Liposomal Ursolic Acid (Merotaine) Increases Ceramides and Collagen in Human Skin

Yarosh, Daniel B.; Both, Dawn; Brown, David A.

doi:10.1159/000053280

Cited by 28 publications

(13 citation statements)

References 10 publications

(15 reference statements)

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“…MMPs are proteolytic enzymes that degrade native collagens and other extracellular matrix components. Previous studies are in agreement with tests done by the cosmetic industry, which indicated that ursolic acid stimulated collagen production in cultured fibroblasts (4) and increased the production of ceramides in human epidermal keratinocytes and human skin (5) . Also, ursolic acid triggered the apoptotic intrinsic pathway characterized by Bax overexpression, concomitant Bcl-2 underexpression, and subsequent collapse of mitochondrial membrane potential (6,7) .…”

supporting

confidence: 88%

Antiproliferative and antiviral mechanisms of ursolic acid and dexamethasone in cervical carcinoma cell lines

Yim

Lee

et al. 2006

Int J Gynecol Cancer

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The chemical structure of ursolic acid is very similar to that of dexamethasone, a synthetic glucocorticoid. Herein, we investigated the antiproliferative and antiviral effects of ursolic acid and dexamethasone in human papillomavirus (HPV)-associated cervical cancer cells. We performed 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazonium bromide assay to measure antiproliferative activity, and also characterized apoptosis by DNA fragmentation, 4'-6-diamidino-2-phenylindole (DAPI) staining, and flow cytometry (FACS) analysis. We investigated apoptosis-related proteins using western blots. After in vitro treatment, we used reverse transcription-polymerase chain reaction for the expression of the HPV E6/E7 gene to observe the antiviral effects. Ursolic acid suppressed the growth of HPV-positive cervical carcinoma cells (HeLa, CaSki, and SiHa) in a dose- and time-dependent manner, but not the HPV-negative cervical cancer cell line (C33A). Ursolic acid-treated HeLa cells showed typical apoptosis characteristics in DNA fragmentation, DAPI staining, and FACS analysis. The expression of Fas protein was induced, and caspase-8, caspase-3, and poly ADP-ribose polymerase (PARP) proteins were cleaved after ursolic acid treatment. HPV-18 E6/E7 gene expression decreased after ursolic acid treatment in HeLa cells, but the levels of p53 and Rb proteins did not change. In contrast, dexamethasone, which has a similar structure, did not inhibit proliferation. Our findings may offer new insight into the mechanism of antiproliferative and antiviral effect of ursolic acid. Also, these results suggest that ursolic acid might be a useful anticancer drug in treatment of HPV-associated cervical neoplasia.

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confidence: 88%

Antiproliferative and antiviral mechanisms of ursolic acid and dexamethasone in cervical carcinoma cell lines

Yim

Lee

et al. 2006

Int J Gynecol Cancer

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“…Both ursolic acid liposomes and retinoic acid decreased markers of keratinocyte differentiation (keratin 1, keratin 10, and involucrin) in cultured normal human epidermal keratinocytes. 144 Skin wrinkling and xerosis associated with aging result from decreases of dermal collagen and stratum corneum ceramide content. Ursolic acid incorporated into liposomes increases both the ceramide content of cultured normal human epidermal keratinocytes and the collagen content of cultured normal human dermal fibroblasts.…”

Section: 3the Treatment Of Wrinkles With Ursolic Acid In Clinical mentioning

confidence: 99%

Clinically useful anticancer, antitumor, and antiwrinkle agent, ursolic acid and related derivatives as medicinally important natural product

