A critical review of a typical research system for food-derived metal-chelating peptides: Production, characterization, identification, digestion, and absorption.

In the past decade, food-derived metal-chelating peptides (MCPs) have attracted significant attention from researchers working towards the prevention of metal (viz., iron, zinc, and calcium) deficiency phenomenon by primarily inhibiting the precipitation of metals caused by the gastrointestinal environment and exogenous substances (including phytic and oxalic acids). However, for the improvement of limits of current knowledge foundations and future investigation directions of MCP or their derivatives, several review categories should be improved and emphasized. The species' uniqueness and differences in MCP productions highly contribute to the different values of chelating ability with particular metal ions, whereas comprehensive reviews of chelation characterization determined by various kinds of technique support different horizons for explaining the chelation and offer options for the selection of characterization methods. The reviews of chelation mechanism clearly demonstrate the involvement of potential groups and atoms in chelating metal ions. The discussions of digestive stability and absorption in various kinds of absorption model in vitro and in vivo as well as the theory of involved cellular absorption channels and pathways are systematically reviewed and highlighted compared with previous reports as well. Meanwhile, the chelation mechanism on the molecular docking level, the binding mechanism in amino acid identification level, the utilizations of everted rat gut sac model for absorption, and the involvement of cellular absorption channels and pathway are strongly recommended as novelty in this review. This review makes a novel contribution to the literature by the comprehensive prospects for the research and development of food-derived mineral supplements.

Arginine Biosynthesis Pathway Found to Play a Key Role in the Neuroprotective Effect of Liu-Wei-Luo-Bi (LWLB) Granules in Diabetic db/db Mice with Peripheral Neuropathy Using an Untargeted Metabolomics Strategy.

Aim: Liu-Wei-Luo-Bi (LWLB) granules was a Chinese compound prescription for treating diabetic peripheral neuropathy (DPN). The aim of this study was to investigate the effect of LWLB granules on diabetic mice with peripheral neuropathy and to elucidate the potential mechanism based on an untargeted metabolomics approach. Methods: One hundred forty db/db mice were randomly divided into seven groups: the Control group, DPN group, Mudan (MD) granules group, Epalrestat (Epa) group, and the LWLB low, medium, or high dose (LW-l, LW-m, or LW-h) group. After 12 weeks of treatment, body weight, blood glucose, mechanical pain threshold, motor conduction velocity (MCV), sensory conduction velocity (SCV), and Pathological Organization of the Sciatic and Caudal Nerves in mice were measured. Serum samples were collected for untargeted metabolomics analysis using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) and multivariate statistics. Disease-related pathways were screened out with function enrichment analyses of candidate biomarkers. Results: LWLB granules can improve the peripheral neuropathy of type 2 diabetic mice with peripheral nerve conduction disorders, mainly through significantly improving the nerve conduction velocity (P < 0.05) and lowering the mechanical pain threshold (P < 0.05). A total of 43 metabolites were identified as potential biomarkers related to the therapeutic effect of LWLB granules. Fifty, 4, and 26; 23, 4, and 22; and 24, 1, and 16 biomarkers were discovered in the LW-l, LW-m, and LW-h groups at the 4th, 6th, and 12th weeks, respectively. Five, three, seven, five, and four metabolic pathways were found in MD, Epa, LW-l, LW-m, and LW-h groups, respectively. The arginine biosynthesis pathway is the overlapping pathway in LW-l, LW-m, and LW-h groups. Conclusion: LWLB granules have an obvious neuroprotective effect on diabetic peripheral neuropathy, and the metabolism mechanism of LWLB is mainly related to the arginine biosynthesis pathway on diabetic db/db mice with peripheral neuropathy.

Characterization of Oyster Protein Hydrolysate-Iron Complexes and their In Vivo Protective Effects against Iron Deficiency-Induced Symptoms in Mice.

