Antidepressant effect of bioactive compounds from Paecilomyces tenuipes in mice and rats

A bioactive compound from Paecilomyces tenuipes（BCPT）has an inhibitory effect on monoamine oxidase A（MAO-A）in vitro.Researchers have thought that BCPT may be a potential antidepressant.The MAO-A suppressor moclobemide served as a control,and this study investigated the mechanisms of BCPT as an antidepressant.Results demonstrated that BCPT induced significantly increased sucrose intake in chronic unpredictable stressed rats,shortened immobility time in forced swimming mice,improved the scores of blepharoptosis and akinesia in reserpine-treated mice,increased the number of 5-hydroxy tryptophan-induced head-twitches,remarkably enhanced the expression of hippocampus mineralcorticoid receptor and glucocorticoid receptor mRNA,decreased the ratio of mineralcorticoid receptor to glucocorticoid receptor and raised the levels of dopamine,norepinephrine and 5-hydroxytryptamine,while decreasing hydroxyindole acetic acid levels or dihydroxy-phenyl acetic acid in chronic unpredictable stressed rats.Behavioral test results suggested that BCPT potentially had antidepressant-like activity.Meanwhile,BCPT increased the levels of neurotransmitters,and mineralcorticoid receptor and glucocorticoid receptor mRNA in the hippocampus,which may be an important mechanism of its antidepressant effect.

Bioactive compounds from Paecilomyces tenuipes regulating the function of the hypothalamo-hypophyseal system axis in chronic unpredictable stress rats

Background A bioactive compound from Paecilomyces tenuipes （BCPT） has an inhibitory effect on monoamine oxidase A （MAO-A） and monoamine oxidase B （MAO-B） in vitro and in vivo, which indicates BCPT may be a potential antidepressant. In this study we aimed to study the antidepressant effects of BCPT in the chronic unpredictable stress （CUS） model in rats and explore underlying mechanisms in the hypothalamic-pituitary-adrenal （HPA） axis. Methods The antidepressant effects of BCPT were studied in the chronic unpredictable stress model in rats. Animals were housed isolated, except the control group. Rats were exposed daily to different random stressors from day 1 to 21. Awarding response was detected by calculating the 24-hour consumption of sucrose water. Cortisol （CORT） and adrenocorticotropic hormone （ATCH） contents in serum and arginine vasopressin （AVP） contents in the pituitary body were detected by radio immunoassays. Total RNA of hippocampus or hypothalamus was extracted and subjected to reverse transcription-polymerase chain reaction （RT-PCR） for the measurement of corticotrophin releasing hormone （CRH） mRNA or mineralocorticoid receptor （MR） mRNA and glucocorticoid receptor （GR） mRNA levels. Statistical analyses were performed using one way analysis of variance （ANOVA） followed by Student-Newman-Keuls （SNK） test. Results Chronic unpredictable stress resulted in reduction of sensitivity to reward and abnormality in the HPA axis in the animal model. BCPT improved the reward reaction as measured by increasing sucrose consumption, remarkably reduced serum CORT and ACTH levels and the AVP content in the pituitary body in the CUS-treated rats, decreased the expression of CRH mRNA, enhanced the expression of hippocampus MR mRNA, GR mRNA and decreased the ratio of MR/GR. Conclusions BCPT has potentially antidepressant-like activity and normalized the HPA axis hyperactivity in a CUS model of depression in rats. This may be an important mechanism of its antidepressant effect.