Natural Product Sciences

The Korean Society of Pharmacognosy (한국생약학회)
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Maslinic Acid, a Triterpenoid from the Root Barks of Ulmus davidiana var. japonica, Affects the Viability of HSC-T6 Hepatic Stellate Cells

  • Received : 2011.04.16
  • Accepted : 2011.07.24
  • Published : 2011.09.30
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Abstract

Activation of hepatic stellate cells (HSCs) characterized by increased proliferation and extracellular matrix deposition is identified as the major pathological feature of hepatic cirrhosis. Therefore, suppression of HSC activation has been proposed as an important antifibrotic therapeutic strategy. In the present study, we investigated the antiproliferative activity of root barks of Ulmus davidiana var. japonica (Ulmaceae) by employing HSC-T6 hepatic stellate cells as an in vitro assay system. Further investigation of the n-hexane and $CHCl_3$ fractions of root barks of U. davidiana var japonica led to the isolation of six triterpenoids: friedelin (1), epifridelanol (2), oleanolic acid (3), maslinic acid (4), ${\beta}$-amyrin (5) and ${\alpha}$-amyrin (6), together with ${\beta}$-sitosterol (7) and daucosterol (8). Among these compounds, 2, 3 and 4 significantly inhibited HSC proliferation. In addition, 4 inhibited HSC proliferation in time- and concentration-related manners, via a partially direct toxic effect, as assessed by morphological changes and release of lactate dehydrogenase.