Iron is one of the trace mineral elements, and iron deficiency is a common phenomenon that negatively influences human health. Food-derived iron supplements were considered excellent candidates for improving this syndrome. In this work, oyster-protein hydrolysates (OPH) and ferrous chloride successfully formed the OPH-Fe complex (6 mg/mL, 40 °C, 30 min), where the main binding sites involved were the carboxyl and amino groups. The OPH-Fe complex showed no obvious changes in the secondary structure, while the iron changed the morphological appearance and also showed fluorescence quenching, an ultraviolet shift, and an increase in size distribution. The OPH-Fe complex showed better dynamic absorption of iron (64.11 µmol/L) than ferrous sulfate (46.90 µmol/L), and the medium dose had better protective effects against iron-deficiency anemia in vivo. Three representative peptides (DGKGKIPEE, FAGDDAPRA, and VLDSGDGVTH) that were absorbed intact were identified. This experiment provided a theoretical foundation for further study of the digestion and absorption of the OPH-Fe complex.

Iron overload promotes intervertebral disc degeneration via inducing oxidative stress and ferroptosis in endplate chondrocytes.

Iron overload is a common phenomenon in the elderly population. Many clinical studies have indicated an association between iron overload and the incidence and pathological progression of intervertebral disc degeneration (IVDD). However, the role and underlying mechanism by which iron participates in the progression of IVDD has not yet been reported. In the present study, we aimed to elucidate the connection between iron overload and IVDD, and explore the underlying mechanisms of disease. Firstly, a clinical epidemiology study was conducted and revealed that iron overload is an independent risk factor for human IVDD. To elucidate the role of iron overload in IVDD, an iron overload mouse model was established, and we observed that iron overload promoted IVDD and cartilage endplate degeneration in a dose dependent manner. Endplate chondrocytes were further isolated and treated with FAC to mimic iron overload in vitro. Excess iron significantly promoted mineralization of endplate chondrocytes in addition to their degeneration via oxidative stress. Moreover, a high dose of excess iron promoted chondrocytes ferroptosis. An iron chelator (DFO), an antioxidant (NAC) and a ferroptosis inhibitor (Fer-1) demonstrated effective inhibition of endplate chondrocyte degeneration induced by iron overload, and our in vivo studies further demonstrated that DFO, NAC and Fer-1 could rescue high dose iron-induced IVDD and cartilage endplate calcification. In conclusion, our results indicate that iron overload is strongly associated with the onset and development of IVDD via oxidative stress and ferroptosis. Inhibiting oxidative stress or ferroptosis could therefore be promising therapeutic strategies for IVDD induced by iron overload.

Evaluation of enhancing effect of soybean oil on polymalic acid production by Aureobasidium pullulans HA-4D.

Polymalic acid (PMA) is a water-soluble polyester produced by Aureobasidium pullulans. In this study, the physiological response of A. pullulans after the addition of vegetable oils was investigated. Soybean oil (SBO) is pivotal for shortening fermentation time and achieving high PMA titer. With the addition of 1% (w/v) SBO, the titer and productivity of PMA was, respectively, increased by 34.2% and 80%. SBO acted as a chemical stimulatory agent rather than a carbon source, the enhancement on PMA production was attributed to the component of fatty acid. SBO induced the dimorphism (yeast-like cells and mycelia) of A. pullulans, in vitro enzyme activities indicated that the TCA oxidative branch for malic acid synthesis might be strengthened, which could generate more ATP for PMA synthesis, and the assay of intracellular energy supply validated this deduction. This study provided a new sight for recognizing the regulatory behavior of SBO in A. pullulans.

Estimating the pollutant loss rate based on the concentration process and landscape unit interactions: a case study of the Dianchi Lake Basin, Yunnan Province, China.

