UPLC-MS/MS-Based Target Screening of 90 Phosphodiesterase Type 5 Inhibitors in 5 Dietary Supplements.

The aim of individuals consuming health supplements is to attain a robust state through nutritional regulation. However, some unscrupulous manufacturers, motivated by profit, fraudulently incorporate drugs or unauthorized components with therapeutic effects into the product for instant product performance enhancement. The long-term use of these products may inadvertently inflict harm on human health and fail to promote nutritive healthcare. The illegal inclusion of these substances is prevalent in kidney-tonifying and sexuality-enhancing products. Developing effective analytical methods to identify these products and screen for illegal added ingredients can effectively prevent such products from reaching and remaining on the market. A target screening method for the detection and quantification of 90 phosphodiesterase type 5 inhibitors (PDE-5is) in 5 kinds of health products was developed and validated. The type of dietary supplements varied from tablets, capsules, and protein powder to wine and beverages. Sample preparation was completed with a one-step liquid phase extraction. The screening process of 90 PDE-5is was done efficiently within 25 min by ultra-high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) using the dynamic multiple reaction monitoring (dMRM) technique. The LODs of 90 PDE-5is were detected at levels ranging from 25 to 85 ng/g or ng/mL. This novel targeting methodology was effective and can be applied to routine market supervision. Among 286 batches of samples, 8 batches were found to be positive. Three kinds of PDE-5is were first detected in healthy products. The screening method demonstrated herein will be a promising and powerful tool for rapid screening of PDE-5is.

Neuroprotective Effect of α-Lipoic Acid against Aß25-35-Induced Damage in BV2 Cells.

The prevalence of Alzheimer's disease (AD) is significantly increasing due to the aging world population, and the currently available drug treatments cannot cure or even slow its progression. α-lipoic acid (LA) is a biological factor widely found in spinach and meat and can dissolve in both lipid and aqueous phases. In medicine, LA has been shown to reduce the symptoms of diabetic polyneuropathy, acute kidney injury, cancers, and some metabolism-related diseases. This study to proves that α-lipoic acid (LA) can stabilize the cognitive function of patients with Alzheimer's disease (AD). BV2 cells were divided into control, LA, Aß25-35, and LA + Aß25-35 groups. Cell growth; IL-6, IL-1ß, TNF-α, IFN-γ, SOD, GPx, CAT, ROS, NO, and iNOS secretion; Wnt-related proteins; cell apoptosis; and cell activation were examined. Here, we found that LA could effectively repress apoptosis and changes in the morphology of microglia BV2 cells activated by Aß25-35, accompanied by the inhibition of the inflammatory response induced by Aß25-35. The Wnt/ß-catenin pathway is also involved in preventing Aß25-35-induced cytotoxicity in microglia by LA. We found an inhibitory effect of LA on microglia toxicity induced by Aß25-35, suggesting that a combination of anti-inflammatory and antioxidant substances may offer a promising approach to the treatment of AD.

The neuroprotective effects of alpha-lipoic acid on an experimental model of Alzheimer's disease in PC12 cells.

With the growth of the aging population, the prevalence of Alzheimer's disease (AD) has increased and influenced the work and daily life of AD patients, imposing a heavy burden on society and the patients' families. AD is a progressive disease with a long duration, and the pathogenesis is very complicated. Here, we found that alpha-lipoic acid (LA), an endogenous, naturally synthesized compound, could attenuate amyloid beta fragment (Aß25-35 )-induced PC12 cell toxicity. Aß25-35 treatment largely decreased the viability of PC12 cells, increased reactive oxygen species (ROS) levels, and increased the percentage of apoptotic cells, which were accompanied by changes in the expression of the apoptosis-related genes. Further, the Wnt pathway was inactivated, and the expression of Wnt pathway-related proteins such as Frizzled2, GSK3ß, and phosphorylated GSK3ß were dysregulated after Aß25-35 treatment. LA efficiently attenuated Aß25-35 -induced PC12 cell apoptosis and downregulated the phosphorylation-mediated degradation of ß-catenin as well as GSK3ß. Our results demonstrate that LA rescues Aß25-35 -induced neurocytotoxicity through the Wnt-ß-catenin pathway.

A chronic oral toxicity study of marine collagen peptides preparation from chum salmon (Oncorhynchus keta) skin using Sprague-Dawley rat.

