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Original Paper

Open Access Gateway

Ginsenoside Rh2 Suppresses Neovascularization in Xenograft Psoriasis Model

Zhou J. · Gao Y. · Yi X. · Ding Y.

Author affiliations

Department of Dermatology, Shanghai Dermatology Hospital, Shanghai, China

Corresponding Author

Yangfeng Ding,

Department of Dermatology, Shanghai Dermatology Hospital, 200 Wuyi Road, Shanghai

200050 (China)

Tel. +862161833000, Fax +862161833021, E-Mail gaoyunlu2002@163.com

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Cell Physiol Biochem 2015;36:980-987

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Abstract

Background/Aims: Psoriasis is a common inflammatory skin disease of undetermined etiology and poor prognosis. The current therapies have focused on direct inhibition of local inflammation, e.g. through hormone treatments. However, neovascularization plays a critical role in the development of psoriasis but so far no therapies have been developed to suppress psoriasis-associated neovascularization. Methods: We treated AGR129 mice that had received human PN skin grafts with different doses of Ginsenoside Rh2 (GRh2). The acanthosis and papillomatosis index were evaluated. The percentage of T lymphocytes in the grafts was quantified by flow cytometry. The levels of vascularization in the grafts were quantified based on CD31-positive area. We examined the levels of VEGF-A in the skin treated with GRh2. We treated AGR129 mice that had received human PN skin grafts with different doses of soluble Flt-1 (sFlt1) and then evaluated the effects on the acanthosis and papillomatosis index, T lymphocyte percentage and vessel density. Results: GRh2 dose-dependently decreased the acanthosis and papillomatosis index, T lymphocyte percentage and vessel density in PN skin grafts in mice. GRh2 inhibited VEGF-A levels in the PN skin grafts. Treatment with sFlt1 mimicked the effects of GRh2 on the acanthosis and papillomatosis index, T lymphocyte percentage and vessel density in PN skin grafts in mice. Conclusions: GRh2 may have an anti-psoriasis effect through neovascularization suppression.

