Effects of Red Liriope platyphylla on NGF secretion ability, NGF receptor signaling pathway and gamma-secretase components in NSE/hAPPsw transgenic mice expressing Alzheimer's Disease / 한국실험동물학회지

Liriope platyphylla (LP) has long been regarded as a curative herb for the treatment of diabetes, asthma, and neurodegenerative disorders. To examine the therapeutic effects of Red LP (RLP) manufactured by steaming process on neurodegenerative disorders, significant alteration of the key factors influencing Alzheimer's Disease (AD) was detected in NSE/hAPPsw transgenic (Tg) mice after RLP treatment. The concentration of nerve growth factor (NGF) in serum increased in RLP-treated NSE/hAPPsw Tg mice compared with vehicle-treated Tg mice. However, downstream effectors of the NGF receptor signaling pathway, including TrkA and p75NTR proteins, were suppressed in RLP-treated NSE/hAPPsw Tg mice. Especially, Tg mice showed decreased levels of TrkA, p75NTR, and RhoA expression. Production of Abeta-42 peptides was lower in RLP-treated NSE/hAPPsw Tg mice than in vehicle-treated Tg mice. Further, analysis of gamma-secretase components showed that Abeta-42 peptide expression was downregulated. Of the four components, the expression of APH-1 and Nicastrin (NCT) decreased in RLP-treated NSE/hAPPsw Tg mice, whereas expression of PS-2 and Pen-2 was maintained or increased within the same group. Overall, these results suggest that RLP can help relieve neurodegenerative diseases, especially AD, through upregulation of NGF secretion ability, activation of NGF signaling pathway, downregulation of Abeta-42 peptide deposition, and alteration of gamma-secretase components.

Aqueous extract of Liriope platyphylla, a traditional Chinese medicine, significantly inhibits abdominal fat accumulation and improves glucose regulation in OLETF type II diabetes model rats / 한국실험동물학회지

Liriope platyphylla is a medical herb that has long been used in Korea and China to treat cough, sputum, neurodegenerative disorders, obesity, and diabetes. The aims of this study were to determine the antidiabetic and antiobesity effects of aqueous extract of L. platyphylla (AEtLP) through glucose and lipid regulation in both pre-diabetes and obesity stage of type II diabetes model. Two concentrations of AEtLP were orally administrated to OLETF (Otsuka Long-Evans Tokushima Fatty) rats once a day for 2 weeks, after which changes in glucose metabolism and fat accumulation were measured. Abdominal fat mass dramatically decreased in AEtLP-treated OLETF rats, whereas glucose concentration slightly decreased in all AEtLP-treated rats. However, compared to vehicle-treated OLETF rats, only AEtLP10 (10% concentration)-treated OLETF rats displayed significant induction of insulin production, whereas AEtLP5 (5% concentration)-treated OLETF rats showed a lower level of insulin. Although serum adiponectin level increased in only AEtLP5-treated rats, significant alteration of lipid concentration was detected in AEtLP5-treated OLETF rats. Expression of Glut-1 decreased in all AEtLP-treated rats, whereas Akt phosphorylation increased only in AEtLP10-treated OLETF rats. Furthermore, the pattern of Glut-3 expression was very similar with that of Glut-1 expression, which roughly corresponded with the phosphorylation of c-Jun N-teminal kinase (JNK) and p38 in the mitogen-activated protein kinase pathway. Therefore, these findings suggest that AEtLP should be considered as a therapeutic candidate during pre-diabetes and obesity stage capable of inducing insulin secretion from pancreatic beta-cells, glucose uptake in liver cells, as well as a decrease in fat and lipid accumulation.

Altered expression of gamma-secretase components in animal model of major depressive disorder induced by reserpine administration / 한국실험동물학회지

Altered expression of neurotrophic factors as well as neuroinflammation is commonly associated with Major depressive disorder (MDD) and Alzheimer's disease (AD). To investigate whether or not reserpine-induced MDD affects the expression of AD-related proteins, the expression of gamma-secretase components and substrate were measured in brains of ICR mice following reserpine treatment for 15 days. In active avoidance test, total response time and peak slightly increased in the 2 mg/kg reserpine (RSP2)-treated group compared to vehicle-treated group (P<0.05). Expression and phosphorylation of MKP-1, which is a key factor in MDD pathology, were both higher in the RSP2-treated group than the vehicle- and 1 mg/kg reserpine (RSP1)-treated groups (P<0.02). Furthermore, full-length expression of amyloid precursor protein (APP) was enhanced in the RSP1 and RSP2-treated groups compared to the vehicle-treated group, whereas expression of gamma-secretase components decreased (P<0.03). Among the three components of the gamma-secretase complex, nicastrin protein underwent the largest decrease in expression, as detected by Western blotting (P<0.03). Therefore, the data presented here provide additional evidence about the pathological correlation between MDD and AD.