Due to the increased consumption of marine collagen peptides preparation (MCP) as ingredients in functional foods and pharmaceuticals, it was necessary to carry out safety requirements in the form of an oral chronic toxicity assessment. In order to define the oral chronic toxicity of MCP, a 24-month feeding study of MCP was carried out. Sprague-Dawley (S-D) rats at the age of four-week of both sexes were treated with MCP at the diet concentrations of 0%, 2.25%, 4.5%, 9% and 18% (wt/wt). The actual food intake and bodyweight of the individual animals were recorded periodically until sacrifice. Blood and urine samples were collected for serum chemistry evaluations and urinalysis. Throughout the experimental period, there was no toxicologically significant difference between the vehicle and MCP-treated animals with respect to the survival rate, body weight, food consumption, urinalysis, clinical biochemistry parameter and relative organ weight in either sex. Moreover, incidences of non-neoplastic lesions in MCP-treated groups did not significantly increase compared with the control group. Under the present experimental conditions, no higher risk of chronic toxic effects was observed in MCP-treated rats at the diet concentrations of 2.25%, 4.5%, 9% and 18% (wt/wt) than in the rats fed with basal rodent diet.

Antioxidant effect of a marine oligopeptide preparation from chum salmon (Oncorhynchus keta) by enzymatic hydrolysis in radiation injured mice.

Marine oligopeptide preparation (MOP) obtained from Chum Salmon (Oncorhynchus keta) by the method of enzymatic hydrolysis, has been found to possess a radioprotective property through stimulation of the radiation-induced immunosuppression. The current study aimed to further investigate the free radicals scavenging and antioxidant effects of MOP in radiation injured mice. Female ICR mice (6-8 weeks old) were randomly divided into 5 groups, i.e., blank control, irradiation control and MOP (0.225, 0.450 and 1.350 g/kg body weight) plus an irradiation-treated group. The result revealed that MOP significantly increased the white blood cell counts after irradiation, and lessened the radiation-induced oxidative damage. These effects may be caused by augmentation of the activities of antioxidant enzymes, such as SOD and GSH-Px, reduction of the lipid peroxidation (MDA level) in liver, and protection against radiation-induced apoptosis. Therefore, we propose that MOP be used as an ideal antioxidant to alleviate radiation-induced oxidation damage in cancer patients.

Protective effect of a marine oligopeptide preparation from chum salmon (Oncorhynchus keta) on radiation-induced immune suppression in mice.

BACKGROUND: A marine oligopeptide preparation (MOP) obtained from Chum Salmon (Oncorhynchus keta) by the method of enzymatic hydrolysis, has been found to enhance the innate and adaptive immunities through stimulation of the secretion of cytokines in mice. The current study aimed to further investigate the protective effect of MOP on radiation-induced immune suppression in mice. RESULTS: Female ICR mice (6-8 weeks old) were randomly divided into three groups, i.e. blank control, irradiation control and MOP (1.350 g kg(-1) body weight) plus irradiation-treated group. MOP significantly increased the survival rate and prolonged the survival times for 30 days after irradiation, and lessened the radiation-induced suppression of T- or B-lymphocyte proliferation, resulting in the recovery of cell-mediated and humoral immune functions. This effect may be produced by augmentation of the relative numbers of radioresistant CD(4) (+) T cells, enhancement of the level of immunostimulatory cytokine, IL-12, reduction of the level of total cellular NF-κB through the induction of IκB in spleen and inhibition of the apoptosis of splenocytes. CONCLUSION: We propose that MOP be used as an ideal adjuvant therapy to alleviate radiation-induced injuries in cancer patients.

Marine collagen peptides prepared from chum salmon (Oncorhynchus keta) skin extend the life span and inhibit spontaneous tumor incidence in Sprague-Dawley Rats.

