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

410 JOURNAL OF COSMETIC SCIENCE matrix mostly affects the aging of the skin (59). Elastase has the ability to cleave proteins by converting polypeptide into fragments, which disrupts the cellular matrix. There are two types of elastase enzymes differing in substrate specificity (60). Elastase inhibitory activity is also used as one of the methods to measure skin antiaging activity. As elastin fibers and collagenous fibers form a network under the epidermis, the inhibition of elastase, which otherwise degrades elastin protein is a crucial factor for the maintenance of the skin structure. As inhibition of elastase leads to disruption of the matrix, it is important to have natural and biologically important molecules that can inhibit elastase activity. Some plants contain a wide variety of active compounds including polyphenols such as flavonoids, tocopherols, phenolic acids, and tannins, which could exert an inhibitory effect on these degrading enzymes (61). According to a study conducted to assess the anti-elastase activity of plant extracts to identify the anti-elastase activity of their components, the highest anti- elastase activity of 117.80% was reported for the ethyl acetate extract of curcumin (60). Another study reported that plants containing polyphenols such as curcumin showed more than 65% inhibition against elastase (61). In a study conducted to evaluate the inhibitory effects of 150 medicinal plant extracts (1,000 µg/ml in methanol) against human leukocyte elastase activity, curcuma longa showed 100% maximum inhibition (62). ANTIHYALURONIDASE ACTION OF CURCUMIN Hyaluronic acid is widely distributed in the extracellular matrix of the skin. Hyaluronic acid has the ability to hold water to a large extent and reduces the formation of wrinkles and makes the skin smooth. Therefore, degradation of hyaluronic acid into small oligosaccharides by the enzyme hyaluronidase can have a significant impact on aging. Hence, hyaluronidase inhibitors are considered major constituents in antiaging cosmetics, as they possess antiwrinkle and antiaging effects (63). According to two similar studies conducted with curcumin at concentrations of 80.94 μg/ mL and 500 μg/mL in ethanol on the inhibition of hyaluronidase, results showed 103% and 95.02% inhibition respectively (60,64). However, methanolic extracts of curcuma longa root powder showed only an inhibition of 7% at a concentration of 2 mg/ml (62). A commercial bioactive curcumin formulation, Cureit™ (Aurea Biolabs, Kerala, India), was reported to have hyaluronidase inhibition of 42% in a study conducted using cell culture studies on antiaging effects (65). Therefore, it is clear that curcumin has shown strong inhibitory action against hyaluronidase and protects skin from the formation of wrinkles, providing healthy, younger-looking skin. Bioactive components in plant extracts like curcumin actively take part in the inhibition of the enzymatic reactions that destabilize the integrity of the skin (65). Use of plant extracts that possess both anti-elastase and antihyaluronidase activities, has overall beneficial effects as these extracts can be added to cosmetics to impart antiaging effects on human skin (66), and curcumin will be an ideal candidate to serve that role. HORMETIC EFFECTS OF CURCUMIN ON SKIN Hormesis, which is defined as a biphasic dose response to an environmental agent, is a characteristic of many biological processes. At a low dose there is a stimulation or beneficial