Exploring the molecular mechanism of action of a mono-herbal formulation of Ayurveda Cesamplous pareira

ABSTRACT: Drugs used in traditional medicine are multisystemicand hence are amenable to repurposing. This coupled with the history of safe usage make it possible for practitioners to rapidly evolve therapies for contemporary diseases. We provide a unique framework that combines principles of Ayurveda with transcriptome signatures of drugs, disease and connectivity map that provides a molecular basis for the traditional uses as well as novel leads for drug repurposing. This study has assumed immense importance as we demonstrate its application in a herbal extract of Cissampelos pareira (Cipa) traditionally used to treat diverse disorders such as female reproductive disorders and fevers, for repurposing in a contemporary pandemic, COVID-19. Gene expression studies using gene ontology and GSEA on MCF7 cell lines treated with Cipa extract reveal downregulation of pathways linked to lipid metabolism, protein processing and estrogen response. Estradiol and tamoxifen binding domain of estrogen receptor alpha is shared by nearly 38 constituents of Cipa having ERα BE ranging from -10.2 to -6.1KJ/mole. Transcriptome signatures were analysed and queried in connectivity map (clue.io) show positive connectivity with protein synthesis inhibitors such as Emetine (99.61), Cycloheximide (99.86) and Homoharringtonine (99.51). Cipa shows a very high positive connectivity (>90) with knockdown signature of RPL7 (99.92), UBA52 (99.76) and RPS6 (98.63) that are linked to protein synthesis and anti-viral mechanisms. When the cmap interface was used to query the links between Cipa and COVID19 signatures we found that CIPA signatures are opposite to COVID-19 BALF signatures in connectivity map, which is also resonated in literature as CIPA transcription signatures intersect with implicated molecular pathways and prioritized family of compounds envisaged for COVID-19 from diverse resources.

ORGANISM(S): Homo sapiens

PROVIDER: GSE156445 | GEO | 2020/09/30

REPOSITORIES: GEO