Salidroside ameliorates neuroinflammation in autistic rats by inhibiting NLRP3/Caspase-1/GSDMD signal pathway

Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder that place a huge economic and emotional burden on society. Salidroside (Sal) has been reported to have therapeutic effects in a variety of neurological disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD), however no studies have been conducted to show whether salidroside is effective in ASD. Pyroptosis is involved in the pathology of a variety of neurological disorders, but has not been reported in ASD. Objectives: The aim of this study was to investigate whether pyroptosis is involved in the pathological mechanisms of ASD, and whether salidroside has an impact on the pathological process of ASD by regulating pyroptosis. Methods: We obtained a rat model of offspring ASD by prenatal intraperitoneal administration of valproic acid (VPA, 500 mg/kg) to pregnant rats, and we treated seven-day-old offspring ASD with salidroside (Sal, 30 mg/kg once daily) by gavage for 28 days as the salidroside treatment group. We examined the hippocampal state of ASD rats and the effect of salidroside on the hippocampus of VPA-induced ASD rats. In addition, in BV2 cells treated with LPS/Nig, we explored the mechanisms by which salidroside regulates neuroinflammation and pyroptosis in vitro. Results: In vivo, we observed VPA-induced hippocampal neuronal damage and activation of the NLRP3/Caspase1/GSDMD signalling pathway in ASD rats, while salidroside alleviated neuronal damage in ASD rats. In vitro, we found that salidroside inhibited LPS/Nig-induced neuroinflammation and activation of the NLRP3/Caspase-1/ GSDMD signalling pathway. These results suggest that the therapeutic effect of salidroside on hippocampal damage in ASD rats may be related to NLRP3/Caspase-1/GSDMD-mediated pyroptosis. Conclusions: Our work showed that salidroside ameliorates hippocampal neurological damage in ASD rats by targeting NLRP3/Caspase-1/GSDMD-mediated pyroptosis, providing a potential therapy drug for ASD.