Anti-anxiety effect of Valeriana jatamansi Jones extract via regulation of the hypothalamus-pituitary-adrenal axis

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 jatamansiJones 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 Valerianajatamansi Jones groups intragastrically injected with 0.3, 0.6, and 0.9 g/kg per day Valerianajatamansi 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 ValerianajatamansiJones extract. Expressions of HPA axis-related genes were measured by cDNA microarray. RESULTS： Blood β-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 Valerianajatamansi Jones extract. CONCLUSION： Valerianajatamansi Jones extract plays a role in regulating HPA axis function in a rat model of anxiety, and this effect was superior to estazolam.

Improvement of Kidney Yang Syndrome by Icariin through Regulating Hypothalamus-Pituitary-Adrenal Axis

Objective： To investigate whether Epimedium brevicornu Maxim （EB） and icariin could exert their protective effects on hydrocortisone induced （HCI） rats by regulating the hypothalamus-pituitary-adrenal （HPA） axis and endocrine system and the possible mechanism. Methods： Male 10-week-old Sprague Dawley （SD） rats were allotted to 6 groups （A-F） with 12 each, group A was injected normal saline （NS） 3 mL/kg.day intraperitoneally, group A and B were given NS 6 mL/kg.day by gastrogavage, group B-F were injected hydrocortisone 15 mg/kg intraperitoneally, group C and D were given EB 8 or 5 g/（kg·day） by gastrogavage, group E and F were given icariin 25 or 50 mg/（kg·day） by gastrogavage. Gene expressions of hypothalamus corticotropin releasing hormone （CRH） and pituitary proopiomelanocortin （POMC） were detected by reverse transcription-polymerase chain reaction （RT-PCR）, and protein of pituitary POMC by Western-blot. Results： The serum T4, testosterone, cortisol and POMC mRNA expression were increased after treatment with EB or icariin in HCI rats, the serum CRH and the hypothalamus CRH mRNA expression released from hypothalamus corticotropin decreased compared with group B （P〈0.05）.The treatment with only icariin increased serum adrenocorticotropic hormone （ACTH） compared with group B （P〈0.05）. Conclusion： EB and icariin might be therapeutically beneficial in the treatment of HCI rats through attuning the HPA axis and endocrine system which was involved in the release of CRH in hypothalamic, and the production of POMC-derived peptide ACTH in anterior pituitary, the secretion of corticosteroids in adrenal cortex.

Relationship between glutamate in the limbic system and hypothalamus-pituitary-adrenal axis after middle cerebral artery occlusion in rats

Objective To investigate the features of glutamate activity in the limbic system and the effects of glutamate on the activation of the hypothalamus-pituitary-adrenal (HPA) axis throughout both acute cerebral ischemia and reperfusion. Methods The changes in glutamate content in the nervous cell gap,in corticotrophin releasing hormone (CHR) mRNA expression level in brain tissue,and in adrenocorticotropic hormone in blood plasma at different time-points after middle cerebral artery occlusion (MCAO) in rats were determined respectively with high-performance liquid chomatography (HPLC) and in situ hybridization.Results Glutamate content in the hippocampus and the hypothalamus increased rapidly at ischemia 15 minutes,and reached peak value (the averages were 21.05 mg/g±2.88 mg/g and 14.20 mg/g±2.58 mg/g,respectively) at 1 hour after middle cerebral artery occlusion. During recirculation,it returned rapidly to the baseline level. At 24 hours after reperfusion,it went up once more,and remained at a relative high level until 48 hours after reperfusion,and then declined gradually. CRH mRNA expression levels in the temporal cortex,hippocampus and hypothalamus were enhanced markedly at 1 hour ischemia and were maintained until 96 hours after reperfusion. At the same time,adrenocorticotropic hormone level in plasma was relatively increased. In the peak stage of reperfusion injury,there was a significantly positive correlation (n=15,r =0.566,P <0.05) of the glutamate contents in the hypothalamus with the number of cells positive for CRH mRNA expression level in the hypothalamus.Conclusion It is probable that the CRH system in the central nervous system is mainly distributed in the limbic system,and glutamate might be one of the trigger factors to induce excessive stress response in the HPA axis.

