| Cordyceps militaris, also called North Cordyceps sinensis, silkworm pupa Cordyceps, pupae grass, etc., belongs to Cordyceps Fungus. Cordyceps militaris fruit body is the main edible and medicinal part of Cordyceps militaris. According to the announcement of Ministry of Health of the People's Republic of China, Cordyceps militaris has been approved as a new resource of food. Cordyceps sinensis is a traditional Chinese medicine in the history, which is used for nourishing bodies and treating diseases. With the increasing 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. Cordyceps militaris, an entomopathogenic fungus belonging to the class ascomycetes, contains various pharmacological components and possesses various pharmacological activities, the same as Cordyceps sinensis, so Cordyceps militaris is the best alternative of Cordyceps sinensis.Oxidative stress refers to the imbalance of oxidation-reduction system in the body, and the overproduction of free oxygen radicals could cause cell and tissue damage, further lead to diseases. With the accelerated pace of life, the changes in life style and the pollution of environment, the diseases mediated by oxidative stress, such as fatigue, diabetes, nephropathy and cancer, have been gradually widespread, and seriously affected the person's health, life quality and lifetime. Therefore, it's very important to carry out the products to inhibit oxidative stress.Although the biological activities of CM have been reported, the breadth and depth of these studies are still not enough, and the action mechanism is still unclear, so it's important for the further research. In this study, various pharmacological activities center on oxidative stress of CM were carried out, and tried to clarify the action mechanism which could provide theoretical basis for further development of CM.First, this experiment studied the process optimization of the aqueous extract of Cordyceps militaris fruit body with the expected value as measure index, which was built with the content of polysaccharide, adenosine, cordycepin and cordyceps acid. Based on single-factor optimization strategy and Box-Behnken design, the optimal extraction process of Cordyceps militaris fruit body was got, and that could be described as Cordyceps militaris fruit body was firstly extracted with 30 volumes of double distilled(D.D.) water at 45 ? for 3.0 h, then 4000 rpm centrifuge for 10 min, the supernatant named ?; after centrifugation, the residue was secondly extracted with 30 volumes of D.D. water at 80 ?for another 3.5 h, 4000 rpm centrifuge for 10 min, the supernatant named ?; the merged supernatant was the aqueous extract of Cordyceps militaris fruit body. Cordyceps militaris fruit body aqueous extract contains 29.01 % polysaccharides, 0.21 % adenosine, 0.42 % cordycepin and 6.13 % cordycepic acid.In the study of anti-fatigue activity of CM, 2-week CM administration significantly delayed fatigue phenomenon which was confirmed via rotating rod test, forced swimming test and forced running test in mouse model. Compared to non-treated mouse, CM administration increased ATP levels and anti-oxidative enzymes activities, and reduced the levels of LD, LDH, MDA and ROS, Further data suggested that CM-induced fatigue recovery was mainly through activating AMPK and AKT/m TOR pathways, and the phosphorylation of AMPK with CM-enhanced contributed to its anti-oxidant effect. Altogether, CM could attenuate oxidative stress for increasing ATP and reducing the accumulation of metabolites then delay fatigue appearance.In the study of antidiabetic and antinephritic effects of CM in diet-streptozotocin(STZ)-induced diabetic rats, the fasting blood glucose and bodyweight of each rat were monitored during four weeks of continuous oral administration of CM at doses of 0.5, 1.0, and 2.0 g/kg and metformin at 100 mg/kg. Compared to non-treated diabetic rats, hypoglycemic effects of CM on diabetic rats were indicated by decreases in plasma glucose, food and water take, and urine output. The hypolipidemic activity of CM was confirmed by the normalization of TC, TG, and LDL-C and HDL-C in diabetic rats. Inhibitory effects on albuminuria, creatinine, urea nitrogen, and inflammatory factors verified its renal protective activity in diabetic rats. Furthermore, CM could enhance the activities of SOD and GSH-Px,and reduce the levels of MDA and ROS, compared to non-treated diabetic rats, CM decreased the expressions of phosphor-AKT and phosphor-GSK-3? in the kidneys. Altogether, via attenuating oxidative stress, CM displayed antidiabetic and antinephritic activities in diet-STZ-induced diabetic rats.In the study of anti- membranous glomerulonephritis(MGN) activity of CM, the cationic bovine serum albumin(C-BSA)-induced rat model were used. Significant renal dysfunction was observed in MGN rats, comparatively, 4-week CM administration strongly decreased the levels of 24-h urine protein, total cholesterol, triglyceride, blood urea nitrogen and serum creatinine, and increased the levels of serum albumin and total serum protein. Strikingly recovering kidney histological architecture was noted in CM-treated MGN rats. Meanwhile, CM could significantly improve the activities of SOD and GSH-Px, reduce the levels of MDA and ROS compared to non-treated MGN rats. Altered levels of inflammatory cytokines including IL-2, IL-6, MCP-1, ICAM-1, VCAM-1, TNF-?, and NF-?B p65 reverted to the normal level upon treatment with CM. The present data suggest that CM protects the rats against membranous glomerulonephritis via the normalization of NF-?B activity, thereby inhibits the oxidative damage and reduces inflammatory cytokines levels.In the experiment of CM on anti-tumor activity, CM reduced cell viability, inhibited cell proliferation and cell migration ability, caused the over-production of ROS, induced mitochondrial dysfunction, then enhanced apoptotic rate in MCF-7 and Hep G2 cells. The expressions of cleaved PARP and caspase-3, the hall-biomarkers of apoptosis, were increased after 24-h CM treatment. Furthermore, in both MCF-7 and Hep G2 cells, the enhanced levels of Bax and cleaved caspase-8 were observed in CM-treated cells. Finally, the anti-tumor activities of CM on hepatocellular carcinoma and breast cancer were confirmed in MCF-7 and Hep G2-xengrafted nude mice model. Collectively, CM could enhance the production of ROS, cause oxidative stress, then activate the mitochondria apoptotic signaling pathways to induce the apoptosis of MCF-7 and Hep G2 cells... |
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