Ononin, a natural isoflavone glycoside, alleviates postoperative cognitive dysfunction in aged mice by regulating neuroinflammation and oxidative stress

Postoperative cognitive dysfunction (POCD) is a common and serious neurological complication. Currently, there is no effective clinical prevention and treatment for POCD. Ononin has been confirmed to exhibit potent neuroprotective effects in many diseases. This study aimed to investigate whether ononin could exert a neuroprotective role against POCD. The animal model of POCD was established in 18-month-old aged mice with unilateral nephrectomy. Ononin (30 mg/kg) was administered intraperitoneally to aged mice 15 min before surgery. On postoperative day 3, the Morris water maze and open field tests were used to assess the changes in cognitive function. Western blotting and immunofluorescence staining were employed to examine the hippocampal levels of Iba1 and microglial activation on postoperative day 3, respectively. An enzyme-linked immunosorbent assay was applied to gauge the expression of hippocampal IL-1β, IL-6, and TNF-α on days 1 and 3 postsurgery. To reflect the oxidative stress status, the levels of hippocampal malondialdehyde (MDA) and superoxide dismutase (SOD) activity were detected using the corresponding assay kits on postoperative days 1 and 3. We found that anesthesia/surgery induced overt memory deficits in aged mice. Conversely, ononin pretreatment significantly rescued the cognitive impairment. Mechanically, anesthesia/surgery triggered acute increases in hippocampal IL-1β, IL-6, TNF-α, Iba1, and MDA, paralleled by a decline in SOD activity. This phenomenon was also partially reversed by ononin. Our findings provide evidence that ononin may ameliorate anesthesia/surgery-induced cognitive deficits through its anti-inflammatory and antioxidant effects, which could be a novel preventive therapeutic strategy for POCD in elderly patients.