The Inhibitory Effect of Curcumin on Virus-Induced Cytokine Storm and Its Potential Use in the Associated Severe Pneumonia

Ziteng Liu, Ying Ying, Ziteng Liu, Ying Ying

Abstract

Coronavirus infection, including SARS-CoV, MERS-CoV, and SARS-CoV2, causes daunting diseases that can be fatal because of lung failure and systemic cytokine storm. The development of coronavirus-evoked pneumonia is associated with excessive 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 suppress overly immune response-mediated lung injury effectively. In light of the low toxicity and its antioxidant, anti-inflammatory, and antiviral activity, it is plausible to speculate that curcumin could be used as a therapeutic drug for viral pneumonia and ALI/ARDS. Therefore, in this review, we summarize the mounting evidence obtained from preclinical 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 exacerbates the inflammatory response. These studies provide a rationale that curcumin can be used as a therapeutic agent against pneumonia and ALI/ARDS in humans resulting from coronaviral infection.

Keywords: coronavirus; curcumin; cytokine storm; lung injury; pneumonia.

Copyright © 2020 Liu and Ying.

Figures

FIGURE 1
FIGURE 1
The diagram of lung injury caused by virus-induced cytokine storms. (A) The viruses attack alveolar epithelial cells and are recognized by dendritic cells and macrophages, which then release cytokines. (B) Cytokines and chemokines help white blood cells in the blood reach the alveoli. (C) Antigen-presenting cells (dendritic cells) activate lymphocytes. Activated lymphocytes produce and release large amounts of cytokines while attacking infected alveolar epithelial cells. (D) Induce cytokine storm, and capillary leak syndrome. (E) Causes atelectasis, pulmonary edema, pulmonary congestion, and ARDS.
FIGURE 2
FIGURE 2
Curcumin inhibits the production of pro-inflammatory cytokine by targeting the NF-κB pathway. Curcumin targets NF-κB signaling through inhibiting activation of IKKβ, enhancing expression or stability of IκBα, activating AMPK, and targeting P65.
FIGURE 3
FIGURE 3
The effects of curcumin in virus associated with severe pneumonia. Curcumin inhibits virus-induced lung injury through its antivirus, anti-inflammation, antioxidant activity. In addition, curcumin could suppress fibrosis by targeting TGF-β signaling. Abbreviations: Nrf2, nuclear factor erythroid-derived 2; NF-κB, nuclear factor-κB; PPARγ, peroxisome proliferator-activated receptor γ; TNF-α, tumor necrosis factor-alpha; COX2, cyclooxygenase-2; IκB, inhibitor of kappa B; IL, interleukin; JNK, c-Jun N-terminal Kinase; TN-C, tenascin-C; α-SMA, alpha-smooth muscle actin.

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