[Analysis of paclitaxel concentration in rat plasma by Raman spectrums combined with partial least square].

Partial least square (PLS) combining with Raman spectroscopy was applied to develop predictive models for plasma paclitaxel concentration detection. In this experiment, 312 samples were scanned by Raman spectroscopy. High performance liquid chromatography (HPLC) was applied to determine the paclitaxel concentration in 312 rat plasma samples. Monte Carlo partial least square (MCPLS) method was successfully performed to identify the outliers and the numbers of calibration set. Based on the values of degree of approach ( D a ), moving window partial least square (MWPLS) was used to choose the suitable preprocessing method, optimum wavelength variables and the number of latent variables. The correlation coefficients between reference values and predictive values in both calibration set ( R c2) and validation set ( R p2) of optimum PLS model were 0.933 1 and 0.926 4, respectively. Furthermore, an independent verification test was performed on the prediction model. The results showed that the correlation error of the 20 validation samples was 9.36%±2.03%, which confirmed the well predictive ability of established PLS quantitative analysis model.

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.

Investigation of the immunomodulatory activity of Tricholoma matsutake mycelium in cyclophosphamide-induced immunosuppressed mice.

Tricholoma matsutake, a popular food and biopharmaceutical resource in Asia, possesses various pharmacological activities. Although T. matsutake mycelium (TM) may enhance immunity, previous studies, to the best of our knowledge, have been performed on normal animals or cells alone. The present study aimed to evaluate the immunomodulatory activity of TM at doses of 0.3, 1.0 and 2.0 g/kg in cyclophosphamide (CTX)­induced immunosuppressed mouse models. TM treatment for 2 weeks markedly improved the gain in bodyweight, increased organ indices, reduced hind paw swelling and positively regulated the cytotoxicity of natural killer cells and the proliferation of lymphocytes. These effects are similar to that of thymosin α1 (0.16 mg/kg) which served as the positive control. In CTX­induced immunosuppressed mice, TM demonstrated marked effects on the modulation of the production of immunoglobulin (Ig)G and IgA, and the levels of interleukin­2, 6, 10 and 12, interferon­α and γ and tumor necrosis factor­α in serum. Compared with CTX mice, the reduced activity of nuclear factor (NF)­κB in serum and spleen, and phosphorylation of inhibitor of NF­κB kinase α/ß in spleen were observed in TM­treated mice. Taken together, TM effectively improved immune function in immunosuppressed mice via modulation of ILs and inflammatory factors associated with the NF­κB signaling pathway.

Anti-Gouty Arthritis and Antihyperuricemia Effects of Sunflower (Helianthus annuus) Head Extract in Gouty and Hyperuricemia Animal Models.

This study was performed to investigate the therapeutic effects and possible mechanisms of sunflower (Helianthus annuus) head extract (SHE) on gout. First, the components of sunflower head powder and SHE were analyzed systematically. SHE, especially SHEB (extracted with 20% ethanol and 80% double-distilled water), strongly suppressed the swelling of the ankles in rats with acute gout induced by monosodium urate (MSU) crystals and reduced the levels of uric acid and xanthine oxidase (XO) in mice with hyperuricemia induced by oteracil potassium and yeast extract powder. Hematoxylin and eosin staining indicated that SHEB reduced inflammation cells and increased the joint space in the ankle compared with the control rats with MSU-induced gout. In the rats with acute gout, among 13 detected inflammatory cytokines, SHEB significantly enhanced the serum levels of interleukin-10 and the monocyte chemoattractant protein 1α. In the mice with hyperuricemia, SHEB reduced the levels of glutathione peroxidase, superoxide dismutase, malondialdehyde, and nitrogen monoxide in liver tissues. The potential therapeutic effects of SHE on gout are probably due to the production of anti-inflammatory cytokines and the suppression of XO activity via the modulation of oxidative stress status.

Synthesis, characterization, and evaluation of mPEG-SN38 and mPEG-PLA-SN38 micelles for cancer therapy.

7-Ethyl-10-hydroxy camptothecin (SN38) is a potent topoisomerase inhibitor and a metabolite of irinotecan. Its clinical development has been hampered by its poor solubility. To address this problem, methoxy poly(ethylene glycol)-2000 (mPEG2K)-SN38 and mPEG2K-poly(lactide) (PLA1.5K)-SN38 conjugates were prepared and then dispersed into an aqueous medium to form micelles. Physicochemical characteristics of SN38-polymer conjugate micelles, for example, micelle diameter, zeta potential, morphology, and drug content, were then evaluated. The results showed that the mean diameters of mPEG2K-SN38 and mPEG2K-PLA1.5K-SN38 micelles were ~130 and 20 nm, respectively. These two micelles had similar drug contents. mPEG2K-PLA1.5K-SN38 micelles were more homogeneous than mPEG2K-SN38 micelles. Moreover, in vitro drug release behavior of the micelles was studied by high performance liquid chromatography. SN38 release from mPEG2K-SN38 micelles was much faster than from mPEG2K-PLA1.5K-SN38 micelles. In vitro cytotoxicity, cellular uptake, and apoptosis assays of the SN38-polymer conjugate micelles were carried out on BEL-7402 human liver cancer cells. In vivo biodistribution and antitumor tumor efficacy studies were carried out in a nude mouse xenograft model derived from BEL-7402 cells. The results showed that mPEG2K-PLA1.5K-SN38 micelles were significantly more effective than mPEG2K-SN38 micelles in tumor inhibition, and the inhibitory effect of mPEG2K-PLA1.5K-SN38 micelles on tumor growth was significantly greater than that of mPEG2K-SN38 micelles (1,042 vs 1,837 mm) at 30 days. In conclusion, mPEG-PLA-SN38 is a promising anticancer agent that warrants further investigation.

