404 J. Cosmet. Sci., 73, 404–420 (November/December 2022) Address all correspondence to I. W. Siriwardane, induni@kln.ac.lk Curcumin Against Skin Aging: A Multimechanistic Solution to a Multi-Origin Issue C. HARSHANI ALGAMA, I. W. SIRIWARDANE AND AZEEZ M. MUBARAK Sri Lanka Institute of Nanotechnology (SLINTEC), Homagama, Sri Lanka (C.H.A., I.W.S., A.M.M.) Department of Applied Computing, Faculty of Computing and Technology, University of Kelaniya, Sri Lanka (I.W.S.) Accepted for publication February 1, 2023. Synopsis Skin aging is a complex phenomenon resulting from multiple rearrangements at the molecular level. Curcumin is historically being used as an ingredient in traditional cosmetic remedies and commercial cosmetic products. Even though curcumin chemistry, its extraction, and applications in biomedical, pharmaceutical, and food industries are reviewed often, a critical review of its antiaging cosmeceutical benefits is rather limited. Therefore, this article gives an overview of the chemical and antiaging properties of curcumin, curcumin-based antiaging cosmetics, and their delivery methods. Skin antiaging benefits of curcumin are primarily derived by its ability to scavenge reactive oxygen species and interact with enzymes. However, the antioxidant and photo-prevention actions that scavenge reactive oxygen species remain the most widely researched antiaging mechanisms of curcumin. The main methods of curcumin delivery in antiaging cosmetics are direct delivery, as conjugates, and as nano-encapsulated curcumin. However, marketed curcumin cosmetics for antiaging mostly utilize direct delivery methods, implying that, despite the vast amount of research done, the application of that knowledge in making market-ready curcumin cosmetic products has not been adequate. Hence, future research on curcumin cosmetics should be more focused on effective and efficient delivery methods, improving the chemical stability of curcumin, and developing market-ready cosmetic formulations. INTRODUCTION Biological aging is a complex phenomenon that is induced by multiple factors including genetic, hormonal, and environmental ones. Skin, being the largest and most visible organ of the body, acts as a “social interface” between an individual and other members of society and is the first organ to indicate the aging signs of that individual. Due to its strategic location at the body’s interface, while subjected to intrinsic (chronologic) aging that is generally driven by genetic and hormonal influences, skin is more prone to extrinsic aging caused by environmental factors, principally ultraviolet radiation (UVR), smoking, diet, chemicals, pollutants, trauma, etc. Intrinsic aging occurs within the tissue itself with time and is biologically characterized by the reduction in dermal mast cells, fibroblasts, collagen production, and flattening of the dermal–epidermal junction/loss of rete ridges

405 Curcumin Against Skin Aging (1). Among the extrinsic factors, UV irradiation is the most prominent causative factor for skin aging. The damage due to photoaging on skin can be varied from acute effects such as sunburn and tanning (2), to chronic effects such as inflammation, immunosuppression, and damage to dermal connective tissues (3). Notably, skin-aging traits such as perceived age, age spots, wrinkles, and sun damage are shown to be equally influenced by genetic and environmental factors (4). Hence it is imperative to understand skin biology and the alterations that happen in the dermatological arrangement during skin aging in order to propose strategies for minimizing skin aging. Skin is conventionally viewed as two main layers called the epidermis and dermis. The structure of the epidermis consists of an outer nonviable layer called the stratum corneum, with more proximal layers making up the viable epidermis comprising primarily keratinocytes (90–95% of cells), together with smaller populations of Langerhans cells (2%), melanocytes (3%), and Merkel cells (0.5%) (5). Generally, the stratum corneum has been found to be unaffected during aging in terms of its thickness, barrier properties, and recoverable substances such as sebum, sweat, components of natural moisturizing factor, and corneocyte debris (6). Keratinocytes in the epidermis are shown to change with age in terms of their morphology, proliferation, and intercellular adhesion. Further, melanocytes in the epidermis also change in their numbers and function, which are causative factors for perceived skin aging. Studies have reported that the number of functional melanocytes decline by up to 20% per decade in the basal layer of the human epidermis (7), which leads to less protection against the harmful effects of UVR. In addition, changes in the melanocyte function is a main driving factor for age spots, which contribute more to perceived age (1). On the other hand, the most consistent change that occurs in skin aging is the flattening of the dermo–epidermal junction, which leads to less shear resistance of skin and to a reduced supply of nutrients and oxygen to the skin (8,9). The dermis consists predominantly of connective tissues made out of collagen and elastin, together with sweat glands, sebaceous units, blood vessels, and nerves. Collagen fibers maintain the tensile strength of skin, whereas elastin fibers contribute to the elasticity and resilience of skin (10). Collagen, the body’s most abundant protein, is the key structural component in dermis. The structural and compositional changes in collagen proteins have been shown to affect wrinkle formation during aging (11). In young adults, dermal collagen bundles are well organized to facilitate the extension of skin. However, during skin aging the collagen bundles lose their extensible configuration, becoming fragmented, disorganized, and less soluble (12). This is due to the impairment of collagen synthesis at dermal fibroblasts mainly by reactive oxygen species (ROS), by affecting the functions of transforming growth factor-β, a cytokine that promotes collagen production, and activator protein-1, a transcription factor that promotes collagen breakdown by upregulating matrix metalloproteinases (MMPs) (13). Elastin, a key structural protein uniquely rich in human skin, if impaired, can also give rise to aging traits on skin (1). Elastin is affected mostly during photoaging due to the production of ROS and thereby upregulating MMPs (14). Glycasoaminoglycans are another structural polysaccharide found in dermis that contribute mainly to maintenance of the moisture content of the skin by holding the moisture-trapping collagen and elastin proteins in skin structure. However, glycasoaminoglycan levels in dermis increase with aging, giving rise to “tetrahedron water” in aged skin (1), which leads to an extra dry condition called xerosis observed in aged skin. In addition, degradation of hyaluronan, a key component in the extracellular matrix in connecting tissues including skin, by the activation of the enzyme hyaluronidase, is also a reason for the dryness in aged skin (15).