Identification of molecular mechanisms underlying the therapeutic effects of Celosia Cristata on immunoglobulin nephropathy

Abstract

Immunoglobulin A (IgA) nephropathy also known as Berger's disease, is a silent monster and perhaps the most prevalent glomerulonephritis that often accounts for end-stage kidney failure, thereby signifying a growing public health problem worldwide. The limited amount of available data and a broad spectrum of dysregulated physiological processes of IgAN make it a challenging task and a disproportionate economic load on the community health sector. Celosia cristata is an Amaranthaceous plant with attractive colorful inflorescences that are used in various regions of earth for the treatment of numerous ailments. A list of studies evidences the therapeutic efficacy of C. cristata against complicated disorders, but the precise molecular mechanism is yet to be discovered. This study is attributed to the identification of bioactive compounds, pathways, and target genes for the better treatment of IgAN. In the current analysis, compound-target genes-pathway networks were explored which uncovered that isorhamnetin, stigmasterol, luteolin, amaranthin, and β-sitosterol may serve as a magic bullet against IgAN by influencing the targets genes involved in the disease pathogenesis. Later, the expression of hub genes was then further analyzed using a microarray dataset (GSE93798). Through expression analysis, it is worth noting that FOS, JUN, and EGFR were considerably upregulated, and at the same moment, AKT1 was considerably downregulated in IgAN patients. Lastly, docking analysis further strengthened the current findings by validating the effective activity of the active ingredients against putative target genes. In summary, we propose that five key compounds including, isorhamnetin, stigmasterol, luteolin, amaranthin, and β-sitosterol, aid in the regulation of JUN, FOS, AKT1, and EGFR, which may serve as a promising and enthralling therapeutic option for IgAN. The overall integration of network pharmacology with molecular docking unveiled the multi-target pharmacological mechanisms of C. cristata against IgAN. This study provides convincing evidence that C. cristata might partially alleviate the IgAN and ultimately lays a foundation for further experimental research on the anti-IgAN activity of C. cristata.

Keywords: Bioactive compounds; Bioinformatics; Celosia cristata; Microarray data; Molecular docking; Network pharmacology.