• The Journal of Internal Korean Medicine
• /
• v.34 no.2
• /
• pp.134-146
• /
• 2013

Objectives : Auklandia Lappa (ALE) is one of the herbs used frequently to treat abdominal pain and diarrhea and reported anti-inflammatory activity by suppressing proinflammatory cytokines. This study was designed to investigate whether ALE could show protective activities on experimental colitis induced by dextran sulfate sodium (DSS) models. Methods : Colitis was induced by DSS in Balb/c mice. ALE 10, 30, 100 and 300 mg/kg were orally administered twice a day for 7 days in DSS model. Mice weight was measured daily. Scoring of clinical findings was measured every other day. Colon length, edema, fecal blood and histological damages were assessed at day 7 in DSS model. In histological analysis, we checked cryptal glands, surface epithelium, submucosa, transmural, stroma and scored degree of inflammatory cell damage by modified histological scoring. We also calculated cytokines concentrations including IFN-${\gamma}$, TNF-${\alpha}$, IL-6, IL-$1{\beta}$, IL-17, IL-23, IL-10 and TGF-${\beta}1$ by Biometric Multiplex Cytokine Profiling method. Results : ALE showed the protective effects on DSS-induced experimental colitis. ALE inhibited shortening of colon length and histological damages of colon does-dependently, but it did not inhibit weight loss. ALE also inhibited IFN-${\gamma}$ and IL-6 expression, and upregulated cytokines (IL-10, TGF-${\beta}1$) related to regulatory T cell differentiation and proliferation. Conclusions : The current results demonstrate the clinical utility of ALE in traditional medicine and indicate the possibility of potent drug development of inflammatory bowel diseases from natural products. Further investigations for exact mechanisms will be needed.

• Biomolecules & Therapeutics
• /
• v.6 no.4
• /
• pp.383-388
• /
• 1998

The present study was aimed to investigate the preventive effects of rebamipide on the multiple organ dysfunction in a rat model of circulatory shock induced by bacterial endotoxin (E. coli lipopolysaccharide; LPS) in comparison with that of methotrexate. Endotoxemia for 6 hours resulted in little change in the levels of hemoglobin and neutrophils. However, treatment with methotrexate decreased significantly the numbers of circulating neutrophils. Significant increases in serum alanine aminotransferase (ALT,958 $\pm$ 250 lU/L, p<0.001) and aspartate aminotransferase (AST, 1350 $\pm$ 295 lU/L, p<0.001) levels induced by endotoxemia were significantly decreased by rebamipide and methotrexate. The increased level of lactic acid dehydrogenase (LDH) by LPS (2850 $\pm$ 467 lU/L, p<0.05) was significantly inhibited by rebamipide, but not by methot.elate. The elevated serum creatinine (1.2$\pm$0.1, p.0.05) and urea levels (55.3$\pm$6.5 mg/dL, p.0.01) by LPS were also decreased by rebamipide, but not by methotrexate. In line with these results, the plasma concentration of tumor necrosis factor-$\alpha$ (TNF-7,167 $\pm$ 20 pg/mL) was significantly increased upon injection of endotoxin at 1 hour by 1570$\pm$100 pg/mL, and declined to 312$\pm$35 pg/mL at 6 hours. The TNF-$\alpha$ level at 6 hours was significantly decreased by rebamipide to 207$\pm$8 pg/mL (P<0.05). Taken together, it is summarized that rebamipide inhibits the development of multiple ogran dysfunction by inhibition of neutrophil activation in association with inhibition of TNF-$\alpha$ formation in a murine model of endotoxemia.

