Proposed mechanisms of action for retinoid derivatives in the treatment of skin aging

Abstract

Skin aging (intrinsic aging) and photoaging (extrinsic aging) involve a similar process that leads to the typical creased appearance of the skin, with the progressive loss of its physical and biologic properties. Photoaging is a premature skin aging caused by long-term exposure to the ultraviolet B radiations of the sun, and is more frequently associated to skin cancer than intrinsic aging. Retinoids are natural and synthetic vitamin A derivatives. They are lipophilic molecules and penetrate the epidermis easily. Their biologically active forms can modulate gene expression by binding to nuclear receptors and then to specific DNA sequences. Because of their ability to modulate genes involved in cellular differentiation and proliferation, they appear as good candidates to treat and prevent photoaging. Hyaluronate and collagen, two major constituents of the dermis, are progressively decreased and altered during aging. Various retinoids were shown to increase their synthesis and concentration in the skin and reduce their rate of degradation. Furthermore, retinoids share a common chemical structure containing several conjugated double bonds that enable them to trap free radicals and absorb UV radiations from the sun, thereby protecting cellular targets such as DNA, lipid membranes, or proteins by preventing direct photochemical damage or UV-induced oxidative stress. Therefore, retinoids may be beneficial in treating skin aging and photoaging because of their biologic, chemical, and physical properties, which act at several levels.

Cosmeceuticals in Dermatology

“…Although the use of tretinoin is well documented in acne and photoaging treatment, retinol is a cosmeceutical which is not as irritating nor as potent as tretinoin. However, retinol is reported to increase water content and collagen synthesis [ 6,7 ] , as well as inhibit melanogenesis and matrix metalloproteinases (MMPs) involved in collagen disruption, thus improving skin texture and reducing the visibility of skin lines and wrinkles. Retinol is a nonprescription cosmeceutical product, particularly used as an alternative approach for sensitive skin that does not tolerate tretinoin.…”

“…The cosmeceutical bene fi ts from vitamin A and its derivates lie in their ability as retinoids to regulate epithelial cell growth and differentiation and, fi nally, to normalize keratinization. Retinoids have been shown to have receptor-speci fi c effects on the skin, resulting in decreased roughness, facial wrinkling and fi ne lines [ 6 ] allowed for the synthesis of novel pharmacologic classes of compounds that have broader structural diversity with greater variance of pharmacological properties than natural retinoids. Topical use of retinoids has shown to be effective in the treatment of acne, photodamage, and psoriasis.…”

Botanical Antioxidants for Skin Health in the World of Cosmeceuticals

“…UVR causes several acute effects in the skin, including immediate pigment darkening, delayed tanning, sunburn, epidermal thickening, as well as several immune responses. Most importantly, UVA and UVB radiation have been observed to contribute to the disruption of extracellular matrix, which is a characteristic symptom of photoaging (Sorg et al, 2005;Talwar et al, 1995). It has long been thought that UVB causes most damage, but it is becoming increasingly evident that the biological effects of UVA is significantly more important; UVA also penetrates the skin more deeply than does UVB (Dekker et al, 2005).…”

“…It has long been thought that UVB causes most damage, but it is becoming increasingly evident that the biological effects of UVA is significantly more important; UVA also penetrates the skin more deeply than does UVB (Dekker et al, 2005). The mechanism of UV radiation associated dermal damage includes, decreased collagen I and III synthesis, increased collagen degradation by TGF-β and activator protein A, infiltration of inflammatory cells predominantly by neutrophils into the dermis releasing ROS (Saha, 2012;Sorg et al, 2005;Talwar et al, 1995). Biomolecules weakly absorb UVA, but it can generate ROS, which oxidize proteins, DNA, and lipids (Cooke et al, 2000;Hattori et al, 1996;Struthers et al, 1998).…”

Untitled

“…Retinoids are therefore ideal for the treatment of photoaging. Numerous studies have confirmed the clinical efficacy of various retinoids [45][46][47][48][49][50] .…”