Abstract
Aloe vera extracts, particularly aloin, have been widely used in traditional Chinese medicine for their anti-inflammatory and detoxifying properties. Recent studies suggest that aloin may also exert neuroprotective effects, though its specific mechanisms remain unclear. Glutamate excitotoxicity, a critical factor in neurodegenerative and pain-related disorders, is mediated primarily by N-methyl-D-aspartic acid (NMDA) receptors, which regulate calcium influx and neuronal excitability. Meanwhile, substantia gelatinosa (SG) of the trigeminal subnucleus caudalis (Vc) plays a central role in processing orofacial pain, where glutamate is a key excitatory neurotransmitter. Using whole-cell patch-clamp electrophysiology and calcium imaging techniques in mice SG neurons of the Vc, we examined aloin's effects on glutamate receptor-mediated responses. Aloin selectively inhibited NMDA-induced responses without affecting AMPA or kainate receptor activity. The suppression of NMDA-mediated currents by aloin was linked to changes in Ca(2+) influx but occurred independently of voltage-gated sodium channels and action potential generation. Calcium imaging revealed that aloin reduced NMDA-induced intracellular calcium influx, supporting its role in mitigating NMDA-mediated excitotoxicity. Furthermore, aloin significantly suppressed the spontaneous firing activity of SG neurons, suggesting its broader regulatory effects on neuronal excitability. Our findings demonstrate that aloin attenuates NMDA receptor-induced excitatory signaling by regulating calcium response. This specificity highlights aloin's potential as a therapeutic candidate for conditions involving glutamate excitotoxicity and orofacial pain regulation.