• 동의생리병리학회지
• /
• 제24권6호
• /
• pp.1034-1041
• /
• 2010

The oriental medicine Jangwonhwan, which is a boiled extract of 12 medicinal herbs/mushroom, has been prescribed for patients with cognitive dysfunction and it is originally from the Korean medical text, DonguiBogam(amnesia chapter). Recently, a modified recipe of Jangwonhwan (LMK02-Jangwonhwan) consisting of seven medicinal plants/mushroom, was shown to reduce ${\beta}$-amyloid deposition in the brain of Tg-APPswe/PS1dE9 mouse model of Alzheimer disease. The toxicity of LMK02 was investigated in SD rats by oral repeated adminstration for 4 weeks and we tried to determine test does for 13 weeks repeated study. Quality control of tablet form of LMK02 was established by estimating indicative components, Ginsenoside Rg3 of Red Ginseng and Decursin of Angelicagigas Nakai. The toxicity of LMK02 was investigated in 6 weeks old specific pathogen free (SPF) Sprageu-Dawley rats by oral administration. Each test group were consist of 5 male and 5 female and they received doses of 500, 1,000 and 2,000 mg/kg/day of test substance for 4 weeks. The clinical signs, death rate, body weight, food consumption, ophthalmic examination, urinalysis, hematological and serum biochemistry, organ weight and pathological changes were examined and compared with those of control group. Urinalysis : We observed increase of PRO(p<0.01), SG(p<0.01) in female rats of 1,000 mg/kg/day and 2,000 mg/kg/day(p<0.01). Also, we observed increase of pH and KET in female rats of 1,000 mg/kg/day(p<0.05) and of 2,000 mg/kg/day(p<0.01). WBC in female rats in 1,000 mg/kg/day and 2,000 mg/kg/day were on increase. Hematological test : We observed increase of MCV in male rats of 250 mg/kg/day. (p<0.05) Serum biochemistry test : We found increase of CHO in female rats of 2,000 mg/kg/day(p<0.05). During the experimental period, there were no animals dead or moribund. There were no treatment related changes of general symptom, food and water consumption, organ weight and autopsy According to the results of 4-week repeated dose range finding study, the highest dose was established as 1000 mg/kg for 13-week repeated dose toxicity study and we determined to put 2 more groups by common ratio two.

• 동의생리병리학회지
• /
• 제22권5호
• /
• pp.1178-1191
• /
• 2008

This experiment was designed to investigate the effect of the SSJHT hot water extract & ultra-fine Powder on Alzheimer's Disease Model Induced by ${\beta}A$. The effects of the SSJHT hot water extract on expression of IL-1RA, $IL-1{\beta}$$, IL-6, IL-10, $TNF-{\alpha}$, NOS-II, COX-2 mRNA and production of $IL-1{\beta}$, IL-6, $TNF-{\alpha}$ in BV2 microglial cell line treated by lipopolysacchaide(LPS). The effects of the SSJHT hot water extract & ultra-fine powder on (1) the behavior (2) expression of $IL-1{\beta}$, $TNF-{\alpha}$, MDA, CD68, CD11b and AChE (3) and the infarction area of the hippocampus in Alzheimer's diseased mice induced with ${\beta}A$ were investigated. The SSJHT hot water extract suppressed the expression of $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$, NOS-II, COX-2 mRNA and increased IL-1RA, IL-10 in BV2 microglia cell line treated with LPS. The SSJHT hot water extract suppressed the production of $IL-1{\beta}$, IL-6, $TNF-{\alpha}$ significantly in BV2 microglial cell line treated with LPS. The SSJHT hot water extract & ultra-fine powder a significant inhibitory effect on the memory deficit was shown for the mice with Alzheimer's disease induced by ${\beta}A$ in the Morris water maze experiment, which measured step-through latency. The SSJHT hot water extract & ultra-fine powder suppressed the expression of $TNF-{\alpha}$$, $L-1{\beta}$ protein significantly in the microglial cell of mice with Alzheimer's disease induced by ${\beta}A$. The SSJHT hot water extract & ultra-fine powder reduced the MDA and suppressed the over-expression of CD68, CD11b in the mice with Alzheimer's disease induced by ${\beta}A$. The SSJHT hot water extract & ultra-fine powder significantly decreased AChE activity in the serum of the mice with Alzheimer's disease induced by ${\beta}A$. The SSJHT hot water extract & ultra-fine powder reduced infarction area of hippocampus. and controlled the injury of brain tissue in the mice with Alzheimer's disease induced by ${\beta}A$. The results suggest that the SSJHT hot water extract & ultra-fine powder may be effective for treatment of Alzheimer's disease. Investigation into the clinical use of the SSJHT hot water extract & ultra-fine powder for Alzheimer's disease is suggested for future research.

