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Table of Contents
Vol. 25, No. 2, 2012
Issue release date: February 2012
Section title: Original Paper
Skin Pharmacol Physiol 2012;25:86–92
(DOI:10.1159/000335261)

Pycnogenol® Effects on Skin Elasticity and Hydration Coincide with Increased Gene Expressions of Collagen Type I and Hyaluronic Acid Synthase in Women

Marini A.a · Grether-Beck S.a · Jaenicke T.a · Weber M.a · Burki C.b · Formann P.a · Brenden H.a · Schönlau F.b · Krutmann J.a
aIUF – Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany; bHorphag Research, Cointrin/Geneva, Switzerland
email Corresponding Author

Abstract

Introduction and Objectives: In recent years there has been an increasing interest in the use of nutritional supplements to benefit human skin. Molecular evidence substantiating such effects, however, is scarce. In the present study we investigated whether nutritional supplementation of women with the standardized pine bark extract Pycnogenol® will improve their cosmetic appearance and relate these effects to expression of corresponding molecular markers of their skin. Materials and Methods: For this purpose 20 healthy postmenopausal women were supplemented with Pycnogenol for 12 weeks. Before, during and after supplementation, their skin condition was assessed (i) by employing non-invasive, biophysical methods including corneometry, cutometry, visioscan and ultrasound analyses and (ii) by taking biopsies and subsequent PCR for gene expression analyses related to extracellular matrix homeostasis. Results: Pycnogenol supplementation was well tolerated in all volunteers. Pycnogenol significantly improved hydration and elasticity of skin. These effects were most pronounced in women presenting with dry skin conditions prior to the start of supplementation. The skin-physiological improvement was accompanied by a significant increase in the mRNA expression of hyaluronic acid synthase-1 (HAS-1), an enzyme critically involved in the synthesis of hyaluronic acid, and a noticeable increase in gene expression involved in collagen de novo synthesis. Conclusions: This study provides skin-physiological and for the first time molecular evidence that Pycnogenol supplementation benefits human skin by increasing skin hydration and skin elasticity. These effects are most likely due to an increased synthesis of extracellular matrix molecules such as hyaluronic acid and possibly collagen. Pycnogenol supplementation may thus be useful to counteract the clinical signs of skin aging.

© 2012 S. Karger AG, Basel


  

Key Words

  • Pycnogenol®
  • Pine bark extract
  • Skin hydration
  • Skin elasticity
  • Collagen expression
  • Hyaluronic acid synthase-1

References

  1. Gilchrest BA, Krutmann J: Photoaging of skin; in Gilchrest BA, Krutmann J (eds): Skin Aging. Berlin, Springer, 2006, pp 33–44.
  2. Krutmann J: Skin aging; in Krutmann J, Humbert P (eds): Nutrition for Healthy Skin: Strategies for Clinical and Cosmetic Practice. Berlin, Springer, 2011, pp 15–24.
  3. Rohdewald P: A review of the French maritime pine bark extract (Pycnogenol®), a herbal medication with a diverse clinical pharmacology. Int J Clin Pharmacol Ther 2002;40:158–168.
  4. Belcaro G, Cesarone MR, Errichi BM, Ledda A, Di Renzo A, Stuard S, Dugall M, Pellegrini L, Gizzi G, Rohdewald P, Ippolito E, Ricci A, Cacchio M, Cipollone G, Ruffini I, Fano F, Hosoi M: Diabetic ulcers: microcirculatory improvement and faster healing with Pycnogenol®. Clin Appl Thromb Hemost 2006;12:318–323.
  5. Petrassi C, Mastromarino A, Spartera C: Pycnogenol® in chronic venous insufficiency. Phytomedicine 2000;7:383–388.
  6. Bayeta E, Bejamin MS, Lau HS: Pycnogenol inhibits generation of inflammatory mediators in macrophages. Nutr Res 2000; 20:249–259.
  7. Blazso G, Gabor M, Schönlau F, Rohdewald P: Pycnogenol® accelerates wound healing and reduces scar formation. Phytother Res 2005;18:579–581.

