The first group includes hyperpigmentation and hypopigmentation (leukodermia). Hyperpigmentation is darkening of the skin color due to excessive pigmentation. Usually, hyperpigmentation issues are major concerns for people DZNeP purchase of color [29]. Hyperpigmentation-related diseases include melasma, lentigines, nevus, ephelis, freckles, postinflammatory hyperpigmentation, and age spots [30]. Postinflammatory hyperpigmentation appears

in many skin conditions, including acne, eczema, and contact dermatitis. Meanwhile, hypopigmentation is lightening of the skin by insufficient pigmentation [31]. Skin color is determined by various factors including melanin content, oxygenation state of hemoglobin in capillary vessels, carotenoid content, water content, and organization of collagen fibers in the dermis. Among these factors, melanin is the major determinant of skin color [32]. In this context, understanding the mechanisms involved in melanogenesis is of great interest pharmaceutically

and cosmetically. Melanogenesis is a biochemical pathway responsible for melanin synthesis that is controlled by complex regulatory mechanisms [33]. Melanogenesis occurs in melanocytes confined in separate cytoplasmic organelles called melanosomes, VE-821 mw which contain key enzymes of melanogenesis. Differences in skin color are related to the size, number, shape, and distribution of melanosomes, whereas melanocyte density typically remains relatively constant [34].

Although tyrosinase is the key regulatory enzyme of melanogenesis, tyrosinase-related protein (TRP)-1, dopachrome Bay 11-7085 tautomerase (DCT/TRP2), and melanosomal matrix proteins (Pmel17, MART-1) carry out important roles in regulating melanogenesis [35]. The genes of tyrosinase, TRP-1, and DCT contain common transcription starting sites, the microphthalmia-associated transcription factor (MITF) binding sites. MITF plays a critical role in the transcriptional regulation of melanogenesis [36]. The intracellular signal transduction pathways of protein kinase C, cyclic AMP (cAMP), and nitrogen oxide are involved in the regulation of melanogenesis [34]. Various endogenous and exogenous factors, such as estrogen and ultraviolet (UV) radiation, affect melanogenesis via signal transduction pathways. These endogenous/exogenous factors exert their actions directly on melanocytes or indirectly via surrounding skin cells [36]. Melanocytes, keratinocytes, dermal fibroblasts, and other skin cells communicate with each other by factors that are secreted and cell–cell contacts [37]. It has been shown that the interactions between keratinocytes and melanocytes are critical in the regulation of melanogenesis [38]. Keratinocytes control melanocyte growth and activity through various soluble factors and cell adhesion molecules [39] and [40].