Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
권호 표지
DOI QR코드

DOI QR Code

The Effects of Yacon (Smallanthus sonchifolius) Extract on Pancreatic Fibrosis in the Rat

야콘(Smallanthus sonchifolius) 추출물이 흰쥐의 췌장 섬유화에 미치는 영향

  • Choi, Nan-Hee (Department of Anatomy, College of Oriental medicine, Dongguk University) ;
  • Kim, Jong-Bong (Department of Medical Life Science, Catholic University of Daegu) ;
  • Kim, Jin-Teak (Department of Anatomy, College of Oriental medicine, Dongguk University) ;
  • Park, In-Sick (Department of Anatomy, College of Oriental medicine, Dongguk University)
  • 최난희 (동국대학교 한의과대학 해부학교실) ;
  • 김종봉 (대구가톨릭대학교 의생명과학과) ;
  • 김진택 (동국대학교 한의과대학 해부학교실) ;
  • 박인식 (동국대학교 한의과대학 해부학교실)
  • Received : 2012.03.06
  • Accepted : 2012.06.17
  • Published : 2012.07.30
Download PDF
⟨ Previous Next ⟩

Abstract

Yacon has been used in folk medicines as a medicinal tea for hypoglycemia treatment. In a recent study described herein, antioxidative, antibacterial, antifungal activities, and cell-protective functions of yacon leaves have been reported. To evaluate the effects on fibrosis on pancreatitis, the efficacy of 1% of yacon extract (YE) on dibutyltin dichloride (DBTC) (8 mg/kg)-induced pancreatitis in rats was examined. On the 21st day after the DBTC treatment, a large increase in collagen was observed in the pancreas in the DBTC-treatment group (DT). But this was noticeably decreased with YE. In relation to the expression of COX-2, there was no response or a very weak response in the pancreas of the control group (CON). However, in DT, strong expression of COX-2 was observed in the pancreas on the 14th day, and COX-2 was present in inflammatory cells in the pancreas of the DT, especially on the 21st day. The expression was decreased for YE compared with DT. A remarkable increase in TGF-${\beta}1$ expression was observed in inflammatory cells in the pancreas in DT on the 21st day, whereas the expression was not found in YE after 21 days. However, on the 21th day, TGF-${\beta}1$ expression was increased in acinar cells of YE compared with DT. VEGF expression was very similar to the expression of in the pancreas. These results suggest that YE has an inhibitory effect on DBTC-induced pancreatic fibrosis.

야콘(Smallanthus sonchifolius)은 저혈당에 민간요법으로 이용해 오고 있는 구근작물이다. 최근에는 야콘잎이 항산화, 항균, 항진균 활성과 세포보호 기능이 있다고 보고되고 있다. 본 실험에서는 이러한 생리활성을 지니는 야콘잎을 이용하여 흰쥐에 DBTC (8 mg/kg)를 주사하여 췌장염을 유발시킨 후 1% 야콘추출물이 췌장의 섬유화에 미치는 영향을 연구하였다. 유발 21일째 처리군에서 췌장의 실질조직의 많은 부분이 collagen으로 재구성되어 있었으나 유발군에서는 처리군에 비해 현저히 감소되어 있었다. COX-2 발현에서, 대조군은 반응이 나타나지 않거나 매우 약한 반응이었으나, 유발군에서는 14일째 매우 증가되었으며, 특히 21일째는 침윤하고 있는 많은 염증세포에서 COX-2의 발현이 확인되었다. 처리군은 유발군에 비해 발현이 감소되었다. TGF-${\beta}1$ 발현은 21일째 염증세포에서는 유발군이 처리군에 비해 현저한 증가 현상이 나타났으나, 샘꽈리세포에서의 TGF-${\beta}1$의 발현은 처리군에서 증가되었다. VEGF 발현은 TGF-${\beta}1$의 발현과 거의 유사한 경향으로 나타났다. 그러므로 야콘추출물이 DBTC로 유도된 췌장염의 섬유화 진행을 억제하는데 매우 효과적임을 확인하였다.

