Allicin as a Modulator of Neuroinflammation in Epilepsy: Targeting the TLR4/MyD88/NF-κB Pathway

Epilepsy is a chronic neurological disorder marked by frequent, unprovoked seizures and is one of the leading causes of long-term disability globally. Nearly one-third of patients continue to experience drug-resistant seizures. This treatment resistance is strongly associated with neuroinflammation, which links initial brain insults to long-term network hyperexcitability, dysfunctional synapses, and seizure recurrence. The TLR4/MyD88/NF-κB signaling pathway is a central mediator of innate immune signaling. It promotes immune activation, cytokine release, glial overactivation, BBB destruction, oxidative stress, and excitotoxic neuronal injury. Although understanding of inflammatory epileptogenesis has increased, effective disease-modifying therapies targeting these pathways remain limited. The neuroprotective properties of allicin, a bioactive organosulfur compound derived from Allium sativum, have demonstrated potential in numerous neuroinflammatory and neurological disease models. The review examines potential therapeutic use of allicin in epilepsy with particular emphasis on its capacity to modulate key pathological mechanisms, including inhibition of TLR4/MyD88/NF-κB signalling, attenuation of pro-inflammatory cytokine production, mitigation of oxidative stress, modulation of mitochondrial activity, and glial activity. In vitro and in vivo preclinical data show that allicin may modulate pathways involved in neuroinflammation-induced epileptogenesis. Nevertheless, challenges related to its bioavailability, formulation, and clinical translation persist. Further research is required to clarify its mechanistic role and evaluate its clinical applicability. A deeper understanding of its actions may facilitate the development of targeted adjunctive therapies for epilepsy.