The landscape analysis model establishes a quantitative relationship between landscape patterns and pollution processes. The spatial heterogeneity within and between landscapes affects the pollutant transmission process and originates from the superposition effect of terrestrial geographical and morphological characteristics. This study aimed to develop a new method to estimate the pollutant loss rate. From the perspective of the flow process of pollutants entering a water body, the interaction between each landscape unit and adjacent unit during pollutant migration was simulated along the pollutant migration flow path. The role of pollutants affected by external forces in the process of migration could be divided into "promoting" and "hindering." Four indices were proposed to simulate the pollutant loads entering the lake. The linear coefficients between the load of the pollutants chemical oxygen demand (CODCr), ammoniacal nitrogen (NH3-N), total nitrogen (TN), and total phosphorus (TP) entering the lake and the pollutant load emission weighted by the upstream and downstream confluence ratio index were 0.930, 0.835, 0.925, and 0.795, respectively, and the non-linear variance explanation coefficients were 87.70%, 87.50%, 87.60%, and 84.70%, respectively. When the surface resistance was integrated into the index as a parameter, the linear and nonlinear correlation coefficients were significantly improved. The linear coefficients were 0.952, 0.897, 0.919, and 0.939, respectively, and the non-linear variance explanations were 99.00%, 97.30%, 95.10%, and 97.30%, respectively. The spatial distribution of landscape surface resistance reflects the spatial movement trend of pollutants from different sources. The indices characterizing the promoting and hindering effects could be integrated to calculate the loss rate of pollutant load entering the lake from landscape units at different locations in the basin space.

Progress in Catalytic Pyrolysis of Oil Shale.

This paper briefly describes the research status of oil shale pyrolysis technology and the main factors affecting oil shale pyrolysis, with emphasis on four kinds of commonly used catalysts: The effects of natural minerals, metal compounds, molecular sixes, and supported catalysts on the pyrolysis of oil shale were discussed. The changes of the pyrolysis mechanism and product composition of oil shale with the addition of different catalysts were discussed. Finally, the development direction of preparation of new catalysts was discussed, in order to provide a prospect for the development and utilization of unconventional and strategic alternative energy resources around the world.

Unraveling the Formation Mechanism of a Hybrid Zr-Based Chemical Conversion Coating with Organic and Copper Compounds for Corrosion Inhibition.

Environmentally friendly chromate-free, zirconium (Zr)-based conversion coating is a promising green technology for corrosion protection. Additives in the surface treatment provide critical functionalities and performance improvements; however, mechanistic understanding as to how the additives influence the coatings remains unclear. In this study, a new organic-inorganic hybrid Zr-based conversion coating combines copper (Cu) compounds and polyamidoamine (PAMAM), taking advantage of the complementary nature of organic and inorganic additives. A multimodal approach combining electron and X-ray characterization is applied to study the interaction of Cu2+ and PAMAM and the resulting impacts on coating formation. Adding PAMAM changed the surface morphology, thickness, distribution of Cu in the clusters, and void formation of the coatings. High PAMAM (100-200 ppm) leads to little conversion coating formation, and low PAMAM (0-25 ppm) shows voids formation under the coatings. Moreover, PAMAM incorporates in the coating in the form of a PAMAM-Cu complex with a higher concentration toward the surface, providing an organic layer at the surface of the coating. X-ray absorption near-edge structure (XANES) spectroscopy shows the difference between the conventional and the hybrid coating treatments in an alkaline solution to simulate the E-coat process, suggesting the contribution of PAMAM in the enhanced chemical stability in an alkaline environment. Therefore, an intermediate range of addition of PAMAM (50 ppm) is optimal to (1) avoid excessive voids formation, (2) promote some Cu cluster formation and thus enhance the Zr-based coating formation, and (3) incorporate organic components into the coating to improve the adhesion of the subsequent coatings. Overall, this work furthers our knowledge on the formation mechanism of an effective and environmentally friendly hybrid conversion coating for corrosion inhibition, demonstrating a critical processing-structure-property relationship. This study will benefit future development of green and effective surface treatment technology.

Photosensitizer-Doped and Plasma Membrane-Responsive Liposomes for Nuclear Drug Delivery and Multidrug Resistance Reversal.

