Morroniside promotes awakening from propofol general anesthesia in gastric cancer surgery by regulating hypothalamic GABAergic neurons

Background: General anesthesia is essential for gastric cancer surgery, but delayed awakening increases postoperative risks and costs. Although morroniside is known for its neuroprotective properties, its role in anesthesia recovery has remained unclear. Objectives: To investigate whether morroniside accelerates awakening from propofol anesthesia and whether hypothalamic GABAergic neurons mediate this effect. Methods: A gastric cancer mouse model was established. Mice were divided into seven groups: normal, model, vehicle control, light anesthesia, deep anesthesia, morroniside-treated and propofol-only. The loss and recovery of righting reflex (LORR/RORR) were measured. EEG recording, immunofluorescence staining for GABA and c-Fos and fiber photometry for Ca2+ signals in hypothalamic GABAergic neurons were performed. Results: Morroniside significantly shortened RORR without affecting LORR. During anesthesia induction, Ca2+ signals in hypothalamic GABAergic neurons increased sharply, then decreased during maintenance and remained low during early recovery. Morroniside increased GABA concentrations in multiple brain regions, especially the hypothalamus and reduced the EEG ?-band power while increasing ?-band power. It also decreased propofol-induced c-Fos expression. Conclusion: Morroniside accelerates awakening from propofol anesthesia in a gastric cancer mouse model, potentially by modulating hypothalamic GABAergic neuron activity and EEG oscillatory patterns. These findings support its potential as an adjuvant in anesthesia.