Crebanine protects aged rats from anesthesia-induced cognitive deficits by restoring mitophagy
The compound suppresses mitochondrial DNA leakage and the cGAS-STING inflammatory pathway in microglial cells following sevoflurane exposure.
Research Square · Zheng G et al. · Paper published 28 Sep 2026
In a preprint study using aged male Sprague-Dawley rats and BV2 microglial cells, researchers examined how the plant alkaloid crebanine counters sevoflurane-induced cognitive impairment. In cell cultures, sevoflurane exposure disrupted mitophagy, leading to reactive oxygen species accumulation and cytosolic leakage of mitochondrial DNA. This leakage activated the cGAS-STING pathway, driving pro-inflammatory microglial polarization. Crebanine treatment restored mitophagic flux, reduced mitochondrial DNA release, and promoted an anti-inflammatory microglial phenotype. Blocking mitophagy or chemically activating STING eliminated these protective effects. In aged rats exposed to sevoflurane, crebanine administration reduced hippocampal neuroinflammation and neuronal apoptosis. These cellular improvements translated to preserved spatial learning and memory performance during Morris water maze testing.
Why it matters
Postoperative cognitive dysfunction disproportionately affects older individuals. Targeting mitochondrial quality control and innate immune activation could help protect aging brains during surgical procedures requiring general anesthesia.
Caveats
This research appeared as a preprint and has not yet completed peer review. The findings are also limited to cell cultures and aged male rats, meaning they may not directly translate to human patients.
Written from the paper’s abstract, and every claim checked against it before publishing. Read the paper for the full methods and data.
The paper
Restoration of mitophagy by crebanine suppresses sevoflurane-induced microglial activation and cognitive deficits by blocking mitochondrial DNA-triggered cGAS–STING pathway
Zheng G, Yang C, Zhang J et al.
Research Square · 28 Sep 2026 · Preprint, not yet peer-reviewed
- Relevance
- Relevant
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- Evidence
- Animals
- Status
- Preprint
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