Postnatal baicalin ameliorates behavioral and neurochemical alterations in valproic acid-induced rodent model of autism: The possible implication of sirtuin-1/mitofusin-2/ Bcl-2 pathway

Autism spectrum disorder (ASD) is characterized by pervasive impairments in social communication along with repetitive or stereotyped behaviors. Although its distinctive etiology isn`t completely understood, genetic and environmental risk factors were incriminated. Being a flavonoid of high biomedical value, baicalin was recently verified as an emerging medicinal herb with numerous pharmacological activities. The objective of this study was to investigate the feasible effects of baicalin on valproic acid (VPA)-induced autism regarding its potential mitochondrial modulatory, antioxidant, and antiapoptotic effects. The present study was performed using a rodent model of autism by exposing rat fetuses to VPA on the 12.5th day of gestation. Ten male Wistar rats that were born from control pregnant females were considered as group I (control group). Twenty male Wistar rats that were born from prenatal VPA- treated females were further divided into two groups: Group II (VPA- induced ASD) and group III (VPA + Baicalin). Postnatal baicalin promoted postnatal growth and maturation. In addition, it improved motor development and ameliorated repetitive behavior as well as social deficits in prenatally exposed VPA rats. Moreover, baicalin enhanced neuronal mitochondrial functions as evidenced by elevation of mitochondrial adenosine triphosphate (ATP) level and promotion of mitofusin-2 expression. Furthermore, baicalin elevated sirtuin-1 (SIRT1) level in VPA rats’ brain tissues and restored the antioxidant defense mechanisms. Besides, it abrogated the neuronal histopathological changes in the brain tissues. Based on the data herein, baicalin may provide a promising pre-clinical therapeutic line in ASD as a mitochondrial function modulator, antioxidant and anti-apoptotic agent. [Display omitted] •Baicalin improved postnatal growth and maturation.•Baicalin improved motor development & ameliorated behavioral changes.•Baicalin enhanced the neuronal mitochondrial functions.•Baicalin elevated sirtuin-1 levels in the brain & restored the antioxidant defenses.•Baicalin abrogated the neuronal histopathological & immunohistochemical changes.