Skip to main content

Advertisement

SpringerLink
Log in

Gingko biloba extract reduces VEGF and CXCL-8/IL-8 levels in keratinocytes with cumulative effect with epigallocatechin-3-gallate

  • Original Paper
  • Published:
Archives of Dermatological Research Aims and scope Submit manuscript

Abstract

In skin inflammation, vascular endothelial growth factor (VEGF) and CXCL-8/IL-8 play an important role and are produced by activated keratinocytes. Extracts from Ginkgo biloba leaves (GBE), widely used in phytotherapy, have been reported to exert antioxidant and anti-inflammatory properties in the skin. We therefore evaluated the effects of GBE on the release of VEGF and CXCL8/IL-8 by normal human keratinocytes (NHKs) activated by tumor necrosis factor α (TNFα). Moreover, as we previously showed that epigallocatechin-3-gallate (EGCG) reduces VEGF and CXCL8/IL-8 secretion in TNFα-activated NHKs, we also tested its effect in association with GBE. Our results showed that GBE exerted a potent inhibition on VEGF and CXCL8/IL-8 levels in activated cells. In association with EGCG, GBE down-regulated VEGF and CXCL8/IL-8 levels in a cumulative manner in TNFα-stimulated NHKs. These results suggest that GBE, alone or in association with EGCG may contribute to moderate inflammatory processes in skin diseases associated with angiogenesis.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

BPE:

Bovine pituitary extract

COX:

Cyclooxygenase

EGCG:

Epigallocatechin-3-gallate

EGF:

Epidermal growth factor

ELISA:

Enzyme-linked immunosorbent assays

GBE:

Ginkgo biloba extract

IL:

Interleukin

MTT:

3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide

NHK:

Normal human keratinocyte

PG:

Propylene glycol

TNFα:

Tumor necrosis factor α

UV:

Ultraviolet

References

  1. Baggiolini M, Dewald B, Moser B (1994) Interleukin-8 and related chemotactic cytokines—CXC and CC chemokines. Adv Immunol 55:97–179

    Article  CAS  PubMed  Google Scholar 

  2. Ballaun C, Weninger W, Uthman A et al (1995) Human keratinocytes express the three major splice forms of vascular endothelial growth factor. J Invest Dermatol 104:7–10

    Article  CAS  PubMed  Google Scholar 

  3. Castelli D, Colin L, Camel E et al (1998) Pretreatment of skin with a Ginkgo biloba extract/sodium carboxymethyl-beta-1, 3-glucan formulation appears to inhibit the elicitation of allergic contact dermatitis in man. Contact Dermat 38:123–126

    Article  CAS  Google Scholar 

  4. Cheung F, Yl Siow, Wz Chen et al (1999) Inhibitory effect of Ginkgo biloba extract on the expression of inducible nitric oxide synthase in endothelial cells. Biochem Pharmacol 58:1665–1673

    Article  CAS  PubMed  Google Scholar 

  5. Defeudis FV, Papadopoulos V, Drieu K (2003) Ginkgo biloba extracts and cancer: a research area in its infancy. Fundam Clin Pharmacol 17:405–417

    Article  CAS  PubMed  Google Scholar 

  6. Ferrara N, Davis-Smyth T (1997) The biology of vascular endothelial growth factor. Endocr Rev 18:4–25

    Article  CAS  PubMed  Google Scholar 

  7. Frank S, Hubner G, Breier G et al (1995) Regulation of vascular endothelial growth factor expression in cultured keratinocytes. Implications for normal and impaired wound healing. J Biol Chem 270:12607–12613

    Article  CAS  PubMed  Google Scholar 

  8. Fujiki H, Suganuma M, Okabe S et al (1999) Mechanistic findings of green tea as cancer preventive for humans. Proc Soc Exp Biol Med 220:225–228

    Article  CAS  PubMed  Google Scholar 

  9. Gomaa AH, Yaar M, Eyada MM et al (2007) Lymphangiogenesis and angiogenesis in non-phymatous rosacea. J Cutan Pathol 34:748–753

    Article  PubMed  Google Scholar 

  10. Huh H, Staba E (1992) The botany and chemistry of Ginkgo biloba L. J Herbs Spices Med Plants 1:92–124

    Article  Google Scholar 

  11. Juarez CP, Muino JC, Guglielmone H et al (2000) Experimental retinopathy of prematurity: angiostatic inhibition by nimodipine, ginkgo-biloba, and dipyridamole, and response to different growth factors. Eur J Ophthalmol 10:51–59

