Dendrobine attenuates postoperative cognitive dysfunction by inhibiting Runx1-mediated NF-κB signaling pathway
- Brain Res Bull. 2026 Feb:235:111746. doi: 10.1016/j.brainresbull.2026.111746.
- 1. Institute for Regenerative Medicine, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200120, China; Department of Anesthesiology, Shanghai Hongkou District Jiangwan Hospital, Shanghai 200081, China.
- 2. Department of Anesthesiology, Shanghai Hongkou District Jiangwan Hospital, Shanghai 200081, China.
- 3. Department of Anesthesiology, Changhai Hospital, Naval Medical University, Shanghai 200433, China.
- 4. Department of Anesthesiology, Changhai Hospital, Naval Medical University, Shanghai 200433, China. Electronic address: [email protected].
- 5. Institute for Regenerative Medicine, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200120, China. Electronic address: [email protected].
Background: Postoperative cognitive dysfunction (POCD) in older adults is strongly linked to neuroinflammation driven by microglial activation and NF-κB signaling. Runx1 has emerged as an upstream regulator of NF-κB, but its role in POCD is unknown. Dendrobine, a sesquiterpenoid alkaloid from Dendrobium species, exhibits anti-inflammatory and neuroprotective activity.
Methods: POCD was induced in aged C57BL/6 mice via sevoflurane anesthesia combined with exploratory laparotomy. Dendrobine (10 or 20 mg/kg) was administered, and cognitive outcomes were evaluated by Morris Water Maze and Novel Object Recognition. RNA Sequencing, Western blotting, immunofluorescence, and in vitro microglia-neuron co-culture systems were employed to investigate inflammatory responses, Apoptosis, synaptic plasticity, and signaling pathway activation. Functional roles of Runx1 were validated via siRNA knockdown, pharmacological inhibition (Ro5-3335), and overexpression in BV2 cells.
Results: Dendrobine improved spatial and recognition memory in POCD mice, reduced hippocampal microglial activation, proinflammatory cytokine expression (TNF-α, IL-1β, IL-6), and neuronal Apoptosis while enhancing synaptic protein levels (BDNF, PSD95, SYN1). Transcriptomic and KEGG analyses revealed suppression of NF-κB signaling by dendrobine, with Runx1 identified as an upstream modulator. Dendrobine downregulated Runx1 expression in vivo and in vitro. Runx1 inhibition enhanced dendrobine's anti-inflammatory effects, whereas RUNX1 overexpression abolished them.
Conclusion: Dendrobine ameliorates POCD by inhibiting the Runx1/NF-κB signaling pathway, suppressing neuroinflammation, promoting synaptic resilience, and preventing neuronal Apoptosis. Runx1 appears to act as a key upstream mediator of NF-κB signaling in POCD. Targeting the Runx1/NF-κB axis represents a promising strategy for perioperative neuroprotection.