Exploring the hypoglycemic mechanism of chlorogenic acids from Pyrrosia petiolosa (Christ) Ching on type 2 diabetes mellitus based on network pharmacology and transcriptomics strategy

Ethnopharmacological relevance: Pyrrosia petiolosa (Christ) Ching (YBSW) is a Traditional Chinese medicine rich in chlorogenic acids. It is an important component in many Traditional Chinese medicinal hypoglycemic formulas and is commonly used by the Miao people to treat diabetes with good efficacy. Our previous research has suggested that chlorogenic acids may be the active ingredients in YBSW. Aim of the study: To explore the mechanisms underlying the anti-type 2 diabetes mellitus (T2DM) hypoglycemic effects of chlorogenic acids contained in YBSW. Materials and methods: In vivo experiments, hematoxylin-eosin staining (HE) staining, and immunohistochemistry (IHC) were used to determine the effects of chlorogenic acids contained in YBSW in rats. mRNA expression profiling, microarray analysis, and network pharmacology were used to analyze the underlying mechanisms of the effects. Finally, apoptosis and changes in the related pathways were evaluated in vitro using a 3-(4,5-dimethyl-2-thia-zolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay, quantitative real-time polymerase chain reaction, immunofluorescence (IF) assessment, and flow cytometry. Results: After the administration of isochlorogenic acid B, the levels of triglycerides, serum total cholesterol, and fasting blood glucose significantly decreased. HE and IHC staining revealed that isochlorogenic acid B signifi-cantly increased insulin expression in islet cells. Using network pharmacology and RNA-seq Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, we screened the advanced glycation end products-receptor for advanced glycation end products (AGE-RAGE) signaling pathway. We also verified that YBSW and its chlorogenic acid can inhibit apoptosis and downregulate the expression of related mRNA in the AGE-RAGE pathway in RIN-m5f cells. Conclusions: YBSW exhibits a significant hypoglycemic effect, with chlorogenic acid being an effective compo-nent. The therapeutic effect of chlorogenic acids contained in YBSW is mainly realized by promoting insulin secretion and pancreatic tissue repair. Moreover, YBSW substantially mitigates apoptosis via the AGE-RAGE pathway in T2DM.