Keywords

References

  1. Alaaeddine, N., Di Battista, J. A., Pelletier, J. P., Kiansa, K., Cloutier, J. M. and Martel-Pelletier, J. 1999. Inhibtion of tumor necrosis factor alpha-induced prostaglandin E2 production by the antiinflammatory cytokines interleukin-4, interleukin-10, and interleukin-13 in osteoarthritic synovial fibroblasts: distinct targeting in the signaling pathways. Arthritis Rheum. 42, 710-718. https://doi.org/10.1002/1529-0131(199904)42:4<710::AID-ANR14>3.0.CO;2-4
  2. Aybar, M. J., Sanchez Riera, A. N. S., Grau, A. and Sánchez, S. 2001. Hypoglycemic effect of the water extract of Smallanutus sonchifolius (yacon) leaves in normal and diabetic rats. J. Ethnopharmacol. 74, 125-132. https://doi.org/10.1016/S0378-8741(00)00351-2
  3. Border, W. A., Okuda, S., Languino, L. R., Sporn, M. B. and Ruoslahti, E. 1990. Suppression of experimental glomerulonephritis by antiserum against transforming growth factor ${\beta}1$. Nature 346, 371-374. https://doi.org/10.1038/346371a0
  4. Broekelmann, T. J., Limper, A. H., Colby, T. V. and McDonald, J. A. 1991.Transforming growth factor-${\beta}1$ is present at sites of extracellular matrix gene expression in human pulmonary fibrosis. Proc. Natl. Acad. Sci. USA. 88, 6642-6646. https://doi.org/10.1073/pnas.88.15.6642
  5. Castilla, A., Prito, J. and Fausto, N. 1991. Transforming growth factor ${\beta}1$ and $1{\alpha}$ in chronic liver disease: effects of interferon ${\alpha}$ therapy. N. Engl. J. Med. 324, 933-940. https://doi.org/10.1056/NEJM199104043241401
  6. Choi, N. H., Choi, S. H., Lim, S. W. and Park, I. S. 2007. The effect of yacon (smallanthus sonchifolius) extract against dibutyltin dichloride-induced pancreatitis. The Korean J. Anat. 40, 259-266.
  7. Dvorak, H. F. 1986. Tumors: wounds that do not heal. Similarity between tumor stroma generation and wound healing. N. Engl. J. Med. 315, 1650-1658. https://doi.org/10.1056/NEJM198612253152606
  8. Dvorak, H. F., Harvey, V. S., Estrella, P., Brown, L. F., McDonagh, J. and Dvorak, A. M. 1987. Fibrin containing gels induce angiogenesis: implications for tumor stroma generation and wound healing. Lab. Invest. 57, 673-686.
  9. Ethridge, R. T., Chung, D. H., Slogoff, M., Ehlers, R. A., Rajaraman, M. R. S., Saito, H., Uchida, T. and Evers, M. 2002. Cyclooxygenase-2 gene disruption attenuates the severity of acute pancreatitis and pancteatitis- associated lung injury. Gastroenterology 123, 1311-1322. https://doi.org/10.1053/gast.2002.35951
  10. Ferrara, N. and Davis-Smyth, T. 1997. The biology of vascular endothelial growth factor. Endocr. Rev. 18, 4-25. https://doi.org/10.1210/er.18.1.4
  11. Frungieri, M. B., Raemsch, M. R. and Mayerhofe, A. 2005. The action of the mast cell product tryptase on cyclooxygenase-2 (COX2) and subsequent fibroblast proliferation involves activation of the extracellular signal-regulated kinase isoforms 1 and 2 (erk1/2). Cellular Signalling 17, 525-533. https://doi.org/10.1016/j.cellsig.2004.09.017
  12. Inoue, A., Tamogami, S., Kato, H., Nakazato, Y., Akiyama, M., Kodama, O., Akatsuka, T. and Hashidoko, Y. 1995. Antifungal melampolides from leaf extracts of smallanthus sonchifolius. Phytochemisty 39, 845-84. https://doi.org/10.1016/0031-9422(95)00023-Z
  13. Jo, Y. S., Moon, H. S., Chung, H. W., Kim, S. C. and Chun, S. H. 2006. The expression of angiopoietin-1, angiopoietin-2, Tie-2 and vascular endothelial growth factor mRNA in normal ovary, benign ovarian cyst, and epithelial ovarian cancer. Int. J. Gynecol. Cancer 17, 134-141.
  14. Kawamori, T., Rao, C. V., Seibert, K. and Reddy, B. S. 1998. Chemopreventive activity of elecoxib, a specific cyclooxygenase-2 inhibitor, against colon carcinogenesis. Cancer Res. 58, 409-412.
  15. Kim, C. D. 2003.Current status of acute pancreatitis in Korea. Korean J. Gastroenterol. 42, 1-11.
  16. Kim, C. D. 2005. Pancreatitis-Etiology and Pathogenesis. Korean J. Gastroenterol. 46, 321-332.
  17. Kloppel, G. and Maillet, B. 1992. The morphological basis for the evolution of acute pancreatitis into chronic pancreatitis. Virchows Arch. A Pathol. Anat. 420, 1-4. https://doi.org/10.1007/BF01605976
  18. Lin, F., Hasegawa, M. and Kodama, O. 2003. Purification and identification of antimicrobial sesquiterpene lactones from yacon (Smallanthus sonchifolius) leaves. Biosci. Biothechnol. Biochem. 67, 2154-2159. https://doi.org/10.1271/bbb.67.2154