    External Resources

  8. Devaraj S, Kaul N, Schönlau F, Rohdewald P, Jialal I: Supplementation with a pine bark extract rich in polyphenols increases plasma antioxidant capacity and alters plasma lipoprotein profile. Lipids 2002;37:931–934.
  9. Blumenthal M: Pycnogenol (French maritime pine bark extract) Pinus pinaster Aiton subsp. atlantica; in Blumenthal M, et al (eds): The American Botanical Council Guide to Herbs. Austin, American Botanical Council, 2003, pp 369–373.
  10. Maimoona A, Naeem I, Saddiqe Z, Jameel K: A review on biological, nutraceutical and clinical aspects of French maritime pine bark extract. J Ethnopharmacol 2011;133: 261–277.
  11. Grimm T, Schäfer A, Högger P: Antioxidant activity and inhibition of matrix metalloproteinases by metabolites of maritime pine bark extract (Pycnogenol). Free Radical Biol Med 2004;36:811–822.
  12. Segger D, Schönlau F: Supplementation with Evelle improves skin smoothness and elasticity in a doubleblind, placebo-controlled study with 62 women. J Dermatol Treat 2004;15:222–226.
  13. Grether-Beck S, Timmer A, Felsner I, Brenden H, Brammertz D, Krutmann J: Ultraviolet A-induced signaling involves a ceramide-mediated autocrine loop leading to ceramide de novo synthesis. J Invest Dermatol 2005:125: 545–553.
  14. Livak KJ, Schmittgen TD: Analysis of relative gene expression data using real time quantitative PCR and the 2 (-delta delta C(T)) method. Methods 2001;25:402–408.
  15. McCallum FS, Maden BE: Human 18S ribosomal RNA sequence inferred from DNA sequence. Variations in 18S sequences and secondary modification pattern between vertebrates. Biochem J 1985;232:725–733.
  16. Tromp G, Kuivaniemi H, Stacey A, Shikata H, Baldwin CT, Jaenisch R, Prockop DJ: Structure of a full-length cDNA clone for the prepro alpha 1(I) chain of human type I procollagen. Biochem J 1988;253:919–922.
  17. Kuivaniemi H, Tromp G, Chu ML, Prockop DJ: Structure of a full-length cDNA clone for the prepro alpha 2(I) chain of human type I procollagen. Comparison with the chicken gene confirms unusual patterns of gene conservation. Biochem J 1988;252:633–640.
  18. Shyjan AM, Heldin P, Butcher EC, Yoshino T, Briskin MJ: Functional cloning of the cDNA for a human hyaluronan synthase. J Biol Chem 1996;271:23395–23399.
  19. Ahn S, Kim S, Lee H, Moon S, Chang I: Correlation between a Cutometer and quantitative evaluation using Moire topography in age-related skin elasticity. Skin Res Technol 2007;13:280–284.
  20. Dobrev H: Application of Cutometer area parameters for the study of human skin fatigue. Skin Res Technol 2005;11:120–122.
  21. Wiedersberg S, Leopold CS, Guy RH: Effects of various vehicles on skin hydration in vivo. Skin Pharmacol Physiol 2009;22:128–130.
  22. Schroeder P, Calles C, Benesova T, Macaluso F, Krutmann J: Photoprotection beyond ultraviolet radiation – effective sun protection has to include protection against infrared A radiation-induced skin damage. Skin Pharmacol Physiol 2010;23:15–17.
  23. Tronnier H, Wiebusch M, Heinrich U: Change in skin physiological parameters in space – report on and results of the first study on man. Skin Pharmacol Physiol 2008;21:283–292.
  24. Dai G, Freudenberger T, Zipper P, Melchior A, Grether-Beck S, Rabausch B, de Groot J, Twarock S, Hanenberg H, Homey B, Krutmann J, Reifenberger J, Fischer JW: Chronic ultraviolet B irradiation causes loss of hyaluronic acid from mouse dermis because of down-regulation of hyaluronic acid synthases. Am J Pathol 2007;171:1451–1461.
  25. Itano N, Kimata K: Molecular cloning of human hyaluronan synthase. Biochem Biophys Res Commun 1996;222:816–820.
  26. Jacobson A, Brinck J, Briskin MJ, Spicer AP, Heldin P: Expression of human hyaluronan synthases in response to external stimuli. Biochem J 2000;348:29–35.
  27. Sugiyama Y, Shimada A, Sayo T, Sakai S, Inoue S: Putative hyaluronan synthase mRNA are expressed in mouse skin and TGF-β upregulates their expression in cultured human skin cells. J Invest Dermatol 1998;110:116–121.
  28. Tammi R, Pasonen-Seppanen S, Kolehmainen E, Tammi M: Hyaluronan synthase induction and hyaluronan accumulation in mouse epidermis following skin injury. J Invest Dermatol 2005;124:898–905.
  29. Laurent TC, Fraser JR: Hyaluronan. FASEB J 1992;6:2397–2404.
  30. Sherman L, Sleeman J, Herrlich P, Ponta H: Hyaluronate receptors: key players in growth, differentiation, migration and tumor progression. Curr Opin Cell Biol 1994;6:726–733.
  31. Toole BP, Wight TN, Tammi MI: Hyaluronan-cell interactions in cancer and vascular disease. J Biol Chem 2002;277:4593–4596.
  32. Tammi R, Ripellino JA, Margolis RU, Tammi M: Localization of epidermal hyaluronic acid using the hyaluronate binding region of cartilage proteoglycan as a specific probe. J Invest Dermatol 1988;90:412–414.
  33. Wang C, Tammi M, Tammi R: Distribution of hyaluronan and its CD44 receptor in the epithelia of human skin appendages. Histochemistry 1992;98:105–112.