To observe the effects of marine collagen peptides (MCPs) prepared from chum salmon (Oncorhynchus keta) skin on life span and spontaneous tumor incidence, Sprague-Dawley rats were fed diets supplemented with MCP at concentrations of 0%, 2.25%, 4.5%, and 9% (wt/wt) from the age of 4 weeks until natural death. There were 40 rats in each group (male:female ratio = 1:1). The results showed that the MCP did not significantly influence body weight or food consumption of rats of either sex throughout the life span; it did dose-dependently inhibit the age-related decrease in the activities of antioxidant enzymes and the age-related increase in the levels of lipid peroxidation product in both sexes. MCP notably increased the mean life span, the life span of the last 30% of the survivors, and the maximal life span; it decreased overall spontaneous tumor incidence of both sexes with significance in the 4.5% and 9% MCP-treated male groups and 9% MCP-treated female group. Compared to the control group, the incidence of death from tumors was decreased in MCP groups in comparison with the control group of both sexes. Therefore, we concluded that MCPs dose-dependently increase life span and decrease spontaneous tumor incidence in Sprague-Dawley rats. Moreover, the antioxidative property of MCPs may be responsible for the increased life span and protection against tumor development.

[Effects of marine collagen peptides on blood glucose and lipid metabolism in hyperinsulinemic rats].

OBJECTIVE: To observe the effects of marine collagen peptides (MCPs) on blood glucose and lipid metabolism in hyperinsulinemic rats. METHODS: Male SD rats fed with high fat diet for 4 months were used to establish a hyperinsulinemic model. Thirty two hyperinsulinemic rats were divided into four groups according to body weight and serum insulin level, namely hyperinsulinemic control (HIC) group and 3 Marine Collagen Peptides treated groups with 8 rats in each group. Another 8 healthy male SD rats fed with basic diet were used as negative control (NC). Rats in MCPs groups were treated by intragastric way with MCPs at the dose of 0.225 g/kg bw, 0.45 g/kg bw and 1.35 g/kg bw respectively for 8 weeks, while rats in HIC and NC groups were treated with tap water in the same manner. During the test period, rats in HIC and MCPs groups were fed with high fat diet sequentially, while rats in NC group were fed with basic diet. Fasting serum glucose (GLU), insulin (INS) and lipids were assayed respectively before and after MCPs treatment. Oral glucose tolerance test, antioxidase activity, serum malondialdehyde (MDA) levels and the ultrastructure of islet beta cell were carried out at the end of the experiment. RESULTS: After 8 weeks of treatment, compared with HIC group, fasting INS, TC and TG of all three MCPs-treated groups decreased obviously, while fasting GLU level lowered significantly in 0.225 g/kg bw and 1.35 g/kg bw MCPs groups. Moreover, GLU level at 0.5 h, 2 h and the area under blood sugar curve in OGTT were evidently lower in 0.45 g/kg bw and 1.35 g/kg bw MCPs groups. Besides, serum SOD activity increased in all MCPs groups, and serum GSH-Px activity elevated obviously in 1.35 g/kg bw MCPs group, while serum MDA reduced. Finally, the ultrastructural impairment of islet resulted from high fat diet was improved evidently by 1.35 g/kg bw MCPs. CONCLUSION: MCPs was effective in improving glucose and lipid metabolism in hyperinsulinemic rats induced by high fat diet.

The protective effects of long-term oral administration of marine collagen hydrolysate from chum salmon on collagen matrix homeostasis in the chronological aged skin of Sprague-Dawley male rats.

To investigate the long-term effects of marine collagen hydrolysate (MCH) from Chum Salmon skin on the aberrant collagen matrix homeostasis in chronological aged skin, Sprague-Dawley male rats of 4-wk-old were orally administrated with MCH at the diet concentrations of 2.25% and 4.5% for 24 mo. Histological and biochemical analysis revealed that MCH had the potential to inhibit the collagen loss and collagen fragmentation in chronological aged skin. Based on immunohistochemistry and western blot analysis, collagen type I and III protein expression levels in MCH-treated groups significantly increased as compared with the aged control group. Furthermore, quantitative real-time polymerase chain reaction and western blot analysis showed MCH was able to increase the expressions of procollagen type I and III mRNA (COL1A2 and COL3A1) through activating Smad signaling pathway with up-regulated TGF-ßRII (TßRII) expression level. Meanwhile, MCH was shown to inhibit the age-related increased collagen degradation through attenuating MMP-1 expression and increasing tissue inhibitor of metalloproteinases-1 expression in a dose-dependent manner. Moreover, MCH could alleviate the oxidative stress in chronological aged skin, which was revealed from the data of superoxide dismutase activity and the thiobarbituric acid reactive substances level in skin homogenates. Therefore, MCH was demonstrated to have the protective effects on chronological skin aging due to the influence on collagen matrix homeostasis. And the antioxidative property of MCH might play an important role in the process.

