Anticonvulsant activity of berberine: a systematic review and meta-analysis of preclinical studies in animal models.

INTRODUCTION AND AIM: Epilepsy affects approximately 50 million people worldwide, and a substantial proportion of patients have drug-resistant disease or experience adverse effects from anticonvulsant medications. Berberine, a blood-brain-barrier-permeant isoquinoline alkaloid, has shown anticonvulsant potential in preclinical models. This systematic review and meta-analysis evaluated the preclinical evidence on berberine's anticonvulsant efficacy, its dose-response and formulation dependence, and its mechanisms of action.

METHODOLOGY: PubMed, Scopus, Web of Science and the Cochrane Library were searched and reported per PRISMA 2020 (PROSPERO CRD420251135006). Random-effects models (DerSimonian-Laird with Hartung-Knapp adjustment) pooled dichotomous outcomes as risk ratios (RR) and continuous outcomes as standardised mean differences (SMD); pre-specified subgroup, dose-response, leave-one-out and GRADE analyses were conducted.

RESULTS

Sixteen studies were included. Berberine reduced the incidence of status epilepticus/generalised seizure (RR 0.73, 95% CI 0.61-0.87; I2 = 35%), the proportion reaching the fully kindled state (RR 0.53, 0.37-0.75; I2 = 0%) and seizure-related mortality (RR 0.72, 0.60-0.85; I2 = 0%), with a trend toward fewer spontaneous recurrent seizures (RR 0.65, 0.40-1.04). Seizure severity decreased (SMD 3.09, 1.45-4.74) and latency increased (SMD 1.50, 0.23-2.76). A monotonic dose-response gradient was observed across ascending dose tiers (≤25, 50 and ≥ 100 mg/kg; RR 0.88 → 0.67 → 0.41), and nano-encapsulated berberine markedly outperformed conventional berberine (kindling RR 0.04 vs 0.53). Mechanistically, berberine reduced lipid peroxidation (MDA, SMD 1.82, 0.63-3.01) and raised the antioxidant enzyme superoxide dismutase (SOD, SMD 1.44, 0.48-2.40).

CONCLUSION

Berberine exerts a consistent, dose-dependent, multi-target anticonvulsant effect that is greatly enhanced by nanoformulation. Certainty was moderate for the primary outcome and low-moderate elsewhere, defining berberine as a rational candidate for further translational development in epilepsy.