Natural Product Sciences

The Korean Society of Pharmacognosy (한국생약학회)
권호 표지

Cytoprotective Effects of Sulfuretin from Rhus verniciflua through Regulating of Heme Oxygenase-1 in Human Dental Pulp Cells

  • Lee, Dong-Sung (Hanbang Body Fluid Research Center, Wonkwang University) ;
  • Kim, Kyoung-Su (Standardized Material Bank for New Botanical Drugs, College of Pharmacy, Wonkwang University) ;
  • Ko, Wonmin (Standardized Material Bank for New Botanical Drugs, College of Pharmacy, Wonkwang University) ;
  • Keo, Samell (Standardized Material Bank for New Botanical Drugs, College of Pharmacy, Wonkwang University) ;
  • Jeong, Gil-Saeng (College of Pharmacy, Wonkwang University) ;
  • Oh, Hyuncheol (Hanbang Body Fluid Research Center, Wonkwang University) ;
  • Kim, Youn-Chul (Hanbang Body Fluid Research Center, Wonkwang University)
  • Received : 2013.03.09
  • Accepted : 2013.03.20
  • Published : 2013.03.31
Download PDF
⟨ Previous Next ⟩

Abstract

Rhus verniciflua Stokes (Anacadiaceae) is a plant that is native to East Asian countries, such as Korea, China, and Japan, and it has been found to exert various biological activities including antioxidative, anti-aggregatory, anti-inflammatory, anti-mutagenic, and apoptotic effects. Sulfuretin is one of the major flavonoid component isolated from the heartwood of R. verniciflua. Reactive oxygen species (ROS), produced via dental adhesive bleaching agents and pulpal disease, can cause oxidative stress. In the present study, we isolated sulfuretin from R. verniciflua and demonstrated that sulfuretin possesses cytoprotective effects against hydrogen peroxide ($H_2O_2$)-induced dental cell death. $H_2O_2$ is a representative ROS and causes cell death through necrosis in human dental pulp (HDP) cells. $H_2O_2$-induced cytotoxicity and production of ROS were blocked in the presence of sulfuretin, and these effects were dose dependent. Sulfuretin also increased heme oxygenase-1 (HO-1) protein expression. In addition, to determine whether sulfuretin-induced HO-1 expression mediated this cytoprotective effect, HDP cells were cotreated with sulfuretin in the absence or presence of SnPP, an inhibitor of HO activity. Sulfuretin-dependent HO-1 expression was required for suppression of $H_2O_2$-induced HDP cell death and ROS generation. These results indicate that sulfuretin-dependent HO-1 expression was required for the inhibition of $H_2O_2$-induced cell death and ROS generation. In addition, sulfuretin may be used to prevent functional dental cell death and thus may be useful as a pulpal disease agent.

