Title:
Dose-dependent Effect of Berberine on SARS-CoV-2 Spike Protein Induced Inflammatory Host Cell Response

Authors:
Ivy Gu and Wei Zhu, USA

Abstract:

The novel Coronavirus disease 2019 (COVID-19) is the cause behind the current global pandemic, capable of inducing pneumonia-like symptoms and lung failure. A key pathway involved in the pathogenesis of COVID-19 is NF-kB, responsible for controlling the expression of pro-inflammatory cytokines such as TNF-alpha and IL-6. Berberine is a compound commonly found in plants belonging to the Berberis family which has previously been researched as an anti-inflammatory drug. The use of berberine has been shown to suppress both TNF-alpha expression and NF-kB activity, suggesting its potential as a treatment for the inflammatory symptoms of COVID-19. This experiment focuses on the dose-dependent effect of berberine on cells treated with COVID-19 spike proteins, which has previously been shown to upregulate the expression of inflammatory cytokines. Cell viability of SK-N-SH (neuroblastoma) and CCD 841 CoN (colon) cells were monitored by MTT and LDH assays after 24 hour treatment with the spike protein.  TNF-alpha and IL-6 cytokine concentrations in CCD 841 CoN were quantified using ELISA assays. The presence of spike proteins appeared to significantly diminish the viability of both cell lines, an effect which berberine managed to reverse dose-dependently. In addition, the ELISA detected a near threefold increase in both inflammatory cytokines after treatment with spike proteins in the CCD 841 CoN cells. Berberine managed to ameliorate this, lowering the concentrations down to near-untreated levels. These results display the damaging effects of the COVID-19 spike protein alone on cells, demonstrated by the decrease in viability and increased inflammatory cytokine levels. Furthermore, they support the anti-inflammatory effect of berberine in regards to these cytokines as berberine was able to increase viability and reduce cytokine production. Coupled with the viability assays, these results suggest that berberine may be either an effective treatment for COVID-19 inflammation or a possible component of a treatment.

DOI: http://dx.doi.org/10.51505/ijmshr.2021.5116