Pharmacodynamic Studies Of Paecilomyces Tenuipesmycelium Aqueous Extract On Oxidative Stress-induced Related Diseases

Paecilomyces tenuipes is the anamorph of Cordyceps takaomontan,bioactive compounds of which are similar to that of Cordyceps sinensis.It has been used as substitute of Cordyceps sinensis in overseas.Meanwhile,Paecilomyces tenuipes,a famous Chinese medicinal entomopathogenic fungus,has been traditionally served as folk medicine in Asia for years.In recent years,with the improvement of people’s health consciousness,the demand of Cordyceps sinensis has been increasing dramatically.The resource of Cordyceps sinensis is on the verge of extinction for over-exploitation.Therefore,the study on Paecilomyces tenuipes will be helpful to alleviat the Cordyceps sinensis resources pressure and sufficient to meet the increasing demand in recent years.Oxidative stress refers to the imbalance of oxidation-reduction system in the body and the overproduction of free oxygen radicals.An imbalance between oxidative stress and antioxidative defense can result in cell and tissue damages and accelerate the development of various diseases.With the changes in lifestyle,the accelerated pace of life and the pollution of environment,the diseases induced by oxidative stress,such as fatigue,depression,immune deficiency and diabetes,have been gradually widespread,and seriously affected the person’s health,life quality and lifetime.Therefore,it is very important and necessary to carry out the related products that inhibit oxidative stress,treat or adjuvant treatment of oxidative stress-induced diseases.Paecilomyces tenuipes possesses various pharmacological activities,although section biological activities of Paecilomyces tenuipes have been reported,the depth and breadth of those studies are still not enough,and the action mechanism is still unclear,more systematic researches are highly demanded.In this study,oxidative stress was used as the center to study the pharmacological activity of Paecilomyces tenuipes on oxidative stress-induced diseases.The pharmacological activity of Paecilomyces tenuipes was also studied.The action mechanism related to pharmacodynamics was describedto provide a theoretical basis for the further development and utilization of Paecilomyces tenuipes.At the same time,through the study of oxidative stress on the efficacy and possible mechanism of Paecilomyces tenuipes,new ideas were provided for the research and development of insect fungus.In the study of Paecilomyces tenuipes mycelium aqueous extract(PTNE)mediated anti-fatigue activity,mice were treated with PTNE for 2 weeks by oral administration.PTNE significantly improved the athletic ability of mice which was confirmed via forced running test,rotating rod test and forced swimming test in mouse model.Compared to non-treated mouse,PTNE administration increased ATP levels,enhanced the activies of SOD and GSH-Px in serum and liver of mice.Meanwhile,the decreased levels of LA,LDH,MDA and ROS were also measured.The results showed that PTNE reduce or inhibit oxidative stress by increasing the expression of antioxidant enzymes and reducing the accumulation of oxygen free radicals.With extending the exercise time and improving the energy supply in mice,PTNE exhibit anti-fatigue activity.Paecilomyces tenuipes shows vicarious pharmacological effects including antidepressant.The chronic unpredictable mild stress(CMUS)induced rats model acts as an important role during antidepressants screening.Our study aims to evaluate the antidepressant-like activity of Paecilomyces tenuipes mycelium aqueous extract(PTNE)in rat model of behavioral despair depression.After 4-week treatment with 3 mg/kg Flu and 0.04,0.2,1 g/kg PTNE,behavioral tests were conducted to investigate its antidepressant-like activity.The levels of neurotransmitters and hormones in blood and hypothalamus were measured.Results showed that PTNE significantly increased the movement in forced running test while reduced the paw withdrawal latency in hot-plate test and the immobility time in forced swim test of depression-like rats.Meanwhile,PTNE normalized the levels of hormones and neurotransmitters in depression-like rats compared with CMUS rats,depressed the increased activity of HPA axis.Furthermore,PTNE enhanced the activity of antioxidant enzymes SOD and GSH-Px,reduced the expression of lipid peroxides and increases the antioxidant levels of depressed rats.In conclusion,All data demonstrate that PTNE may be a potential pharmaceutical agent in the treatment resistant depression partly mediated by normalizing the levels of neurotransmitters and increasing the antioxidant levels of CMUS rats.In the PTNE-mediated immune regulatory activity,the immunomodulatory activityof PTNE was evaluated in cyclophosphamide(CTX)-induced immunosuppressed mice model,which were trated with PTNE at doses of 0.04,0.2,2 g/kg.Two-week PTNE administration significantly improved the loss of bodyweight,increased organ indices,positively regulated the cytotoxicity of NK cells and the proliferation of lymphocyte compared with the model group.In addition,PTNE showed strikingly effects on modulation of the production of Ig G,Ig A and Ig M,and the levels of interleukin-2,6,12,interferon-γ and tumor necrosis factor-ɑin serum and spleen of immunosuppressed mice.Futhermore,PTNE strongly increased the activity of i NOS and antioxidant enzymes in serum and spleen of immunosuppressed mice.Therefore,this study suggested that PTNE improves the immunological function of mice by improving the levels of immunoglobulins and cytokines in serum and spleen of immunosuppressed mice,inhibiting oxidative stress,protecting immune organs and enhancing the immune function of mice.In present study aims to investigate the hypoglycemic,hypolipidemic and anti-nephritic effects of Paecilomyces tenuipes mycelium aqueous extracts(PTNE)in high fat diet-STZ-induced diabetic rats,which were treated with 120 mg/kg metformin and PTNE at doses of 0.04,0.2 and 1.0 g/kg for 4 weeks.The hypoglycemic activity of PTNE was confirmed not only by the reduced fasting blood glucose level,but also by the normalization on oral glucose tolerance.PTNE suppressed the concentration of total cholesterol and triglycerides,and balanced the levels of low-density and high-density lipoprotein cholesterol.The suppressive effects of PTNE on the levels of creatinine,urea nitrogen,IL-2,IL-6 and nuclear factor kappa B indicated its protection against diabetic nephropathy.The beneficial effects of PTNE on superoxide dismutase,malondialdehyde and glutathione peroxidase levels suggested that the excellent anti-diabetic and anti-nephropathic activities of PTNE may be related to the relief on oxidative damage during type 2 diabetic mellitus.