A comprehensive review on modulation of SIRT1 signaling pathways in the immune system of COVID ‐19 patients by phytotherapeutic melatonin and epigallocatechin‐3‐gallate

Abstract

SARS‐CoV‐2 infection has now become the world's most significant health hazard, with the World Health Organization declaring a pandemic on March 11, 2020. COVID‐19 enters the lungs through angiotensin‐converting enzyme 2 (ACE2) receptors, alters various signaling pathways, and causes immune cells to overproduce cytokines, resulting in mucosal inflammation, lung damage, and multiple organ failure in COVID‐19 patients. Although several antiviral medications have been effective in managing the virus, they have not been effective in lowering the inflammation and symptoms of the illness. Several studies have found that epigallocatechin‐3‐gallate and melatonin upregulate sirtuins proteins, which leads to downregulation of pro‐inflammatory gene transcription and NF‐κB, protecting organisms from oxidative stress in autoimmune, respiratory, and cardiovascular illnesses. As a result, the purpose of this research is to understand more about the molecular pathways through which these phytochemicals affect COVID‐19 patients' impaired immune systems, perhaps reducing hyperinflammation and symptom severity. Practical applications Polyphenols are natural secondary metabolites that are found to be present in plants. EGCG a polyphenol belonging to the flavonoid family in tea has potent anti‐inflammatory and antioxidative properties that helps to counter the inflammation and oxidative stress associated with many neurodegenerative diseases. Melatonin, another strong antioxidant in plants, has been shown to possess antiviral function and alleviate oxidative stress in many inflammatory diseases. In this review, we propose an alternative therapy for COVID‐19 patients by supplementing their diet with these nutraceuticals that perhaps by modulating sirtuin signaling pathways counteract cytokine storm and oxidative stress, the root causes of severe inflammation and symptoms in these patients.

Is Melatonin the “Next Vitamin D”?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements

“…Although not absorbed in the GI tract to a great extent, polyphenols have become highlighted for their impacts on gut health, particularly due to the secondary metabolites that form from their interaction with the microbiota [ 47 ]. There are initial indications that the antioxidant and anti-inflammatory actions of melatonin may work together with select polyphenols (e.g., resveratrol, epigallocatechin 3-gallate) for therapeutic indications [ 48 , 49 , 50 , 51 , 52 , 53 , 54 ].…”

Camellia sinensis L. Extract Suppresses Inflammation on Acute Respiratory Distress Syndrome Cells Models via Decreasing IL-1ß, IL-6 and COX-2 Expressions

“…ACE-2 prevents LPS-induced ARDS by blocking MAPKs and NF-κB signaling pathway and also protect against lung inflammation [7]. Epigallocatechin-3-gallate in C. sinensis increased sirtuins proteins which leads to decrease in pro-inflammatory gene transcription and NF-kB, protecting organisms from oxidative stress in autoimmune, respiratory, and cardiovascular diseases [55].…”

Expression patterns of lncRNA MALAT-1 in SARS-COV-2 infection and its potential effect on disease severity via miR-200c-3p and SIRT1

“…This is in accordance with [ 60 ] who detected significantly decreased SIRT1 expression in COVID-19 patients, which was negatively correlated with p53, IL1-β, and TNF. [ 16 ] showed that SIRT1 can reduce inflammation in COVID-19 patients. [ 75 ] found that SIRT1 inactivation was linked to COVID-19 severity and its low level served as a predictor of COVID-19 that was not under control.…”

“…Sirtuins also provide defense against viral infections [ 15 ]. SIRT1 can suppress NF-κB [ 16 ], as well as bind to ACE2 promotor enhancing its expression [ 17 , 18 ].…”