Keywords

References

  1. Bae, K.H., The medicinal plants of Korea, Kyo-Hak Publishing Co., Seoul, pp 63-67, 2000.
  2. Bataller, R. and Brenner, D.A., Liver fibrosis. J. Clin. Invest. 115, 209-218 (2005). https://doi.org/10.1172/JCI24282
  3. Choi, Y., Lee, M.K., Lim, S.Y., Sung, S.H., and Kim, Y.C., Inhibition of inducible NO synthase, cyclooxygenase-2 and interleukin-1 beta by torillin is mediated by mitogen-activated protein kinases in microglical BV2 cells. Br. J. Pharmacol. 156, 933-940 (2009). https://doi.org/10.1111/j.1476-5381.2009.00022.x
  4. de Melo, C.L., Queiroz, M.G.R., Fonseca, S.G.C., Bizerra, A.M.C., Lemos, T.L.G., Melo, T.S., Santos, F.A., and Rao, V.S., Oleanolic acid, a natural triterpenoid improves blood glucose tolerance in normal mice and ameliorates visceral obesity in mice fed a high-fat diet. Chem. Biol. Int., 185, 59-65 (2010). https://doi.org/10.1016/j.cbi.2010.02.028
  5. Hsum, Y.W., Yew, W.T., Hong, P.L., Soo, K.K., Hoon, L.S., Chieng, Y.C., and Mooi, L.Y., Cancer chemopreventive activity of maslinic acid: suppression of COX-2 expression and inhibition of NF-kB and AP-1 activition in Raji cells. Planta Med., 77, 152-157 (2011). https://doi.org/10.1055/s-0030-1250203
  6. Kim, K.W., Park, J.S., Kim, K.S., Jin, U.H., Kim, J.K., Suh, S.J., and Kim, C.H., Inhibition of Ulmus davidiana Planch (Ulmaceae) on bone resorption mediated by processing of cathepsin K in cultured mouse osteoclast. Phytother. Res. 22, 511-517 (2008). https://doi.org/10.1002/ptr.2366
  7. Kim, Y.C., Lee, M.K., Sung, S.H., and Kim, S.H., Sesquiterpenoids from Ulmus davidiana var. japonica with the inhibitory effects on lipopolysaccharide-induced nitric oxide production. Fitoterapia 78, 196-199 (2007). https://doi.org/10.1016/j.fitote.2006.11.013
  8. Lee, G.Y., Jang D.S., Kim, J., Kim, C.S., Kim, Y.S., Kim, J.H., and Kim, J.S., Flavan-3-ols from Ulmus davidiana var. japonica with inhibitory activity on protein glycation. Planta Med. 74, 1800-1802 (2008). https://doi.org/10.1055/s-0028-1088324
  9. Lee, J.H., Kim, D.H., Bang, M.H., Yang, H.J., Bang, S.H., Chung, I.S., Kwon, B.M., Kim, S.H., Kim, D.K., Park, M.H., and Baek, N.I., Isolation of sterols from the methanol extracts of Cymbidium goeringii Reichb. J. Kor. Soc. Appl. Biol. Chem. 48, 263-266 (2005)
  10. Lee, M.K. and Kim, Y.C., Five novel neuroprotective triterpene esters of Ulmus davidiana var. japonica. J. Nat. Prod. 64, 328-331 (2001). https://doi.org/10.1021/np0004799
  11. Lee, M.K., Sung, S.H., Lee, H.S., Cho, J.H., and Kim, Y.C., Lignan and neolignan glycosides from Ulmus davidiana var. japonica. Arch. Pharm. Res. 24, 198-201 (2001) https://doi.org/10.1007/BF02978256
  12. Li, D. and Friedman, S.L., Liver fibrogenesis and the role of hepatic stellate cells: new insights and prospects for therapy. J. Gastroenterol. Hepatol. 14, 618-633 (1999). https://doi.org/10.1046/j.1440-1746.1999.01928.x
  13. Li, Y.Z., Li, Z.L., Yin, S.L., Shi, G., Liu, M.S., Jing, Y.K. and Hua, H.M., Triterpenoids from Calophyllum inophyllum and their growth inhibitory effects on human leukemia HL-60 cells. Fitoterapia 81, 586-589 (2010). https://doi.org/10.1016/j.fitote.2010.02.005
  14. Mahato, S.B. and Kundu, A.P., $^{13}C$ NMR spectra of pentacyclic triterpenoid - a complication and some salient features. Phytochemistry 37, 1517-1575 (1994). https://doi.org/10.1016/S0031-9422(00)89569-2
  15. Reyes-Zurita, F.J., Rufino-Palomares, E.E., Lupianez, J.A. and Cascante, M., Maslinic acid, a natural triterpenes from Olea europaea L., induced apoptosis in HT29 human colon-cancer cells via the mitochondrial apoptotic pathway. Cancer Lett. 273, 44-54 (2009). https://doi.org/10.1016/j.canlet.2008.07.033
  16. Saimaru, H., Orihara, Y., Tansakul, P., Kang, Y.H., Shibuya, M., and Ebizuka, Y., Production of triterpene acids by cell suspension cultures of Olea europaea. Chem. Pharm. Bull. 55, 784-788 (2007). https://doi.org/10.1248/cpb.55.784
  17. Taniguchi, S., Imayoshi, Y., Kobayashi, E., Takamatsu, Y., Ito, H., Hatano, T., Sakagami, H., Tokuda, H., Nishino, H., Sugita, D., Shimura, S. and Yoshida, T., Production of bioactive triterpenes by Eriobotrya japonica calli. Phytochemistry 59, 315-323 (2002). https://doi.org/10.1016/S0031-9422(01)00455-1
  18. Tsukada, S., Parsons, C.J. and Rippe, R.A., Mechanisms of liver fibrosis. Clin. Chim. Acta. 364, 33-60 (2006). https://doi.org/10.1016/j.cca.2005.06.014
  19. Wu, J. and Zern, M.A., Hepatic stellate cells: a target for the treatment of liver fibrosis. J. Gastroenterol. 35, 665-672 (2000). https://doi.org/10.1007/s005350070045
  20. Zheng, M.S., Lee, Y.K., Li, Y., Hwangbo, K., Lee C.S., Kim, J.R., Lee, S.K., Chang, H.W., and Son, J.K., Inhibition of DNA topoisomerases I and II and cytotoxicity of compounds from Ulmus davidiana var. japonica. Arch. Pharm. Res. 33, 1307-1315 (2010). https://doi.org/10.1007/s12272-010-0903-0