Skin wrinkling and xerosis associated with aging result from decreases of dermal collagen and stratum corneum ceramide content. This study demonstrates that ursolic acid incorporated into liposomes (MerotaineTM) increases both the ceramide content of cultured normal human epidermal keratinocytes and the collagen content of cultured normal human dermal fibroblasts. In clinical tests, Merotaine increased the ceramide content in human skin over an 11-day period. Merotaine has effects on keratinocyte differentiation and dermal fibroblast collagen synthesis similar to retinoids. However, unlike retinoids, Merotaine increases ceramide content of human keratinocytes. Ursolic acid may bind to members of the glucocorticoid receptor family to initiate changes in keratinocyte gene transcription.

Keywords:
Merotaine, Hydroxy-ceramides, Procollagen, Keratinocytes, Fibroblasts, Barrier function, Glucocorticoid receptors
1.
Griffiths, CEM, Voorhees JJ: Topical retinoic acid for photoaging: Clinical response and underlying mechanisms. Skin Pharmacol 1993;6(suppl 1):70–77.
2.
Uitto J, Bernstein EF: Molecular mechanisms of cutaneous aging: Connective tissue alterations in the dermis. J Invest Dermatol 1998;3:41–44.
3.
Imokawa G, Abe A, Jin K, Higaki Y, Kawashima M, Hidano A: Decreased level of ceramides in stratum corneum of atopic dermatitis: An etiologic factor in atopic dry skin. J Invest Dermatol 1991;96:523–526.
4.
Rogers J, Harding C, Mayo A, Banks J, Rawlings A: Stratum corneum lipids: the effect of ageing and the seasons. Arch Dermatol Res 1996;288:765–770.
5.
Griffiths CEM, Russman AN, Majmudar G, Singer RS, Hamilton TA, Voorhess JJ: Restoration of collagen formation in photodamaged human skin by Tretinoin (retinoic acid). N Engl J Med 1993;329:530–535.
6.
Liu J: Pharmacology of oleanolic acid and ursolic acid. J Ethnopharmacol 1995;49:57–68.
7.
Huang MT, Ho CT, Wang ZY, Ferraro T, Lou YR, Stauber K, Ma W, Georgiadis C, Laskin JD, Conney AH: Inhibition of skin tumorigenesis by rosemary and its constituents carnosol and ursolic acid. Cancer Res 1994;54:701–708.
8.
Suh N, Honda T, Finlay HJ, Barchowsky A, Williams C, Benoit NE, Xie QW, Nathan C, Gribble GW, Sporn MB: Novel triterpenoids suppress inducible nitric oxide synthase (iNOS) and inducible cyclooxygenase (COX-2) in mouse macrophages. Cancer Res 1998;58:717–723.
9.
Ponec M, Weerheim A: Retinoids and lipid changes in keratinocytes. Methods Enzymol 1990;190:30–41.
10.
Bontè F, Saunois A, Pinguet P, Meybeck A: Existence of a lipid gradient in the upper stratum corneum and its possible biological significance. Arch Dermatol Res 1997;289:78–82.
11.
Gendimenico GJ, Mezick JA: Pharmacological effects of retinoids on skin cells. Skin Pharmacol 1993;6(suppl 1):24–34.
12.
Cha HJ, Park MT, Chung HY, Kim ND, Sato H, Seiki M, Kim KW: Ursolic acid-induced down-regulation of MMP-9 gene is mediated through the nuclear translocation of glucocorticoid receptor in HT1080 human fibrosarcoma cells. Oncogene 1998;16:771–778.
13.
Affinito P, Palomba S, Sorrentino C, DiCarlo C, Bifulco G, Arienzo MP, Nappi C: Effects of postmenopausal hypoestrogenism on skin collagen. Maturitas 1999;15:239–247.
14.
Radoja N, Komine M, Jho SH, Blumenburg M, Tomic-Canic M: Novel mechanism of steroid action in skin through glucocorticoid receptor monomers. Mol Cell Biol 2000;20:4328–4339.
© 2001 S. Karger AG, Basel
2001
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.
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 government 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.
You do not currently have access to this content.