Background Post-operative recognition dysfunction (POCD) is a kind of central nervous system complication that appears after operative anesthesia. Recent studies on the mechanism of long non-coding RNA (lncRNA) in neurodegenerative diseases are abundant. Aims The study aimed to explore the expression pattern and role of lncRNA OIP5-AS1 in POCD and to investigate its underlying mechanism in old rats. Methods The old rats were exposed to isoflurane to mimic the POCD in the elderly, and their cognitive function was tested via Morris water maze (MWM) test. Enzyme linked immunosorbent assay was applied for the concentration detection of inflammation and oxidative stress-related factors. Luciferase reporter assay was done for the target gene analysis. Results Downregulation of OIP5-AS1 was accompanied by isoflurane treatment in rats, overexpression of OIP5-AS1 induced the rats to spend more time in the target quadrant, and shorten escape latency time. OIP5-AS1 inhibited the release of TNF-α, IL-6 and IL-1β, GSH and superoxide dismutase, decreased the activation of caspase-3, but promoted malondialdehyde release. miR-186-5p was a target miRNA of OIP5-AS1, and exhibited high expression in rats after isoflurane exposure. miR-186-5p can abolish the beneficial role of OIP5-AS1 against cognitive impairment, inflammatory response, oxidative stress and neuron apoptosis. Conclusion OIP5-AS1 plays a neuroprotective role in elderly POCD rats through sponging miR-186-5p, and it is related to OIP5-AS1/miR-186-5p mediated inflammatory response, oxidative stress and neuron apoptosis.

Context The co-administration of abemaciclib and astragaloside IV might occur in the treatment of breast cancer. Objective This study evaluates the interaction between abemaciclib and astragaloside IV in rats and describes the potential mechanism. Materials and methods Male Sprague Dawley rats were randomly divided into four groups: single dose of abemaciclib (control), abemaciclib + 50 mg/kg/d astragaloside IV, abemaciclib + 100 mg/kg/d astragaloside IV, and abemaciclib + 150 mg/kg/d astragaloside IV. Abemaciclib and astragaloside IV were orally administrated, and astragaloside IV was pre-administrated for 7 d in the co-administrated groups. The pharmacokinetics and transport of abemaciclib were assessed in the absence or presence of astragaloside IV. In mechanism, the activity of CYP3A4 was estimated in human liver microsomes in the presence of astragaloside IV. Results Astragaloside IV significantly increased the C max (from 991.5 ± 116.99 up to 2308.5 ± 55.29 μg/L) and AUC (from 24.49 ± 2.86 up to 66.14 ± 1.17 μg/mL × h) and prolonged the t 1/2 (from 19.85 ± 4.65 up to 66.17 ± 28.73 h) of abemaciclib, and the effect was enhanced with the increasing astragaloside IV concentration. Astragaloside IV also suppressed the transport of abemaciclib with the efflux ratio decreasing to 1.35. Astragaloside IV suppressed the activity of CYP3A4 with an IC 50 value of 21.78 μM. Discussion and conclusions The co-administration of abemaciclib and astragaloside IV induced the increasing systemic exposure of abemaciclib through the inhibition of CYP3A4. Further clinical validations could be carried out according to the study design of the present investigation.

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