  

Author Contacts

Univ.-Prof. Dr. Jean Krutmann
IUF – Leibniz Research Institute for Environmental Medicine
Auf’m Henekamp 50
DE–40225 Düsseldorf (Germany)
Tel. +49 211 3389 225, E-Mail krutmann@uni-duesseldorf.de

  

Article Information

A.M. and S.G.-B. contributed equally to this work.

Received: July 21, 2011
Accepted after revision: November 17, 2011
Published online: January 21, 2012
Number of Print Pages : 7
Number of Figures : 5, Number of Tables : 2, Number of References : 33

  

Publication Details

Skin Pharmacology and Physiology (Journal of Pharmacological and Biophysical Research)

Vol. 25, No. 2, Year 2012 (Cover Date: February 2012)

Journal Editor: Lademann J. (Berlin)
ISSN: 1660-5527 (Print), eISSN: 1660-5535 (Online)

For additional information: http://www.karger.com/SPP


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Abstract

Introduction and Objectives: In recent years there has been an increasing interest in the use of nutritional supplements to benefit human skin. Molecular evidence substantiating such effects, however, is scarce. In the present study we investigated whether nutritional supplementation of women with the standardized pine bark extract Pycnogenol® will improve their cosmetic appearance and relate these effects to expression of corresponding molecular markers of their skin. Materials and Methods: For this purpose 20 healthy postmenopausal women were supplemented with Pycnogenol for 12 weeks. Before, during and after supplementation, their skin condition was assessed (i) by employing non-invasive, biophysical methods including corneometry, cutometry, visioscan and ultrasound analyses and (ii) by taking biopsies and subsequent PCR for gene expression analyses related to extracellular matrix homeostasis. Results: Pycnogenol supplementation was well tolerated in all volunteers. Pycnogenol significantly improved hydration and elasticity of skin. These effects were most pronounced in women presenting with dry skin conditions prior to the start of supplementation. The skin-physiological improvement was accompanied by a significant increase in the mRNA expression of hyaluronic acid synthase-1 (HAS-1), an enzyme critically involved in the synthesis of hyaluronic acid, and a noticeable increase in gene expression involved in collagen de novo synthesis. Conclusions: This study provides skin-physiological and for the first time molecular evidence that Pycnogenol supplementation benefits human skin by increasing skin hydration and skin elasticity. These effects are most likely due to an increased synthesis of extracellular matrix molecules such as hyaluronic acid and possibly collagen. Pycnogenol supplementation may thus be useful to counteract the clinical signs of skin aging.

© 2012 S. Karger AG, Basel


  

Author Contacts

Univ.-Prof. Dr. Jean Krutmann
IUF – Leibniz Research Institute for Environmental Medicine
Auf’m Henekamp 50
DE–40225 Düsseldorf (Germany)
Tel. +49 211 3389 225, E-Mail krutmann@uni-duesseldorf.de

  

Article Information

A.M. and S.G.-B. contributed equally to this work.