    CAS  PubMed  Google Scholar 

  12. Kanowski S, Herrmann WM, Stephan K et al (1996) Proof of efficacy of the ginkgo biloba special extract EGb 761 in outpatients suffering from mild to moderate primary degenerative dementia of the Alzheimer type or multi-infarct dementia. Pharmacopsychiatry 29:47–56

    Article  CAS  PubMed  Google Scholar 

  13. Katiyar SK, Ahmad N, Mukhtar H (2000) Green tea and skin. Arch Dermatol 136:989–994

    Article  CAS  PubMed  Google Scholar 

  14. Kim BH, Lee YS, Kang KS (2003) The mechanism of retinol-induced irritation and its application to anti-irritant development. Toxicol Lett 146:65–73

    Article  CAS  PubMed  Google Scholar 

  15. Kim SJ (2001) Effect of biflavones of Ginkgo biloba against UVB-induced cytotoxicity in vitro. J Dermatol 28:193–199

    CAS  PubMed  Google Scholar 

  16. Kwak WJ, Han CK, Son KH et al (2002) Effects of Ginkgetin from Ginkgo biloba Leaves on cyclooxygenases and in vivo skin inflammation. Planta Med 68:316–321

    Article  CAS  PubMed  Google Scholar 

  17. Larsen CG, Anderson AO, Oppenheim JJ et al (1989) Production of interleukin-8 by human dermal fibroblasts and keratinocytes in response to interleukin-1 or tumour necrosis factor. Immunology 68:31–36

    CAS  PubMed  Google Scholar 

  18. Lim H, Son KH, Chang HW et al (2006) Effects of anti-inflammatory biflavonoid, ginkgetin, on chronic skin inflammation. Biol Pharm Bull 29:1046–1049

    Article  CAS  PubMed  Google Scholar 

  19. Lim H, Son KH, Chang HW et al (2006) Inhibition of chronic skin inflammation by topical anti-inflammatory flavonoid preparation, Ato Formula. Arch Pharm Res 29:503–507

    Article  CAS  PubMed  Google Scholar 

  20. Longuet-Perret I, Schmitt D, Viac J (1998) Tumour necrosis factor-alpha is involved in the contrasting effects of ultraviolet B and ultraviolet A1 radiation on the release by normal human keratinocytes of vascular permeability factor. Br J Dermatol 138:221–224

    Article  CAS  PubMed  Google Scholar 

  21. Mahadevan S, Park Y (2008) Multifaceted therapeutic benefits of Ginkgo biloba L.: chemistry, efficacy, safety, and uses. J Food Sci 73:R14–R19

    Article  CAS  PubMed  Google Scholar 

  22. Mizuno M, Mt Droy-Lefaix, Packer L (1996) Gingko biloba extract EGb 761 is a suppresser of AP-1 transcription factor stimulated by phorbol 12-myristate 13-acetate. Biochem Mol Biol Int 39:395–401

    CAS  PubMed  Google Scholar 

  23. Neufeld G, Cohen T, Gengrinovitch S et al (1999) Vascular endothelial growth factor (VEGF) and its receptors. FASEB J 13:9–22

    CAS  PubMed  Google Scholar 

  24. Nishida S, Satoh H (2003) Mechanisms for the vasodilations induced by Ginkgo biloba extract and its main constituent, bilobalide, in rat aorta. Life Sci 72:2659–2667

    Article  CAS  PubMed  Google Scholar 

  25. Parsad D, Pandhi R, Juneja A (2003) Effectiveness of oral Ginkgo biloba in treating limited, slowly spreading vitiligo. Clin Exp Dermatol 28:285–287

    Article  CAS  PubMed  Google Scholar 

  26. Pernet I, Sagot V, Schmitt D et al (1999) UVA1 and UVB radiation but not PGE2 stimulate IL-8 release in normal human keratinocytes. Arch Dermatol Res 291:527–529

    Article  CAS  PubMed  Google Scholar 

  27. Pietrzak AT, Zalewska A, Chodorowska G et al (2008) Cytokines and anticytokines in psoriasis. Clin Chim Acta 394:7–21

    Article  CAS  PubMed  Google Scholar 

  28. Rimbach G, Gohil K, Matsugo S et al (2001) Induction of glutathione synthesis in human keratinocytes by Ginkgo biloba extract (EGb761). Biofactors 15:39–52

    Article  CAS  PubMed  Google Scholar 

  29. Rosenberger C, Solovan C, Rosenberger AD et al (2007) Upregulation of hypoxia-inducible factors in normal and psoriatic skin. J Invest Dermatol 127:2445–2452

