Scutellariae radix Ameliorates Prenatal Stress-Induced Anxiety-Like and Depression-Like Behavior in the Offspring via Reversing HPA Axis Hyperfunction and Ameliorating Neurodevelopmental Dysfunction

Abstract

Introduction: This study aimed to explore the impact and mechanism of Scutellariae radix (SR), dried root of Scutellaria baicalensis Georgi of Labiatae, on prenatal stress (PS)-induced anxiety-like and depression-like behavior in the offspring in a mouse prenatal stress model. Methods: The open field test (OFT), tail suspension test (TST), and forced swimming test (FST) were utilized to assess the behavior of the offspring. Histological changes were evaluated using HE staining and Nissl staining. ELISA was employed to detect the levels of related factors in the serum and fetal brains of offspring mice. Immunohistochemistry was used to determine the expressions of doublecortin and neurotrophic factors in the hippocampus, and RT-PCR reflected the expression of factors in the hippocampus and placenta of offspring mice. These various techniques collectively provided insight into the neurodevelopmental status by detecting indicators related to neurodevelopmental status. LC-MS/MS and molecular docking were used to clarify the chemical constituents and the pharmacodynamic components in S. radix. Results: S. radix ameliorated prenatal stress-induced anxiety-like and depression-like behavior in the offspring. It also alleviated hippocampal neurogenesis impairment caused by prenatal stress and restored abnormal expression of hippocampal glutamate (Glu) and brain-derived neurotrophic factor in the offspring. Additionally, S. radix maintained normal 11β-HSD1 expression in the placenta of prenatal stress mice, ensuring a normal level of glucocorticoids (GCs) and glucocorticoid receptors (GRs) in the fetus. Furthermore, S. radix increased the mRNA expression of GR and 11β-HSD2 while decreasing the mRNA expression of 11β-HSD1, thereby normalizing levels of serum CRH, ACTH, and GC in the offspring. Finally, docking results indicated that baicalein, wogonin, wogonoside, and baicalin exhibited stronger binding ability with the target. Conclusion: The results of our study indicate that S. radix may have the potential to alleviate prenatal stress-induced anxiety-like and depression-like behaviors in offspring, at least partially through protecting placental barrier function, reversing HPA axis hyperfunction, and ameliorating neurodevelopmental dysfunction.