Long-term ginsenoside administration prevents memory impairment in aged C57BL/6J mice by up-regulating the synaptic plasticity-related proteins in hippocampus.

Memory impairment is considered to be one of the most prominent consequences of aging. Deterioration of memory begins in advance of old age in animals, including humans. Thus, it is extremely important to prevent memory decline for increasing healthy aging. Ginsenoside, the effective ingredient of ginseng, has been reported to have a neuron beneficial effect, but the preventive role on memory impairment and the underlying mechanisms have not been well determined. In the present study, C57BL/6J mice aged 12 months were chronically treated with ginsenoside 100mg/kg per day for 8 months. Placebo-treated aged mice, young and adult ones (4- and 8-month-old, respectively) were used as controls. The efficacious effect of ginsenoside was manifested in the amelioration of memory impairment in aged mice by Morris water maze and step-down tests. Compared with aged control group, the plasticity-related proteins including phospho-N-methyl-d-aspartate receptor1 (NMDAR1), phospho-calcium-calmodulin dependent kinase II (CaMK II), phospho-PKA catalytic beta subunit (PKA Cbeta), phospho-cAMP-response element binding protein (CREB) and brain derived neurotrophic factor (BDNF) in hippocampus significantly increased in ginsenoside treated group. These findings suggest that ginsenoside is effective on the prevention of age-related memory impairment, and the up-regulation of plasticity-related proteins in hippocampus may be one of the mechanisms.

Effects of cod bone gelatin on bone metabolism and bone microarchitecture in ovariectomized rats.

Several animal studies have showed that gelatin may be effective for minimizing bone loss in OVX rats with established osteopenia. To gain insight into how cod bone gelatin administration affects bone loss after ovariectomy, studies were carried out focusing on bone quality and the molecular mechanisms. Eighty-four female rats were ovariectomized, 12 sham-operated, divided into six groups of 12 each and treated one week after ovariectomy either with vehicle or cod bone gelatin (0.375, 0.75, 1.5, 3, 6 mg/kg body weight) for 90 days. Bone densitometry, microCT analysis, real-time PCR analysis and biochemical analysis were used at the end of the study. After 90 days, BMD of proximal tibia and femoral neck decreased in OVX rats, whereas the loss of BMD in those regions was prevented at 3 g/kg (P<0.05). However, the BMD of midshaft femurs showed no significant differences. BV/TV, Tb.N. and Tb.Th. in the 3 g/kg group were, respectively, 30.4% (P<0.05), 145.5% (P<0.05) and 81.5% (P<0.05) higher than in the OVX group. A significant decrease was detected in urine CTX, NTX and DPD, suggesting decreased bone resorption. Treatment with 3 g/kg and 6 g/kg cod bone gelatin attenuated the increase in serum IL-1beta, IL-6 and TNF-alpha observed in the OVX group. Real-time PCR showed significantly decreased levels of mRNA expression for RANKL at the dosage of 6 g/kg and the RANKL/OPG mRNA ratio in the 3 g/kg and 6 g/kg group significantly decreased compared to the OVX group (P<0.05). In conclusion, our data confirmed that the cod bone gelatin treatment at 3 g/kg is effective in the prevention of estrogen deficient bone loss by modulating the expression of RANKL and OPG and suppressing the release of proinflammatory cytokines.

Long-term ginsenoside consumption prevents memory loss in aged SAMP8 mice by decreasing oxidative stress and up-regulating the plasticity-related proteins in hippocampus.

