Background: Pentacyclic triterpenoids improve epidermal barrier function and induce collagen production. Here, their effects on cutaneous aging by means of objective instrumental measurements were elucidated. Methods: Reconstituted human epidermis, cultivated keratinocytes and fibroblasts were incubated with Terminalia arjuna triterpenes (T. arjuna bark extract), and mRNA and protein expression of various genes was determined using microarray analysis, qRT-PCR and ELISA techniques. Clinical efficacy of T. arjuna bark extract versus vehicle control cream was elucidated in 30 patients and transepidermal water loss (TEWL), skin hydration and elasticity were measured. Another 30 female patients in their postmenopausal phase were treated with a similar regime, and skin sebum content, cutaneous blood microcirculation and skin density/echogenicity were assessed. Results: Incubation with T. arjuna triterpenes increased FGF-2, TSP-1, TGF-β and CTGF expression, and VEGF secretion in vitro. Elevated lactate dehydrogenase release upon sodium dodecyl sulphate challenge was reversed by the application of T. arjuna bark extract. T. arjuna bark extract decreased TEWL, improved skin moisturization, reduced scaliness and led to significantly improved skin elasticity. Also, increases in blood microflow and skin sebum content as well as improved skin thickness/echogenicity were noted on postmenopausal skin, resulting in visible reduction of sagging skin on the jowls as demonstrated by digital photography. Conclusion:T. arjuna bark extract appears as an innovative active ingredient that exerts versatile antiaging properties in vitro and in vivo.

Keywords:
Arjunolic acid, Triterpenes, Antiaging properties, Skin blood microcirculation, Skin penetration
1.
Kohl E, Steinbauer J, Landthaler M, Szeimies RM: Skin ageing. J Eur Acad Dermatol Venereol 2011;25:873-884.
2.
Makrantonaki E, Zouboulis CC: William J Cunliffe Scientific Awards. Characteristics and pathomechanisms of endogenously aged skin. Dermatology 2007;214:352-360.
3.
Verdier-Sevrain S: Effect of estrogens on skin aging and the potential role of selective estrogen receptor modulators. Climacteric 2007;10:289-297.
4.
Uitto J: Understanding premature skin aging. New Engl J Med 1997;337:1463-1465.
5.
Quatresooz P, Pierard GE: Immunohistochemical clues at aging of the skin microvascular unit. J Cutan Pathol 2009;36:39-43.
6.
Lavker RM: Structural alterations in exposed and unexposed aged skin. J Invest Dermatol 1979;73:59-66.
7.
Pavicic T, Gauglitz GG, Lersch P, Schwach-Abdellaoui K, Malle B, Korting HC, Farwick M: Efficacy of cream-based novel formulations of hyaluronic acid of different molecular weights in anti-wrinkle treatment. J Drugs Dermatol 2011;10:990-1000.
8.
Goldberg RA, McCann JD, Fiaschetti D, Ben Simon GJ: What causes eyelid bags? Analysis of 114 consecutive patients. Plast Reconstr Surg 2005;115:1395-1402, discussion 1403-1394.
9.
James JT, Dubery IA: Pentacyclic triterpenoids from the medicinal herb, Centella asiatica (L.) Urban. Molecules 2009;14:3922-3941.
10.
Liu J, Liu Y, Parkinson A, Klaassen CD: Effect of oleanolic acid on hepatic toxicant-activating and detoxifying systems in mice. J Pharmacol Exp Ther 1995;275:768-774.
11.
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.
12.
Lee HK, Nam GW, Kim SH, Lee SH: Phytocomponents of triterpenoids, oleanolic acid and ursolic acid, regulated differently the processing of epidermal keratinocytes via PPAR-α pathway. Exp Dermatol 2006;15:66-73.
13.
Lim SW, Hong SP, Jeong SW, Kim B, Bak H, Ryoo HC, Lee SH, Ahn SK: Simultaneous effect of ursolic acid and oleanolic acid on epidermal permeability barrier function and epidermal keratinocyte differentiation via peroxisome proliferator-activated receptor-α. J Dermatol 2007;34:625-634.
14.
Rane MM, Mengi SA: Comparative effect of oral administration and topical application of alcoholic extract of Terminalia arjuna bark on incision and excision wounds in rats. Fitoterapia 2003;74:553-558.
15.
Mehul B, Asselineau D, Bernard D, Leclaire J, Regnier M, Schmidt R, Bernerd F: Gene expression profiles of three different models of reconstructed human epidermis and classical cultures of keratinocytes using cDNA arrays. Arch Dermatol Res 2004;296:145-156.
16.
