Abstract
Nuclear factor erythroid 2-related factor 2 (Nrf2) is an essential transcription factor that maintains the cell’s redox balance state and reduces inflammation in different adverse stresses. Under the oxidative stress, Nrf2 is separated from Kelch-like ECH-associated protein 1 (Keap1), which is a key sensor of oxidative stress, translocated to the nucleus, interacts with the antioxidant response element (ARE) in the target gene, and then activates the transcriptional pathway to ameliorate the cellular redox condition. Curcumin is a yellow polyphenolic curcuminoid from Curcuma longa (turmeric) that has revealed a broad spectrum of bioactivities, including antioxidant, anti-inflammatory, anti-tumor, and anti-viral activities. Curcumin significantly increases the nuclear expression levels and promotes the biological effects of Nrf2 via the interaction with Cys151 in Keap1, which makes it a marvelous therapeutic candidate against a broad range of oxidative stress-related diseases, including type 2 diabetes (T2D), neurodegenerative diseases (NDs), cardiovascular diseases (CVDs), cancers, viral infections, and more recently SARS-CoV-2. Currently, the multifactorial property of the diseases and lack of adequate medical treatment, especially in viral diseases, result in developing new strategies to finding potential drugs. Curcumin potentially opens up new views as possible Nrf2 activator. However, its low bioavailability that is due to low solubility and low stability in the physiological conditions is a significant challenge in the field of its efficient and effective utilization in medicinal purposes. In this review, we summarized recent studies on the potential effect of curcumin to activate Nrf2 as the design of potential drugs for a viral infection like SARS-Cov2 and acute and chronic inflammation diseases in order to improve the cells’ protection.
Highlights
Under healthy conditions, there is a balance between antioxidant defense systems and free radical generation
In-silico molecular modeling showed that curcumin could attach to spike glycoprotein-receptor binding domain (RBD) and peptidase domain (PD)-angiotensin-converting enzyme 2 (ACE2), which are necessary for viral entrance and infection [171]
Nuclear factor erythroid 2-related factor 2 (Nrf2) has a variety of protective effects on toxic, acute, and chronic diseases and viral infection
Summary
There is a balance between antioxidant defense systems and free radical generation. Under impaired balance between antioxidants and oxidants, oxidative stress develops, and cellular damage occurs [1], which is featured by multiple pathological chronic diseases, and the severity of viral infections like as recently pandemic of coronavirus disease 2019 (COVID-19). Thereby, Nrf and associated proteins account as an ideal target against oxidative stress-related diseases, including neurodegenerative diseases, cancers, viral infection, cardiomyopathy, insulin resistance, and ischemia-reperfusion injury, as well as to protect other tissues or organs by regulating its level [8,9]. It has been shown that curcumin mediates the mitochondrial dysfunction inhibition and Nrf release/translocate into the nucleus in order to regulate the cell antioxidant pathways and provide cell survivability [9,17]. We summarize the recent studies on the Nrf activation by curcumin and its derivatives as potential drugs and provide a brief overview of strategies in order to improve curcumin bioavailability in the target cells with the aim of its clinical applications
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