Anti-diabetic activities of Paecilomyces tenuipes N45 extract in alloxan-induced diabetic mice.

Due to the limitations of existing anti-diabetic drugs, the treatment of diabetes mellitus remains a significant challenge. The present study aimed to investigate the hypoglycemic, hypolipidemic and antioxidant effects of Paecilomyces tenuipes N45 extracts on alloxan-induced type I diabetes mellitus in mice. Diabetic Kunming mice were orally administered with water extract (WE) at doses of 2.50, 0.25 and 0.05 g/kg) or alcohol extract (AE) at doses of 2.00, 0.20 and 0.04 g/kg, for 3 weeks, following which the levels of factors associated with blood glucose, lipids and free radicals were determined. The anti-diabetic activities of AE and WE were further confirmed via an oral glucose tolerance test. Similar to the effects of metformin, Paecilomyces tenuipes N45 extracts led to a significant reduction in blood glucose levels, increase in serum insulin concentration and normalization in the densities of low-density lipoprotein cholesterol and high density lipoprotein cholesterol. The Paecilomyces tenuipes N45 extracts exerted antioxidative effects, indicated by regulation in the levels of superoxide dismutase, malondialdehyde and glutathione peroxidase. Taken together, the results of the present study demonstrated that Paecilomyces tenuipes N45 extract, a safe pharmaceutical agent, exerted anti-diabetic and anti-nephropathic activities and, thus, offers potential as a novel therapeutic agent in the treatment of diabetes.

Cordyceps militaris induces tumor cell death via the caspase­dependent mitochondrial pathway in HepG2 and MCF­7 cells.

Cordyceps militaris (CM), an entomopathogenic fungus belonging to the class ascomycetes, possesses various pharmacological activities, including cytotoxic effects, on various types of human tumor cells. The present study investigated the anti­hepatocellular carcinoma (HCC) and anti­breast cancer effects of CM in in vitro and in vivo models. CM aqueous extract reduced cell viability, suppressed cell proliferation, inhibited cell migration ability, caused the over-release of lactate dehydrogenase, induced mitochondrial dysfunction and enhanced apoptotic rates in MCF­7 and HepG2 cells. The expression levels of cleaved poly (ADP ribose) polymerase and caspase­3, biomarkers of apoptosis, were increased following treatment with CM aqueous extract for 24 h. Furthermore, in the MCF­7 and HepG2 cells, enhanced levels of B cell­associated X protein and cleaved caspase­8 were observed in the CM­treated cells. Finally, the antitumor activities of CM in HCC and breast cancer were also confirmed in MCF­7­ and HepG2­xengraft nude mice models. Collectively, the data obtained in the present study suggested that the cytotoxic effects of CM aqueous extract on HCC and breast cancer are associated with the caspase­dependent mitochondrial pathway.

Antidiabetic and Antinephritic Activities of Aqueous Extract of Cordyceps militaris Fruit Body in Diet-Streptozotocin-Induced Diabetic Sprague Dawley Rats.

Cordyceps militaris has long been used as a crude drug and folk tonic food in East Asia. The present study aims to evaluate the antidiabetic and antinephritic effects of the aqueous extract of the Cordyceps militaris fruit body (CM) in diet-streptozotocin- (STZ-) induced diabetic rats. 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, the fasting blood glucose and bodyweight of each rat were monitored. Hypoglycemic effects of CM on diabetic rats were indicated by decreases in plasma glucose, food and water intake, and urine output. The hypolipidemic activity of CM was confirmed by the normalization of total cholesterol, triglycerides, and low- and high-density lipoprotein cholesterol in diabetic rats. Inhibitory effects on albuminuria, creatinine, urea nitrogen, and n-acetyl-ß-d-glucosaminidase verified CM's renal protective activity in diabetic rats. Furthermore, CM exerted beneficial modulation of inflammatory factors and oxidative enzymes. Compared with untreated diabetic rats, CM decreased the expression of phosphor-AKT and phosphor-GSK-3ß in the kidneys. Altogether, via attenuating oxidative stress, CM displayed antidiabetic and antinephritic activities in diet-STZ-induced diabetic rats.

Studies on the Antifatigue Activities of Cordyceps militaris Fruit Body Extract in Mouse Model.

Cordyceps militaris has been used extensively as a crude drug and a folk tonic food in East Asia due to its various pharmacological activities. Our study aims to investigate the effect of Cordyceps militaris fruit body extract (CM) on antifatigue in mouse model. Two week CM administration significantly delayed fatigue phenomenon which is confirmed via rotating rod test, forced swimming test and forced running test. Compared to nontreated mouse, CM administration increased ATP levels and antioxidative enzymes activity and reduced the levels of lactic acid, lactic dehydrogenase, malondialdehyde, and reactive oxygen species. Further data suggests that CM-induced fatigue recovery is mainly through activating 5'-AMP-activated protein kinase (AMPK) and protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathways and regulating serum hormone level. Moreover, CM-enhanced the phosphorylation of AMPK contributes to its antioxidant effect. Our data provides experimental evidence in supporting clinical use of CM as an effective agent against fatigue.