Clinically approved doxorubicin (Dox)-loaded liposomes (e.g., Doxil) guarantee good biosafety, but their insufficient nuclear delivery of Dox (<0.4%) after cellular uptake significantly hampers their final anticancer efficacy. Here, we report that simply doping protoporphyrin IX (PpIX, a commonly used hydrophobic photosensitizer) into the lipid bilayers of Dox-loaded liposomes (the resultant product is termed PpIX/Dox liposomes) is a feasible way to promote the nuclear delivery of Dox. This facile strategy relies on a unique property of PpIX-it presents considerably higher affinity for the real plasma membrane over its liposomal carrier, which drives the doped PpIX molecules to detach from the liposomes when encountering cancer cells. We demonstrate that this process can trigger the efficient release of the loaded Dox molecules and allow them to enter the nuclei of MCF-7 breast cancer cells without being trapped by lysosomes. Regarding the drug-resistant MCF-7/ADR cells, the aberrant activation of the efflux pumps in the plasma membranes expels the internalized Dox. However, we strikingly find that the robust drug resistance can be reversed upon mild laser irradiation because the photodynamic effect of PpIX disrupts the drug efflux system (e.g., P-glycoprotein) and facilitates the nuclear entry of Dox. As a proof-of-concept, this PpIX doping strategy is also applicable for enhancing the effectiveness of cisplatin-loaded liposomes against both A549 and A549/DDP lung cancer cells. In vivo experimental results prove that a single injection of PpIX/Dox liposomes completely impedes the growth of MCF-7 tumors in nude mice within 2 weeks and, in combination with laser irradiation, can synergistically ablate MCF-7/ADR tumors. Biosafety assessments reveal no significant systemic toxicity caused by PpIX/Dox liposomes. This work exemplifies a facile method to modulate the subcellular fate of liposomal drugs and may inspire the optimization of nanopharmaceuticals in the near future.

Improving the oxidative stability and lengthening the shelf life of DHA algae oil with composite antioxidants.

Based on various antioxidant mechanisms, four kinds of antioxidants including ascorbyl palmitate (AP), vitamin E (VE), phytic acid (PA) and one of the polyphenols (antioxidant of bamboo leaves, tea polyphenol palmitate or tea polyphenols (TP)) were used in combination to improve oxidative stability of docosahexaenoic acid (DHA) algae oil. To achieve the best effect, the formulations and mixture ratios of the antioxidant combinations were optimized. The effects were monitored by peroxide value, thiobarbituric acid-reactive substances, acid value, free radicals, Rancimat induction time and fatty acid composition of DHA algae oil undergoing accelerated storage. Finally, the DHA algae oil containing 80 mg/kg AP, 80 mg/kg VE, 40 mg/kg PA and 80 mg/kg TP had the highest oxidative stability. Furthermore, the shelf life of DHA algae oil containing the optimum composite antioxidant was predicted by using accelerated shelf life testing coupled with Arrhenius model, which was 3.80-fold longer than the control sample.

From perinuclear to intranuclear localization: A cell-penetrating peptide modification strategy to modulate cancer cell migration under mild laser irradiation and improve photothermal therapeutic performance.

Tumor metastasis is a key cause that leads to the failure of cancer treatment. Inhibition of metastasis, rather than the simple removal of the primary tumor, is critical to the survival improvement. Here, we report a cell-penetrating peptide-modification strategy to realize substantial perinuclear accumulation and subsequent near-infrared (NIR) laser-triggered nuclear entry of palladium nanosheets (Pd NSs) for inhibition of cancer cell metastasis and photothermal cancer therapy. Specifically, it was found that the cell-penetrating peptide TAT-modified Pd NSs (abbreviated as Pd-TAT) mainly accumulated in the perinuclear region and showed the enhanced endocytosis and reduced efflux compared with the counterpart without TAT modification. On the one hand, Pd-TAT could inhibit cell migration and invasion. It was proposed that Pd-TAT located in the perinuclear region could promote the overexpression of lamin A/C proteins (related with nuclear stiffness) and increase the mechanical stiffness of the nucleus. More importantly, the introduction of NIR laser irradiation with a laser density of 0.3 W/cm2 (below the permitted value 0.329 W/cm2 for skin exposure) significantly enhanced the inhibitory effect of Pd-TAT on cancer cell migration, which might be due to the increased nuclear stiffness caused by the enhanced nuclear entry of Pd-TAT under the effect of mild laser-induced local hyperthermia in the perinuclear region. On the other hand, the increased nuclear entry of Pd-TAT under NIR laser irradiation greatly enhanced their photothermal therapeutic efficacy due to the susceptibility of the nucleus to hyperthermia. Taken together, the Pd-TAT-based and laser-promoted perinuclear-to-intranuclear localization strategy allows us to not only destroy the primary tumor more effectively, but also inhibit cancer metastasis more persistently.