• Food Science of Animal Resources
• /
• v.35 no.1
• /
• pp.91-100
• /
• 2015

The present study was conducted to screen candidate probiotic strains for anti-inflammatory activity. Initially, a nitric oxide (NO) assay was used to test selected candidate probiotic strains for anti-inflammatory activity in cultures of the murine macrophage cell line, RAW 264.7. Then, the in vitro probiotic properties of the strains, including bile tolerance, acid resistance, and growth in skim milk media, were investigated. We also performed an in vitro hydrophobicity test and an intestinal adhesion assay using Caenorhabditis elegans as a surrogate in vivo model. From our screening, we obtained 4 probiotic candidate lactic acid bacteria (LAB) strains based on their anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated RAW 264.7 cell cultures and the results of the in vitro and in vivo probiotic property assessments. Molecular characterization using 16S rDNA sequencing analysis identified the 4 LAB strains as Lactobacillus plantarum. The selected L. plantarum strains (CAU1054, CAU1055, CAU1064, and CAU1106) were found to possess desirable in vitro and in vivo probiotic properties, and these strains are good candidates for further investigations in animal models and human clinical studies to elucidate the mechanisms underlying their anti-inflammatory activities.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• v.36 no.3
• /
• pp.177-185
• /
• 2010

Introduction: Epidermal growth factor receptor (EGFR) is expressed in human epithelial tumors including salivary cancers, and known to be correlated with tumor progression and poor clinical courses in some epithelial tumors. In this study, we determined the therapeutic effect of the anti-EGFR monoclonal antibody Erbitux (C225, cetuximab) in combination with the DNA topoisomerase I inhibitor irinotecan (CPT-11) on human salivary adenoid cystic carcinoma (SACC) cells growing in nude mice. Materials and Methods: At first, immunocytochemical analysis for the expression of EGFR and phosphorylated EGFR (pEGFR) on a human salivary ACC cell line (ACC3). To determine the in vivo effects of Erbitux and CPT-11, nude mice with orthotopic parotid tumors were randomized to receive intraperitoneal Erbitux (1 mg) two times per week, intraperitoneal Irinotecan (50 mg/kg) once per week, Erbitux plus CPT-11, or placebo. (control) Tumor volume and weight were measured. And mechanisms of in vivo activity of Erbitux and/or CPT-11 were determined by immunohistochemical/ immunofluorescent analyses. Results: Immunocytochemical staining of ACC3 demonstrated that EGFR was expressed and phosphorylated. CPT-11 inhibited ACC tumor growth in nude mice. Tumors of mice treated with CPT-11 and CPT-11 plus Erbitux exhibited increased tumor cell apoptosis and decreased microvessel density, which correlated with a decrease in the tumor volume in nude mice. But, CPT-11 seems not to be synergistic with Erbitux in our ACC3 model system. Conclusion: These results suggest that anti-EGFR monoclonal antibody and the DNA topoisomerase I inhibitor will be effective in the treatment of recurred or metastatic lesions of salivary ACC.

• Nutrition Research and Practice
• /
• v.12 no.2
• /
• pp.101-109
• /
• 2018

BACKGROUD/OBJECTIVES: The objective of this study was to investigate the effects of vitamin C on inflammation, tumor development, and dysbiosis of intestinal microbiota in an azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced inflammation-associated early colon cancer mouse model. MATERIALS/METHODS: Male BALB/c mice were injected intraperitoneally with AOM [10 mg/kg body weight (b.w)] and given two 7-d cycles of 2% DSS drinking water with a 14 d inter-cycle interval. Vitamin C (60 mg/kg b.w. and 120 mg/kg b.w.) was supplemented by gavage for 5 weeks starting 2 d after the AOM injection. RESULTS: The vitamin C treatment suppressed inflammatory morbidity, as reflected by disease activity index (DAI) in recovery phase and inhibited shortening of the colon, and reduced histological damage. In addition, vitamin C supplementation suppressed mRNA levels of pro-inflammatory mediators and cytokines, including cyclooxygenase-2, microsomal prostaglandin E synthase-2, tumor necrosis $factor-{\alpha}$, Interleukin $(IL)-1{\beta}$, and IL-6, and reduced expression of the proliferation marker, proliferating cell nuclear antigen, compared to observations of AOM/DSS animals. Although the microbial composition did not differ significantly between the groups, administration of vitamin C improved the level of inflammation-related Lactococcus and JQ084893 to control levels. CONCLUSION: Vitamin C treatment provided moderate suppression of inflammation, proliferation, and certain inflammation-related dysbiosis in a murine model of colitis associated-early colon cancer. These findings support that vitamin C supplementation can benefit colonic health. Long-term clinical studies with various doses of vitamin C are warranted.

