Abstract. The widespread COVID-19 pandemic has been, currently, converted to a catastrophic human health challenge. Vitamin D (VD) and its metabolites have been used as a palliative treatment for chronic inflammatory and infectious diseases from ancient times. In the current study, some molecular aspects of the potential effects of VD against COVID-19 side-effects have been discussed. An arguable role in autophagy or apoptosis control has been suggested for VD through calcium signaling at the mitochondrial and ER levels. 1,25(OH)2D3 is also an immunomodulator that affects the development of B-cells, T-cells, and NK cells in both innate and acquired immunity. The production of some anti-microbial molecules such as defensins and cathelicidins is also stimulated by VD. The overexpression of glutathione, glutathione peroxidase, and superoxide dismutase, and down-regulation of NADPH oxidase are induced by VD to reduce the oxidative stress. Moreover, the multi-organ failure due to a cytokine storm induced by SARS-CoV2 in COVID-19 may be prevented by the immunomodulatory effects of VD. It can also downregulate the renin-angiotensin system which has a protective role against cardiovascular complications induced by COVID-19. Given the many experimental and molecular evidences due to the potential protective effects of VD on the prevention of the COVID-19-induced morbidities, a VD supplementation is suggested to prevent the lethal side-effects of the infection. It is particularly recommended in VD-deficient patients or those at greater risk of serious or critical effects of COVID-19, including the elderly, and patients with pre-existing chronic diseases, especially those in nursing homes, care facilities, and hospitals.

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BACKGROUND: Nowadays, medicinal plants have attracted great interest in treatment of human diseases. Rosemary is a well-known medicinal plant which has been widely used for different therapeutic purposes. METHODS: This is a narrative review using databases including PubMed, ISI, Scopus, ScienceDirect, Cochrane, and google scholar, the most authoritative articles were searched, screened, and analyzed. RESULTS: Rosemary is a natural antioxidant which removes reactive oxygen species from tissues and increases expression on Nrf2 gene. Rosemary and its metabolites reduce inflammation by inhibiting production of pro-inflammatory cytokines, decreasing expression of NF-κB, inhibiting infiltration of immune cells to inflamed sites, and affecting gut microbiome. Besides, rosmarinic acid in rosemary extract has positive effects on renin-angiotensin-system. Rosemary affects respiratory system by reducing oxidative stress, inflammation, muscle spasm, and also through anti-fibrotic properties. Carnosic acid is able to penetrate blood-brain-barrier and act against free radicals, ischemia and neurodegeneration in brain. Cardioprotective effects include correcting lipid profile, controlling blood pressure by inhibition of ACE, prevention of atherosclerosis, and reduction of cardiac muscle hypertrophy. CONCLUSIONS: Accordingly, rosemary supplementation has potential protective effects against COVID-19 and other cytokine storm associated infections, a conclusion that needs more evaluations in the next clinical trials.

Currently, the COVID-19 pandemic is the most discussed subject in medical researches worldwide. As the knowledge is expanded about the disease, more hypotheses become created. A recent study on the viral protein interaction map revealed that SARS-CoV-2 open reading frame 8 (ORF8) interacts with human DNA methyl transferase1 (DNMT1), an active epigenetic agent in DNA methylation. Moreover, DNMT1 is a contributor to a variety of chronic diseases which could cause some epigenetic dysregulation in infected cells, especially leukocytes, pancreatic beta, and endothelial cells. Regarding the fact that epigenetic alterations have a partial, but not completely reversible phenomena, it raises the question that if this interaction may cause long-term complications such as diabetes, atherosclerosis, cancer, and autoimmune diseases. Accordingly, long follow-up studies on the recovered patients from COVID-19 are recommended.

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