Isolation and identification of zinc-chelating peptides from sea cucumber (Stichopus japonicus) protein hydrolysate.

BACKGROUND: Zinc is known to play an essential role in the biological activities in the human body. In this study, a zinc-chelating peptide (ZCP) produced by Alcalase-assisted hydrolysis of the body wall of sea cucumber was isolated and identified. The ZCP was purified stepwise by ultrafiltration, anion-exchange chromatography, and gel filtration chromatography, in conjunction with ultraviolet-visual (UV-visual) spectrophotometry, which was used to analyze each purified fraction. RESULTS: Analysis of the purified ZCP revealed that its zinc-chelating ability was 33.31%. Analysis of isothermal titration calorimetry suggested that the binding of ZCP and zinc (N ≈ 2) was endothermic, with weak binding affinity. Fourier transform infrared spectroscopy spectra (FTIR) indicated that carboxylic and amide groups in ZCP were the primary binding sites of Zn. Sequencing the result by ultra-performance liquid chromatography-quadrupole/time of flight mass spectrometry (UPLC-Q-TOF-MS/MS) showed that a representative ZCP had the sequence WLTPTYPE with a molecular weight of 1005.5 Da. CONCLUSION: These results provide a promising foundation for the production of zinc supplements from sea-cucumber-derived ZCPs. © 2019 Society of Chemical Industry.

Effects of natural phenolics on shelf life and lipid stability of freeze-dried scallop adductor muscle.

Effects of natural phenolics on the shelf life of dried scallop adductor muscle predicted by accelerated shelf life testing (ALST) combined with Arrhenius model were investigated. This allows the food industries to reliably and rapidly determine the shelf life of dried shellfish species treated with antioxidants. The shelf life of dried scallop adductor muscle treated with antioxidants of bamboo leaves (AOB) and tea polyphenols (TP) was more than 1.70-fold that of dried control scallop adductor muscle. Thus, the highly nutritional value of dried scallop adductor muscle, based on its lipid constituents, is maintained during storage. OXITEST method further confirmed the improvement of lipid stability of antioxidant treated dried scallop adductor muscle by protecting polyunsaturated fatty acids, especially eicosapentaenoic and docosahexaenoic acids, against autoxidation. Moreover, the natural phenolics employed effectively limited lipid oxidation by breaking the autoxidative chain reaction and/or inhibiting free radical formation in dried scallop adductor muscle during storage.

Methyl-ß-cyclodextrin potentiates the BITC-induced anti-cancer effect through modulation of the Akt phosphorylation in human colorectal cancer cells.

