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1.
J Evid Based Integr Med ; 26: 2515690X211036875, 2021.
Article in English | MEDLINE | ID: covidwho-1495800

ABSTRACT

Worldwide, the turmoil of the SARS-CoV-2 (COVID-19) pandemic has generated a burst of research efforts in search of effective prevention and treatment modalities. Current recommendations on natural supplements arise from mostly anecdotal evidence in other viral infections and expert opinion, and many clinical trials are ongoing. Here the authors review the evidence and rationale for the use of natural supplements for prevention and treatment of COVID-19, including those with potential benefit and those with potential harms. Specifically, the authors review probiotics, dietary patterns, micronutrients, antioxidants, polyphenols, melatonin, and cannabinoids. Authors critically evaluated and summarized the biomedical literature published in peer-reviewed journals, preprint servers, and current guidelines recommended by expert scientific governing bodies. Ongoing and future trials registered on clinicaltrials.gov were also recorded, appraised, and considered in conjunction with the literature findings. In light of the controversial issues surrounding the manufacturing and marketing of natural supplements and limited scientific evidence available, the authors assessed the available data and present this review to equip clinicians with the necessary information regarding the evidence for and potential harms of usage to promote open discussions with patients who are considering dietary supplements to prevent and treat COVID-19.


Subject(s)
Antioxidants/therapeutic use , COVID-19/drug therapy , Dietary Supplements , Micronutrients/therapeutic use , Plant Extracts/therapeutic use , Antioxidants/pharmacology , Cannabinoids/pharmacology , Cannabinoids/therapeutic use , Humans , Melatonin/pharmacology , Melatonin/therapeutic use , Micronutrients/pharmacology , Niacinamide/pharmacology , Niacinamide/therapeutic use , Plant Extracts/pharmacology , Polyphenols/pharmacology , Polyphenols/therapeutic use , Probiotics/therapeutic use , SARS-CoV-2
3.
J Evid Based Integr Med ; 26: 2515690X211036875, 2021.
Article in English | MEDLINE | ID: covidwho-1356989

ABSTRACT

Worldwide, the turmoil of the SARS-CoV-2 (COVID-19) pandemic has generated a burst of research efforts in search of effective prevention and treatment modalities. Current recommendations on natural supplements arise from mostly anecdotal evidence in other viral infections and expert opinion, and many clinical trials are ongoing. Here the authors review the evidence and rationale for the use of natural supplements for prevention and treatment of COVID-19, including those with potential benefit and those with potential harms. Specifically, the authors review probiotics, dietary patterns, micronutrients, antioxidants, polyphenols, melatonin, and cannabinoids. Authors critically evaluated and summarized the biomedical literature published in peer-reviewed journals, preprint servers, and current guidelines recommended by expert scientific governing bodies. Ongoing and future trials registered on clinicaltrials.gov were also recorded, appraised, and considered in conjunction with the literature findings. In light of the controversial issues surrounding the manufacturing and marketing of natural supplements and limited scientific evidence available, the authors assessed the available data and present this review to equip clinicians with the necessary information regarding the evidence for and potential harms of usage to promote open discussions with patients who are considering dietary supplements to prevent and treat COVID-19.


Subject(s)
Antioxidants/therapeutic use , COVID-19/drug therapy , Dietary Supplements , Micronutrients/therapeutic use , Plant Extracts/therapeutic use , Antioxidants/pharmacology , Cannabinoids/pharmacology , Cannabinoids/therapeutic use , Humans , Melatonin/pharmacology , Melatonin/therapeutic use , Micronutrients/pharmacology , Niacinamide/pharmacology , Niacinamide/therapeutic use , Plant Extracts/pharmacology , Polyphenols/pharmacology , Polyphenols/therapeutic use , Probiotics/therapeutic use , SARS-CoV-2
4.
Biomed Pharmacother ; 141: 111823, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1272313

ABSTRACT

Here, we demonstrate that the two distinct formulations of our anti-sepsis drug candidate Rejuveinix (RJX), have a very favorable safety profile in Wistar Albino rats at dose levels comparable to the projected clinical dose levels. 14-day treatment with RJX-P (RJX PPP.18.1051) or RJX-B (RJX-B200702-CLN) similarly elevated the day 15 tissue levels of the antioxidant enzyme superoxide dismutase (SOD) as well as ascorbic acid in both the lungs and liver in a dose-dependent fashion. The activity of SOD and ascorbic acid levels were significantly higher in tissues of RJX-P or RJX-B treated rats than vehicle-treated control rats (p < 0.0001). There was no statistically significant difference between tissue SOD activity or ascorbic acid levels of rats treated with RJX-P vs. rats treated with RJX-B (p > 0.05). The observed elevations of the SOD and ascorbic acid levels were transient and were no longer detectable on day 28 following a 14-day recovery period. These results demonstrate that RJX-P and RJX-B are bioequivalent relative to their pharmacodynamic effects on tissue SOD and ascorbic acid levels. Furthermore, both formulations showed profound protective activity in a mouse model of sepsis. In agreement with the PD evaluations in rats and their proposed mechanism of action, both RJX-P and RJX-B exhibited near-identical potent and dose-dependent anti-oxidant and anti-inflammatory activity in the LPS-GalN model of ARDS and multi-organ failure in mice.