Social rank and cortisol among female rhesus macaques(Macaca mulatta)

In animal societies,some stressful events can lead to higher levels of physiological stress.Such stressors,like social rank,also predict an increased vulnerability to an array of diseases.However,the physiological relationship between social rank and stress varies between different species,as well as within groups of a single species.For example,dominant individuals are more socially stressed at times,while at other times it is the subordinate ones who experience this stress.Together,these variations make it difficult to assess disease vulnerability as connected to social interactions.In order to learn more about how physiological rank relationships vary between groups of a single species,cortisol measurements from hair samples were used to evaluate the effects of dominance rank on long-term stress levels in despotic and less stringent female rhesus macaque hierarchal groups.In despotic groups,cortisol levels were found not to be correlated with social rank,but a negative correlation was found between social rank and cortisol levels in less stringent hierarchies.Low ranking monkeys in less stringent groups secreted elevated levels of cortisol compared to higher ranking animals.These data suggest that variations in the strictness of the dominance hierarchy are determining factors in rank related stress physiology.The further consideration of nonhuman primate social system diversity and the linear degree of their hierarchies may allow for the development of valid rank-related stress models that will help increase our understanding and guide the development of new therapeutics for diseases related to human socioeconomic status.

The Ventral Ascending Noradrenergic Bundles Are Involved in the Stress Response to Immobilization in Rats

Stressful stimuli induced by immobilization are perceived as acute stress in rats. This acute stress activates corticotropin-releasing hormone (CRH) neurons in the hypothalamic paraventricular nucleus (PVN), resulting in stimulation of the hypothalamic-pituitary-adrenal (HPA) axis. The ventral ascending noradrenergic bundles (V-NAB) from the brainstem innervate the PVN. To investigate the relationship between the response of the HPA axis and the V-NAB, we examined changes in plasma corticosterone, the final output of the HPA axis, and extracellular noradrenaline (NA) in the PVN following immobilization stress in rats that received bilateral 6-hydroxydopamine (6-OHDA) lesions of the V-NAB. 6-OHDA microinjection into the V-NAB reduced the magnitude of the responses of plasma corticosterone and extracellular NA in the PVN following immobilization stress. Our results suggest that V-NAB innervation of the PVN is involved in immobilization stress-induced activation of the HPA axis.

The mechanism of the hypothalamus-pituitary-endocrine axis in anxiety disorder

Anxiety disorder is a common and serious mental disorder.At present,the pathogenesis of anxiety disorder includes hypothalamus-pituitary-adrenal(HPA)axis,neuroimmune,and brain-gut axis disorders,among others.This paper discusses the correlation between anx-iety disorder and the hypothalamus-pituitary-endocrine axis and finds that immune inflammation can be used as a“bridge”between the hypothalamus-pituitary-endocrine axis and anxiety disorder.

New hypothesis and treatment targets of depression:an integrated view of key findings

Major depressive disorder（MDD） is a common and devastating psychiatric disorder characterized by persistent low mood,cognitive disorder,and impaired social function. Despite its complex mechanisms,increasing evidence has identified the involvement of neurotrophic factors,inflammatory cytokines,the hypothalamuspituitary-adrenal axis,and glutamate receptors in the pathophysiology of this illness. The present review synthesizes recent research achievements to defi ne the network between different hypotheses of MDD and to understand which part is most pivotal for its pathogenesis. By integrating MDD-related signal pathways,we highlight brain-derived neurotrophic factor（BDNF） dysfunction and increased apoptosis as the fi nal common cascades,and new therapeutic strategies aiming to enhance BDNF function have been shown to exert a rapid and effective antidepressant action.