Keywords

References

  1. Alam, J., Stewart, D., Touchard, C., Bionapally, S., Choi, A.M., and Cook, J.L., Nrf2, a Cap'n'Collar transcription factor, regulates induction of the heme oxygenase-1 gene. J. Biol. Chem. 274, 26071- 26078 (1999). https://doi.org/10.1074/jbc.274.37.26071
  2. Chen, J. and Regan, R.F., Increasing expression of heme oxygenase-1 by proteasome inhibition protects astrocytes from heme-mediated oxidative injury. Curr. Neurovasc. Res. 2, 189-196 (2005) https://doi.org/10.2174/1567202054368344
  3. Gerlach, R.W., Barker, M.L., and Tucker, H.L., Clinical response of three whitening products having different peroxide delivery: comparison of tray, paint-on gel, and dentifrice. J. Clin. Dent. 15, 112-117 (2004).
  4. Jeon, W.K., Kim, J.H., Lee, A.Y., and Kim, H.K., Inhibition of whole blood platelet aggregation from traditional medicines. Kor. J. Orient. Med. 9, 55-67 (2003).
  5. Jeong, G.S., Lee, D.S., Li, B., Lee, H.J., Kim, E.C., and Kim, Y.C., Effects of sappanchalcone on the cytoprotection and anti-inflammation via heme oxygenase-1 in human pulp and periodontal ligament cells. Eur. J. Pharmacol. 644, 230-237 (2010). https://doi.org/10.1016/j.ejphar.2010.06.059
  6. Kim, I.T., Park, Y.M., Shin, K.M., Ha, J.H., Choi, J.W., Jung, H.J., Park, H.J., and Le, K.T., Anti-inflammatory and anti-nociceptive effects of the extract from Kalopanax pictus, Pueraria thunbergiana and Rhus verniciflua. J. Ethnopharmacol. 94, 165-173 (2004). https://doi.org/10.1016/j.jep.2004.05.015
  7. Kitagawa, M., Ueda, H., Iizuka, S., Sakamoto, K., Oka, H., Kudo, Y., Ogawa, I., Miyauchi, M., Tahara, H., and Takata, T., Immortalization and characterization of human dental pulp cells with odontoblastic differentiation. Arch. Oral Biol. 52, 727-731 (2007). https://doi.org/10.1016/j.archoralbio.2007.02.006
  8. Ko, J.H., Lee, S.J., and Lim, K.T., 36-kDa glycoprotein isolated from Rhus verniciflua Stokes fruit has a protective activity to glucose/ glucose oxidase-induced apoptosis in NIH/3T3 cells. Toxicol. in Vitro 19, 353-363 (2005). https://doi.org/10.1016/j.tiv.2004.10.006
  9. Koehn, F.E. and Carter, G.T., The evolving role of natural products in drug discovery. Nat. Rev. Drug Discov. 4, 206-220 (2005). https://doi.org/10.1038/nrd1657
  10. Lee, D.S., Jeong, G.S., Li, B., Park, H., and Kim, Y.C., Anti-inflammatory effects of sulfuretin from Rhus verniciflua Stokes via the induction of heme oxygenase-1 expression in murine macrophages. Int. Immunopharmacol. 10, 850-858 (2010). https://doi.org/10.1016/j.intimp.2010.04.019
  11. Lee, J.C., Kim, J., Lim, K.T., Yang, M.S., and Jang, Y.S., Ethanol eluted extract of Rhus verniciflua Stokes showed both antioxidant and cytotoxic effects on mouse thymocytes depending on the dose and time of the treatment. Biochem. Mole. Biol. 34, 250-258 (2001).
  12. Lee, J.C., Lim, K.T., and Jang, Y.S., Identification of Rhus verniciflua Stokes compounds that exhibit free radical scavenging and antiapoptotic properties. Biochim. Biophys. Acta. 1570, 181-191 (2002). https://doi.org/10.1016/S0304-4165(02)00196-4
  13. Lee, K.W., Chung, K.S., Seo, J.H., Yim, S.V., Park, H.J., Choi, J.H., and Lee, K.T., Sulfuretin from heartwood of Rhus verniciflua triggers apoptosis through activation of Fas, Caspase-8, and the mitochondrial death pathway in HL-60 human leukemia cells. J. Cell. Biochem. 113, 2835-2844 (2012a). https://doi.org/10.1002/jcb.24158
  14. Lee, Y.R., Hwang, J.K., Koh, H.W., Jang, K.Y., Lee, J.H., Park, J.W., and Park, B.H., Sulfuretin, a major flavonoid isolated from Rhus verniciflua, ameliorates experimental arthritis in mice. Life Sci. 90, 799-807 (2012b). https://doi.org/10.1016/j.lfs.2012.04.015
  15. Lim, K.T., Hu, C., Kitts, and D.D., Antioxidant activity of a Rhus verniciflua Stokes ethanol extract. Food Chem. Toxicol. 39, 229-237 (2001). https://doi.org/10.1016/S0278-6915(00)00135-6
  16. Maines, M.D., Heme oxygenase: function, multiplicity, regulatory mechanisms, and clinical applications. J. Biol. Chem. 263, 3348-3353 (1988).
  17. Matés, J.M., and Sánchez-Jiménez, F., Antioxidant enzymes and their implications in pathophysiologic processes. Front. Biosci. 4, Matés, J.M., and Sánchez-Jiménez, F., Antioxidant enzymes and their implications in pathophysiologic processes. Front. Biosci. 4, D339- D345 (1999). https://doi.org/10.2741/Mates
  18. Min, K.S., Lee, H.J., Kim, S.H., Lee, S.K., Kim, H.R., Pae, H.O., Chung, H.T., Shin, H.I., Lee, S.K., and Kim, E.C., Hydrogen peroxide induces heme oxygenase-1 and dentin sialophosphoprotein mRNA in human pulp cells. J. Endod. 34, 983-989 (2008). https://doi.org/10.1016/j.joen.2008.05.012
  19. Montellano, P.R., The mechanism of heme oxygenase. Curr. Opin. Chem. Biol. 4, 221-227 (2000). https://doi.org/10.1016/S1367-5931(99)00079-4
  20. Mosmann, T., Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J. Immunol. Methods 65, 55-63 (1983). https://doi.org/10.1016/0022-1759(83)90303-4
  21. Newman, D.J., Cragg, G.M., and Snader, K.M., Natural products as sources of new drugs over the period 1981-2002. J. Nat. Prod. 66, 1022-1037 (2003). https://doi.org/10.1021/np030096l
  22. Otterbein, L.E., Soares, M.P., Yamashita, K., and Bach, F.H., Heme oxygenase-1: unleashing the protective properties of heme. Trends Immunol. 24, 449-455 (2003). https://doi.org/10.1016/S1471-4906(03)00181-9
  23. Park, K.Y., Jung, G.O., Lee, K.T., Choi, J.W., Choi, M.Y., Kim, G.T., Jung, J.J., and Park, H.J., Antimutagenic activity of flavonoids from the heartwood of Rhus verniciflua. J. Ethnopharmacol. 90, 73-79 (2004). https://doi.org/10.1016/j.jep.2003.09.043
  24. Paterson, I. and Anderson, E.A., The renaissance of natural products as drug candidates. Science 310, 451-453 (2005). https://doi.org/10.1126/science.1116364
  25. Ryter, S.W., Otterbein, L.E., Morse, D., and Choi, A.M.K., Heme oxygenase/carbon monoxide signaling pathways: regulation and functional significance. Mol. Cell Biochem. 234-235, 249-263 (2002).
  26. Sloan, A.J. and Smith, A.J., Stem cells and the dental pulp: potential roles in dentine regeneration and repair. Oral. Dis. 13, 151-157 (2007). https://doi.org/10.1111/j.1601-0825.2006.01346.x
  27. Son, Y.O., Lee, K.Y., Lee, J.C., Jang, H.S., Kim, J.G., Jeon, Y.M., and Jang, Y.S., Selective antiproliferative and apoptotic effects of flavonoids purified from Rhus verniciflua Stokes on normal versus transformed hepatic cell lines. Toxicol. Lett. 155, 115-125 (2005). https://doi.org/10.1016/j.toxlet.2004.09.003
  28. Song, M.Y., Jeong, G.S., Lee, H.S., Kwon, K.S., Lee, S.M., Park, J.W., Kim, Y.C., and Park, B.H., Sulfuretin attenuates allergic airway inflammation in mice. Biochem. Biophys. Res. Commun. 400, 83-88 (2010). https://doi.org/10.1016/j.bbrc.2010.08.014