Neuroprotective effects of Apigenin on prenatal Valproic acid-induced autism spectrum disorder in rats

Valproic acid (VPA) demonstrates teratogenic effects during pregnancy. Prenatal exposure to VPA may result in autism spectrum disorder (ASD) -like phenotypes. Apigenin, a natural flavonoid, has been shown to have neuroprotective impacts due to its antioxidant properties. This study aimed to investigate the protective effects of apigenin in prenatal Valproic acid-induced autism in rats. Female rats (220-240 g, 2-3 months) received a single dose of VPA (600 mg/kg, i.p.) on the 12.5th day of gestational. The male offspring were given oral apigenin (50 mg/kg, p.o.) or the vehicle for 30 days. Behavioral tests, biochemical assessments for oxidative stress markers and pro-inflammatory cytokines were performed. VPA-treated rats exhibited increased anxiety-like behavior, and repetitive behavior. Social interaction was reduced, and detection of the novel object was impaired. Also, VPAtreated rats have shown higher levels of oxidative stress malondialdehyde (MDA) and lower GPX and superoxide dismutase (SOD) levels. Furthermore, IL-6 and TNF-alpha increased in the prefrotalcortex decreased. On the other hand, apigenin-treated rats restored the cognitive consequences and lowered oxidative stress and inflammation in the prefrotalcortex. Conclusion: Chronic apigenin treatment restored the behavioral and biochemical abnormalities caused by prenatal VPA exposure.