Ginsenoside, the effective component of ginseng, has been reported to have a neuron protective effect, but the preventive effect on Alzheimer's disease (AD) related memory loss and the underlying mechanisms have not been well determined. The senescence-accelerated mouse (SAM) is a useful model of AD-related memory impairment. In the present study, SAMP8 mice aged 4 months were chronically treated with ginsenoside (3 dose groups were given ginsenoside in drinking water for 7 months). The three groups were treated with ginsenoside 50, 100 and 200 mg/kg per day, respectively. Placebo-treated aged mice and young ones (4 months old) were used as controls. In addition, SAMR1 mice were used as "normal aging" control. The beneficial role of ginsenoside was manifested in the prevention of memory loss in aged SAMP8 mice. The optimal dose of ginsenoside is 100 or 200 mg/kg per day. In ginsenoside treated groups, the Abeta level markedly decreased in hippocampus and antioxidase level significantly increased in serum. In addition, the plasticity-related proteins in hippocampus significantly increased in the two ginsenoside treated groups. The plasticity-related proteins were checked in the present study including postsynaptic density-95 (PSD-95), phosphor-N-methyl-D-aspartate receptor 1 (p-NMDAR1), phospho-calcium-calmodulin dependent kinase II (p-CaMKII), phospho-protein kinase A Catalyticbeta subunit (p-PKA Cbeta) and protein kinase Cgamma subunit (PKCgamma), phospho-CREB (p-CREB) and brain derived neurotrophic factor (BDNF) etc. These findings suggest that the increase of antioxidation and up-regulation of plasticity-related proteins in hippocampus may be one of the mechanisms of ginsenoside on the memory loss prevention in aged SAMP8 mice.

Ethanol exposure induces differential microRNA and target gene expression and teratogenic effects which can be suppressed by folic acid supplementation.

BACKGROUND: microRNAs (miRNAs) play an important role in development and are associated with birth defects. Data are scant on the role of miRNAs in birth defects arising from exposure to environmental factors such as alcohol. METHODS: In this study, we determined the expression levels of 509 mature miRNAs in fetal mouse brains with or without prenatal ethanol exposure using a miRNA microarray technique, verified by northern blot and PCR. Mouse embryos in culture were used to examine the effect of ethanol treatment on expression of the putative target genes of miR-10a (Hoxa1 and other Hox members) at mRNA and protein level. Open field and Morris water maze tests were also performed at post-natal day 35. RESULTS: Ethanol treatment induced major fetal teratogenesis in mice and caused mental retardation in their offspring, namely lower locomotor activity (P < 0.01) and impaired task acquisition. Of the screened miRNAs, miR-10a, miR-10b, miR-9, miR-145, miR-30a-3p and miR-152 were up-regulated (fold change >1.5) in fetal brains with prenatal ethanol exposure, whereas miR-200a, miR-496, miR-296, miR-30e-5p, miR-362, miR-339, miR-29c and miR-154 were down-regulated (fold change <0.67). Both miR-10a and miR-10b were significantly up-regulated (P < 0.01) in brain after prenatal ethanol exposure. Ethanol treatment also caused major obstruction in the development of cultured embryos, with down-regulated Hoxa1. Co-incubation with folic acid blocked ethanol-induced teratogenesis, with up-regulated Hoxa1 and down-regulated miR-10a (P < 0.01). CONCLUSIONS: The study provided new insights into the role of miRNAs and their target genes in the pathogenesis of fetal alcohol syndrome.

[The study on the immunomodulating effect of marine protein peptides in mice].

OBJECTIVE: To observe the effects of marine protein peptide (MPP) on immunomodulating in mice and its possible mechanism. METHODS: Female ICR mice (6-8 weeks old) were administered the MPP for 4 weeks with the dose of 0.22 g/kgBW, 0.45 g/kgBW and 1.35 g/kgBW. Spleen and thymus were weighted and cell-mediated immune functions, humoral immune functions, phagocytic functions of mononuclear phagocyte, NK cell activity assays, the T cell subpopulation of the spleen tissue by the flow cytometer and the concentrations of cytokines in serum by cytometric bead array were examined. RESULTS: The capacity of lymphocyte proliferation induced by Con A (0.33 +/- 0.21), DTH response (0.36 +/- 0.11) mm in MPP 0.22 g/kgBW group were significantly increased in comparison with these values in control group (0.15 +/- 0.10) and (0.21 +/- 0.10)mm, respectively, P < 0.05. IgM-PFC number of MPP 0.22 g/kgBW group (1.64 +/- 0.06), 0.45 g/kgBW group (1.59 +/- 0.05) and 1.35 g/kgBW group (1.56 +/- 0.10) were higher than those in control group (1.38 +/- 0.10), P < 0.01; and the level of serum HC50 of MPP 0.22 g/kgBW group (141.00 +/- 23.00) and 0.45 g/kgBW group (130.40 +/- 33.20) were greater than the control (100.30 +/- 19.40) , P < 0.01. The activity of NK cells in MPP 0.22 g/kgBW group (1.672 +/- 0.142) was significantly elevated in comparison with this value in control group (1.392 +/- 0.182), P < 0.05. The percentage of CD4 T helper (Th) cell in spleen of MPP 0.22 g/kgBW group (32.84 +/- 3.776)% and 0.45 g/kgBW group (32.42 +/- 3.507) % was higher than those in control group (25.06 +/- 0.354) %, P < 0.05. The concentrations of IL-2 in serum of MPP 0.22 g/kgBW group 181.06 pg/ml, 0.45 g/kgBW group 94.84 pg/ml and 1.35 g/kgBW group 102.61 pg/ml were higher than those in control group 0.50 pg/ml, P < 0.05; and the level of IL-5 of MPP 0.22 g/kgBW group (38.31) pg/ml was greater than the control 0.50 pg/ml, P < 0.05. Nevertheless, no obvious effects on weight increasing, the ratio of immune organ and body weight and phagocytosis capacity were observed in our study. CONCLUSION: MPP could improve the immune functions in mice, and might be by the mechanism of enhancing the function of Th cells stimulating the secretion of Th1 and Th2 type cell cytokines.

