Curcumin Protects Skin against UVB‐Induced Cytotoxicity via the Keap1‐Nrf2 Pathway: The Use of a Microemulsion Delivery System

Abstract

Curcumin was found to be beneficial in treating several skin pathologies and diseases, providing antioxidant protection due to its reducing properties and its electrophilic properties (the ability to activate the Nrf2 pathway and induce phase II cytoprotective enzymes). Nevertheless, clinical applications of curcumin are being hampered by its insufficient solubility, chemical instability, and poor absorption, leading to low efficacy in preventing skin pathologies. These limitations can be overcome by using a nanotechnology-based delivery system. Here, we elucidated the possibility of using curcumin encapsulated in a microemulsion preserving its unique chemical structure. We also examined whether curcumin microemulsion would reduce UVB-induced toxicity in skin. A significant curcumin concentration was found in the human skin dermis following topical application of a curcumin microemulsion. Moreover, curcumin microemulsion enhanced the reduction of UV-induced cytotoxicity in epidermal cells, paving the way for other incorporated electrophiles in encapsulated form protecting skin against stress-related diseases.

Contribution of Nrf2 Modulation to the Mechanism of Action of Analgesic and Anti-inflammatory Drugs in Pre-clinical and Clinical Stages

“…Importantly, all these chemopreventive drugs reduce at low doses the uncontrollable oxidative stress generated by carcinogens that would damage DNA and induce persistent inflammation (Hayes et al, 2010; Hu et al, 2010; Sporn and Liby, 2012). So far, the beneficial role of Nrf2 induction has been widely explored at multiple organ sites including skin (Ben Yehuda Greenwald et al, 2017; Alyoussef and Taha, 2018), lungs (Kumar et al, 2011; To et al, 2015; Creelan et al, 2017; Lin et al, 2017), bladder (Iida et al, 2004; Leone et al, 2017), breast (Pledgie-Tracy et al, 2007; Soto-Balbuena et al, 2018; Soundararajan and Kim, 2018), colon (Rajendran et al, 2015; Guo et al, 2018), pancreas (Kallifatidis et al, 2009), stomach (Fahey et al, 2002), and oral cancer (Bauman et al, 2016; Soundararajan and Kim, 2018).…”

Synergistic Promotion on Tyrosinase Inhibition by Antioxidants

“…Nrf2, an essential transcription factor for controlling oxidative stress [ 33 ], is expressed in human skin tissues, such as human keratinocytes [ 34 , 35 ], melanocyte [ 4 ], and human dermal fibroblasts [ 36 ]. Cytoprotective antioxidants can be increased by antioxidant compounds through the nuclear accumulation of Nrf2 [ 36 , 37 ]. Some necessary connections seemingly exist between these two protective mechanisms of skin tissues because they both participate in ROS removal.…”

“…The activity of tyrosinase is the first step in melanogenesis, indicating the oxidation of phenols to ortho -quinones by oxy-tyrosinase [ 47 , 48 ]. The activity mentioned above also shows the oxidation of bisphenol to quinone at the same time [ 2 , 3 , 5 , 13 , 14 , 18 , 32 , 34 , 37 , 38 , 49 ]. Thus, the activity of tyrosinase reflects the whole oxidation process of phenol to quinone through monooxygenase activity.…”

Emerging Trends in Topical Delivery of Curcumin Through Lipid Nanocarriers: Effectiveness in Skin Disorders

“…For the topical route, the stratum corneum layer of the skin behaves as a major barrier for penetration of the drug. Moreover, highly lipophilic nature of CUR makes topical delivery more challenging (13)(14)(15). Permeation of CUR is found to increase 7-8-fold when formulated with permeation enhancers (methanol) and in the form of gel (16).…”