Terminalia bellirica Extract Suppresses SARS-Cov-2 Nucleocapsid-Induced Inflammation in A549 Cells

SARS-CoV-2 infection triggers a host-immune response via cytokine release that, when excessive, leads to severe inflammation and life-threatening complications. To reduce the risks associated with cytokine storms, alternative approaches are needed. Traditional Thai herbal extracts are recognized for their potential as safe and effective anti-inflammatory agents against various diseases. Hence, this study aims to examine the anti-inflammatory effects of ethanolic extracts from Terminalia chebula, Terminalia bellirica, Phyllanthus emblica, and Andrographis paniculata in reducing inflammation in the A549 alveolar basal epithelial cell lines. We conducted a comparative analysis of the anti-inflammation efficacy of four extracts in reducing the COX-2 upregulation induced by TNF-α stimulation in A549 cells. Among them, T. bellirica exhibited the highest effectiveness in reducing COX-2 levels to 0.38-fold. Furthermore, we validated the anti-inflammation properties of T. bellirica in diminishing inflammation-induced SARS-CoV-2 nucleocapsid. Lentivirus transduction expressing SARS-CoV-2 nucleocapsid demonstrated a dose-dependent increase in the expression of pro-inflammatory cytokines and mediators including TNF-α, IL-8, CXCL-10, and COX-2. Interestingly, treatment with sublethal doses of T. bellirica (30 and 60 μg/mL) led to a significant reduction in COX-2 expression by 30% and 70%, TNF-α by 46% and 75%, IL-8 by 39% and 48%, and CXCL-10 by 46% and 80%, respectively. These findings confirm the potent anti-inflammatory effects of T. bellirica, highlighting its potential as a novel treatment for alleviating the severity of cytokine storms in SARS-CoV-2 and related diseases.