Screening of Active Ingredients in Rehmannia glutinosa and Its Mechanism of Action in the Treatment of Liver Diseases

Abstract

Rehmannia glutinosa extracts have profound medicinal value in the treatment of liver diseases. It contains micro ribonucleic acid molecules that have an average of 21 nucleotides. These micro ribonucleic acids are responsible for gene regulation and expression during the treatment of liver diseases. The study's main objective is to screen for active ingredients in Rehmannia glutinosa and its mechanism of action in treating liver diseases. Our study used the gene expression omnibus database to obtain datasets associated with liver diseases. The GSE167308 dataset consisted of 19 samples of ribonucleic acid profiles of micro dissected hepatocytes from the human liver in 3 groups (alcoholic hepatitis (n=7), alcoholic cirrhosis (n=7) and controls (n=5)). The GSE54350 dataset involving CD14+ cells from diabetic and non-diabetic samples. We used the GEO2R tool, ShinyGO, R software, STRING, and Network Analyst tools to analyze differentially expressed genes. We obtained 25 significantly expressed genes with an adjusted p-value of 0.05 and log(Fold Change) of -1.0. Also, we obtained seven active ingredients of Rehmannia glutinosa, their descriptions and target proteins. The differentially expressed genes were enriched in various Kyoto Encyclopedia of Genes and Genomes pathways such as nuclear factor-κB, Mitogen-activated protein kinases, glycolysis, Protein kinase B-serine/threonine kinase 1 signaling, regulation of autophagy, or Transforming growth factor-beta signaling pathways. The protein-protein interaction networks revealed 9 hub genes (Interleukin 6, Superoxide dismutase 1, Catalase, tumor necrosis factor, toll-like receptor 4, Proliferator-Activated Receptor Gamma, Nuclear Factor Kappa B Subunit 1, NOD-Like Receptor family Pyrin domain containing 3 and prostaglandin-endoperoxide synthase 2) that were significant in liver diseases. Rehmannia glutinosa exerts its anti-inflammatory response through active ingredients such as catalpol, Rehmannioside A, B, C, and Shanzhiside. These ingredients are mainly iridoid glycosides that activates the Nuclear factor kappa B and mitogen-activated protein kinase signaling pathways and reduces the production of pro-inflammatory cytokines. Rehmannia glutinosa contains several active components (for example, Catalpol, Rehmannioside A and Shanzhiside) that are crucial in regulating pro-inflammatory cytokines and hub genes associated with liver diseases.