In Vitro Analyses of the Multifocal Effects of Natural Alkaloids Berberine, Matrine, and Tabersonine against the O'nyong-nyong Arthritogenic Alphavirus Infection and Inflammation.
Anne-Laure Sandenon SeteyenPascale GuiraudPhilippe GasqueEmmanuelle Girard-ValenciennesJimmy SélambaromPublished in: Pharmaceuticals (Basel, Switzerland) (2023)
O'nyong-nyong virus (ONNV) is a member of the reemerging arthritogenic alphaviruses that cause chronic debilitating polyarthralgia and/or polyarthritis via their tropism for the musculoskeletal system. Thus, the discovery of dual antiviral and anti-inflammatory drugs is a great challenge in this field. We investigated the effects of the common plant-derived alkaloids berberine (isoquinoline), matrine (quinolizidine), and tabersonine (indole) at a non-toxic concentration (10 μM) on a human fibroblast cell line (HS633T) infected by ONNV (MOI 1). Using qRT-PCR analyses, we measured the RNA levels of the gene coding for the viral proteins and for the host cell immune factors. These alkaloids demonstrated multifocal effects by the inhibition of viral replication, as well as the regulation of the type-I interferon antiviral signaling pathway and the inflammatory mediators and pathways. Berberine and tabersonine proved to be the more valuable compounds. The results supported the proposal that these common alkaloids may be useful scaffolds for drug discovery against arthritogenic alphavirus infection.
Keyphrases
- drug discovery
- signaling pathway
- anti inflammatory drugs
- oxidative stress
- sars cov
- endothelial cells
- single cell
- genome wide
- high throughput
- cell therapy
- stem cells
- copy number
- epithelial mesenchymal transition
- gene expression
- dendritic cells
- dna methylation
- high resolution
- transcription factor
- immune response
- mesenchymal stem cells
- bone marrow
- real time pcr