Monitoring of antibiotic resistance in bacteria isolated from laboratory animals / 한국실험동물학회지

The drug resistance of microorganisms isolated from laboratory animals never treated with antibiotics is being reported consistently, while the number of laboratory animals used in medicine, pharmacy, veterinary medicine, agriculture, nutrition, and environmental and health science has increased rapidly in Korea. Therefore, this study examined the development of antimicrobial resistance in bacteria isolated from laboratory animals bred in Korea. A total of 443 isolates (7 species) containing 5 Sphingomonas paucimobilis, 206 Escherichia coli, 60 Staphylococcus aureus, 15 Staphylococcus epidermidis, 77 Enterococcus faecalis, 27 Citrobacter freundii, 35 Acinetobacter baumannii were collected from the nose, intestine, bronchus and reproductive organs of ICR mice and SD rats. Of these species, Acinetobacter baumannii and Enterococcus faecalis showed significant antimicrobial resistance according to the minimum inhibition concentration (MIC) in E-test. In case of Acinetobacter baumannii, several isolates showed MIC values 16-128 microg/mL for cefazolin and cefoxitin, and higher resistance (128-512 microg/mL) to nitrofurantoin than that of standard type. Resistance to cefazolin, cefoxitin and nitrofurantoin was detected in 17.14, 20.00, and 8.57% of the Acinetobacter baumannii isolates, respectively. In addition, 44.1% of the Enterococcus faecalis isolates collected from the laboratory animals were resistant to oxacillin concentration of 16-32 microg/mL range, while MIC value of standard type was below oxacillin concentration of 6 microg/mL. These results suggest that in rodent species of laboratory animals, Acinetobacter baumannii are resistance to cefazolin, cefoxitin and nitrofurantoin, whereas those of Enterococcus faecalis were resistance to oxacillin.

Overexpression of Insulin Degrading Enzyme could Greatly Contribute to Insulin Down-regulation Induced by Short-Term Swimming Exercise / 한국실험동물학회지

Exercise training is highly correlated with the reduced glucose-stimulated insulin secretion (GSIS), although it enhanced insulin sensitivity, glucose uptake and glucose transporter expression to reduce severity of diabetic symptoms. This study investigated the impact of short-term swimming exercise on insulin regulation in the Goto-Kakizaki (GK) rat as a non-obese model of non-insulin-dependent diabetes mellitus. Wistar (W/S) and GK rats were trained 2 hours daily with the swimming exercise for 4 weeks, and then the changes in the metabolism of insulin and glucose were assessed. Body weight was markedly decreased in the exercised GK rats compare to their non-exercised counterpart, while W/S rats did not show any exercise-related changes. Glucose concentration was not changed by exercise, although impaired glucose tolerance was improved in GK rats 120 min after glucose injection. However, insulin concentration was decreased by swimming exercise as in the decrease of GSIS after running exercise. To identify the other cause for exercise-induced insulin down-regulation, the changes in the levels of key factors involved in insulin production (C-peptide) and clearance (insulin-degrading enzyme; IDE) were measured in W/S and GK rats. The C-peptide level was maintained while IDE expression increased markedly. Therefore, these results showed that insulin down-regulation induced by short-term swimming exercise likely attributes to enhanced insulin clearance via IDE over-expression than by altered insulin production.

