Polyporenic acid C

Poria cocos (PC) is a traditional Chinese herbal medicine that plays an important role in the treatment of allergic rhinitis (AR); however, its specific mechanism of action has rarely been reported. This study was based on network pharmacology and molecular docking to explore the molecular mechanisms of PC in the treatment of AR. TCMSP, GeneCards, DrugBank, TTD, and OMIM databases were used to screen potential targets of Poria cocos for AR treatment. The STRING platform and Cytoscape 3.7.0 software (Cytoscape Consortium, San Diego) were used to construct a protein–protein interaction (PPI) network and screen core targets. Gene ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted on potential target genes. Finally, molecular docking was conducted between the key active components and the core targets to validate their relevance. Fifteen active components of PC were identified and 94 common targets related to both PC and AR were screened. The top ten hub genes identified were TNF, IL1B, AKT1, prostaglandin G/H synthase 2 (PTGS2), epidermal growth factor receptor (EGFR), MMP9, PPARG, BCL2, NR3C1, and PTGS1. GO and KEGG enrichment analyses indicated that these core targets were involved in various biological processes, including the regulation of inflammatory responses, responses to exogenous stimuli, and modulation of defense responses. These targets influence AR through pathways such as the neuroactive ligand-receptor interaction pathway and PI3K-Akt signaling pathway. Molecular docking results indicated that pachymic acid-PTGS2, polyporenic acid C-EGFR, and PTGS2 exhibited strong binding activity, while pachymic acid, polyporenic acid C-TNF and cerevisterol-AKT1 demonstrated good binding activity. Our study found that the key active components of PC for treating AR are pachymic acid, polyporenic acid C, and cerevisterol. PTGS2, EGFR, TNF, and AKT1 are the key targets, while the neuroactive ligand-receptor interaction pathway and PI3K-Akt signaling pathway are the key pathways. These results indicate that PC may intervene in the intrinsic molecular mechanism of AR through multiple targets and pathways. Although further experimental verification is required, our study provides a theoretical basis for the clinical application of PC in AR treatment and subsequent related research.

Ultra performance liquid chromatography-quadrupole-time-of-flight-mass spectrometry/mass spectrometry(UPLC-Q-TOF-MS/MS), network pharmacology, and animal experiments were integrated o explore the blood glucose-lowering effects and mechanisms of Poria aqueous extract. Firstly, the active components of Poria aqueous extract were identified by UPLC-Q-TOF-MS/MS. Subsequently, network pharmacology was employed to predict the blood glucose-lowering components and mechanisms of Poria aqueous extract. Finally, a rat model of diabetes mellitus, 16S rDNA sequencing, and Western blot were employed to investigate the blood glucose-lowering effect and mechanism of Poria aqueous extract. A total of 39 triterpenoids were identified in the Poria aqueous extract, among them, 25-hydroxypachymic acid, 25α-hydroxytumulosic acid, 16α-hydroxytrametenolic acid, polyporenic acid C, and tumulosic acid may be the main active ingredients for treating diabetes. The Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis revealed that Poria might exert its therapeutic effects through multiple pathways such as NOD-like receptor signaling pathway, nuclear factor-kappa B(NF-κB) signaling pathway, and tumor necrosis factor(TNF) signaling pathway. The results of animal experiments demonstrated that Poria aqueous extract significantly reduced the levels of blood glucose and lipids and regulated the intestinal flora in diabetic rats. The main affected taxa included g＿Escherichia-Shigella, g＿Corynebacterium, g＿Prevotella＿9, g＿Prevotellaceae＿UCG-001, and g＿Bacteroidota＿unclassified. In addition, Poria aqueous extract lowered the levels of D-lactic acid and lipopolysaccharide, alleviated colonic mucosal damage, significantly down-regulated the protein levels of NOD-like receptor pyrin domain-containing protein 3(NLRP3), NF-κB, and TNF-α, and significantly up-regulated the protein levels of zonula occludens 1 and occludin in diabetic rates. Poria aqueous extract may play a role in treating diabetes mellitus by repairing the intestinal flora disturbance, protecting the intestinal barrier function, and inhibiting the NF-κB/NLRP3 signaling pathway. The results provide a scientific basis for clinical application and expansion of indications of Poria.