  19. Maquart, F., Gillery, X. P., Kalis, B. and Borel, J. P. 1994. Cytokines and fibrosis. Eur. J. Dermatol. 4, 91-97.
  20. McCartney-Francis, N. L. and Wahl, S. M. 1994. Transforming growth factor ${\beta}$: a matter of life and death. J. Leukoc Biol. 55, 401-409.
  21. Merkord, J. and Hennighausen, G. 1989. Acute pancreatitis and bile duct lesions in rat induced by dibutyltin dichloride. Exp. Pathol. 36, 59-62. https://doi.org/10.1016/S0232-1513(89)80113-6
  22. Merkord, J., Jonas, L., Weber, H., Kröning, G., Nizze, H. and Hennighausen, G. 1997. Acute interstitial pancreatitis in rats induced by dibutyltin dichloride (DBTC): Pathogenesis and natural course of lesions. Pancreas. 15, 392-401. https://doi.org/10.1097/00006676-199711000-00010
  23. Mitchell, I. A., Larkim, S. and Williams, T. J. 1995. Cyclooxygenase-2: regulation and relevance in inflammation. Biochem. Pharmacol. 50, 1535-1542. https://doi.org/10.1016/0006-2952(95)00212-X
  24. Mohle, R., Green, D., Moore, M. A., Nachman, R. L. and Rafii. S. 1997. Constitutive production and thrombin-induced release of vascular endothelial growth factor by human megakaryocytes and platelets. Proc. Natl. Acad. Sci. USA. 94, 663-668. https://doi.org/10.1073/pnas.94.2.663
  25. Niiro, H., Otsuka, T., Ogami, E., Yamaoka, K., Nagano, S., Akahoshi, M., Nakashima, H., Arinobu, Y., Izuhara, K. and Niho, Y. 1998. MAP kinase pathways as a route for regulatory mechanisms of IL-10 and IL-4 which inhibit COX-2 expression in human monocytes. Biochem. Biophys. Res. Commun. 250, 200-205. https://doi.org/10.1006/bbrc.1998.9287
  26. Pertovaara, L., Kaipainen, A., Mustonen, T., Orpana, A., Ferrara, N., Saksela, O. and Alitalo, K. 1994. Vascular endothelial growth factor is induced in response to transforming growth factor-b in fibroblastic and epithelial cells. J. Biol. Chem. 269, 6271-6274.
  27. Reddy, S. T., Gilbert, R. S., Xie, W., Luner, S. and Herschman, H. R. 1994. TGF-beta 1 inhibits both endotoxin-induced prostaglandin synthesis and expression of the TIS10/prostaglandin synthase 2 gene in murine macrophages. J. Leukoc Biol. 55, 192-200.
  28. Roberts, W. G. and Palade, G. 1995. Increased microvascular permeability and endothelial fenestration induced by vascular endothelial growth factor. J. Cell Sci. 108, 2369-2379.
  29. Rousseau, S., Houle, F., Kotanides, H., Witte, L., Waltenberger, J., Landry, J. and Huot, J. 2000. Vascular endothelial growth factor (VEGF)-driven actin-based motility is mediated by VEGFR2 and requiers concerted activation of stress-activated protein kinase 2 (SAPK2/p38) and geldanamycin-sensitive phosporylation of focal adhesion kinase. J. Biol. Chem. 275, 10661-10672. https://doi.org/10.1074/jbc.275.14.10661
  30. Smith, W. C., Meade, E. A. and Dewitt, D. L. 1994. Pharmacology of prostaglandin endoperoxide synthase isozymes-1 and -2. Ann. NY Acad. Sci. 714, 136-142. https://doi.org/10.1111/j.1749-6632.1994.tb12037.x
  31. Sparmann, G., Merkord, J., Jäschke, A., Nizze, H., Jonas, L., Löhr, M., Liebe, S. and Emmrich, J. 1997. Pancreatic fibrosis in experimental pancreatitis induced by dibutyltin dichloride. Gastroenterology 112, 1664-1672. https://doi.org/10.1016/S0016-5085(97)70049-0
  32. Valentova, K. and Ulrichova, J. 2003. Smallanthus sonchifolius and Lepidium meyenii prospective Andean crops for the prevention of chronic diseases. Biomed Papers 147, 119-130. https://doi.org/10.5507/bp.2003.017
  33. Valentova, K., Frcek, J., and Ulrichova, J. 2001. Yacon (Smallanthus sonchifolius) and Maca (Lepidium meyenii), traditional Andean crops as new functional foods on the European market. Chem. Listy. 95, 594-601.
  34. Valentova, K., Cvak, L., Muck, A., Ulrichova, J. and Simanek, V. 2003. Antioxidant activity of extracts from the leaves of Smallanthus sonchifolius. Eur. J. Nutr. 42, 61-66. https://doi.org/10.1007/s00394-003-0402-x
  35. Van Laethem, J. L., Deviere, J., Resibois, A., Rickaert, F., Vertongen, P., Ohtani, H., Cremer, M., Miyazono, K. and Robberecht, P. 1995. Localization of transforming growth factor ${\beta}1$ and its latent binding protein in human chronic pancreatitis. Gastroenterology 108, 1873-1881. https://doi.org/10.1016/0016-5085(95)90152-3

Cited by

  1. In vitro cytotoxic potential of Yacon (Smallanthus sonchifolius) against HT-29, MCF-7 and HDFn cell lines vol.11, pp.10, 2017, https://doi.org/10.5897/JMPR2016.6205