Anti-seizure Effects and Mechanisms of Berberine: A Systematic Review.

Abstract

Epilepsy is one of the most common in all age groups and disabling neurologic disorders around the world. This systematic review was to explore whether berberine (BBR) has any anti-seizure or anti-epileptic effects and also reviewed this possible mechanism. The EMBASE, Scopus, Cochrane Library, PubMed, and Web of Science databases were searched before Sep 2023. All types of studies that investigated the effects of BBR on epilepsy or chemical-induced seizures were eligible for inclusion. Two authors independently evaluated and reviewed titles/abstracts to identify publications for potential eligibility, and a third team member resolved discrepancies. Data were extracted in an Excel form, and the outcomes were discussed. BBR showed its neuroprotective properties by reducing oxidative stress, neuroinflammation, and anti-apoptosis effects. It also increases brain-derived neurotrophic factor (BDNF) release and reduces transforming growth factor-beta (TGF-β1) and hypoxia-inducible factor 1α (HIF-1α). BBR by increasing scavenging reactive oxygen species (ROS), nuclear factor erythroid 2-related factor 2 (Nrf2), endogenous antioxidant enzymes, heme oxygenase-1 (HO-1), and inhibition of lipid peroxidation insert its antioxidant activity. Moreover, BBR showed antiinflammatory activity by reducing Interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha (TNF-α) levels and through inhibiting cyclooxygenase-2 (COX-2), and including nuclear factor κB (NF-κB). In addition, it modulated c-fos expression and neuronal excitability in the brain. BBR indicated promising anti-seizure effects with remarkable antioxidant, antiinflammatory, anti-apoptotic, and neuroprotective activity. Future studies should be based on well-designed clinical trial studies that are integrated with new methods related to increasing bioavailability.