Subject(s)
Ascorbic Acid/chemistry , Ascorbic Acid/therapeutic use , Magnesium Sulfate/chemistry , Magnesium Sulfate/therapeutic use , Niacinamide/chemistry , Niacinamide/therapeutic use , Pantothenic Acid/chemistry , Pantothenic Acid/therapeutic use , Pyridoxine/chemistry , Pyridoxine/therapeutic use , Riboflavin/chemistry , Riboflavin/therapeutic use , Sepsis/drug therapy , Sepsis/metabolism , Thiamine/chemistry , Thiamine/therapeutic use , Animals , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Antioxidants/chemistry , Antioxidants/pharmacology , Antioxidants/therapeutic use , Ascorbic Acid/pharmacology , Dogs , Dose-Response Relationship, Drug , Drug Combinations , Drug Compounding , Female , Humans , Lipopolysaccharides/toxicity , Magnesium Sulfate/pharmacology , Male , Mice , Mice, Inbred BALB C , Niacinamide/pharmacology , Oxidative Stress/drug effects , Oxidative Stress/physiology , Pantothenic Acid/pharmacology , Pyridoxine/pharmacology , Rats , Rats, Sprague-Dawley , Rats, Wistar , Riboflavin/pharmacology , Sepsis/pathology , Superoxide Dismutase/metabolism , Thiamine/pharmacology
5.
Nutrients ; 12(6)2020 May 31.
Article in English | MEDLINE | ID: covidwho-1178369

ABSTRACT

Nicotinamide riboside (NR) has recently become one of the most studied nicotinamide adenine dinucleotide (NAD+) precursors, due to its numerous potential health benefits mediated via elevated NAD+ content in the body. NAD+ is an essential coenzyme that plays important roles in various metabolic pathways and increasing its overall content has been confirmed as a valuable strategy for treating a wide variety of pathophysiological conditions. Accumulating evidence on NRs' health benefits has validated its efficiency across numerous animal and human studies for the treatment of a number of cardiovascular, neurodegenerative, and metabolic disorders. As the prevalence and morbidity of these conditions increases in modern society, the great necessity has arisen for a rapid translation of NR to therapeutic use and further establishment of its availability as a nutritional supplement. Here, we summarize currently available data on NR effects on metabolism, and several neurodegenerative and cardiovascular disorders, through to its application as a treatment for specific pathophysiological conditions. In addition, we have reviewed newly published research on the application of NR as a potential therapy against infections with several pathogens, including SARS-CoV-2. Additionally, to support rapid NR translation to therapeutics, the challenges related to its bioavailability and safety are addressed, together with the advantages of NR to other NAD+ precursors.


Subject(s)
Dietary Supplements , Niacinamide/analogs & derivatives , Aging , Animals , Betacoronavirus , Biological Availability , COVID-19 , Cardiovascular Diseases/therapy , Coronavirus Infections/therapy , Humans , Longevity , Metabolism , Neurodegenerative Diseases/therapy , Niacinamide/pharmacokinetics , Niacinamide/pharmacology , Pandemics , Pneumonia, Viral/therapy , Pyridinium Compounds , SARS-CoV-2
6.
Biosci Rep ; 40(10)2020 10 30.
Article in English | MEDLINE | ID: covidwho-989979

ABSTRACT

COVID-19 induces a proinflammatory environment that is stronger in patients requiring intensive care. The cytokine components of this environment may determine efficacy or otherwise of glucocorticoid therapy. The immunity modulators, the aryl hydrocarbon receptor (AhR) and the nuclear NAD+-consuming enzyme poly (ADP-ribose) polymerase 1 (PARP 1) may play a critical role in COVID-19 pathophysiology. The AhR is overexpressed in coronaviruses, including COVID-19 and, as it regulates PARP gene expression, the latter is likely to be activated in COVID-19. PARP 1 activation leads to cell death mainly by depletion of NAD+ and adenosine triphosphate (ATP), especially when availability of these energy mediators is compromised. PARP expression is enhanced in other lung conditions: the pneumovirus respiratory syncytial virus (RSV) and chronic obstructive pulmonary disease (COPD). I propose that PARP 1 activation is the terminal point in a sequence of events culminating in patient mortality and should be the focus of COVID-19 immunotherapy. Potent PARP 1 inhibitors are undergoing trials in cancer, but a readily available inhibitor, nicotinamide (NAM), which possesses a highly desirable biochemical and activity profile, merits exploration. It conserves NAD+ and prevents ATP depletion by PARP 1 and Sirtuin 1 (silent mating type information regulation 2 homologue 1) inhibition, enhances NAD+ synthesis, and hence that of NADP+ which is a stronger PARP inhibitor, reverses lung injury caused by ischaemia/reperfusion, inhibits proinflammatory cytokines and is effective against HIV infection. These properties qualify NAM for therapeutic use initially in conjunction with standard clinical care or combined with other agents, and subsequently as an adjunct to stronger PARP 1 inhibitors or other drugs.


Subject(s)
Coronavirus Infections/drug therapy , Niacinamide/pharmacology , Pneumonia, Viral/drug therapy , Poly (ADP-Ribose) Polymerase-1/antagonists & inhibitors , Poly(ADP-ribose) Polymerase Inhibitors/pharmacology , Basic Helix-Loop-Helix Transcription Factors/metabolism , Betacoronavirus/drug effects , COVID-19 , Cell Line , Coronavirus Infections/pathology , Cytokines/blood , Humans , Immunotherapy/methods , Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism , Kynurenine/metabolism , Pandemics , Pneumonia, Viral/pathology , Poly (ADP-Ribose) Polymerase-1/metabolism , Receptors, Aryl Hydrocarbon/metabolism , SARS-CoV-2
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