Deciphering the action mechanism of paeoniflorin in suppressing pancreatic cancer: A network pharmacology study and experimental validation

Abstract

Background: Paeoniflorin (PF) is the main active component of Chinese herbaceous peony that has been shown to have an anti-tumor effect. However, there are few studies on the prevention and treatment of pancreatic cancer with PF.Methods: We gathered Microarray data pertaining to paeoniflorin intervention in pancreatic cancer by utilizing the GEO database (GSE97124). Then, the DEGs were filtered by the 33R program. RNA-seq data of pancreatic cancer and normal tissue samples were taken from the TCGA and GTEx databases, respectively, and the WGCNA technique was utilized to examine the pancreatic cancer-specific genes. Paeoniflorin target genes for the treatment of pancreatic cancer were determined based on the overlap between DEGs and WGCNA. GO and KEGG enrichment analyses were then performed on paeoniflorin target genes to discover which biological processes were impacted. Using the 3 hierarchical methods included in the Cytohubba plugin, we re-screened the hub genes in the target genes to find the genes most relevant to paeoniflorin treatment. The overall survival effects of hub genes were confirmed using the TCGA database. Finally, the paeoniflorin targets identified by the network pharmacology analysis were validated using PANC-1 and Capan-2 cells.Results: We identified 148 main potential PF targets, and gene enrichment analysis suggested that the aforementioned targets play a crucial role in the regulation of MAPK, PI3K-AKT, and other pathways. The further screening of the prospective targets resulted in the identification of 39 hub genes. Using the TCGA database, it was determined that around 33.33% of the hub gene’s high expression was linked with a bad prognosis. Finally, we demonstrated that PF inhibits IL-6 and IL-10 expression and p38 phosphorylation in pancreatic cancer cells, thereby reducing inflammation.Conclusion: PF may regulate inflammatory factors mainly through the p38 MAPK signal pathway. These findings provide theoretical and experimental evidence suggesting the PF as a promising natural source of anti-tumor compounds for pancreatic cancer.

Paeoniflorin improves ulcerative colitis via regulation of PI3K‑AKT based on network pharmacology analysis

“…PF is the primary active compound of Paeonia suffruticosa , Paeonia suffruticosa , and Paeonia lactiflora and has good, anti-tumor, anti-ulcer, immunoregulatory, and neuroprotective effects ( 25 , 26 ). In a network pharmacology and experimental validation study, Cao et al ( 58 ) revealed that PF can regulate inflammatory factors including IL-6 and IL-10 expression through the p38 MAPK signaling pathway in the treatment of pancreatic cancer. Sun et al ( 59 ) found that PF downregulated IL-18, TNF-α, and IL-1β expression levels in a rat model of diabetic foot ulcers and was related to NLRP3/ASC/caspase-1 inflammasome formation and NF-κB transcription.…”

“…Sun et al (59) found that PF downregulated IL-18, TNF-α, and IL-1β expression levels in a rat model of diabetic foot ulcers and was related to NLRP3/ASC/caspase-1 inflammasome formation and NF-κB transcription. Several studies have revealed that PF regulates the activation of immune cells, decreases the release of inflammatory cytokines, and participates in the regulation of the GPCR and PI3K/AKT/mTOR pathways (58)(59)(60)(61)(62)(63). PF has also been shown to regulate GPCR signaling by suppressing the expression of β-arrestin 2 and upregulating cAMP-PKA signaling, and this regulation was important for its therapeutic effect in rheumatoid arthritis (60).…”

Heyingwuzi formulation alleviates diabetic retinopathy by promoting mitophagy via the HIF-1α/BNIP3/NIX axis

“…This result found that HYWZF treatment increased the expression levels of ZO-1, occludin, and claudin-5 proteins, indicating that HYWZF affected tissue integrity and barrier function. HE staining revealed that the retinal tissues in the model group were significantly swollen and infiltrated with inflammatory cells, indicating the presence of a large number of free radicals appeared[ 32 ]. Flow cytometry analysis further proved that there were a large number of ROS in the model group.…”

Integrating Network Pharmacology and Experimental Verification to Explore the Pharmacological Mechanisms of Radix Paeoniae Rubra Against Glioma

“…Recent years have witnessed an increasing interest in traditional Chinese medicine for cancer treatment, especially in reducing recurrence and metastasis of cancer and improving the quality of life for cancer patients. Several studies have shown that the active ingredients in RPR have inhibitory effects on the growth of various types of tumor cells, including lung cancer(20), pancreatic cancer(21), breast cancer(22), gastric cancer, colorectal cancer, bladder cancer and liver cancer(23). While many studies have shown the e cacy of single compounds in RPR extracts against diverse tumor types, comprehensive research on all active ingredients remains limited.…”