Morin, a bioflavonoid from a traditional medicinal plant, attenuates inflammasome-associated neuroinflammation in drug-resistant epilepsy.

Morin, a bioflavonoid abundant in Morus alba (Moraceae) and traditionally used in Ayurveda and Chinese medicine for the treatment of convulsions and inflammation, modulates neuroinflammatory pathways relevant to epilepsy. This study investigated the effects of morin on inflammasome-associated neuroinflammation, assessed using downstream markers such as caspase-1 and IL-1β, in a rotenone-lamotrigine-PTZ-induced model of drug-resistant epilepsy (DRE). Drug resistance was established through chronic co-administration and confirmed by non-responsiveness to carbamazepine and valproate. Morin (20 and 40 mg/kg), alone or in combination with valproate, was evaluated against vigabatrin for its impact on seizure severity, neurochemistry, and neuropathology. Morin dose-dependently reduced seizure scores and partially normalized whole-brain glutamate and GABA levels, with the 40 mg/kg morin-valproate combination most effectively restoring the glutamate: GABA ratio. Additionally, morin-based treatments reduced caspase-1, IL-1β, and NQO1 levels in the hippocampus and cortex, improved neuronal architecture, and attenuated microglial and astroglial activation. These findings suggest that morin may be a promising adjunctive candidate for DRE by modulating seizure severity, excitatory-inhibitory imbalance, oxidative stress, and inflammation associated with inflammasome-linked signaling.