The "two flowers therapy": clinical efficacy and mechanisms of a total glucosides of paeony -colchicine dual-drugs for Behçet's disease derived from Chinese physicians' medication experience.

OBJECTIVE

To elucidate the synergistic mechanism of "Two flowers therapy" - a Behçet's disease (BD) treatment regimen used in China for more than 30 years, namely Total Glucosides of Paeony (TGP)-colchicine - and its efficacy, safety in BD with mucocutaneous involvement.

METHODS

A retrospective clinical cohort study integrated with computational biology was performed. Five bioactive components were chosen, among which four were from TGP and one was colchicine; 31 overlapping BD-related targets were identified via multi-omics, finally 6 core genes confirmed. 355 BD patients were divided into combination group (CG, n=231) and monotherapy group (MG, n=124).

RESULTS

Four active components of TGP (oxypaeoniflorin, albiflorin, benzoyl paeoniflorin, paeoniflorin) and colchicine constituted five bioactive compounds. A total of 837 BD-related targets were retrieved from GeneCards, with 31 overlapping targets between the five compounds and BD. A PPI network (31 nodes, 197 edges) was constructed, and core targets (MMP9, ICAM1, FGF2, TLR4, EGFR, NOS3) were identified. Molecular docking confirmed their high affinity: colchicine formed hydrogen bonds with EGFR, ICAM1, NOS3 (2.2-3.4 Å) and hydrophobic interactions with TLR4; TGP components formed 2-4 hydrogen bonds with EGFR, FGF2, MMP9 (2.2-3.9 Å). GO analysis involved inflammation- and immune-related biological processes; KEGG identified 10 enriched pathways (including Lipid and atherosclerosis, AGE-RAGE) regulating inflammation, immunity and vascular function. Clinically, CG had superior early (M1-M2) efficacy: oral ulcer prevalence was 0.0% vs. 21.0% (M1) and 0.0% vs. 100.0% (M2), genital ulcer prevalence 0.9% vs. 6.5% (M1) (all p<0.05). Both groups achieved complete ulcer resolution from M3. ESR in CG was significantly lower at M2 (p<0.001), with no CRP difference. CG had transient diarrhea; no drug-associated cytopenia was reported in either group.

CONCLUSION

TGP combined with colchicine, a regimen used in China for more than 30 years, exerts therapeutic effects on BD by regulating core targets and inflammatory pathways. Clinically, this regimen more effectively controls early mucocutaneous lesion recurrence in BD patients, with good long-term efficacy and safety.