Received: July 21, 2011
Accepted after revision: November 17, 2011
Published online: January 21, 2012
Number of Print Pages : 7
Number of Figures : 5, Number of Tables : 2, Number of References : 33

  

Publication Details

Skin Pharmacology and Physiology (Journal of Pharmacological and Biophysical Research)

Vol. 25, No. 2, Year 2012 (Cover Date: February 2012)

Journal Editor: Lademann J. (Berlin)
ISSN: 1660-5527 (Print), eISSN: 1660-5535 (Online)

For additional information: http://www.karger.com/SPP


Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 7/21/2011 2:41:11 PM
Accepted: 11/17/2011
Published online: 1/21/2012
Issue release date: February 2012

Number of Print Pages: 7
Number of Figures: 5
Number of Tables: 2

ISSN: 1660-5527 (Print)
eISSN: 1660-5535 (Online)

For additional information: http://www.karger.com/SPP


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Gilchrest BA, Krutmann J: Photoaging of skin; in Gilchrest BA, Krutmann J (eds): Skin Aging. Berlin, Springer, 2006, pp 33–44.
  2. Krutmann J: Skin aging; in Krutmann J, Humbert P (eds): Nutrition for Healthy Skin: Strategies for Clinical and Cosmetic Practice. Berlin, Springer, 2011, pp 15–24.
  3. Rohdewald P: A review of the French maritime pine bark extract (Pycnogenol®), a herbal medication with a diverse clinical pharmacology. Int J Clin Pharmacol Ther 2002;40:158–168.
  4. Belcaro G, Cesarone MR, Errichi BM, Ledda A, Di Renzo A, Stuard S, Dugall M, Pellegrini L, Gizzi G, Rohdewald P, Ippolito E, Ricci A, Cacchio M, Cipollone G, Ruffini I, Fano F, Hosoi M: Diabetic ulcers: microcirculatory improvement and faster healing with Pycnogenol®. Clin Appl Thromb Hemost 2006;12:318–323.
  5. Petrassi C, Mastromarino A, Spartera C: Pycnogenol® in chronic venous insufficiency. Phytomedicine 2000;7:383–388.
  6. Bayeta E, Bejamin MS, Lau HS: Pycnogenol inhibits generation of inflammatory mediators in macrophages. Nutr Res 2000; 20:249–259.
  7. Blazso G, Gabor M, Schönlau F, Rohdewald P: Pycnogenol® accelerates wound healing and reduces scar formation. Phytother Res 2005;18:579–581.

