Benefits of Curcumin in Deadly / Life Threatening Viral Diseases

Viral infection, including SARS-CoV, MERS-CoV, and SARS-CoV2, causes difficult to treat diseases that can be fatal because of lung failure and systemic cytokine storm.

The development of coronavirus-induced pneumonia is related to extreme inflammatory responses in the lung, known as “cytokine storms,” which results in pulmonary edema, atelectasis, and acute lung injury (ALI) or fatal acute respiratory distress syndrome (ARDS).

No drugs are available to subdue overly immune response-mediated lung injury effectively. But because of the low toxicity and its antioxidant, anti-inflammatory, and antiviral activity, it is possible to say that curcumin could be used as an option for viral pneumonia and ALI / ARDS.

Presymptomatic studies using animal models of lethal pneumonia where curcumin exerts protective effects by regulating the expression of both pro- and anti-inflammatory factors such as IL-6, IL-8, IL-10, and COX-2, promoting the apoptosis of PMN cells, and scavenging the reactive oxygen species (ROS), which aggravates the inflammatory response.

Studies provides a rationale hypothesis that curcumin can be used as a compound against pneumonia and ALI/ARDS in humans induced by viral infection.

Curcumin Blocks Inflammatory Reaction

Various in vivo and in vitro studies have been shown that curcumin and its analogs noticebly inhibit the production and release of pro-inflammatory cytokines, such as IL-1, IL-6, IL-8, TNF-α. In compliance with this, have observed that direct pulmonary delivery of solubilized curcumin dramatically plummets pro-inflammatory cytokines IL-1β, IL-6, TNF-α in the BAL cells, the lung and serum of mice with severe pneumonia induced by Klebsiella.

Futhermore, curcumin also decreases expression of many other inflammatory mediators, including MCP1(CCL2), MIPI1 (CCL3), GROα (CXCL1), GROβ (CXCL2), IP10 (CXCL10), SDF1 (CXCL12), MMP-2, IFN-γ, and MMP-9, which regulate the activity of immune cells and inflammatory responses and promote fibrosis in the lung after infection.

Scavenges Reactive Oxygen Species (ROS)

It has been described that curcumin acts to directly hunt ROS as a polyphenolic antioxidant. Curcumin has two active groups, one hydroxyl-hydrogen on the benzene ring that has an anti-oxidation effect and the other a β-diketone moiety.

In vitro experiments have shown that curcumin effectively scavenges on ROS removal and anti-oxidation, curcumin has been shown effective at scavenging the superoxide anion radical produced by illuminating riboflavin and the OH– produced by the Fenton reaction. Curcumin also inhibits the peroxidation of lecithin and DNA oxidative damage caused by ROS.

Curcumin Reduces Lung Edema Caused by Inflammation

Inflammation plays a crucial role in the pathogenesis of lung complications of viral infection, as manifested by lung edema, hemorrhage, neutrophil infiltration, and alveolar thickening. Studies show that curcumin and its analogs are capable of attenuating lung injury.

Similar protective effects of curcumin have been reported in the rodent model of ventilator-induced lung injury and Staphylococcus S.aureus-induced ALI as evidenced by attenuation of inflammatory cell infiltration, lung edema due to its anti-inflammatory and antioxidant effects.

In a chronic obstructive pulmonary disease model, curcumin treatment effectively reduces the degree of airway inflammation and disrupts airway remodeling by inhibiting the proliferation of bronchial epithelial cells.

Mechanistically, curcumin shields the lung by inhibiting inflammation and production of ROS through regulation of multiple signaling pathways engaging peroxisome proliferator-activated receptor γ (PPARγ), JNK, NF-κB, and Nrf2.

Notably, the role of curcumin in regulating Nrf2/HO-1 has been reported in IAV infection. The Nrf2 enhances the expression of HO-1, an immunoregulatory and anti-inflammation molecule, and other enzymes for maintaining redox homeostasis.

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The Potential Role of Curcumin in the Prevention and Control of Viral Infection by targeting cytokine storm

Targeting cytokine storm is considered as an integral strategy for viral infections. In clinical settings, glucocorticoids have been used to treat deadly viral pneumonia and shown therapeutic benefits. In the treatment of patients with SARS in 2003, glucocorticoids were widely used to suppress the cytokine storm in severe cases.

However, it has been found that large doses of glucocorticoids create various side effects such as osteoporosis and secondary infection with other pathogenic microbes, and small doses have little effect on improving lung injury. These clinical findings indicate that it is increasingly important to seek alternative agents with effectiveness and low toxicity.

Many studies on virus-induced pneumonia have highlighted the potential usage of curcumin in the improvement of lung index and survival rate. Curcumin mitigates the severity of viral pneumonia through inhibiting the production of inflammatory cytokines and NF-κB signaling in macrophages.

Curcumin has also been shown to activate Nrf2 in association with reduced oxidative stress and inhibit TLR2/4, p38/JNK MAPK, and NF-κB in response to IAV infection; and as a result, pneumonia is improved.

Up to now, it has been claimed that curcumin benefits human health and prevents diseases. Studies suggested that a low dose of curcumin produced a variety of health-promoting actions, such as direct and indirect antioxidant actions. Additionally, gathering evidence from animal studies has shown that curcumin prevents the development of severe pneumonia.

The similar protective role of curcumin has been found in preclinical studies of viral-induced pneumonia. Treatment with curcumin (50 mg/kg/day) beginning at 5 days prior to reovirus 1/L infection protects CBA/J mice from the development of ALI/ARDS and suppresses subsequent fibrosis have reported that pre-infection or post-infection administration of curcumin significantly improves the lung index and prolongs the survival rate.

Interestingly, the fatality rate is also reduced by pre-administration with curcumin. All these studies suggest that curcumin administration could have both prophylactic and therapeutic effects on virus-induced pneumonia and mortality.

Clinical investigations have suggested that curcumin might be effective in improving inflammation and the treatment of virus infections. A clinical trial conducted by scientists have demonstrated that curcumin nanomicelle supplement ameliorates oxidative stress, and reduces inflammatory biomarkers, including TNF-α, compared to a placebo.

SUMMARY

• Cytokine storm syndrome triggered by viral infections is the culprit of death.
• It is heightened by unchecked regulation of the production of pro-inflammatory cytokines and ROS, leading to pneumonia, ALI, multiple organs failures, and eventually death.
• No effective therapy is available for the cytokine storm syndrome and linked lung and other organ failures.
• Curcumin is a natural plant extract with high safety and low toxicity such that people take it as a dietary supplement, and growing evidence from studies demonstrates that it effectively attacks viral infection, alleviates the severity of lung injury through offsetting the cytokine storm, inhibits subsequent fibrosis, and increases survival rates.
• Additionally, its anti-SARS-CoV replication and 3CL protease have been reported in an in vitro study.