Langmann T, Moehle C, Mauerer R, Scharl M, Liebisch G, Zahn A, Stremmel W, Schmitz G: Loss of detoxification in inflammatory bowel disease: dysregulation of pregnane X receptor target genes. Gastroenterology 2004;127:26-40.
17.
Langmann T, Mauerer R, Zahn A, Moehle C, Probst M, Stremmel W, Schmitz G: Real-time reverse transcription-PCR expression profiling of the complete human ATP-binding cassette transporter superfamily in various tissues. Clin Chem 2003;49:230-238.
18.
Jachowicz J, McMullen R, Prettypaul D: Alteration of skin mechanics by thin polymer films. Skin Res Technol 2008;14:312-319.
19.
Akhtar N, Zaman SU, Khan BA, Amir MN, Ebrahimzadeh MA: Calendula extract: effects on mechanical parameters of human skin. Acta Pol Pharm 2011;68:693-701.
20.
Verdier-Sevrain S, Bonte F, Gilchrest B: Biology of estrogens in skin: implications for skin aging. Exp Dermatol 2006;15:83-94.
21.
Chung JH, Kang S, Varani J, Lin J, Fisher GJ, Voorhees JJ: Decreased extracellular signal-regulated kinase and increased stress-activated MAP kinase activities in aged human skin in vivo. J Invest Dermatol 2000;115:177-182.
22.
Senftleben U, Karin M: The IKK/NF-κB pathway. Crit Care Med 2002;30:S18-S26.
23.
Quan T, Shao Y, He T, Voorhees JJ, Fisher GJ: Reduced expression of connective tissue growth factor (CTGF/CCN2) mediates collagen loss in chronologically aged human skin. J Invest Dermatol 2010;130:415-424.
24.
Kuroda K, Utani A, Hamasaki Y, Shinkai H: Up-regulation of putative hyaluronan synthase mRNA by basic fibroblast growth factor and insulin-like growth factor-1 in human skin fibroblasts. J Dermatol Sci 2001;26:156-160.
25.
Pilcher BK, Gaither-Ganim J, Parks WC, Welgus HG: Cell type-specific inhibition of keratinocyte collagenase-1 expression by basic fibroblast growth factor and keratinocyte growth factor. A common receptor pathway. J Biol Chem 1997;272:18147-18154.
26.
Melnik BC, Schmitz G, Zouboulis CC: Anti-acne agents attenuate FGFR2 signal transduction in acne. J Invest Dermatol 2009;129:1868-1877.
27.
Yano K, Kajiya K, Ishiwata M, Hong YK, Miyakawa T, Detmar M: Ultraviolet B-induced skin angiogenesis is associated with a switch in the balance of vascular endothelial growth factor and thrombospondin-1 expression. J Invest Dermatol 2004;122:201-208.
28.
Ballaun C, Weninger W, Uthman A, Weich H, Tschachler E: Human keratinocytes express the three major splice forms of vascular endothelial growth factor. J Invest Dermatol 1995;104:7-10.
29.
Chung JH, Yano K, Lee MK, Youn CS, Seo JY, Kim KH, Cho KH, Eun HC, Detmar M: Differential effects of photoaging versus intrinsic aging on the vascularization of human skin. Arch Dermatol 2002;138:1437-1442.
30.
Kelly RI, Pearse R, Bull RH, Leveque JL, de Rigal J, Mortimer PS: The effects of aging on the cutaneous microvasculature. J Am Acad Dermatol 1995;33:749-756.
31.
Armstrong LC, Bornstein P: Thrombospondins 1 and 2 function as inhibitors of angiogenesis. Matrix Biol 2003;22:63-71.
32.
Yano K, Oura H, Detmar M: Targeted overexpression of the angiogenesis inhibitor thrombospondin-1 in the epidermis of transgenic mice prevents ultraviolet-B-induced angiogenesis and cutaneous photo-damage. J Invest Dermatol 2002;118:800-805.
33.
Schiemann Y, Wegmann M, Lersch P, Heisler E, Farwick M: Polar emollients in cosmetic formulations enhance the penetration and biological effects of phytosphingosine on skin. Colloids Surf A Physicochem Eng Asp 2008;331:103-107.
34.
Jackson RL, Greiwe JS, Schwen RJ: Ageing skin: oestrogen receptor-β agonists offer an approach to change the outcome. Exp Dermatol 2011;20:879-882.
35.
Patriarca MT, Goldman KZ, Dos Santos JM, Petri V, Simoes RS, Soares JM Jr, Simoes MJ, Baracat EC: Effects of topical estradiol on the facial skin collagen of postmenopausal women under oral hormone therapy: a pilot study. Eur J Obstet Gynecol Reprod Biol 2007;130:202-205.
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