• Biomolecules & Therapeutics
• /
• v.17 no.2
• /
• pp.168-174
• /
• 2009

Epilepsy is one of the most common neurological disorders, and topiramate (TPM) is one of the most effective drugs that can render patients seizure-free. The focus of the present study was to evaluate the immunological safety of TPM in a mouse model. We examined the in vitro effect of TPM on immune functions of BV2 microglial cells, RAW 264.7 macrophages, B cells, T cells, and dendritic cells. We also examined the in vivo effect of TPM on mouse immune organs, such as lymph node, spleen, and thymus. When cells were directly treated with TPM at concentrations from 1 to $30{\mu}g/ml$, TPM did not affect nitrite production by BV2 cells and macrophages, proliferation of B cells and T cells, or maturation of dendritic cells. In addition, TPM did not change the weight and cellularity of lymph nodes, spleen, and thymus in vivo at doses from 3 to 100 mg/kg injected i.p. into mice once a day for 4 consecutive days. These data showed that TPM, which is widely used as an anti-epileptic drug, is immunologically safe.

• Journal of Korean Medicine Rehabilitation
• /
• v.29 no.2
• /
• pp.101-113
• /
• 2019

Objectives Bogol-tang has clinically been used to protect joint cartilage and to treat osteoarthritis. Our objective was to study the protective effect of Bogol-tang extract (BGT) in functional impairment, behavioral disorders, cartilage loss and pathological changes in a monoiodoacetate (MIA)-induced murine osteoarthritis (OA) model and interleukin (IL)-$1{\beta}$ -treated primary rat chondrocytes. Methods Mouse knee joints were injected with MIA, a chemical that inhibits glycolysis and causes joint inflammation and matrix loss. MIA-OA induced mice orally administered BGT or acetaminophen (AAP) for 18 days by daily. Primary rat chondrocytes were pretreated with BGT or dexamethasone (DEX) and followed by co-incubation with IL-$1{\beta}$ (10 ng/mL). Results In MIA-OA mice model, BGT led to delayed response on hot plate analysis, and suppressed the cartilage loss and damages in joint tissues. BGT suppressed the elevated levels of inflammatory mediators, nitrite and $PGE_2$, the gene expression of matrix degrading enzymes, and extracellular-signal-regulated kinases 1/2 and c-JunN-terminal kinase phosphorylation in IL-$1{\beta}$-treated primary rat chondrocytes. Conclusions Our results suggest that BGT improve the knee joint function and delay the cartilage damages by anti-nociceptive, anti-inflammatory and ant-catabolic effects, which indicate BGT could be a potential candidate for osteoarthritis treatment.

• BMB Reports
• /
• v.55 no.12
• /
• pp.615-620
• /
• 2022

The murine leukemia virus-based semi-retroviral replicating vectors (MuLV-based sRRV) had been developed to improve safety and transgene capacity for cancer gene therapy. However, despite the apparent advantages of the sRRV, improvements in the in vivo transduction efficiency are still required to deliver therapeutic genes efficiently for clinical use. In this study, we established a gibbon ape leukemia virus (GaLV) envelope-pseudotyped semi-replication-competent retrovirus vector system (spRRV) which is composed of two transcomplementing replication-defective retroviral vectors termed MuLV-Gag-Pol and GaLV-Env. We found that the spRRV shows considerable improvement in efficiencies of gene transfer and spreading in both human glioblastoma cells and pre-established human glioblastoma mouse model compared with an sRRV system. When treated with ganciclovir after intratumoral injection of each vector system into pre-established U-87 MG glioblastomas, the group of mice injected with spRRV expressing the herpes simplex virus type 1-thymidine kinase (HSV1-tk) gene showed a survival rate of 100% for more than 150 days, but all control groups of mice (HSV1-tk/PBS-treated and GFP/GCV-treated groups) died within 45 days after tumor injection. In conclusion, these findings sug-gest that intratumoral delivery of the HSV1-tk gene by the spRRV system is worthy of development in clinical trials for the treatment of malignant solid tumors.