    Article  CAS  PubMed  Google Scholar 

  30. Sagar SM, Yance D, Wong RK (2006) Natural health products that inhibit angiogenesis: a potential source for investigational new agents to treat cancer-Part 1. Curr Oncol 13:14–26

    CAS  PubMed  Google Scholar 

  31. Smith JR, Lanier VB, Braziel RM et al (2007) Expression of vascular endothelial growth factor and its receptors in rosacea. Br J Ophthalmol 91:226–229

    Article  PubMed  Google Scholar 

  32. Takematsu H, Tagami H (1993) Mode of release of interleukin-8 from proliferating human epidermal keratinocytes in vitro. Exp Dermatol 2:121–124

    Article  CAS  PubMed  Google Scholar 

  33. Trompezinski S, Denis A, Schmitt D et al (2003) Comparative effects of polyphenols from green tea (EGCG) and soybean (genistein) on VEGF and IL-8 release from normal human keratinocytes stimulated with the proinflammatory cytokine TNFalpha. Arch Dermatol Res 295:112–116

    Article  CAS  PubMed  Google Scholar 

  34. Trompezinski S, Pernet I, Schmitt D et al (2001) UV radiation and prostaglandin E2 up-regulate vascular endothelial growth factor (VEGF) in cultured human fibroblasts. Inflamm Res 50:422–427

    Article  CAS  PubMed  Google Scholar 

  35. Viac J, Palacio S, Schmitt D et al (1997) Expression of vascular endothelial growth factor in normal epidermis, epithelial tumors and cultured keratinocytes. Arch Dermatol Res 289:158–163

    Article  CAS  PubMed  Google Scholar 

  36. Wei Z, Peng Q, Bh Lau et al (1999) Ginkgo biloba inhibits hydrogen peroxide-induced activation of nuclear factor kappa B in vascular endothelial cells. Gen Pharmacol 33:369–375

    Article  CAS  PubMed  Google Scholar 

  37. Xia YP, Li B, Hylton D et al (2003) Transgenic delivery of VEGF to mouse skin leads to an inflammatory condition resembling human psoriasis. Blood 102:161–168

    Article  CAS  PubMed  Google Scholar 

  38. Yang PY, Rui YC, Zhang L et al (2002) Expression of vascular endothelial growth factor in U937 foam cells and the inhibitory effect of drugs. Yao Xue Xue Bao 37:86–89

    CAS  PubMed  Google Scholar 

  39. Yoshikawa T, Naito Y, Kondo M (1999) Ginkgo biloba leaf extract: review of biological actions and clinical applications. Antioxid Redox Signal 1:469–480

    Article  CAS  PubMed  Google Scholar 

  40. Zhang L, Rui YC, Yang PY et al (2002) Inhibitory effects of Ginkgo biloba extract on vascular endothelial growth factor in rat aortic endothelial cells. Acta Pharmacol Sin 23:919–923

    CAS  PubMed  Google Scholar 

  41. Zheng SX, Zhou LJ, Chen ZL et al (2000) Bilobalide promotes expression of glial cell line-derived neurotrophic factor and vascular endothelial growth factor in rat astrocytes. Acta Pharmacol Sin 21:151–155

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank pediatric service (Tbis) of Edouard Herriot Hospital in Lyon for their cooperation in collecting skin biopsy samples.

Conflict of interest statement

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Université de Lyon, EA4169, Hôpital E. Herriot, 69437, Lyon, France

    Sandra Trompezinski, Daniel Schmitt & Jacqueline Viac

  2. DIPTA, 505, rue Pierre Berthier, 13855, Aix-en-Provence, France

    Sandra Trompezinski & Ingrid Pernet

  3. Laboratoire Dermatologique Bioderma, 75 Cours Albert Thomas, 69003, Lyon, France

    Marlène Bonneville & Alain Denis

Authors
  1. Sandra Trompezinski
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marlène Bonneville
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ingrid Pernet
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Alain Denis
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Daniel Schmitt
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jacqueline Viac
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sandra Trompezinski.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Trompezinski, S., Bonneville, M., Pernet, I. et al. Gingko biloba extract reduces VEGF and CXCL-8/IL-8 levels in keratinocytes with cumulative effect with epigallocatechin-3-gallate. Arch Dermatol Res 302, 183–189 (2010). https://doi.org/10.1007/s00403-009-0979-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00403-009-0979-x

Keywords

Search

Navigation