© 2015 S. Karger AG, Basel


References

  1. Wagner EF, Schonthaler HB, Guinea-Viniegra J, Tschachler E: Psoriasis: What we have learned from mouse models. Nat Rev Rheumatol 2010;6:704-714.
  2. Perera GK, Di Meglio P, Nestle FO: Psoriasis. Annu Rev Pathol 2012;7:385-422.
  3. Nestle FO, Kaplan DH, Barker J: Psoriasis. N Engl J Med 2009;361:496-509.
  4. Xiong H, Xu Y, Tan G, Han Y, Tang Z, Xu W, Zeng F, Guo Q: Glycyrrhizin ameliorates imiquimod-induced psoriasis-like skin lesions in balb/c mice and inhibits tnf-alpha-induced icam-1 expression via nf-kappab/mapk in hacat cells. Cell Physiol Biochem 2015;35:1335-1346.
  5. Olah A, Szollosi AG, Biro T: The channel physiology of the skin. Rev Physiol, Biochem Pharmacol 2012;163:65-131.
  6. Danilenko DM: Review paper: Preclinical models of psoriasis. Vet Pathol 2008;45:563-575.
  7. Gudjonsson JE, Johnston A, Dyson M, Valdimarsson H, Elder JT: Mouse models of psoriasis. J Invest Dermatol 2007;127:1292-1308.
  8. Diani M, Altomare G, Reali E: T cell responses in psoriasis and psoriatic arthritis. Autoimmun Rev 2015;14:286-292.
  9. Novelli L, Chimenti MS, Chiricozzi A, Perricone R: The new era for the treatment of psoriasis and psoriatic arthritis: Perspectives and validated strategies. Autoimmun Rev 2014;13:64-69.
  10. Christophers E, Metzler G, Rocken M: Bimodal immune activation in psoriasis. Br J Dermatol 2014;170:59-65.
  11. Trowbridge RM, Pittelkow MR: Epigenetics in the pathogenesis and pathophysiology of psoriasis vulgaris. J Drugs Dermatol 2014;13:111-118.
  12. Kere J: Mapping and identifying genes for asthma and psoriasis. Philos Trans R Soc Lond B Biol Sci 2005;360:1551-1561.
  13. Xiao X, Prasadan K, Guo P, El-Gohary Y, Fischbach S, Wiersch J, Gaffar I, Shiota C, Gittes GK: Pancreatic duct cells as a source of vegf in mice. Diabetologia 2014;57:991-1000.
  14. Xiao X, Guo P, Chen Z, El-Gohary Y, Wiersch J, Gaffar I, Prasadan K, Shiota C, Gittes GK: Hypoglycemia reduces vascular endothelial growth factor a production by pancreatic beta cells as a regulator of beta cell mass. J Biol Chem 2013;288:8636-8646.
  15. Ferrara N, Gerber HP, LeCouter J: The biology of vegf and its receptors. Nat Med 2003;9:669-676.
  16. Ma J, Sawai H, Ochi N, Matsuo Y, Xu D, Yasuda A, Takahashi H, Wakasugi T, Takeyama H: Pten regulates angiogenesis through pi3k/akt/vegf signaling pathway in human pancreatic cancer cells. Mol Cell Biochem 2009;331:161-171.
  17. Cabebe E, Fisher GA: Clinical trials of vegf receptor tyrosine kinase inhibitors in pancreatic cancer. Expert Opin Investig Drugs 2007;16:467-476.
  18. Hotz HG, Hines OJ, Masood R, Hotz B, Foitzik T, Buhr HJ, Gill PS, Reber HA: Vegf antisense therapy inhibits tumor growth and improves survival in experimental pancreatic cancer. Surgery 2005;137:192-199.
  19. Mao D, Zhang Y, Lu H, Zhang H: Molecular basis underlying inhibition of metastasis of gastric cancer by anti-vegfa treatment. Tumour Biol 2014;35:8217-8223.
  20. Zhou X, Qi Y: Plgf inhibition impairs metastasis of larynx carcinoma through mmp3 downregulation. Tumour Biol 2014;35:9381-9386.
  21. Coimbra S, Figueiredo A, Castro E, Rocha-Pereira P, Santos-Silva A: The roles of cells and cytokines in the pathogenesis of psoriasis. Int J Dermatol 2012;51:389-395; quiz 395-388.
  22. Sweeney CM, Tobin AM, Kirby B: Innate immunity in the pathogenesis of psoriasis. Arch Dermatol Res 2011;303:691-705.
  23. Shibata S: Chemistry and cancer preventing activities of ginseng saponins and some related triterpenoid compounds. J Kor Med Sci 2001;16:S28-37.
  24. Fraki JE, Briggaman RA, Lazarus GS: Transplantation of psoriatic skin onto nude mice. J Invest Dermatol 1983;80:31s-35s.

Article / Publication Details

First-Page Preview
Abstract of Original Paper

Accepted: May 20, 2015
Published online: June 15, 2015
Issue release date: June 2015

Number of Print Pages: 8
Number of Figures: 5
Number of Tables: 0

ISSN: 1015-8987 (Print)
eISSN: 1421-9778 (Online)