[The lipid-lowering and antioxidative effects of marine collagen peptides].

OBJECTIVE: To determine the relative molecular mass of marine collagen peptides (MCPs) and investigate the effects of MCPs on serum lipids, anti-oxidative enzymes and malondialdehyde (MDA) in hyperlipidemic rats. METHODS: Sephadex G-25, high performance liquid chromatography (HPLC) and matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS) methods were used to determine the relative molecular mass of MCPs. Then 50 healthy male SD rats were divided into 5 groups, which were normal control (NC) group, hyperlipidemic model control (HC) group and 1.0, 3.0, 9.0 g/kgbw MCPs groups, MCPs were orally administered by gavage to rats in MCPs group for 45 consecutive days (2 ml/100 kgbw per day), and the control rats were given vehicle only, all animals (except NC rats) were fed with a high fat diet composed of 79% basic diet, 10% lard, 10% yolk powder and 1% cholesterol. The levels of serum lipids, the content of MDA and activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) in serum were measured. RESULTS: The levels of serum total cholesterol (TC) in 1.0, 3.0, 9.0 g/kgbw MCPs groups were 1.89 +/- 0.29, 2.07 +/- 0.39 and 1.99 +/- 0.29 mmol/L respectively, each of which was significantly lower than that in HC group (3.37 +/- 0.24 mmol/L); low-density lipoprotein cholesterol (LDL-C) levels in 1.0, 3.0, 9.0 g/kgbw MCPs groups were 0.83 +/- 0.16, 1.01 +/- 0.35 and 0.91 +/- 0.26 mmol/L respectively, each of which was significantly lower than that in HC group(2.20 +/- 0.34 mmol/L); triglyceride (TG) levels in 3.0 and 9.0 g/kgbw MCPs groups (0.90 +/- 0.15 and 0.86 +/- 0.12 mmol/L) were reduced significantly compared with that in HC group (1.18 +/- 0.18 mmol/L); MDA level in 9.0 g/kgbw MCPs group was 7.1 +/- 4.1 nmol/ml, which was significantly lower than that in HC group ( 15.9 +/- 9.9 nmol/ml); and atherogenic index (AI) in hyperlipidemic rats fed with 1.0, 3.0, 9.0 g/kgbw MCPs were 1.14 +/- 0.22, 1.16 +/- 0.27 and 0.99 +/- 0.31 respectively, each of which was significantly lower than that in HC group (2.27 +/- 0.55). The activities of SOD in 1.0, 3.0, 9.0 g/kgbw MCPs groups (218.6 +/- 33.2, 242.7 +/- 21.4 and 242.1 +/- 44.8 U/ml) were obviously increased compared with that in HC group (119.7 +/- 47.8 U/ml), and anti-atherogenic index (AAI) were also increased significantly (0.47 +/- 0.04, 0.47 +/- 0.06, 0.51 +/- 0.09 vs 0.31 +/- 0.05). CONCLUSION: MCPs should have antioxidative and lipid-lowering effects, and might play a preventive role in hyperlipidemia and atherogenesis.

[Effects of marine collagen peptide on delaying the skin aging].

