Studies On The Anti-fatigue And Anti-depressant Activties Of Paecilomyces Hepiali

The main causes of fatigue are the shortage of ATP level in vivo due to hypoxia and the oxidative damage of multicellular organelles caused by production of ROS.Therefore,improving hypoxia is an effective means of anti-fatigue drug development.In depressed patients,the dopaminergic system and the serotonergic system are out of balance,and the levels of various neurotransmitters are reduced.Therefore,adjusting the balance between the dopaminergic system and the serotonergic system can effectively improve depression.Cordyceps sinensis possesses anti-fatigue and antidepression properties.Due to the high demand for cordyceps sinensis,its harsh growth conditions and slow growth rate,people are increasingly focus on developing replacements of cordyceps sinensis.Paecilomyces Hepiali is a natural parasitic fungus of cordyceps.A great deal of previous researches have shown that the compositions and activities of Paecilomyces Hepiali mycelia are similar to that of Cordyceps sinensis.It possesses potential antioxidant,immunomodulatory,antitumor and anti-inflammatory properties.It has been approved as a fungal species that can be used for health food products.However,whether it has anti-fatigue and anti-depression effects and related mechanisms have not been reported.In this paper,the water extract of Paecilomyces Hepiali was obtained by hot water extraction.PHC administration for 7 days had no effect on mouse horizontal or vertical movement,indicating no neurotoxicity at the selected doses was observed.The study aims to investigate the anti-fatigue and anti-depression effects of PHC and its related molecular mechanisms and further to evaluate its potential as a substitute for Cordyceps.It provides a certain experimental basis and theoretical basis for its research and development as a therapeutic drug.In anti-fatigue research,using a rotating rod,forced swimming and running assessment,the antifatigue activity of PHC was determined.Using a normobaric hypoxia,sodium nitrite toxicosis and acute cerebral ischemia assessments,PHC was confirmed to possess antihypoxic effects.PHC treatment for 7 days significantly enhanced the serum and liver levels of adenosine triphosphate,superoxide dismutase and glutathione peroxidase,prior to and following 60 min of swimming.The levels of antioxidant-associated proteins in the livers of the mice were analyzed using western blotting.PHC effectively increased the expression levels of p-AMPK,p-AKT and pmTOR.These results indicate that Paecilomyces Hepiali can attenuate intracellular oxidative damage by AMPK mediated autophagy pathway,protect mitochondria and other organelles to ensure ATP supply,and simultaneously remove ROS through AMPK pathway ultimately relieving the fatigue of the mice.These results confirm the potential of this natural product as an antioxidant in the treatment of fatigue and related diseases.In anti-depressive research,the present study aims to investigate the antidepressant-like activity of PHC in chronic unpredictable mild stress(CUMS)-induced rat model of depression.Following four weeks of treatment,similar to fluoxetine at 3 mg/kg(positive drug),PHC strongly increased sucrose preference and reduced the immobility time of depression-like rats in forced swimming test.Furthermore,the hypo-level of adrenocorticotropic hormone,noradrenaline,dopamine and glucocorticoid receptor in serum and hypothalamus of depression-like rats was enhanced by PHC.PHC enhanced the expression of tyrosine hydroxylase and reduced the levels of dopamine D2 receptor and 5-HT2 A receptor in hypothalamus.Moreover,PHC normalized CUMS-induced disorders of dihydroxyphenylacetic acid,5 ?hydroxytryptamine and 5-hydroxyindoleacetic acid in serum and hypothalamus of depression?like rats.The above results indicate that Paecilomyces Hepiali can improve the imbalance of dopaminergic system and serotonergic system,restore it to the normal level,and alleviate depression,despair,anorexia and unhappiness in CUMS rats.Paecilomyces Hepiali is expected to be an effective drug for clinical treatment of depression.