For additional information: https://www.karger.com/CPB

References

  1. Wagner EF, Schonthaler HB, Guinea-Viniegra J, Tschachler E: Psoriasis: What we have learned from mouse models. Nat Rev Rheumatol 2010;6:704-714.
  2. Perera GK, Di Meglio P, Nestle FO: Psoriasis. Annu Rev Pathol 2012;7:385-422.
  3. Nestle FO, Kaplan DH, Barker J: Psoriasis. N Engl J Med 2009;361:496-509.
  4. Xiong H, Xu Y, Tan G, Han Y, Tang Z, Xu W, Zeng F, Guo Q: Glycyrrhizin ameliorates imiquimod-induced psoriasis-like skin lesions in balb/c mice and inhibits tnf-alpha-induced icam-1 expression via nf-kappab/mapk in hacat cells. Cell Physiol Biochem 2015;35:1335-1346.
  5. Olah A, Szollosi AG, Biro T: The channel physiology of the skin. Rev Physiol, Biochem Pharmacol 2012;163:65-131.
  6. Danilenko DM: Review paper: Preclinical models of psoriasis. Vet Pathol 2008;45:563-575.
  7. Gudjonsson JE, Johnston A, Dyson M, Valdimarsson H, Elder JT: Mouse models of psoriasis. J Invest Dermatol 2007;127:1292-1308.
  8. Diani M, Altomare G, Reali E: T cell responses in psoriasis and psoriatic arthritis. Autoimmun Rev 2015;14:286-292.
  9. Novelli L, Chimenti MS, Chiricozzi A, Perricone R: The new era for the treatment of psoriasis and psoriatic arthritis: Perspectives and validated strategies. Autoimmun Rev 2014;13:64-69.
  10. Christophers E, Metzler G, Rocken M: Bimodal immune activation in psoriasis. Br J Dermatol 2014;170:59-65.
  11. Trowbridge RM, Pittelkow MR: Epigenetics in the pathogenesis and pathophysiology of psoriasis vulgaris. J Drugs Dermatol 2014;13:111-118.
  12. Kere J: Mapping and identifying genes for asthma and psoriasis. Philos Trans R Soc Lond B Biol Sci 2005;360:1551-1561.
  13. Xiao X, Prasadan K, Guo P, El-Gohary Y, Fischbach S, Wiersch J, Gaffar I, Shiota C, Gittes GK: Pancreatic duct cells as a source of vegf in mice. Diabetologia 2014;57:991-1000.
  14. Xiao X, Guo P, Chen Z, El-Gohary Y, Wiersch J, Gaffar I, Prasadan K, Shiota C, Gittes GK: Hypoglycemia reduces vascular endothelial growth factor a production by pancreatic beta cells as a regulator of beta cell mass. J Biol Chem 2013;288:8636-8646.
  15. Ferrara N, Gerber HP, LeCouter J: The biology of vegf and its receptors. Nat Med 2003;9:669-676.
  16. Ma J, Sawai H, Ochi N, Matsuo Y, Xu D, Yasuda A, Takahashi H, Wakasugi T, Takeyama H: Pten regulates angiogenesis through pi3k/akt/vegf signaling pathway in human pancreatic cancer cells. Mol Cell Biochem 2009;331:161-171.
  17. Cabebe E, Fisher GA: Clinical trials of vegf receptor tyrosine kinase inhibitors in pancreatic cancer. Expert Opin Investig Drugs 2007;16:467-476.
  18. Hotz HG, Hines OJ, Masood R, Hotz B, Foitzik T, Buhr HJ, Gill PS, Reber HA: Vegf antisense therapy inhibits tumor growth and improves survival in experimental pancreatic cancer. Surgery 2005;137:192-199.
  19. Mao D, Zhang Y, Lu H, Zhang H: Molecular basis underlying inhibition of metastasis of gastric cancer by anti-vegfa treatment. Tumour Biol 2014;35:8217-8223.
  20. Zhou X, Qi Y: Plgf inhibition impairs metastasis of larynx carcinoma through mmp3 downregulation. Tumour Biol 2014;35:9381-9386.
  21. Coimbra S, Figueiredo A, Castro E, Rocha-Pereira P, Santos-Silva A: The roles of cells and cytokines in the pathogenesis of psoriasis. Int J Dermatol 2012;51:389-395; quiz 395-388.
  22. Sweeney CM, Tobin AM, Kirby B: Innate immunity in the pathogenesis of psoriasis. Arch Dermatol Res 2011;303:691-705.
  23. Shibata S: Chemistry and cancer preventing activities of ginseng saponins and some related triterpenoid compounds. J Kor Med Sci 2001;16:S28-37.
  24. Fraki JE, Briggaman RA, Lazarus GS: Transplantation of psoriatic skin onto nude mice. J Invest Dermatol 1983;80:31s-35s.

Open Access License / Drug Dosage / Disclaimer

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