, S., and Hiraga, Y. J., New prenylflavones and dibenzoylmethane from glycyrrhiza inflata. J. Nat. Prod., 55, 1197–1203 (1992).

    Article  CAS  Google Scholar 

  • Katsube, T., Yamasaki, M., Shiwaku, K., Ishijima, T., Matsumoto, I., Abe, K., and Yamasaki, Y., Effect of flavonol glycoside in mulberry (Morus alba L.) leaf on glucose metabolism and oxidative stress in liver in diet-induced obese mice. J. Sci. Food Agric., 90, 2386–2392 (2010).

    Article  PubMed  CAS  Google Scholar 

  • Klatt, P., Pineda Molina, E., Perez-Sala, D., and Lamas, S., Novel application of S-nitrosoglutathione-Sepharose to identify proteins that are potential targets for Snitrosoglutathione-induced mixed-disulphide formation. Biochem. J., 349, 567–578 (2000).

    Article  PubMed  CAS  Google Scholar 

  • Kusano, G., Orihara, S., Tsukamoto, D., Shibano, M., Coskun, M., Guvenc, A., and Erdurak, C. S., Five new nortropane alkaloids and six new amino acids from the fruit of Morus alba LINNE growing in Turkey. Chem. Pharm. Bull. (Tokyo), 50, 185–192 (2002).

    Article  CAS  Google Scholar 

  • Lee, S. H., Choi, S. Y., Kim, H., Hwang, J. S., Lee, B. G., Gao, J. J, and Kim, S. Y., Mulberroside F isolated from the leaves of Morus alba inhibits melanin biosynthesis. Biol. Pharm. Bull., 25, 1045–1048 (2002).

    Article  PubMed  CAS  Google Scholar 

  • Li, L., Feng, Z., and Porter, A. G., JNK-dependent phosphorylation of c-Jun on serine 63 mediates nitric oxideinduced apoptosis of neuroblastoma cells. J. Biol. Chem., 279, 4058–4065 (2004).

    Article  PubMed  CAS  Google Scholar 

  • Lim, W., Kim, J. H., Gook, E., Kim, J., Ko, Y., Kim, I., Kwon, H., Lim, H., Jung, B., Yang, K., Choi, N., Kim, M., Kim, S., Choi, H., and Kim, O., Inhibition of mitochondria-dependent apoptosis by 635-nm irradiation in sodium nitroprusside-treated SH-SY5Y cells. Free Radic. Biol. Med., 47, 850–857 (2009).

    Article  PubMed  CAS  Google Scholar 

  • Miglio, G., Varsaldi, F., Francioli, E., Battaglia, A., Canonico, P. L., and Lombardi, G., Cabergoline protects SH-SY5Y neuronal cells in an in vitro model of ischemia. Eur. J. Pharmacol., 489, 157–165 (2004).

    Article  PubMed  CAS  Google Scholar 

  • Nakamura, T. and Lipton, S. A., Molecular mechanisms of nitrosative stress-mediated protein misfolding in neurodegenerative diseases. Cell. Mol. Life Sci., 64, 1609–1620 (2007).

    Article  PubMed  CAS  Google Scholar 

  • Nomura, T, Fukai, T., Yamada, S., and Katayanagi, M., Phenolic constituents of the cultivated Mulberry Tree (Morus alba L.). Chem. Pharm. Bull. (Tokyo), 24, 2898–2900 (1976).

    Article  Google Scholar 

  • Nomura, T. and Fukai, T., Constituents of the cultivated mulberry tree. Planta Med., 42, 79–88 (1981).

    Article  PubMed  CAS  Google Scholar 

  • Nomura, T., Fukai, T., Matsumoto, J., and Ohmori, T., Constituents of the cultivated mulberry tree. Planta Med., 46, 28–32 (1982).

    Article  PubMed  CAS  Google Scholar 

  • Nomura, T., Fukai, T., Shimada, T., and Chen, I. S., Components of root bark of morus australis. Planta Med., 49, 90–94 (1983).

    Article  PubMed  CAS  Google Scholar 

  • Oshima, Y., Konno, C., and Hikino, H., Structure of moracenin D, a hypotensive principle of morus root barks. Heterocycles, 16, 979–982 (1981).

    Article  CAS  Google Scholar 

  • Patel, R. P., McAndrew, J., Sellak, H., White, C. R., Jo, H., Freeman, B. A., and Darley-Usmar, V. M., Biological aspects of reactive nitrogen species. Biochim. Biophys. Acta, 1411, 385–400 (1999).

    Article  PubMed  CAS  Google Scholar 

  • Qiu, F., Komatsu, K., Kawasaki, K., Saito, K., Yao, X., and Kano, Y., A novel stilbene glucoside, oxyresveratrol 3′-Obeta-glucopyranoside, from the root bark of morus alba. Planta Med., 62, 559–561 (1996).

