Effects on mammalian cell transcriptome reveal a plant extract's medicinal properties: Potential anti-COVID-19 and anti-cancer properties of Sarcopoterium spinosum

Plants with medicinal properties are usually identified based on traditional medicine knowledge or using low-throughput screens for specific pharmacological activities. Here, we suggest a different approach to uncover a range of pharmacological activities of a chosen plant extract without the need for functional screening. This tactic predicts biological activities of a plant extract based on pathway analysis of transcriptome changes caused by the extract in mammalian cell culture. In this work, we identified transcriptome changes after exposure of cultured cells to an extract of the medicinal plant Sarcopoterium spinosum. Gene Set Enrichment Analysis (GSEA) confirmed known anti-inflammatory and anti-cancer activities of the extract and predicted novel biological effects on oxidative phosphorylation and interferon pathways. Experimental validation of these pathways uncovered strong activation of autophagy, including mitophagy, and astounding protection from SARS-CoV-2 infection. Our study shows that gene expression analysis alone is insufficient for predicting biological effects since some of the changes reflect compensatory effects, and additional biochemical tests provide necessary corrections. In conclusion, this study defines the advantages and limitations of an approach towards predicting the biological and medicinal effects of plant extracts based on transcriptome changes caused by these extracts in mammalian cells.