Skip to main content
Log in

Inhibitory effect of 2-arylbenzofurans from the Mori Cortex Radicis (Moraceae) on oxygen glucose deprivation (OGD)-induced cell death of SH-SY5Y cells

  • Research Articles
  • Drug Actions
  • Published:
Archives of Pharmacal Research Aims and scope Submit manuscript

Abstract

Three known 2-arylbenzofurans, moracin P (1), moracin O (2) and mulberrofuran Q (3) were isolated from the MeOH extract of the Mori Cortex Radicis. These compounds 13 enhanced cell viability in dose-dependent manner against oxygen-glucose deprivation (OGD)-induced cell death in neuroblastoma SH-SY5Y cells, which was measured by MTT reduction assay. (EC50 values of 10.4, 12.6, and 15.9 μM, respectively). In addition, the compounds 1–3 were examined for their inhibitory effect on OGD-induced ROS production by FACS analysis. We observed these compounds reduced ROS production in OGD-induced cell death (IC50 values of 1.9, 0.3 and 12.1 μM, respectively). Consequently, reactive oxygen species (ROS) were overexpressed in OGD-induced cells and all three compounds reduced ROS induced by OGD in dosedependent manner. Taken together, compounds 1–3 might protect neuronal cell death against the oxidative stress induced by OGD, though further studies in vitro and in vivo models are necessary.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Albrecht, J., Hanganu, I. L., Heck, N., and Luhmann, H. J., Oxygen and glucose deprivation induces major dysfunction in the somatosensory cortex of the newborn rat. Eur. J. Neurosci., 22, 2295–2305 (2005).

    Article  PubMed  Google Scholar 

  • 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 

  • Bass, D. A., Parce, J. W., Dechatelet, L. R., Szejda, P., Seeds, M. C., and Thomas, M., Flow cytometric studies of oxidative product formation by neutrophils: a graded response to membrane stimulation. J. Immunol., 130, 1910–1917 (1983).

    PubMed  CAS  Google Scholar 

  • Blokhina, O. and Fagerstedt, K. V., Oxidative metabolism, ROS and NO under oxygen deprivation. Plant Physiol. Biochem., 48, 359–373 (2010).

    Article  PubMed  CAS  Google Scholar 

  • Christophe, M. and Nicolas, S., Mitochondria: a target for neuroprotective interventions in cerebral ischemia-reperfusion. Curr. Pharm. Des., 12, 739–757 (2006).

    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 

  • 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 

  • Du, J., He, Z. D., Jiang, R. W., Ye, W. C., Xu, H. X., and But, P. P., Antiviral flavonoids from the root bark of Morus alba L. Phytochemistry, 62, 1235–1238 (2003).

    Article  PubMed  CAS  Google Scholar 

  • El-Beshbishy, H. A., Singab, A. N., Sinkkonen, J., and Pihlaja, K., Hypolipidemic and antioxidant effects of Morus alba L. (Egyptian mulberry) root bark fractions supplementation in cholesterol-fed rats. Life Sci., 78, 2724–2733 (2006).

    Article  PubMed  CAS  Google Scholar 

  • Fatokun, A. A., Stone, T. W., and Smith, R. A., Oxidative stress in neurodegeneration and available means of protection. Front. Biosci., 13, 3288–3311 (2008).

    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 

  • 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., 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, K., Someya, T., and Nomura, T., Structure of mulberrofuran M, a novel 2-arylbenzofuran derivative from the cultivated mulberry Tree (Morus alba L.). Heterocycles, 24, 1251–1255 (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 

  • 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 

  • Kang, T. H., Oh, H. R., Jung, S. M., Ryu, J. H., Park, M. W., Park, Y. K., and Kim, S. Y., Enhancement of neuroprotection of mulberry leaves (Morus alba L.) prepared by the anaerobic treatment against ischemic damage. Biol. Pharm. Bull., 29, 270–274 (2006).

