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BACKGROUND: Hypothalamus-pituitary-adrenal (HPA) axis dysfunction has been closely linked to anxiety. Previous studies have shown that Valeriana jatamansi Jones extract exhibits clear anxiolytic effects, but it is unclear about the mechanism underlying regulation of the HPA axis dysfunction in these anxiolytic effects.OBJECTIVE: To observe the effects of Valeriana jatamansi Jones (Zhizhu Xiang) extract on HPA axis function in a rat model of anxiety, and to compare these effects with positive control estazolam.DESIGN, TIME AND SETTING: Randomized, controlled, animal experiment was performed at Chengdu University of Traditional Chinese Medicine, China, between February and September in 2006.MATERIALS: Estazolam was purchased from Shanghai Jiufu Pharmaceutical, China; Valeriana jatamansi Jones was purchased from the Lotus Pond Market for Chinese Herbal Medicine in Chengdu. It consisted of iridoids and flavonoid components.METHODS: A total of 72 Sprague Dawley rats, aged 2 months, were randomly assigned to 6 groups:low-, medium-, and high-dose Valeriana jatamansi Jones groups intragastrically injected with 0.3,0.6, and 0.9 g/kg per day Valeriana jatamansi Jones extract, respectively; estazolam group intragastrically injected with 1.5 mg/kg per day estazolam; model and normal groups administered 5 mL physiological saline. Anxiety was established in all groups, except the normal group, through the use of elevated plus-maze test at 7 days following drug administration.MAIN OUTCOME MEASURES: Blood β-endorphin and corticosterone levels were determined using enzyme-linked immunosorbent assay following treatment with Valeriana jatamansi Jones extract. Expressions of HPA axis-related genes were measured by cDNA microarray.RESULTS: Blood p-endorphin and corticosterone levels were significantly greater in the model group than in the normal group. Compared with the model group, levels decreased with Valeriana jatamansi Jones extract or estazolam treatment, particularly in the low-dose Valeriana jatamansi Jones group (P< 0.01). cDNA microarray results demonstrated that corticotropin-releasing hormone and Orexin, which are associated with HPA axis function, were differentially expressed;expression increased in the model group, but decreased in rats treated with Valeriana jatamansi Jones extract.CONCLUSION: Valeriana jatamansi Jones extract plays a role in regulating HPA axis function in a rat model of anxiety, and this effect was superior to estazolam.