Boswellic Acids Reduce Systemic Inflammation in Patients with Moderate COVID-19 Through Modulation of NF-κB Pathway

Prevention and/or management of the dysregulated immune response in patients with COVID-19 is expected to help in the treatment of COVID-19. Boswellic acids (BAs) have great therapeutic potential because they have anti-inflammatory and immunomodulatory effects. Here, we aimed to investigate the mechanism of action of a BA formulation, Inflawell syrup, which was previously shown to be effective in reducing disease symptoms in patients who suffer from mild to moderate COVID-19. Patients with mild to moderate COVID-19 were treated with either Inflawell containing boswellic acids or a placebo for 14 days. The serum levels of inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin (IL)-8, IL-1α, IL-17, IL-1Ra, and Monocyte Chemoattractant Protein-1 (MCP-1), were measured both at study onset and on day 14 after treatment started. In addition, to further investigate the signaling pathway(s) underlying the changes in cytokine levels, we evaluated the expression of tumor necrosis factor receptor 1 (TNFR1), tumor necrosis factor receptor 2 (TNFR2), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65 mRNAs and phospho-inhibitor of nuclear factor kappa B (IκB) and IκB proteins. In our study, a significant decrease in the serum levels of IL-1α (<i>p</i> < .009), IL-8 (<i>p</i> < .04), TNF-α (<i>p</i> < .0001), and MCP-1 (<i>p</i> < .007) was detected in patients treated with Inflawell. Additionally, our data revealed a decrease in phospho-IκB protein levels (<i>p</i> < .02) and NF-κB p65 mRNA levels (<i>p</i> < .002), whereas the amount of IκB protein (<i>p</i> < .01) in the Inflawell group was significantly greater than that in the placebo group. Furthermore, despite the decreasing trend in the expression of TNFR1 and TNFR2 in the Inflawell group, there was no statistically significant difference compared with that in the placebo group. In general, treatment with Inflawell syrup led to a lower level of proinflammatory cytokines and a decrease in the activity of the TNF-α/NF-κB signaling pathway.