    Article  PubMed  CAS  Google Scholar 

  • Ridnour, L. A., Isenberg, J. S., Espey, M. G., Thomas, D. D., Roberts, D. D., and Wink, D. A., Nitric oxide regulates angiogenesis through a functional switch involving thrombospondin-1. Proc. Natl. Acad. Sci. U. S. A., 102, 13147–13152 (2005).

    Article  PubMed  CAS  Google Scholar 

  • Shi, Y. Q., Fukai, T., Sakagami, H., Chang, W. J., Yang, P. Q., Wang, F. P., and Nomura, T., Cytotoxic flavonoids with isoprenoid groups from Morus mongolica. J. Nat. Prod., 64, 181–188 (2001).

    Article  PubMed  CAS  Google Scholar 

  • Sohn, H. Y., Son, K. H., Kwon, C. S., Kwon, G. S., and Kang, S. S., Antimicrobial and cytotoxic activity of 18 prenylated flavonoids isolated from medicinal plants: Morus alba L., Morus mongolica Schneider, Broussnetia papyrifera (L.) Vent, Sophora flavescens Ait and Echinosophora koreensis Nakai. Phytomedicine, 11, 666–672 (2004).

    Article  PubMed  CAS  Google Scholar 

  • Stvolinsky, S. L. and Dobrota, D., Anti-ischemic activity of carnosine. Biochemistry, 65, 849–855 (2000).

    PubMed  CAS  Google Scholar 

  • Stvolinsky, S. L., Bulygina, E. R., Fedorova, T. N., Meguro, K., Sato, T., Tyulina, O. V., Abe, H., and Boldyrev, A. A., Biological activity of novel synthetic derivatives of carnosine. Cell. Mol. Neurobiol., 30, 395–404 (2010).

    Article  PubMed  CAS  Google Scholar 

  • Su, B. N., Park, E. J., Mbwambo, Z. H., Santarsiero, B. D., Mesecar, A. D., Fong, H. H., Pezzuto, J. M., and Kinghorn, A. D., New chemical constituents of Euphorbia quinquecostata and absolute configuration assignment by a convenient Mosher ester procedure carried out in NMR tubes. J. Nat. Prod., 65, 1278–1282 (2002).

    Article  PubMed  CAS  Google Scholar 

  • Tati, S., Yandri, A. S., Sutopo, H., and Jhons, F. S., Morusin, a bioactive compound from the root bark of Artocarpus dadah. Eur. J. Sci. Res., 38, 643–648 (2009).

    Google Scholar 

  • Ueda, S., Nomura, T., Fukai, T., and Matsumoto, J., Kuwanon J, a new diels-alder adduct and chalcomoracin from callus culture of Morus alba L. Chem. Pharm. Bull. (Tokyo), 30, 3042–3045 (1982).

    Article  CAS  Google Scholar 

  • Ueda, S., Matsumoto, J., and Nomura, T., Four new natural diels-alder type adducts, mulberrofuran E, kuwanon Q, R, and V from callus culture of Morus alba L. Chem. Pharm. Bull. (Tokyo), 32, 350–353 (1984).

    Article  CAS  Google Scholar 

  • Valko, M., Leibfritz, D., Moncol, J., Cronin, M. T., Mazur, M., and Telser, J., Free radicals and antioxidants in normal physiological functions and human disease. Int. J. Biochem. Cell. Biol., 39, 44–84 (2007).

    Article  PubMed  CAS  Google Scholar 

  • Yadav, A. V. and Nade, V. S., Anti-dopaminergic effect of the methanolic extract of morus alba L. leaves. Indian J. Pharmacol., 40, 221–226 (2008).

    Article  PubMed  Google Scholar 

  • Yoshida, T., Limmroth, V., Irikura, K., and Moskowitz, M. A., The NOS inhibitor, 7-nitroindazole, decreases focal infarct volume but not the response to topical acetylcholine in pial vessels. J. Cereb. Blood Flow Metab., 14, 924–929 (1994).

    Article  PubMed  CAS  Google Scholar 

  • Zhang, M., Wang, R. R., Chen, M., Zhang, H. Q., Sun, S., and Zhang, L. Y., A new flavanone glycoside with anti-proliferation activity from the root bark of morus alba. Chinese J. Nat. Med., 7, 105–107 (2009).

    Article  Google Scholar 

  • Zhang, Y. and Zhao, B., Green tea polyphenols enhance sodium nitroprusside-induced neurotoxicity in human neuroblastoma SH-SY5Y cells. J. Neurochem., 86, 1189–1200 (2003).

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Dongho Lee or Woongchon Mar.

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Lee, H.J., Lyu, D.H., Koo, U. et al. Protection of prenylated flavonoids from mori cortex radicis (Moraceae) against nitric oxide-induced cell death in neuroblastoma SH-SY5Y cells. Arch. Pharm. Res. 35, 163–170 (2012). https://doi.org/10.1007/s12272-012-0118-7

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