• 대한한의학회지
• /
• 제28권2호통권70호
• /
• pp.137-154
• /
• 2007

Objective : This experiment was designed to investigate the effect of the GYZB hot water extract & ultra-fine powder on the Alzheimer's disease model induced by amyloid ${\beta}$ protein (${\beta}A$). Method : We measured the effects of the GYZB hot water extract on expression of $IL-1{\beta}$, IL-6 mRNA and production of IL-6, $TNF-{\alpha}$ in the BV2 microglial cell line treated with lipopolysaccharide (LPS). The effects of the GYZB hot water extract & ultra-fine powder on (1) the behavior, (2) expression of $IL-1{\beta}$ and $TNF-{\alpha}$, (3) glucose in serum, (4) the infarction area of the hippocampus, and brain tissue injury in mice induced with Alzheimer's diseased by ${\beta}A$ were investigated. Results : The GYZB hot water extract suppressed the expression of $IL-1{\beta}$ and IL-6 mRNA and significantly suppressed the production of IL-6 and $TNF-{\alpha}$ in the BV2 microglial cell line treated with LPS. The GYZB hot water extract & ultra-fine powder showed a significant inhibitory effect on the memory deficit of the mice with Alzheimer's disease induced by ${\beta}A$ in the Morris water maze experiment, which measured stop-through latency and distance movement-through latency. The GYZB ultra-fine powder significantly suppressed the expression of $IL-1{\beta}$ and $TNF-{\alpha}$ protein, and the GYZB hot water extract significantly suppressed the expression of $TNF-{\alpha}$ protein in the microglial cell of mice with Alzheimer's disease induced by ${\beta}A$. The GYZB hot water extract & ultra-fine powder reduced the infarction area of hippocampus in the mice with Alzheimer's disease induced by ${\beta}A$. Conclusions : These results suggest that GYZB hot water extract & ultra-fine powder may be effective for the prevention and treatment of Alzheimer's disease. Investigation into the clinical use of GYZB for Alzheimer's disease is suggested for future research.

• Asian-Australasian Journal of Animal Sciences
• /
• 제31권4호
• /
• pp.595-606
• /
• 2018

Objective: The Fusarium mycotoxins of deoxynivalenol (DON) and zerolenone (ZEN) cause health hazards for both humans and farm animals. Therefore, the main intention of this study was to reveal DON and ZEN effects on the mRNA expression of pro-inflammatory cytokines and other immune related genes in the liver of piglets. Methods: In the present study, 15 six-week-old piglets were randomly assigned to the following three different dietary treatments for 4 weeks: control diet, diet containing 8 mg DON/kg feed, and diet containing 0.8 mg ZEN/kg feed. After 4 weeks, liver samples were collected and sequenced using RNA-Seq to investigate the effects of the mycotoxins on genes and gene networks associated with the immune systems of the piglets. Results: Our analysis identified a total of 249 differentially expressed genes (DEGs), which included 99 upregulated and 150 downregulated genes in both the DON and ZEN dietary treatment groups. After biological pathway analysis, the DEGs were determined to be significantly enriched in gene ontology terms associated with many biological pathways, including immune response and cellular and metabolic processes. Consistent with inflammatory stimulation due to the mycotoxin-contaminated diet, the following Kyoto encyclopedia of genes and genomes pathways, which were related to disease and immune responses, were found to be enriched in the DEGs: allograft rejection pathway, cell adhesion molecules, graft-versus-host disease, autoimmune thyroid disease (AITD), type I diabetes mellitus, human T-cell leukemia lymphoma virus infection, and viral carcinogenesis. Genome-wide expression analysis revealed that DON and ZEN treatments downregulated the expression of the majority of the DEGs that were associated with inflammatory cytokines (interleukin 10 receptor, beta, chemokine [C-X-C motif] ligand 9), proliferation (insulin-like growth factor 1, major facilitator superfamily domain containing 2A, insulin-like growth factor binding protein 2, lipase G, and salt inducible kinase 1), and other immune response networks (paired immunoglobulin-like type 2 receptor beta, Src-like-adaptor-1 [SLA1], SLA3, SLA5, SLA7, claudin 4, nicotinamide N-methyltransferase, thyrotropin-releasing hormone degrading enzyme, ubiquitin D, histone $H_2B$ type 1, and serum amyloid A). Conclusion: In summary, our results demonstrated that high concentrations DON and ZEN disrupt immune-related processes in the liver.

• Asian-Australasian Journal of Animal Sciences
• /
• 제29권3호
• /
• pp.343-351
• /
• 2016

Although the chemical, physical, and nutritional properties of bovine milk have been extensively studied, only a few studies have attempted to characterize milk-synthesizing genes using RNA-seq data. RNA-seq data was collected from 21 Holstein samples, along with group information about milk production ability; milk yield; and protein, fat, and solid contents. Meta-analysis was employed in order to generally characterize genes related to milk production. In addition, we attempted to investigate the relationship between milk related traits, parity, and lactation period. We observed that milk fat is highly correlated with lactation period; this result indicates that this effect should be considered in the model in order to accurately detect milk production related genes. By employing our developed model, 271 genes were significantly (false discovery rate [FDR] adjusted p-value<0.1) detected as milk production related differentially expressed genes. Of these genes, five (albumin, nitric oxide synthase 3, RNA-binding region (RNP1, RRM) containing 3, secreted and transmembrane 1, and serine palmitoyltransferase, small subunit B) were technically validated using quantitative real-time polymerase chain reaction (qRT-PCR) in order to check the accuracy of RNA-seq analysis. Finally, 83 gene ontology biological processes including several blood vessel and mammary gland development related terms, were significantly detected using DAVID gene-set enrichment analysis. From these results, we observed that detected milk production related genes are highly enriched in the circulation system process and mammary gland related biological functions. In addition, we observed that detected genes including caveolin 1, mammary serum amyloid A3.2, lingual antimicrobial peptide, cathelicidin 4 (CATHL4), cathelicidin 6 (CATHL6) have been reported in other species as milk production related gene. For this reason, we concluded that our detected 271 genes would be strong candidates for determining milk production.