The role of 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) in erectile dysfunction: an integrated mendelian randomization, network pharmacology, and multi-omics study.

PURPOSE: This study investigated the causal effect of 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) on erectile dysfunction (ED) and elucidated its underlying molecular mechanisms through multi-omics integration.

METHODS

Mendelian randomization (MR) was applied to evaluate the causal effects of CMPF on ED and metabolic risk factors. Network pharmacology was used to identify overlapping molecular targets, followed by molecular docking to assess binding affinity. Multi-omics validation incorporated Summary-data-based MR (SMR) analyses of expression and protein quantitative trait loci (eQTL/pQTL) to confirm genetically regulated CMPF-related targets.

RESULTS

MR analyses demonstrated a protective effect of CMPF on ED in both discovery (OR: 0.78, 95% CI: 0.62-0.98) and replication cohorts (OR: 0.82, 95% CI: 0.69-0.98), along with favorable associations with glucose metabolism, blood pressure, and lipid traits. Network analysis identified 42 shared targets, with DPP4, LGALS3, and NR3C2 as hub targets. Molecular docking showed strong binding affinities (≤-6.0 kcal/mol). SMR analyses highlighted LGALS3 as a key genetic mediator, supported by consistent eQTL and pQTL signals.

CONCLUSIONS

CMPF exerts protective effects against ED and metabolic dysfunction through multi-target modulation, with LGALS3, DPP4, and NR3C2 as central regulators. These findings support CMPF as a diet-derived bioactive metabolite with potential for nutritional interventions and multi-target therapeutic strategies in ED.