Self-Assembled pH-Sensitive Polymeric Nanoparticles for the Inflammation-Targeted Delivery of Cu/Zn-Superoxide Dismutase.

The use of superoxide dismutase (SOD) is currently limited by its short half-life, rapid plasma clearance rate, and instability. We synthesized a small library of biofriendly amphiphilic polymers that comprise methoxy poly(ethylene glycol)-poly(cyclohexane-1,4-diyl acetone dimethyleneketal) (mPEG-PCADK) and mPEG-poly((cyclohexane86.7%, 1,5-pentanediol13.3%)-1,4-diyl acetone dimethylene ketal) (PK3) for the targeted delivery of SOD. The novel polymers could self-assemble into micellar nanoparticles with favorable hydrolysis kinetics, biocompatibility, long circulation time, and inflammation-targeting effects. These materials generated a better pH-response curve and exhibited better hydrolytic kinetic behavior than PCADK and PK3. The polymers showed good biocompatibility with protein drugs and did not induce an acidic microenvironment during degradation in contrast to materials such as PEG-block-poly(lactic-co-glycolic acid) (PLGA) and PLGA. The SOD that contained reverse micelles based on mPEG2000-PCADK exhibited good circulation and inflammation-targeting properties. Pharmacodynamic results indicated exceptional antioxidant and anti-inflammatory activities in a rat adjuvant-induced arthritis model and a rat peritonitis model. These results suggest that these copolymers are ideal protein carriers for targeting inflammation treatment.

Studies on the anti-fatigue activities of Irpex lacteus polysaccharide-enriched extract in mouse model.

Irpex lacteus is a white rot basidiomycete proposed for a wide spectrum of biotechnological applications. However, few studies examined its effects on exercise performance and physical fatigue. The present study evaluated the potential beneficial effects of I. lacteus extract (ILE) on physical fatigue in mice. Anti-fatigue activities of ILE were evaluated in Kunming mice using the forced swim test, rotating rod and forced running test. Serum and liver biochemical parameters were determined by an autoanalyzer and commercially available kits. Seven-day ILE administration at doses of 0.04, 0.2 and 1.0g/kg failed to influence mouse horizontal and vertical movement indicating its safety on the central nervous system. Compared with normal mice, ILE significantly increased persistent period during rotating rod and swimming tests, and reduced shock times in forced running test. Additionally, ILE resulted in 23.4% and 64.5% increments on adrenocorticotropic hormone and cortisol levels in serum. Compared with normal mice, and 209.0% increment on adenosine triphosphate level in liver (up to 2.5 mmol/gHb) were noted in ILE-treated mice. Moreover, ILE increased the level of super oxide dismutase and reduced the level of malondialdehyde in the liver suggesting its antioxidant activity. Data obtained from western bolt suggests that ILE-improved endurance capacity is mainly acquired through activating 5'-AMP-activated protein kinase (AMPK). ILE enhanced the endurance capacity of mouse by an elevation of antioxidant at least partially associated with AMPK pathway. Our data highlight the potential of I. lacteus as an antioxidant in the treatment of fatigue-related diseases.

Hepatoprotective Effects of Antrodia cinnamomea: The Modulation of Oxidative Stress Signaling in a Mouse Model of Alcohol-Induced Acute Liver Injury.

In the present study, the components of A. cinnamomea (AC) mycelia were systematically analyzed. Subsequently, its hepatoprotective effects and the underlying mechanisms were explored using a mouse model of acute alcohol-induced liver injury. AC contained 25 types of fatty acid, 16 types of amino acid, 3 types of nucleotide, and 8 types of mineral. The hepatoprotective effects were observed after 2 weeks of AC treatment at doses of 75 mg/kg, 225 mg/kg, and 675 mg/kg in the mouse model. These effects were indicated by the changes in the levels of aspartate aminotransferase, alanine aminotransferase, several oxidation-related factors, and inflammatory cytokines in serum and/or liver samples. AC reduced the incidence rate of necrosis, inflammatory infiltration, fatty droplets formation, and cell apoptosis in liver detecting via histological and TUNEL assay. In addition, AC reduced the expression of cleaved caspase-3, -8, and -9 and the levels of phosphor-protein kinase B (Akt) and phosphor-nuclear factor-κB (NF-κB) in the liver samples. Collectively, AC-mediated hepatoprotective effects in a mouse model of acute alcohol-induced liver injury are the result of reduction in oxidative stress. This may be associated with Akt/NF-κB signaling. These results provide valuable evidence to support the use of A. cinnamomea as a functional food and/or medicine.

The Neuroprotective Properties of Hericium erinaceus in Glutamate-Damaged Differentiated PC12 Cells and an Alzheimer's Disease Mouse Model.

Hericium erinaceus, an edible and medicinal mushroom, displays various pharmacological activities in the prevention of dementia in conditions such as Parkinson's and Alzheimer's disease. The present study explored the neuroprotective effects of H. erinaceus mycelium polysaccharide-enriched aqueous extract (HE) on an l-glutamic acid (l-Glu)-induced differentiated PC12 (DPC12) cellular apoptosis model and an AlCl3 combined with d-galactose-induced Alzheimer's disease mouse model. The data revealed that HE successfully induced PC12 cell differentiation. A 3 h HE incubation at doses of 50 and 100 µg/mL before 25 mM of l-Glu effectively reversed the reduction of cell viability and the enhancement of the nuclear apoptosis rate in DPC12 cells. Compared with l-Glu-damaged cells, in PC12 cells, HE suppressed intracellular reactive oxygen species accumulation, blocked Ca2+ overload and prevented mitochondrial membrane potential (MMP) depolarization. In the Alzheimer's disease mouse model, HE administration enhanced the horizontal and vertical movements in the autonomic activity test, improved the endurance time in the rotarod test, and decreased the escape latency time in the water maze test. It also improved the central cholinergic system function in the Alzheimer's mice, demonstrated by the fact that it dose-dependently enhanced the acetylcholine (Ach) and choline acetyltransferase (ChAT) concentrations in both the serum and the hypothalamus. Our findings provide experimental evidence that HE may provide neuroprotective candidates for treating or preventing neurodegenerative 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.