Transcriptomics reveals that Yang-Yin-He-Xue-Jie-Du formula promotes anal fistula healing by regulating tryptophan metabolism

BACKGROUND Anal fistula (AF), a debilitating condition characterized by chronic inflammatory tracts between the anorectal lumen and perianal skin, presents substantial clinical challenges because of persistent infection, recurrent drainage, and impaired wound healing following surgical interventions.Although fistulotomy is the standard treatment, postoperative complications, such as delayed healing, fibrosis, and secondary infections, remain prevalent, thereby necessitating novel therapeutic approaches.The traditional Chinese medicine formula Yang-Yin-He-Xue-Jie-Du (YYHXJD) has demonstrated clinical efficacy in accelerating postsurgical recovery in patients with AF; however, its pharmacological mechanisms remain unclear.AIM To evaluate the therapeutic efficacy of YYHXJD in a rat model of AF and to elucidate its molecular mechanisms using transcriptomic analysis.METHODS A rat AF model was established, and the animals were administered low-, medium-, or high-dose YYHXJD or saline control after fistulotomy.Therapeutic efficacy was evaluated on days 3, 7, and 14 post-treatment through wound healing assessment, histopathological examination (hematoxylin-eosin and Masson staining), and molecular analyses including quantitative polymerase chain reaction, Western blot, enzyme-linked immunosorbent assay, and reactive oxygen species measurement.Transcriptomic sequencing was performed on fistula tissues collected on day 14 to identify differentially expressed genes and enriched pathways. RESULTSAmong the tested conditions within the 14-day observation period, high-dose YYHXJD administered for 14 days exhibited the greatest therapeutic effect.Core Tip: This study investigated the traditional Chinese medicine Yang-Yin-He-Xue-Jie-Du (YYHXJD) in a rat model of anal fistula and identified a high-dose 14-day regimen as the most effective within the 14-day observation period.Transcriptomic analysis suggested that YYHXJD may promote tissue repair by inducing aldehyde oxidase 1 to influence tryptophan metabolism, which is associated with reduced oxidative stress and inflammation while enhancing granulation tissue formation.However, metabolomic validation is required to confirm the proposed mechanism.