    External Resources

  8. Devaraj S, Kaul N, Schönlau F, Rohdewald P, Jialal I: Supplementation with a pine bark extract rich in polyphenols increases plasma antioxidant capacity and alters plasma lipoprotein profile. Lipids 2002;37:931–934.
  9. Blumenthal M: Pycnogenol (French maritime pine bark extract) Pinus pinaster Aiton subsp. atlantica; in Blumenthal M, et al (eds): The American Botanical Council Guide to Herbs. Austin, American Botanical Council, 2003, pp 369–373.
  10. Maimoona A, Naeem I, Saddiqe Z, Jameel K: A review on biological, nutraceutical and clinical aspects of French maritime pine bark extract. J Ethnopharmacol 2011;133: 261–277.
  11. Grimm T, Schäfer A, Högger P: Antioxidant activity and inhibition of matrix metalloproteinases by metabolites of maritime pine bark extract (Pycnogenol). Free Radical Biol Med 2004;36:811–822.
  12. Segger D, Schönlau F: Supplementation with Evelle improves skin smoothness and elasticity in a doubleblind, placebo-controlled study with 62 women. J Dermatol Treat 2004;15:222–226.
  13. Grether-Beck S, Timmer A, Felsner I, Brenden H, Brammertz D, Krutmann J: Ultraviolet A-induced signaling involves a ceramide-mediated autocrine loop leading to ceramide de novo synthesis. J Invest Dermatol 2005:125: 545–553.
  14. Livak KJ, Schmittgen TD: Analysis of relative gene expression data using real time quantitative PCR and the 2 (-delta delta C(T)) method. Methods 2001;25:402–408.
  15. McCallum FS, Maden BE: Human 18S ribosomal RNA sequence inferred from DNA sequence. Variations in 18S sequences and secondary modification pattern between vertebrates. Biochem J 1985;232:725–733.
  16. Tromp G, Kuivaniemi H, Stacey A, Shikata H, Baldwin CT, Jaenisch R, Prockop DJ: Structure of a full-length cDNA clone for the prepro alpha 1(I) chain of human type I procollagen. Biochem J 1988;253:919–922.
  17. Kuivaniemi H, Tromp G, Chu ML, Prockop DJ: Structure of a full-length cDNA clone for the prepro alpha 2(I) chain of human type I procollagen. Comparison with the chicken gene confirms unusual patterns of gene conservation. Biochem J 1988;252:633–640.
  18. Shyjan AM, Heldin P, Butcher EC, Yoshino T, Briskin MJ: Functional cloning of the cDNA for a human hyaluronan synthase. J Biol Chem 1996;271:23395–23399.
  19. Ahn S, Kim S, Lee H, Moon S, Chang I: Correlation between a Cutometer and quantitative evaluation using Moire topography in age-related skin elasticity. Skin Res Technol 2007;13:280–284.
  20. Dobrev H: Application of Cutometer area parameters for the study of human skin fatigue. Skin Res Technol 2005;11:120–122.
  21. Wiedersberg S, Leopold CS, Guy RH: Effects of various vehicles on skin hydration in vivo. Skin Pharmacol Physiol 2009;22:128–130.
  22. Schroeder P, Calles C, Benesova T, Macaluso F, Krutmann J: Photoprotection beyond ultraviolet radiation – effective sun protection has to include protection against infrared A radiation-induced skin damage. Skin Pharmacol Physiol 2010;23:15–17.
  23. Tronnier H, Wiebusch M, Heinrich U: Change in skin physiological parameters in space – report on and results of the first study on man. Skin Pharmacol Physiol 2008;21:283–292.
  24. Dai G, Freudenberger T, Zipper P, Melchior A, Grether-Beck S, Rabausch B, de Groot J, Twarock S, Hanenberg H, Homey B, Krutmann J, Reifenberger J, Fischer JW: Chronic ultraviolet B irradiation causes loss of hyaluronic acid from mouse dermis because of down-regulation of hyaluronic acid synthases. Am J Pathol 2007;171:1451–1461.
  25. Itano N, Kimata K: Molecular cloning of human hyaluronan synthase. Biochem Biophys Res Commun 1996;222:816–820.
  26. Jacobson A, Brinck J, Briskin MJ, Spicer AP, Heldin P: Expression of human hyaluronan synthases in response to external stimuli. Biochem J 2000;348:29–35.
  27. Sugiyama Y, Shimada A, Sayo T, Sakai S, Inoue S: Putative hyaluronan synthase mRNA are expressed in mouse skin and TGF-β upregulates their expression in cultured human skin cells. J Invest Dermatol 1998;110:116–121.
  28. Tammi R, Pasonen-Seppanen S, Kolehmainen E, Tammi M: Hyaluronan synthase induction and hyaluronan accumulation in mouse epidermis following skin injury. J Invest Dermatol 2005;124:898–905.
  29. Laurent TC, Fraser JR: Hyaluronan. FASEB J 1992;6:2397–2404.
  30. Sherman L, Sleeman J, Herrlich P, Ponta H: Hyaluronate receptors: key players in growth, differentiation, migration and tumor progression. Curr Opin Cell Biol 1994;6:726–733.
  31. Toole BP, Wight TN, Tammi MI: Hyaluronan-cell interactions in cancer and vascular disease. J Biol Chem 2002;277:4593–4596.
  32. Tammi R, Ripellino JA, Margolis RU, Tammi M: Localization of epidermal hyaluronic acid using the hyaluronate binding region of cartilage proteoglycan as a specific probe. J Invest Dermatol 1988;90:412–414.
  33. Wang C, Tammi M, Tammi R: Distribution of hyaluronan and its CD44 receptor in the epithelia of human skin appendages. Histochemistry 1992;98:105–112.