Anti-Viral Potential and Modulation of Nrf2 by Curcumin: Pharmacological Implications

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.

Nutraceuticals in the Prevention of Viral Infections, including COVID-19, among the Pediatric Population: A Review of the Literature

“…In addition to the nutraceuticals analyzed, the role of other nutraceuticals has been explored. Curcumin is a yellow polyphenolic curcuminoid from Curcuma longa (turmeric) that seems to have a broad spectrum of bioactivities, including antioxidant, antiapoptotic, and antifibrotic properties with inhibitory effects on Toll-like receptors, NF-κB, inflammatory cytokines and chemokines, and bradykinin [ 235 , 236 ]. Interestingly, Curcumin can be appraised to hinder cellular entry and replication of SARS-CoV-2 and to prevent and repair COVID-19-associated damage of pneumocytes, renal cells, cardiomyocytes, and hematopoietic stem cells [ 237 ].…”

Curcumin Inhibits Replication of Human Parainfluenza Virus Type 3 by Affecting Viral Inclusion Body Formation

“…As a natural compound, curcumin has been reported to have antiviral activity against various viruses, including the novel SARS-CoV-2 [ 28 , 29 ]. Our research confirmed that curcumin could inhibit HPIV3 infection, and its antiviral effect is dose-dependent.…”

Nanotechnology-Based Drug Delivery to Improve the Therapeutic Benefits of NRF2 Modulators in Cancer Therapy

“…Phenolic compounds, such as curcumin and resveratrol, are potential NRF2 modulators in cancer prevention and therapy [ 72 ], and their chemopreventive properties can be enhanced by encapsulation in nanoemulsions. Curcumin, (1E,6E)-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione, is a natural hydrophobic polyphenol that presents in the dried rhizomes of the medicinal plant Curcuma longa (turmeric), and its biological and pharmacological activities have been widely reported [ 119 , 120 ].…”

“…Several studies demonstrated the ability of curcumin to reactivate the expression of antioxidant enzymes, such as glutathione S-transferase, aldose reductase, and HO-1, through KEAP1/NRF2 signaling [ 119 ]. Curcumin could be a possible NRF2 activator to regulate the cell signaling pathway in stress environments and be beneficial in treating several oxidative stress-related disorders, such as cancer (including breast, gastrointestinal, and prostate), neurodegenerative diseases (NDs), autoimmune diseases, and cardiovascular diseases (CVDs), among others [ 119 , 120 ].…”