OBJECTIVES: The hypothalamic-pituitary-adrenal (HPA) axis plays an important role in maintaining homeostasis and its dysregulation is characterized by elevated levels of glucocorticoids leading to depression. Therefore, therapies targeting the stress mechanisms at molecular level are of research interests. The objective of this study is to elucidate the neuroprotective and anti-inflammatory activity of Gossypetin-3′-Oglycoside (G-3′gly) isolated from the endophyte Daldinia eschscholtzii.