Coronavirus disease-19 (COVID-19), a devastating respiratory illness caused by SARS-associated coronavirus-2 (SARS-CoV-2), has already affected over 64 million people and caused 1.48 million deaths, just 12 months from the first diagnosis. COVID-19 patients develop serious complications, including severe pneumonia, acute respiratory distress syndrome (ARDS), and or multiorgan failure due to exaggerated host immune response following infection. Currently, drugs that were effective against SARS-CoV are being repurposed for SARS-CoV-2. During this public health emergency, food nutraceuticals could be promising prophylactic therapeutics for COVID-19. Curcumin, a bioactive compound in turmeric, exerts diverse pharmacological activities and is widely used in foods and traditional medicines. This review presents several lines of evidence, which suggest curcumin as a promising prophylactic, therapeutic candidate for COVID-19. First, curcumin exerts antiviral activity against many types of enveloped viruses, including SARS-CoV-2, by multiple mechanisms: direct interaction with viral membrane proteins; disruption of the viral envelope; inhibition of viral proteases; induce host antiviral responses. Second, curcumin protects from lethal pneumonia and ARDS via targeting NF-κB, inflammasome, IL-6 trans signal, and HMGB1 pathways. Third, curcumin is safe and well-tolerated in both healthy and diseased human subjects. In conclusion, accumulated evidence indicates that curcumin may be a potential prophylactic therapeutic for COVID-19 in the clinic and public health settings.
Naringenin (NAR) is a naturally occurring plant flavonoid, found predominantly in citrus fruits, possesses a wide range of pharmacological properties. However, despite the therapeutic potential of NAR, its clinical development has been hindered due to low aqueous solubility and inefficient transport across biological membranes resulting in low bioavailability at tumor sites. In our previous studies, nanosuspension of naringenin (NARNS) was prepared using high pressure homogenization method using different polymers. D-α-Tocopheryl polyethylene glycol succinate 1000 (TPGS) was added as a co-stabilizer. All formulation characterization studies were performed. As a continuation of our previous research, current study has further evaluated the ability of the TPGS-coated NARNS, to reverse drug-resistance of P-gp-over expressing MCF-7 human breast adenocarcinoma cell line and animal model. MTT-based colorimetric assay revealed higher cytotoxic efficacy of NARNS than free NAR in MCF-7 cells. NARNS treatment significantly increased intracellular ROS level, mitochondrial membrane potential, caspase-3 activity, lipid peroxidation status (TBARS) and decreased GSH levels when compared to free NAR treatment in MCF-7 cells. It has been also noticed that the presence of apoptotic indices (membrane blebbing, nuclear fragmentation) in NARNS treated cancer cells. Further, NARNS exhibited dose-dependent in vitro antitumor activity with DLA cells. A significant increase in the life span and a decrease in the cancer cell number and tumor weight were noted in the tumor-induced mice after treatment with NARNS.
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