Huang'e Capsule Alleviates Experimental Autoimmune Prostatitis in Rats Through Regulation of Linoleic Acid and Arachidonic Acid Metabolism by Metabolomics

Huang'e capsule (HEC) is used for prostatitis, but its mechanism remains unclear. This study investigated HEC effects on experimental autoimmune prostatitis (EAP) in rats and the underlying metabolic pathways. EAP was induced by intraprostatic injection of prostate homogenate with Freund's adjuvant, followed by 21‐day low, medium, high doses of HEC treatment. Serum and prostate interleukin‐6 (IL‐6), interleukin‐8 (IL‐8), interleukin‐1 beta (IL‐1β), and tumor necrosis factor‐alpha (TNF‐α) levels were measured by enzyme‐linked immunosorbent assay (ELISA), histopathology assessed, and serum metabolomics performed using ultra‐high‐performance liquid chromatography coupled with quadrupole‐exactive orbitrap tandem mass spectrometry (UHPLC‐Q‐Exactive Orbitrap MS/MS). HEC dose‐dependently reduced pro‐inflammatory cytokine levels, restored glandular architecture, and decreased inflammatory infiltration. Metabolomics identified 21 differential metabolites between model and HEC‐treated groups. Pathway enrichment showed linoleic acid metabolism as the most affected, followed by arachidonic acid metabolism, bile acid biosynthesis, and fatty acid β‐oxidation. Pearson correlation revealed that arachidonic acid and related fatty acids positively correlated with cytokines, whereas cholic and hyocholic acids showed negative correlations. In conclusion, HEC alleviates prostatitis primarily by regulating linoleic and arachidonic acid metabolism, suppressing pro‐inflammatory eicosanoid production, with additional contributions from bile acid and fatty acid β‐oxidation pathways. These findings provide metabolomic evidence for HEC's clinical use.