Ginsenoside Rg1 mitigates the prolonged isoflurane anesthesia-induced neuroimmune disruptions

Ginsenoside Rg1, a primary bioactive component of Panax ginseng, has been historically used in traditional Chinese medicine to replenish qi, nourish vitality, and restore cognitive function. Its neuroprotective properties have been documented in conditions involving neurological exhaustion and immune dysregulation.

This study investigated the therapeutic potential and mechanisms of ginsenoside Rg1 in mitigating neurobehavioral and systemic immune dysfunction induced by prolonged general anesthesia.

Mice exposed to 6 h of isoflurane anesthesia received ginsenoside Rg1 (10 mg/kg, i.p.) every 24 h for three doses. Neurobehavioral outcomes were assessed using Y-maze and open field tests. Hippocampal synaptic function (mIPSCs), systemic inflammation (IL-6, TNF-α), gut barrier integrity (FITC-dextran assay), and colonic regulatory T cell (Treg) populations were quantified. Treg dependency was validated using DEREG mice with diphtheria toxin-mediated ablation.

Mice exposed to prolonged isoflurane anesthesia exhibited anxiety-like behaviors, cognitive deficits, elevated IL-6 and TNF-α levels in the hippocampus and bloodstream, impaired synaptic transmission, increased intestinal permeability, and reduced regulatory T cells, indicative of gut-immune-brain axis disruption. Treatment with Ginsenoside Rg1 effectively reversed these deficits by improving behavior, reducing inflammation, restoring synaptic function, and preserving gut-immune integrity. Crucially, Treg ablation in DEREG mice abolished Rg1's benefits, while Treg levels correlated with cognitive improvement.

Ginsenoside Rg1 ameliorates anesthesia-induced neuroimmune dysfunction through Treg-mediated gut-immune-brain axis restoration, offering a novel therapeutic strategy for postoperative neurological complications.