key: cord-0889958-hlxz07ip
authors: Rocha, Francisco Airton Castro; de Assis, Marcos Renato
title: Curcumin as a potential treatment for COVID‐19
date: 2020-05-22
journal: Phytother Res
DOI: 10.1002/ptr.6745
sha: f27c74baf4ba7be34a1aff52493e03afc2a1b596
doc_id: 889958
cord_uid: hlxz07ip

nan

hit-by-us-sanctions-against-iran/articleshow/70446034.cms?from=mdr; downloaded in May 06, 08:53 AM, 2020). Community isolation has been hard to implement in those Southeast Asian countries which, like Iran, do also experience a shortage of health facilities and supplies to face this epidemic.

We were also impressed by the great difference between the number of deaths attributed to COVID-19 in those heavy curcumin-consuming countries and those in some western European countries. We should also consider that some of those European countries have implemented severe rules restricting social activities as an attempt to mitigate disease spreading, in addition to having far better health systems available. We started this observation in the early days of March 2020, but the death toll is persistently very low in those Southeast Asian countries, thus reinforcing its relevance. There are a lot of possible confounders impacting this epidemiological observation. Why would more people die from COVID-19 in such wealthy countries and why would Iranians be so heavily penalized? Considering the excellence of health systems in most Western European countries, we may assume they provide more accurate data on diagnostic testing, which are lacking in those Southeast Asian countries as well as in Iran. Thus, counting the number of deaths attributed to COVID-19 might better illustrate the burden of this disease across different populations.

Although ethnicity could play a role, the large variability across those heavy curcumin consumers both within and between countries make it unlikely to be relevant. The vast geographical area at stake argues against environmental issues including temperature, altitude and other weather conditions to explain this consistently sustained very low death toll among the curcumin consumers.

There is controversy as to whether drugs acting in the angiotensin converting enzyme serum activity, which can be used to evaluate the efficacy of RAA blockers, may not reflect ACE activity at the tissue level, particularly in the lung, a major target of SARS-CoV-2 infection (Vaduganathan et al., 2020) . Furthermore, after using ACE2 as a cell entry mechanism, SARS-CoV-2 down-regulates ACE2 expression, a process that has been associated with enhanced inflammation in the lungs. Apparently, the subsequent activation of the RAA system via increased activity of angiotensin II, which would no This article is protected by copyright. All rights reserved.

Accepted Article longer be converted to angiotensin, could increase vascular permeability, yielding pulmonary edema and severe acute respiratory syndrome. Discussing this issue would be too speculative given that the relevance of ACE2 expression during a COVID-19

infection is yet to be clarified (Vaduganathan et al., 2020) . There are data showing that curcumin may either increase or decrease ACE in vivo activity. Curcumin has been shown to protect rats subjected to thioacetamide-induced hepatotoxicity via downregulation of ACE gene expression (Fazal et al., 2015) . Rats subjected to induced systemic arterial hypertension were protected by pre-treatment with ginger and turmeric rhizome supplementation, a response that was associated with reduced ACE activity (Akinyemi et al., 2015) . On the other hand, administration of curcumin to rats subjected to angiotensin II infusion attenuated the development of myocardial fibrosis, which was associated with increased protein levels of ACE2 in the myocardium (Pang Accepted Article incidence map, and has been a repeated pattern in many countries with similar consumption of turmeric. There is some consistency between epidemiological and laboratory findings given that curcumin may interfere with the major pathway for COVID-19 cell entry. We cannot yet claim specificity or biological gradient (doseresponse relationship). Temporality is guaranteed because the consumption of saffron has long been incorporated into the culture of those countries. Provided that in vitro data prove curcumin to be effective, preferably showing a defined mechanism, clinical studies could then be proposed. However, the excellent safety profile of curcumin shown in various human studies (Aggarwal et al., 2013) may justify a pragmatic clinical protocol using the primum non nocere principle.

List of Abbreviations: angiotensin converting enzyme (ACE); COVID-19, coronavirus disease; severe acute respiratory syndrome (SARS)-coronavirus (Cov)-2. SARS-Cov-2.

FACR conceived, wrote, revised, and approved the final version of the manuscript.

MR wrote, revised and approved the final version of the manuscript.

Curcumin: an orally bioavailable blocker of TNF and other pro-inflammatory biomarkers

FACR and MRA report no conflicts of interest regarding the preparation of this manuscript.