Protective effects of chlorogenic acid on isoflurane‐induced cognitive impairment of aged mice

Postoperative cognitive dysfunction (POCD) is characterized by impairment in cognitive functions in patients following anesthesia and surgery. Chlorogenic acid (CGA) is a plant‐derived compound possessing numerous bioactive properties. The aim of this study was to investigate the therapeutic potential of CGA in isoflurane (ISO)‐induced cognitive dysfunction of aged mice, and further identify the mechanisms involved in the protective effects of CGA. A total of 80 male C57BL/6 mice, 20‐month‐old, were randomly divided into control group, isoflurane group (ISO), and ISO + 30 mg/kg CGA group and ISO + 60 mg/kg CGA. CGA was given orally once daily for 7 days to the mice and they were exposed to ISO (1.5%; 4 h). The open‐field and Morris water maze tests were used to investigate the cognitive function of mice. Pretreatment with CGA significantly attenuated ISO‐induced cognitive impairment. The levels of IL‐1β, TNF‐α, IL‐6, nuclear p65 NF‐kB, cleaved caspase‐3, and Bax were significantly increased, while the levels of IkBα and Bcl‐2 were decreased in the hippocampus 24 h after the ISO anesthesia. All the mentioned effects induced by ISO were reversed by CGA pretreatment. Furthermore, ISO exposure induced marked downregulation of SOD, CAT, HO‐1, and NQO‐1 and elevation of MDA and nuclear translocation of Nrf2 in the hippocampus tissue. All these parameters were reversed by CGA treatment. Importantly, the higher dose of CGA (60 mg/kg) showed a greater neuroprotective effect. In conclusion, these findings suggest that CGA attenuates the ISO‐induced cognitive impairment via its anti‐inflammatory, anti‐oxidative, and anti‐apoptotic properties in aged mice.