Sultana

2011

Journal of Enzyme Inhibition and Medicinal Chemistry

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Medicinal plants are becoming an important research area for novel and bioactive molecules for drug discovery. Novel therapeutic strategies and agents are urgently needed to treat different incurable diseases. Many plant derived active compounds are in human clinical trials. Currently ursolic acid is in human clinical trial for treating cancer, tumor, and skin wrinkles. This review includes the clinical use of ursolic acid in various diseases including anticancer, antitumor, and antiwrinkle chemotherapies, and the isolation and purification of this tritepernoid from various plants to update current knowledge on the rapid analysis of ursolic acid by using analytical methods. In addition, the chemical modifications of ursolic acid to make more effective and water soluble derivatives, previous and current information regarding, its natural and semisynthetic analogs, focusing on its anticancer, cytotoxic, antitumor, antioxidant, antiinflammatory, anti-HIV, acetyl cholinesterase, α-glucosidase, antimicrobial, and hepatoprotective activities, briefly discussion is attempted here for its research perspectives. This review article contains fourteen medicinally important ursolic acid derivatives and 351 references.

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“…Recently vitamin C has been shown to activate PKC, increase ceramide synthesis and improve the ceramide subspecies profile in epidermal skin equivalents [133]. Yarosh and Brown [134] also demonstrated that ursolic acid increased ceramides in human skin. For a complete analysis of agents that stimulate lipid biosynthesis see Table II.…”

Section: Epidermotherapy: Lipid Synthesis Enhancersmentioning

confidence: 99%

Trends in stratum corneum research and the management of dry skin conditions

Rawlings¹

2003

Intern J of Cosmetic Sci

172

140

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The structure, composition, formation and function of the stratum corneum have been the subject of intense research over the last few decades. As has become apparent, stratum corneum barrier function is not only dependent on one single component but also on its total architecture. Recent developments in understanding lipid composition have led to a new ceramide nomenclature system, a new proposal for a molecular model of the interactions between ceramides, cholesterol and fatty acids, and the demonstration of the presence of crystalline orthorhombic and gel hexagonal lipid phases in the stratum corneum. Linoleate-containing ceramide one, now known as CER EOS, have been shown to be essential for the formation of the 13 nm long periodicity phase (LPP) observed by electron microscopy and X-ray diffraction studies, whereas long-chain fatty acids are important for the formation of the crystalline lipid phases essential for barrier function. The role of the corneocyte envelope, its constituent proteins and its transglutaminase-mediated maturation processes have been shown to be essential for good skin condition. Several proteases may have a role in corneodesmolysis, particularly serine and cathepsin-like enzymes. Novel filaggrin polymorphisms have been identified that may be involved in the expression of a dry skin phenotype. Disturbances in lipid packing states, reduction in ceramide levels (particularly the phytosphingosine-containing ceramides), reductions in the levels of long-chain fatty acids and loss of the LPP largely account for the perturbations in lipid structure that occur in dry skin. The reduced corneodesmolysis that occurs in this xerotic skin disorder is now well accepted and is caused by reductions in the levels and activities of stratum corneum proteases together with elevated levels of corneodesmosomal glycoproteins in the superficial layers of the stratum corneum. Additionally, increased levels of fragile corneocytes are associated with reduced transglutaminase activity and corneocyte envelope cross-linking events. However, in comparison with the advances in our understanding of the textural changes that occur in dry skin, the somatosensory changes are poorly understood and the itching associated with dry skin is still an under-researched area. The unique biosensor role of the stratum corneum essential for a competent natural moisturizing barrier may also have a role to play in the action of anti-ageing technologies by controlling the expression and secretion of epidermal cytokines and growth factors. Technologies to treat the surface textural skin problems, enhance the differentiation process, particularly lipid biosynthesis, and to control the somatosensory problems in dry skin have received much attention in the last decade. This paper will review the state of the art of stratum corneum biology and the trends in the management of dry skin.

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Liposomal Ursolic Acid (Merotaine) Increases Ceramides and Collagen in Human Skin

Cited by 28 publications

References 10 publications

Antiproliferative and antiviral mechanisms of ursolic acid and dexamethasone in cervical carcinoma cell lines

Antiproliferative and antiviral mechanisms of ursolic acid and dexamethasone in cervical carcinoma cell lines

Clinically useful anticancer, antitumor, and antiwrinkle agent, ursolic acid and related derivatives as medicinally important natural product

Trends in stratum corneum research and the management of dry skin conditions

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