Curcuminoid supplementation alters proteomic profiles and clinical outcomes in canine primary epilepsy: A pilot study

In dogs, primary epilepsy syndrome (PES) requires lifelong pharmacological management. Curcuminoids possess anti-inflammatory and antioxidant properties with potential neuroprotective effects. This pilot study preliminarily evaluated the clinical efficacy and molecular mechanisms of curcuminoid supplementation in canine PES.

In this prospective, open-label pilot study, eight dogs with PES on stable AED therapy received adjunctive oral curcuminoid supplementation (10-20 mg/kg/day) for 60 days. Clinical response, serum GSH/GSSG ratio (DTNB-glutathione reductase recycling assay), serum cytokine concentrations (ELISA), and global serum proteomic profiles (nano-LC-MS/MS) were assessed.

Clinical response, defined as a reduction in seizure frequency (3/8) or decreased severity (1/8) was observed in 4 of 8 dogs (50%). Curcuminoid supplementation significantly increased the GSH/GSSG ratio (P = 0.046) and induced distinct proteomic changes: downregulation of mammalian target of rapamycin (mTOR) pathway components (Ras-related GTP-binding protein C and regulatory-associated protein of mTOR) and Toll-like receptor 2 (TLR2) signaling and upregulation of one-carbon metabolism (methylenetetrahydrofolate dehydrogenase) and serine/glycine/threonine metabolism (phosphoserine aminotransferase 1) enzymes.

Curcuminoid supplementation was safe, well tolerated, and demonstrated a clinical response rate of 50% in dogs with PES. These findings provide preliminary molecular evidence of enhanced antioxidant capacity, mTOR/TLR2 modulation, and metabolic reprogramming. As pilot observations, definitive neuroprotective conclusions require confirmation in larger controlled trials with direct neurological endpoints. Nonetheless, these data provide a molecular rationale for curcuminoids as adjunctive therapy in canine epilepsy.