Plant microRNAs: a natural anti-inflammatory activity in a cross-kingdom regulation

Medicinal plants have been used for millennia to treat a wide range of diseases, particularly those with an inflammatory nature. Plants are rich in bioactive compounds, which exhibit antimicrobial, anti-tumor, antioxidant, and anti-inflammatory properties. However, these molecules often reduce the activity of key players in inflammatory and tumor pathways, indirectly. Plants are also a source of microRNAs, which are naturally methylated at the 3’-end. In animals, microRNAs can control a wide range of biological processes including inflammation, by acting as direct down regulators of genes involved in inflammation. So, we asked if plant-derived-miRNAs could be a potential anti-inflammatory molecules, as well as in animals. To explore this possibility, we aimed to identify plant miRNAs with potential anti-inflammatory activity, since it has been reported that plant-derived miRNAs could bind and regulate the expression of human mRNA, in a cross-kingdom regulation. Through a bioinformatics approach, we identified plant miRNAs which are menage to induce a significant reduction in mRNA and protein levels of target genes implicated in inflammation. Moreover, the luciferase assay demonstrated that the plant miRNAs effectively reduced luciferase activity by targeting the 3’-UTRs of target genes. Subsequently, to assess their anti-inflammatory activity, mimic plant-miRs were transfected in two inflammatory cellular lines in which they significantly reduced the levels of pro-inflammatory cytokines, underscoring their ability to inhibit the NF-κB inflammatory pathway. Moreover, we are developing enhanced plants, implemented to produce high levels of the two plant-derived miRs, as molecular farming. These miRNAs will be extracted and utilized to assess their anti-inflammatory activity through in vitro and in vivo assays. In conclusion, these results collectively underscore both the potential of plant miRNAs in regulating animal inflammatory genes of the NF-kB pathway and the possibility to use them as candidates for the development of new anti-inflammatory therapies.