Methyl-ß-cyclodextrin (MßCD) is an effective agent for the removal of plasma membrane cholesterol. In this study, we investigated the modulating effects of MßCD on the antiproliferation induced by benzyl isothiocyanate (BITC), an ITC compound mainly derived from papaya seeds. We confirmed that MßCD dose-dependently increased the cholesterol level in the medium, possibly through its removal from the plasma membrane of human colorectal cancer cells. The pretreatment with a non-toxic concentration (2.5 mM) of MßCD significantly enhanced the BITC-induced cytotoxicity and apoptosis induction, which was counteracted by the cholesterol supplementation. Although BITC activated the phosphoinositide 3-kinase (PI3K)/Akt pathway, MßCD dose-dependently inhibited the phosphorylation level of Akt. On the contrary, the treatment of MßCD enhanced the phosphorylation of mitogen activated protein kinases, but did not potentiate their BITC-induced phosphorylation. These results suggested that MßCD might potentiate the BITC-induced anti-cancer by cholesterol depletion and thus inhibition of the PI3K/Akt-dependent survival pathway. Abbreviations: CDs: cyclodextrins; MßCD: methyl-ß-cyclodextrin; ITCs: isothiocyanates; BITC: benzyl isothiocyanate; PI3K: phosphoinositide 3-kinase; PDK1: phosphoinositide-dependent kinase-1; MAPK: mitogen activated protein kinase; ERK1/2: extracellular signal-regulated kinase1/2; JNK: c-Jun N-terminal kinase; PI: propidium iodide; FBS: fatal bovine serum; TLC: thin-layer chromatography; PBS(-): phosphate-buffered saline without calcium and magnesium; MEK: MAPK/ERK kinase; PIP2: phosphatidylinositol-4,5-bisphosphate; PIP3: phosphatidylinositol-3,4,5-trisphosphate.

Effect of combined chondroitinase ABC and hyperbaric oxygen therapy in a rat model of spinal cord injury.

The present study aimed to investigate the effect of combined hyperbaric oxygen (HBO) and chondroitinase ABC (ChABC) enzyme therapy in a rat model of spinal cord injury (SCI) and to explore the underlying mechanisms. A total of 48 healthy male Wistar rats were randomly divided into six groups: Sham, SCI, vehicle, HBO, ChABC enzyme and HBO + ChABC. Excluding the sham group, SCI was established in rats by a clip compression injury and rats subsequently received HBO treatment for 2 weeks with or without an intraspinal injection of 0.1 U/µl ChABC. Neuromotor functions were examined using the Basso­Beattie­Bresnahan locomotor rating scale and the inclined plane assessment at baseline and for 4 weeks following SCI establishment. Superoxide dismutase (SOD) and malondialdehyde (MDA) levels were also measured, in addition to the expression of glycogen synthase kinase­3ß (GSK3ß) and aquaporin 4 (AQP4). Results revealed that combined HBO and ChABC treatment significantly improved neuromotor function compared with the HBO or ChABC treatments alone. HBO and/or ChABC treatment significantly increased SOD and decreased MDA levels, as well as GSK3ß expression, compared with the sham and SCI rats. The combined HBO and ChABC treatment significantly inhibited SCI­induced AQP4 expression, but ChABC alone did not. Functional recovery in the HBO + ChABC group was significantly increased compared with the HBO or ChABC groups. These results indicate that combined HBO and ChABC treatment is more effective in treating SCI than either therapy alone.

Hybrid MoSe2-indocyanine green nanosheets as a highly efficient phototheranostic agent for photoacoustic imaging guided photothermal cancer therapy.

Phototheranostic technology based on photoacoustic imaging (PAI) and photothermal therapy (PTT) is emerging as a powerful tool for tumor theranostic applications. For effective tumor eradication, a novel PAI/PTT theranostic nanoagent with an excellent optical absorption and photothermal capability is highly desired. Herein, we present a new PAI/PTT nanohybrid named sMoSe2-ICG NSs by covalently conjugating aminated indocyanine green (ICG) onto a single layer of molybdenum selenide nanosheets (sMoSe2 NSs). We first validate the sMoSe2-ICG NS agent for the PAI and PTT effect in vitro and then use it for highly-sensitive PAI guided highly efficient tumor PTT in vivo. The sMoSe2-ICG NS hybrid possesses several advantages for PAI/PTT applications: (1) the sMoSe2-ICG NSs have strong absorbance in the broad near-infrared (NIR) region, enabling a highly efficient PAI/PTT theranostic effect and the selection of the most widely used excitation wavelength of 808 nm for PTT; (2) the photothermal ability of ICG in sMoSe2-ICG NSs is augmented due to ICG aggregation induced fluorescence quenching and the re-absorbance of ICG fluorescence by sMoSe2 NSs, which further enhances the PAI/PTT theranostic effect. (3) The characteristic absorption peak of sMoSe2-ICG NSs is red-shifted compared to free ICG, resulting in a higher PAI signal-to-noise ratio (SNR) in vivo. Thus, combined with the good stability, high biocompatibility and minimal toxicity properties, the obtained sMoSe2-ICG NSs hybrid has bright prospects for use in future PAI/PTT clinical applications.

