OBJECTIVE Hyperactivityof hypothalamic-pituitary-adrenal(HPA) axis is an important aetiological risk factor for the development of depression. Previous studies have demonstrated that the phenolic monomer baicalin has antidepressant-like effects and decreases serum corticosterone levels.However,the mechanism by which baicalin regulates hyperactivity of HPA axis remains unclear. This work aimed to investigate the effects of baicalin on hyperactivity of HPA axis using the olfactory bulbectomised(OBX) rat model of depression. METHODS Animals were anaesthetised with 10% chloral hydrate(3.3 mL·kg~(-1),ip). Using disinfected surgical equipment,the skull covering the olfactory bulbs was exposed by a midline incision. Two burr holes(2 mm diameter) were drilled 8 mm anterior to the bregma and 2 mm lateral to the midline. Both olfactory bulbs were aspirated and the holes filled with glass ionomer cement. The scalp was sutured closed. Sham-operated rats underwent every surgical procedure except the aspiration of the bulbs. The animals received penicillin(8×10~5U) intramuscularly(0.2 mL/300 g) once per day for 3 d post-surgery to prevent infection,and were subsequently housed alone in polypropylene cages. The experiments continued after 14 d of rehabilitation. The following groups were used for experiments: sham-operated(underwent surgical procedure without aspiratedolfactory bulbs and administration of vehicle only),OBX-model(underwent every surgical procedure and administration of vehicle only),OBX-amitriptyline treated(10 mg·kg~(-1)),and OBX-baicalin treatment(20 and 40 mg·kg~(-1)). Amitriptyline and baicalin were dissolved in physiological saline. RESULTS We examined how baicalin altered OBX-induced changes in serum glucocorticoid level as wel as inflammatory responses,sirtuin 1(SIRT1) expression,and p65 acetylation in the hypothalamus. Similar experiments were performed to analyse the effects of baicalin on lipopolysaccharide-induced inflammatory responses inhypothalamus. CONCLUSION Our results indicate that activation of the SIRT1 in the hypothalamus contributes to hyperactivity of HPA axis,which can be alleviated by baicalin. OBJECTIVE Hyperactivity of hypothalamic-pituitary-adrenal (HPA) axis is an important aetiological risk factor for the development of depression. Previous studies have demonstrated that the phenolic monomer baicalin has antidepressant-like effects and decreases serum corticosterone levels. However, the mechanism by which baicalin This work aimed to investigate the effects of baicalin on hyperactivity of HPA axis using the olfactory bulbectomy (OBX) rat model of depression. METHODS Animals were anaesthetised with 10% chloral hydrate (3.3 mL · kg ~ -1), ip). Using disinfected surgical equipment, the skull covering the olfactory bulbs was exposed by a midline incision. Both burr holes (2 mm diameter) were drilled 8 mm anterior to the bregma and 2 mm lateral to the midline. Both olfactory bulbs were aspirated and the holes filled with glass ionomer cement. The scalp was sutured closed. Sham-operated rats underwent every surgical procedure except t he aspiration of the bulbs. The animals received penicillin (8 × 10 ~ 5U) intramuscularly (0.2 mL / 300 g) once per day for 3 d post-surgery to prevent infection, and were subsequently housed separately in polypropylene cages. The experiments continued after 14 d of rehabilitation. The following groups were used for experiments: sham-operated (underwent surgical procedure without aspiratedolfactory bulbs and administration of vehicle only), OBX-model (underwent every surgical procedure and administration of vehicle only), OBX-amitriptyline treated (10 mg · kg -1), and OBX-baicalin treatment (20 and 40 mg · kg -1). Amitriptyline and baicalin were dissolved in physiological saline. in serum glucocorticoid level as wel as inflammatory responses, sirtuin 1 (SIRT1) expression, and p65 acetylation in the hypothalamus. Similar effects were performed to analyze the effects of baicalin on lipopolysaccharide-induced inflammatory responses in hypyphaha s. CONCLUSION Our results indicate that activation of the SIRT1 in the hypothalamus contributes to hyperactivity of HPA axis, which can be alleviated by baicalin.