OBJECTIVE: To investigate the protective effect of marine collagen peptides (MCPs) on the skin of aged mice induced by D-galactose. METHODS: Subchronic toxicity study was conducted while D-galactose induced subacute aging model was established. D-galactose dose of 0.125 g/kg body weight was intraperitoneally injected daily for 90 days. Marine collagen peptide 0.225, 0.450, 1.350 g/kg body weight were administered by oral gavage. Superoxide dismutase (SOD), catalase (CAT) activity and malondialdehyde (MDA) content in blood serum were measured, along with cutaneous histopathology examination. RESULTS: Epidermal thickness was significantly higher in MCPs treated group. Number and activity of fibroblast in MCPs treated dermis was increased prominently. The activity of SOD in 0.225, 0.450, 1.350 g/kgbw MCPs treated groups were 455.52 +/- 11.39, 460.15 +/- 18.09, 468.59 +/- 27.25 U/ml respectively, each of which was significantly higher than that in model control group; the activity of serum CAT in 0.225, 1.350 g/kgbw MCPs treated groups (21.33 +/- 4.82, 21.69 +/- 1.68 U/ml) were obviously increased compared with that in model control group (17.14 +/- 2.81 U/ml); MDA level in 0.450, 1.350 g/kgbw MCPs treated groups were 5.67 +/- 0.93, 5.76 +/- 1.02 nmol/ml respectively, each of which was significantly lower than that in model control group (7.63 +/- 1.37 nmol/ml). CONCLUSIONS: The results showed that MCPs might play a protective role on skin aging by improving the activity of antioxidant.

[Effects of Di(2-ethylhexyl) phthalate(DEHP) on mouse embryos development in vitro].

Whole-embryo culture was used as the model system to study the effects of Di(2-ethylhexyl) phthalate (DEHP) on mice embryonic development. Mouse embryos (8.5 days old) during the period of organogenesis were exposed to immediately centrifugal serum (ICS) with DEHP at concentrations of: 0, 12.5, 25, 50, 100, 200 mg/L for 48 hours. The results showed that DEHP could cause damage to embryonic development and there was a significant dose-response and dose-effect relationship between concentration of DEHP and its embryonic developmental toxicity. At higher levels ((25 mg/L), DEHP could induce embryonic developmental retardation and significant morphological abnormalities. Abnormal heart, neural system, arch and small limb-bud development were the most common gross morphological abnormalities. But there was no significant increase in the number of nonviable embryos. The finding suggested that DEHP can induce developmental toxicity in vitro at higher level and teratogenicity may be the major effect.

[Teratogenicity of bisphenol A on post-implanted rat and mouse embryos: an in vitro study].

In order to evaluate the developmental toxicity of BPA and to investigate the possible mechanism of it in vitro, whole embryo culture was used for the study. The embryos that removed from mother mice on gestational 8.5d (GD8.5) and mother rats on gestational 9.5d (GD9.5) were cultured immediately in centrifugal serum (ICS) with a series of concentrations of 0, 40, 60, 80, 100 mg/L of BPA for 48 h to evaluate the embryo development and morphological differentiation. The results showed that the BPA inhibited the development of embryos in vitro and there was a dose-response relationship between concentrations of BPA. At high level (> or = 60 mg/L), BPA could delayed the growth and cardiac tube differentiation of visceral yolk sac (VYS), and induced various embryo defects, including abnormal neural system, arch, optic, flexion and small limb bud, etc. It is concluded that at high level, BPA had toxicity to mice and rat embryos in vitro. The damage on structure and function of VYS might be part of teratogenic mechanisms of BPA.

[Study on the developmental toxicity of Bisphenol A by using micromass culture in vitro].

The micromass culture of Wistar rat embryo limb bud cells was used to investigate the characteristic of developmental toxicity of Bisphenol A (BPA) and its mechanism in vitro. The results showed that BPA inhibited both proliferation and differentiation of rat limb bud cells in vitro. The high level of BPA appeared to be cytotoxic to Wistar rat embryo limb bud cells in culture and inhibited the clone formation with dose-response relationship. The concentration of BPA for IP50 and ID50 were 38.74 mg/L and 27.93 mg/L respectively. According to Renaults' teratogenic criteria, BPA belonged to a positive teratogen. And the data suggested that the specific inhibition of cell proliferation and differentiation might be one of the mechanisms of high level BPA.