Effects of polyprenols from pine needles of Pinus massoniana on ameliorating cognitive impairment in a D-galactose-induced mouse model.

Cognitive deficiency and oxidative stress have been well documented in aging and in neurodegenerative disorders such as Alzheimer's disease. In this study, we assessed the therapeutic effect of polyprenols on D-galactose-induced cognitive impairment in mice by testing on of behavioral and cognitive performance. In order to explore the possible role of polyprenols against D-galactose-induced oxidative damages, we assessed various biochemical indicators. Chronic administration of D-galactose (150 mg/kg·d, s.c.) for 7 weeks significantly impaired cognitive performance (both in step-through passive and active avoidance tests) and locomotor activity (in open-field test) and the ability of spatial learning and memory (in Morris water maze test) compared with the control group. The results revealed that polyprenols treatment for 2 weeks significantly ameliorated model mice's cognitive performance and oxidative defense. All groups of polyprenols enhanced the learning and memory ability in step-through passive and active avoidance tests, locomotor activity in open-field test, and the ability of spatial learning and memory in Morris water maze test. Furthermore, high and middle level of polyprenols significantly increased total antioxidative capacity (T-AOC), glutathione peroxidase (GSH-Px), super oxide dismutase (SOD) activity, neprilysin (NEP), and ß-site AßPP cleaving enzyme 1 (BACE1) expression, while nitric oxide (NO), nitric oxide synthase (NOS) activity, malondialdehyde (MDA) concentration, and the level of Aß1-42 and presenilin 1 (PS1) were decreased. Polyprenols have a significant relieving effect on learning, memory, and spontaneous activities in a D-galactose-induced mouse model and ameliorates cognitive impairment and biochemical dysfunction in mice. In summary, we have demonstrated that polyprenols may ameliorate memory and cognitive impairment via enhancing oxidative defense and affecting generation and dissimilation of Aß-related enzymes, suggesting that polyprenols represent a novel drug for treating Alzheimer's disease.

Effects of dl-praeruptorin A on interleukin-6 level and Fas, bax, bcl-2 protein expression in ischemia-reperfusion myocardium.

AIM: To investigate the effects of dl-praeruptorin (Pd-Ia) on interleukin-6 (IL-6) level and apoptosis-related protein expression in ischemia-reperfusion myocardium. METHODS: Left anterior descending coronary artery was subjected to 30 min ischemia followed by 120 min reperfusion in open-chest anesthetized rats. Serum IL-6 level was measured by radioimmunoassay. Apoptosis-related protein Fas, bax, and bcl-2 expression was detected by immunohistochemistry and computer image analysis system. Infiltration of neutrophils was observed using Hematoxylin-Eosin staining under optical microscope. RESULTS: Pd-Ia 2.0 mg/kg iv lowered serum IL-6 level and Fas, bax, bcl-2 expression under conditions with hypotension and without changes on heart rate, but increased the ratio of bcl-2/bax. There existed a close linearity and positive correlation between IL-6 level and Fas, bax, bcl-2 expression. Whereas, the infiltration of neutrophils was mild. CONCLUSION: Pd-Ia elicits a novel target in the therapeutic prevention of postischemic cardiomyocyte death. The reason might be associated with modulating the expression of some immediate-early genes including IL-6, Fas, bax, and bcl-2 in ischemia-reperfusion myocardium.