    Article  PubMed  CAS  Google Scholar 

  • Koo, U., Lee, H. J., Lee, D., Lee, H. J., Ham, A. R., and Mar, W. C., Neuroprotective effects of some plant extracts against dopamine-induced oxidative stress on neuronal cell. Kor. J. Pharmacogn., 40, 41–45 (2009).

    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., 50, 185–192 (2002).

    Article  PubMed  CAS  Google Scholar 

  • Lecht, S., Arien-Zakay, H., Marcinkiewicz, C., Lelkes, P. I., and Lazarovici, P., Nerve growth factor-induced protection of brain capillary endothelial cells exposed to oxygen-glucose deprivation involves attenuation of Erk phosphorylation. J. Mol. Neurosci., 41, 183–192 (2010).

    Article  PubMed  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, G., Zou, L. Y., Cao, C. M., and Yang, E. S., Coenzyme Q10 protects SHSY5Y neuronal cells from beta amyloid toxicity and oxygen-glucose deprivation by inhibiting the opening of the mitochondrial permeability transition pore. Biofactors, 25, 97–107 (2005).

    Article  PubMed  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 

  • 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 

  • Oh, H., Ko, E. K., Jun, J. Y., Oh, M. H., Park, S. U., Kang, K. H., Lee, H. S., and Kim, Y. C., Hepatoprotective and free radical scavenging activities of prenylflavonoids, coumarin, and stilbene from Morus alba. Planta Med., 68, 932–934 (2002).

    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 

  • Park, K. M., You, J. S., Lee, H. Y., Baek, N. I., and Hwang, J. K., Kuwanon G: an antibacterial agent from the root bark of Morus alba against oral pathogens. J. Ethnopharmacol., 84, 181–185 (2003).

    Article  PubMed  CAS  Google Scholar 

  • Park, W. J., Lee, H. J., and Yang, S. G., The inhibitory effect of sanggenon C from the root-bark of Morus alba L. on the growth and the cellular adherence of Streptococcus mutans. Yakhakhoe Chi, 34, 434–438 (1990).

    CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    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 

  • Tabakman, R., Jiang, H., Shahar, I., Arien-Zakay, H., Levine, R. A., and Lazarovici, P., Neuroprotection by NGF in the PC12 in vitro OGD model: involvement of mitogen-activated protein kinases and gene expression. Ann. N. Y. Acad. Sci., 1053, 84–96 (2005).

    Article  PubMed  CAS  Google Scholar 

  • Taylor, C. P., Burke, S. P., and Weber, M. L., Hippocampal slices: glutamate overflow and cellular damage from ischemia are reduced by sodium-channel blockade. J. Neurosci. Methods, 59, 121–128 (1995).

    Article  PubMed  CAS  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., 30, 3042–3045 (1982).

    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., 32, 350–353 (1984).

    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 

  • Zhang, M., Wang, R. R., Chen, M., Zhang, H. Q., Sun, S., and Zhang, L. Y., A New flavanone glycoside with antiproliferation activity from the root bark of Morus alba. Chin. J. Nat. Med., 7, 105–107 (2009).

    Article  Google Scholar 

  • Zhu, Y., Hoell, P., Ahlemeyer, B., Sure, U., Bertalanffy, H., and Krieglstein, J., Implication of PTEN in production of reactive oxygen species and neuronal death in in vitro models of stroke and Parkinson’s disease. Neurochem. Int., 50, 507–516 (2007).

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Dongho Lee or Woongchon Mar.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lee, H.J., Lyu, D.H., Koo, U. et al. Inhibitory effect of 2-arylbenzofurans from the Mori Cortex Radicis (Moraceae) on oxygen glucose deprivation (OGD)-induced cell death of SH-SY5Y cells. Arch. Pharm. Res. 34, 1373–1380 (2011). https://doi.org/10.1007/s12272-011-0818-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12272-011-0818-4

Key words

Navigation