Abstract
CP1Hao Decoction (CP1HD) is a traditional Chinese herbal prescription used to treat chronic prostatitis, but the therapeutic effects and underlying mechanisms of CP1HD, particularly those involving arachidonic acid metabolism and gut microbiota, remain unclear. This study evaluated the pharmacological efficacy of CP1HD in a carrageenan-induced rat model of prostatitis and explored its potential targets and pathways through integrated transcriptomics, 16S rRNA sequencing, and metabolomics analyses. CP1HD treatment significantly alleviated prostate histopathological damage, reduced the prostate index, and suppressed inflammatory responses. ELISA results showed that CP1HD markedly decreased the levels of TNF-α, IL-6, PGE2, LTB4, and COX-2, while regulating EETs levels, and inhibited M1 macrophage polarization and neutrophil infiltration while promoting M2 polarization. Transcriptomic analysis revealed that CP1HD reversed differentially expressed genes associated with inflammation and arachidonic acid metabolism, which was further confirmed by Western blot analysis of cPLA2, LTA4H, and sEH. In addition, CP1HD modulated gut microbiota composition by restoring the relative abundance of
Bacteroides
,
Alistipes
, and the
Eubacterium_siraeum group
. Metabolomic profiling demonstrated that CP1HD regulated arachidonic acid metabolism and related lipid mediators, with notable effects on phosphatidylethanolamine metabolism and fatty acid β-oxidation. Overall, CP1HD ameliorates prostatitis by reducing inflammation and prostate injury while modulating arachidonic acid metabolism, gut microbiota, and associated metabolic pathways.