COVID-19 is a global catastrophic event that causes severe acute respiratory syndrome. The mechanism of the disease remains unclear, and hypoxia is one of the main complications. There is no currently approved protocol for treatment. The microbial threat as induced by COVID-19 causes the activation of macrophages to produce a huge amount of inflammatory molecules and nitric oxide (NO). Activation of macrophages population into a pro-inflammatory phenotype induces a self-reinforcing cycle. Oxidative stress and NO contribute to this cycle, establishing a cascade inflammatory state that can kill the patient. Interrupting this vicious cycle by a simple remedy may save critical patients’ lives. Nitrite, nitrate (the metabolites of NO), methemoglobin, and prooxidant-antioxidant-balance levels were measured in 25 ICU COVID-19 patients and 25 healthy individuals. As the last therapeutic option, five patients were administered methylene blue-vitamin C–N-acetyl Cysteine (MCN). Nitrite, nitrate, methemoglobin, and oxidative stress were significantly increased in patients in comparison to healthy individuals. Four of the five patients responded well to treatment. In conclusion, NO, methemoglobin and oxidative stress may play a central role in the pathogenesis of critical COVID-19 disease. MCN treatment seems to increase the survival rate of these patients. Considering the vicious cycle of macrophage activation leading to deadly NO, oxidative stress, and cytokine cascade syndrome; the therapeutic effect of MCN seems to be reasonable. Accordingly, a wider clinical trial has been designed. It should be noted that the protocol is using the low-cost drugs which the FDA approved for other diseases. Trial registration number NCT04370288.

Propolis is a sticky, resinous material gather from plants and is blended with wax and other constituents. It is reported to have anti-inflammatory, anti-oxidative and blood glucose-lowering properties. This review aims to summarise evidences for the cellular and molecular mechanism of Propolis in inflammation, oxidative stress, and glycemic control. Propolis stimulate the production and secretion of anti-inflammatory cytokines and to inhibit the production of inflammatory cytokines and due to its various antioxidant and poly-phenolic compounds may has a role in control and treating some of the chronic diseases. Most studies have shown that Propolis may affect metabolic factors including plasma insulin levels, and it has proposed that it could be used in the prevention and treatment of T2D Mellitus. In general, to demonstrate the definite effects of Propolis on chronic diseases, more studies are required using larger sample sizes and various doses of Propolis, using better characterized and standardized agents.

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Background & Objective: The present study aimed to investigate the effects of propolis and melatonin supplementation on inflammation, clinical outcomes, and oxidative stress markers in patients with primary pneumosepsis. Materials and Methods: This pilot randomized controlled trial was conducted on 55 patients with primary pneumosepsis who were randomly assigned to the intervention and control groups. In the three intervention groups, the patients received propolis alone (1,000 mg/day), propolis (1,000 mg/day) plus melatonin (20 mg/day), and melatonin alone (20 mg/day). The control group received placebo. The inflammatory and oxidative stress markers as well as clinical outcomes were evaluated before and after the intervention, and the 28-day survival rate was also recorded. Results: After the intervention, the combination of propolis and melatonin significantly reduced interleukin-6 (-55.282 pg/ml ) and C-reactive protein (-21.656 mg/l ) levels, while increasing gavage intake (326.680 ml/day ) and improving some clinical outcomes (APACHE II, SOFA and NUTRIC scores) compared to control group. However, no significant difference was observed between the groups in terms of oxidative stress and hematological indices. In addition, the 28-day survival rate had no significant difference between the groups (P=0.07). Conclusion: Supplementation with propolis and melatonin may improve clinical outcomes by reducing inflammation. Further investigations are required to confirm these findings.