Investigations on the antifatigue and antihypoxic effects of Paecilomyces hepiali extract.

Paecilomyces hepiali, one of the most valuable and effective Chinese medicinal herbs, possesses potential antioxidant, immunomodulatory, antitumor and anti­inflammatory properties. The present study aimed to investigate the antifatigue and antihypoxic effects of Paecilomyces hepiali extract (PHC) in a mouse model. Using a rotating rod, forced swimming and running assessment, the antifatigue activity of PHC was determined. PHC administration for 7 days had no effect on mouse horizontal or vertical movement, indicating no neurotoxicity at the selected doses was observed. 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 antioxidant­associated proteins in the livers of the mice were analyzed using western blotting. PHC effectively increased the expression levels of phosphorylated (p)­5'­monophosphate (AMP)­activated protein kinase (AMPK), p­protein kinase B (AKT) and p­mammalian target of rapamycin (mTOR). The results of the present study demonstrated that PHC efficiently enhanced endurance from fatigue and had antihypoxic effects through elevation of the antioxidant capacity in the serum and liver, at least in part through the AMPK and AKT/mTOR pathways. These results indicate the potential of this natural product as an antioxidant in the treatment of fatigue, hypoxia and their associated diseases.

Synthesis and hypoglycemic activity of esterified-derivatives of mangiferin.

AIM: To synthesize three novel esterified-derivatives of mangiferin and evaluate their hypoglycemic activities. METHODS: Acetic, propionic, and butyric anhydride were reacted with mangiferin, respectively. The hypoglycemic activity of the derivatives was evaluated using a hyperglycemic mouse model induced by streptozotocin (STZ), and the islet cells were checked by biopsy inspection. RESULTS: 7, 2', 3', 4', 6'-penta-acetyl-mangiferin (PAM), 3, 6, 7, 2', 3', 4', 6'-hepta-propionyl-mangiferin (HPM) and 3, 6, 7, 2', 3', 4'-hexa-butyryl-mangiferin (HBM) were synthesized and their structures were identified by MS,(1)H, (13)C NMR, and 2D NMR. These three compounds were reported for the first time. PAM group (0.5, 0.25 mmol·kg(-1)), HPM group (0.5, 0.25 mmol·kg(-1)), and HBM group (0.5, 0.25, 0.125 mmol·kg(-1)) mice showed strong hypoglycemic activity (P < 0.01); mangiferin group (1, 0.5 mmol·kg(-1)), PAM group (0.125 mmol·kg(-1)) and HPM group (0.125 mmol·kg(-1)) showed marginal hypoglycemic activity (P < 0.05); mangiferin group (0.25 mmol·kg(-1)) had the potential for a hypoglycemic effect, although it did not demonstrate that statistically. In histological examination, the islet cells of the PAM, HPM, and HBM groups could recover from the STZ damage; islet cells of the mangiferin group could recover also, but less than the esterified-derivative groups. CONCLUSION: Derivatives could repair the damaged islet cells, and had higher lipid-solubility and stronger hypoglycemic activity than mangiferin itself. There existed a structure activity effect, and a solubility effect relationship: the larger esterification moieties, or the higher lipid-solubility, the stronger the hypoglycemic activity (no ester → acetyl → propionyl → butyryl). Esterified derivatives of mangiferin are potential compounds for new anti-diabetes drugs.