408 JOURNAL OF COSMETIC SCIENCE to inhibit lipid peroxidation by quenching radicals via hydrogen atom donation and catalyzing hydrogen peroxide degradation (34). The incapability of these enzymes to respond effectively due to the imbalance of oxidant–antioxidant in skin cells results in oxidative stress in skin cells. Curcumin is considered a potent antioxidant against not only skin aging but also several other age-related diseases caused by the generation of ROS (35). The presence of phenolic groups with hydrogen-donating ability in curcumin makes it an effective antioxidant (36). Moreover, it is also reported that the consumption of curcumin significantly increases the activities of natural antioxidant enzymes as well (34,37). Curcumin has been reported to reverse the age-related alteration by free-radical scavenging activity as well as by elevating the antioxidant enzymes (38). According to a recent study, curcumin has showed powerful inhibition of peroxidation damage on human keratinocytes and fibroblast in skin (39). Several investigations on antioxidant activity of curcumin using DPPH (2,2-diphenyl-1-picrylhydrazl) radical scavenging assay and ferric reducing antioxidant power (FRAP) assay has showed that curcumin has an effective ferric ion reducing capacity of 56.7% compared with conventional reference antioxidants such as tocopherol (31.3%), trolox (45.2%), butylated hydroxyanisole (BHA) (69.9%), and butylated hydroxytoluene (BHT) (60.0%). Comparison of the DPPH scavenging capacity with other antioxidants also showed comparable activity: curcumin (62.2%), tocopherol (64.9%), trolox (29.4%), BHA (67.8%), and BHT (62.5%) (40). Moreover, curcumin being extracted from turmeric, its antioxidant activity also depends on external factors such as the area of turmeric cultivation as well as the chemical processes used for extractions. For example, a study conducted using different solvents for curcumin extraction reported that turmeric extracted using ethanol had the highest DPPH radical scavenging activity and the highest FRAP-reducing values compared to those in water (41). On the other hand, a study evaluating the antioxidant activities of the active materials from different plant origins (turmeric, curry leaf, torch ginger, and lemongrass) using different solvent extracts (ethanol, methanol, and acetone) revealed that the turmeric extract in acetone (80% v/v in 20% water) had the highest total phenolic content of 221.7 mg gallic acid equivalent per gram and DPPH antioxidant activity of 67.8% (42). PHOTO-PROTECTIVE EFFECT OF CURCUMIN Exposure to solar radiation, especially ultraviolet radiation (UVR, especially UVB, 280– 320 nm), is a major environmental factor for developing skin disorders, skin aging, and skin cancer (43). High levels of UVR can either kill or severely damage the cells (32). UVR is also responsible for jeopardizing the intergrity of the skin by the generation of ROS (44). Consistent and repetitive exposure, which is known as chronic sun exposure, results in photoaging of the skin (45). Direct exposure to UVR has shown to deplete catalase activity in the skin. It also causes DNA damage, oxidative stress, immunotoxicity, and imbalance in antioxidant defense enzymes (46). Sunlight can pass through skin cells and damage the dermal mitichondrial DNA. The primary response of the skin to sun exposure is the tanning of skin, which reduces further damages from exposure (45,47). The commonly used remedies to reduce the risk of UVR are avoiding exposure to the sun (primary treatment) and pretreating skin with antioxidants such as sunscreens before exposure to the sun (43). However these methods have limited success in preventing the damage to skin aging over time (44).
409 Curcumin Against Skin Aging Several studies had been conducted to evaluate the potential ability of curcumin treatment to reverse photoaged–related alterations in skin (34). It has been shown that topical application of curcumin has a direct effect on significantly inhibiting acute UVB-induced dermititis (48). Another study conducted on mice has revealed that short-term topical application of emulsified curcumin at a concentration of 2 mg/mL in carboxymethyl cellulose sodium reduced the photoaging effect on mouse skin when exposed to UVB radiation (49). Moreover, a study conducted to evaluate the novel delivery methods to obtain an enhanced photoprotective effect of curcumin on mouse fibroblasts and human keratinocytes (HaCaTs) has shown that application of curcumin nanoparticles formed by the encapsulation of curcumin with a biodegradable polymer, polylactic-co-glycolic acid, ensures the slow release of curcumin to the skin (47). This formulation has shown to be exceptionally effective in photoprotecting against exposure to UVB radiation. Another study has revelaed that curcumin, by preventing UV damage, decreases the formation of skin tumors and thereby prevents mature-skin aging (32). Furthermore, treatment with curcumin has also shown to decrease the formation of free radicals and increase the amount of cellular antioxidants (50). The abilities of curcumin to inhibit the collagen breakdown by downregulating enzymes called MMPs and inhibition of Nuclear factor kappa B (NF-κB) in human dermal fibroblasts have been postulated as key roles played by curcumin in the reduction of UV-exposure–induced skin damage (50,51). ANTI-INFLAMMATORY ACTION OF CURCUMIN Inflammation is considered the body’s natural defense mechanism resulting in a complex series of responses originated by the immune system. Inflammatory reactions act against harmful stimuli such as pathogens with the combination of immune cells, blood vessels, and molecular mediators (32,52). Nuclear factor kappa B (NF-κB) is a transcription factor that has the ability to regulate the expression of genes that are important in controlling inflammatory responses, mostly during the initial stages of the inflammatory response (53). By a study conducted using mice models, it has been reported that the inhibition of the NF-κB signaling pathway has a direct effect in delaying the aging process and age- related pathologies (54). Inflammations can also cause skin aging, which is often known as “inflammaging” (55). Curcumin acts as an anti-inflammatory agent by suppressing the NF-κB signaling pathway (35). Curcumin contributes to the slowing of the inflammatory protein synthesis by inhibiting the activation of NF-κB (56) by suppressing the inhibitory protein IκB, which prevents translocation of NF-κB to the nucleus. Further, curcumin can also suppress the binding of NF-κB with DNA, which has a direct effect in the reduction of oxidative stress, which ultimately contributes to the delay in skin aging (57). Moreover, curcumin is reported to decrease the level of tumor necrosis factor, a cytokine that is important in regulating the inflammatory response by the activation of NF-κB (32,52,55). ANTI-ELASTASE ACTIVITY OF CURCUMIN The disruption of the extracellular matrix has a direct effect on extrinsic as well as intrinsic aging. Wrinkles tend to appear due to the reduction of collagen elastic fibers and hyaluronic acid (58). Essential molecules such as collagen, proteoglycans, and fibronectin are assembled in the extracellular matrix in the epidermis of the skin. The degradation of the extracellular
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