Stellarine A attenuates anxiety in rats through ERK/CREB/BDNF signaling: A 1HNMR metabolomics study revealing metabolic pathways and biomarkers

Abstract

Anxiety is one of the most prevalent mental health issues. Stellariae Radix, a specialty medicinal material from Ningxia, is known for its ability to clear defunct heat. Research group prior research demonstrated that the ethanol extract of Stellariae Radix possesses a significant anxiolytic effect. We have separated and identified the β-carboline alkaloid compounds from Stellariae Radix. The anxiolytic properties of Stellarine A were assessed in rats by conducting behavioral assays and examining pathological histology. Concurrently, ELISA was utilized to detect changes in neurotransmitter and hormone levels, and molecular biology techniques were employed to explore its mechanisms of action. ¹HNMR analysis was conducted to examine metabolic changes in rats, aiming to identify biomarkers and metabolic pathways. The pharmacodynamic data demonstrated that Stellarine A can significantly improve rat anxiety behavior. Moreover, Stellarine A significantly ameliorates the reduction and disarray of neurons. Immunohistochemical and molecular biology techniques reveal that Stellarine A upregulates the expression of CB1 and CB2, enhances ERK, CREB, and BDNF mRNA and protein expression. ¹HNMR analysis identified 28 endogenous differential metabolites associated with the anxiety model, and Stellarine A significantly modulates 21 endogenous metabolites, thereby improving anxiety symptoms by regulating multiple metabolites. The component Stellarine A in Stellariae Radix possesses anxiolytic potential, which may exert its effects by activating the ERK/CREB/BDNF pathway. The anxiolytic action of Stellarine A is associated with metabolic pathways such as amino acid metabolism, sugar metabolism, and lipids. Therefore, Stellarine A shows promise in the development of therapeutic drugs for anxiety disorders.