• Journal of Microbiology and Biotechnology
• /
• v.33 no.7
• /
• pp.915-925
• /
• 2023

Sarcopenia is defined as loss of muscle mass and strength due to aging. Recent studies show that sarcopenia may improve via the gut-muscle axis, suggesting that gut health may affect muscle phenotypes. In this study, we aimed to investigate the ability of Lactobacillus rhamnosus JY02 as a probiotic strain isolated from kimchi to alleviate sarcopenia. L. rhamnosus JY02-conditioned medium (CM) reduced dexamethasone (DEX)-induced myotube diameter atrophy and expression of muscle degradation markers (MuRF1 and atrogin-1) in C2C12 cells. The amelioration of sarcopenia was investigated by measuring body composition (lean mass), hand grip strength, myofibril size (using histological analysis), and mRNA and protein expression of muscle-related factors in a DEX-induced mouse model. The results of these analyses showed that L. rhamnosus JY02 supplementation promoted the production of muscle-enhancement markers (MHC Iβ, MHC IIα, and Myo-D) and reduced both the production of muscle degradation markers and the symptoms of muscle atrophy (loss of lean mass and muscle strength). We also found decreased levels of pro-inflammatory cytokines (IL-6, IFN- γ) and increased levels of anti-inflammatory cytokines (IL-10) in the serum of DEX+JY02-administered mice compared to those in DEX-treated mice. Overall, these results suggest that L. rhamnosus JY02 is a potent probiotic supplement that prevents sarcopenia by suppressing muscle atrophy.

• Journal of Veterinary Science
• /
• v.25 no.1
• /
• pp.4.1-4.14
• /
• 2024

Background: Lawsonia intracellularis is the causative agent of proliferative enteropathy and is associated with several outbreaks, causing substantial economic loss to the porcine industry. Objectives: In this study, we focused on demonstrating the protective effect in the mouse model through the immunological bases of two vaccine strains against porcine proliferative enteritis. Methods: We used live-attenuated Salmonella Typhimurium (ST) secreting two selected immunogenic LI antigens (Lawsonia autotransporter A epitopes and flagellin [FliC]-peptidoglycan-associated lipoprotein-FliC) as the vaccine carrier. The constructs were cloned into a Salmonella expression vector (pJHL65) and transformed into the ST strain (JOL912). The expression of immunogenic proteins within Salmonella was evaluated via immunoblotting. Results: Immunizing BALB/c mice orally and subcutaneously induced high levels of LI-specific systemic immunoglobulin G and mucosal secretory immunoglobulin A. In immunized mice, there was significant upregulation of interferon-γ and interleukin-4 cytokine mRNA and an increase in the subpopulations of cluster of differentiation (CD) 4⁺ and CD 8⁺ T lymphocytes upon splenocytes re-stimulation with LI antigens. We observed significant protection in C57BL/6 mice against challenge with 10^6.9 times the median tissue culture infectious dose of LI or 2 × 10⁹ colony-forming units of the virulent ST strain. Immunizing mice with either individual vaccine strains or co-mixture inhibited bacterial proliferation, with a marked reduction in the percentage of mice shedding Lawsonia in their feces. Conclusions: Salmonella-mediated LI gene delivery induces robust humoral and cellular immune reactions, leading to significant protection against LI and salmonellosis.