Peroxiredoxin I regulates the component expression of gamma-secretase complex causing the Alzheimer's disease / 한국실험동물학회지

Peroxiredoxin I (Prx I) is a member of the peroxiredoxins (Prxs) family, which are antioxidant enzymes that regulate various cellular process via intracellular oxidative signal pathways. In order to investigate the correlation between Prx I and the gamma-secretase complex, which causes Alzheimer's disease (AD), the expression level of Prx I was firstly evaluated in an animal model for AD. NSE/hPen-2 transgenic (Tg) mice, which were used as animal model in this study, showed a high level of Pen-2 expression and accumulation of Abeta-42 peptides in the hippocampus of brain. The expression level of Prx I was significantly higher on the mRNA and protein level in the brain of this model, while not change in Prx VI expression was observed. Furthermore, to verify the effect of Prx I on the gamma-secretase components in vitro, the expression level of these components was analyzed in the Prx I transfectants. Of the components of the gamma-secretase complex, the expression of PS-2 and Pen-2 was lower in the transfectants overexpressing Prx I compared to the vector transfectants. However, the expression of APP, NCT and APH-1 did not change in Prx I transfectants. Therefore, these results suggested that the expression of Prx I may be induced by the accumulation of Abeta-42 peptides and the overexpression of Prx I in neuroblastoma cells may regulate the expression of gamma-secretase components.

Effects of Steaming Time and Frequency for Manufactured Red Liriope platyphylla on the Insulin Secretion Ability and Insulin Receptor Signaling Pathway / 한국실험동물학회지

In oriental medicine, Liriope platyphylla (LP) has long been regarded as a curative herb useful for the treatment of diabetes, asthma, and neurodegenerative disorders. The principal objective of this study was to assess the effects of steaming time and frequency for manufactured Red LP (RLP) on insulin secretion ability and insulin receptor signaling pathway. To achieve our goal, several types of LPs manufactured under different conditions were applied to INS cells and streptozotocin (STZ)-induced diabetic ICR mice, after which alterations in insulin concentrations were detected in the culture supernatants and sera. The optimal concentration for the investigation of insulin secretion ability was found to be 50 ug/mL of LP. At this concentration, maximum insulin secretion was observed in the INS cells treated with LP extract steamed for 3 h (3-SLP) with two repeated steps (3 h steaming and 24 h air-dried) carried out 9 times (9-SALP); no significant changes in viability were detected in any of the treated cells. Additionally, the expression and phosphorylation levels of most components in the insulin receptor signaling pathway were increased significantly in the majority of cells treated with steaming-processed LP as compared to the cells treated with LP prepared without steaming. With regard to glucose transporter (GLUT) expression, alterations of steaming time induced similar responses on the expression levels of GLUT-2 and GLUT-3. However, differences in steaming frequency were also shown to induce dose-dependent responses in the expression level of GLUT-2 only; no significant differences in GLUT-3 expression were detected under these conditions. Furthermore, these responses observed in vitro were similarly detected in STZ-induced diabetic mice. 24-SLP and 9-SALP treatment applied for 14 days induced the down-regulation of glucose concentration and upregulation of insulin concentration. Therefore, these results indicated that the steaming processed LP may contribute to the relief of diabetes symptoms and should be regarded as an excellent candidate for a diabetes treatment.

The Symptoms of Atopic Dermatitis in NC/Nga Mice Were Significantly Relieved by the Water Extract of Liriope platyphylla / 한국실험동물학회지

Atopic dermatitis is an well-known skin disease showing inflammatory, chronically relapsing, non-contagious and pruritic symptoms. The aims of this study were to investigate the effects of Liriope platyphylla (LP) on atopic dermatitis of NC/Nga mice. To achieve this, NC/Nga mice were treated with four different conditions including vehicle, phthalic anhydride (PA), PA+5% LP and PA+10% LP, and the changes of immune-related factors were detected after 2 weeks. The pathological phenotypes of atopic dermatitis such as erythema, ear thickness, edema, scab and discharge were significantly decreased in PA+10% LP cotreated groups compare to PA treated group. Also, the weight of lymph node and thymus in immune organs were gradually decreased in LP treated groups, while the weight of spleen was slightly increased in same group. Furthermore, toluidine blue staining analysis, a method used to specifically identify the mast cell, showed that the decrease of master cell infiltration into the dermis were statistically observed in PA+5% LP and PA+10% LP5% cotreated groups. Especially, the decrease of IgE concentration was detected only PA+10% LP cotreated group, although this level was maintained in PA+5% LP cotreated group. Therefore, these results suggested that the water extracts of LP may contribute the relieve of atopic dermatitis symptoms and be considered as an excellent candidate for a atopic dermatitis-therapeutic drug.