• Journal of Korean Medicine Rehabilitation
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• v.21 no.1
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• pp.57-77
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• 2011

Objectives : This study was to investigate the suppression effects of Sopunghwalhyeol-tang(Shufenghuoxie-tang) on the monosodium iodoacetate-induced osteoarthritis in rats. Methods : Arthritis was induced by injection of monosodium iodoacetate(0.5 mg) into the both knee joints of rats. Arthritic rats were divided into control(n=8) and treated(n=8) group. Control group was taken distilled water for 20 days. Treated group was taken extracts of Sopunghwalhyeol-tang(Shufenghuoxie-tang) by oraly for same duration. Normal group(n=8) was injected with normal saline and was taken distilled water for 20 days. Macroscopic examination and histopathological study on articular cartilage of knee joint were operated at 20 days after injection. Proteoglycan(PG) content of articular cartilages of knee joint was represented by safranine O staining, was measured at 20 days after injection. Tumor necrosis $factor-{\alpha}(TNF-{\alpha})$, $interleukin-1{\beta}(IL-1{\beta})$, in synovial fluid were measured with enzyme-linked immuno sorbent assay(ELISA) kit at 20 days after injection. Immunohistochemical staining of cyclo-oxygenase-2(COX-2), inducible nitric oxide synthase(iNOS) in knee joints were observed at 20 days after injection. Results : 1. Lymphocytes in peripheral blood the treated group was significantly decreased compared with the control group. 2. PG content in articular cartilage of the treated group was significantly increased compared with the control group. 3. Histopathologically, osteoarthritic scores of the treated group was significantly decreased compared with the control group. 4. $TNF-{\alpha}$ content in synovial fluid of the treated group was significantly decreased compared with the control group. 5. COX-2 revelation index in chondrocytes and synovial membrane of the treated group was significantly decreased compared with the control group. 6. Matrix metalloproteinase-3(MMP-3) revelation index in chondrocytes and synovial membrane of the treated group was significantly decreased compared with the control group. Conclusions : On the basis of these results, we concluded that Sopunghwalhyeol-tang(Shufenghuoxie-tang) has inhibiting effects on the $TNF-{\alpha}$, COX-2 and MMP-3 secretion of chondrocytes and synovial membrane in Monosodium Iodoacetate-induced osteoarthritis model of rats.

• Journal of Korean Medicine Rehabilitation
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• v.21 no.1
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• pp.79-95
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• 2011

Objectives : This study was to investigate the antiarthritic effect of Hwallak-dan(Huoluo-dan) on the complete freund's adjuvant(CFA)-induced arthritis in Lewis rats. Methods : Arthritis was induced by intradermal injection of CFA into base of tail. Experimental groups divided into normal(n=10), control(n=10) and treated(n=10) group. Animals of control group received normal saline for twenty days, treated group received extracts Hwallak-dan(Huoluo-dan) for same duration, light mineral oil only injected non-arthritic rats were served as normal group. The incidence of arthritis and arthritic index were observed after treatment. Body weight, paw edema volume and thickness of ankle joint were measured at 0, 11, 14, 17, 20 days after treatment. White blood cell(WBC) counts in blood were analysed at 20 days after treatment and tumor necrosis $factor-{\alpha}(TNF-{\alpha})$, $interleukin-1{\beta}(IL-1{\beta}$), IL-6 contents in paw exudate were analysed by ELISA at 20 days after treatment. Histopathology on the ankle joint were performed at 20 days after treatment. Results : 1. Incidence of arthritis of treated group was 60% and control group was 100% at 20 days after treatment. 2. Arthritic index of treated group was significantly decreased compared with control group at 20 days after treatment. 3. Paw edema volume and thickness of ankle joint of treated group was significantly decreased compared with control group at 20 days after treatment. 4. Total WBC of treated group was significantly decreased compared with control group at 20 days after treatment. 5. Neutrophils of treated group was significantly decreased compared with control group at 20 days after treatment. 6. $TNF-{\alpha}$ content in paw exudate of treated group was significantly decreased compared with control group at 20 days after treatment. 7. $IL-1{\beta}$ content content in paw exudate of treated group was significantly decreased compared with control group at 20 days after treatment. 8. IL-6 content content in paw exudate of treated group was significantly decreased compared with control group at 20 days after treatment. 9. Histopathological arthritic index of treated group was significantly decreased compared with control group at 20 days after treatment. Conclusions : These results indicate that Hwallak-dan(Huoluo-dan) has inhibitory effect on the development and progression of CFA-induced arthritis in rats.

• Journal of Ginseng Research
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• v.44 no.2
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• pp.282-290
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• 2020

Background: Ginseng is a commonly used herbal medicine in treating various medical conditions. Chronic gut inflammation is a recognized factor for the development of colorectal cancer (CRC). In this project, Asian ginseng berry polysaccharide preparations were used to assess their effects on CRC and related immune regulation mechanisms. Methods: Ginseng berry polysaccharide extract (GBPE) and purified ginseng berry polysaccharide portion (GBPP) were used to evaluate their activities on human HCT-116 and HT-29 CRC cell proliferation. Interleukin-8 secretion analysis was performed on HT-29 cells. Naive CD4 cell isolation and T-helper cell differentiation were performed and determined using flow cytometry for Th1 and Treg in addition to cell cycle and apoptotic investigation. Results: GBPE and GBPP significantly inhibited interleukin-8 secretion and cancer cell proliferation, inhibited CD4⁺IFN-γ⁺ cell (Th1) differentiation, and decreased CD4⁺FoxP3⁺ cell (Treg) differentiation. Compared to the GBPE, GBPP showed more potent antiinflammatory activities on the malignant cells. This is consistent with the observation that GBPP can also inhibit Th1-cell differentiation better, suggesting that it has an important role in antiinflammation, whereas Treg cells hinder the body's immune response against malignancies. Supported by cell cycle and apoptosis data, GBPE and GBPP, at various degrees, remarkably enhanced the anticancer activities of 5-fluorouracil. Conclusion: Data from this project suggested that Asian ginseng berry potentially has clinical utility in managing enteric inflammation and suppressing CRC through immunomodulation mechanisms.

• Journal of Life Science
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• v.22 no.9
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• pp.1137-1144
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• 2012

Inflammation is a host defense mechanism that is activated in response to harmful substances or pathogens. However, an excessive inflammatory response is a problem in itself. Macrophages secrete inflammatory mediators such as nitric oxide (NO) or cytokines through various pathways such as the nuclear factor kappa B (NF-${\kappa}B$)-activated pathway after recognizing pathogen-like lipopolysaccharides (LPSs). In this study, anti-inflammatory effects of Eupatorium chinensis var. simplicifolium (EUC) extracts were investigated using LPS-stimulated RAW 264.7 macrophages. The EUC root extract significantly reduced NO production, inducible nitric oxide synthase (iNOS) expression, and cyclooxygenase-2 expression in a concentration-dependent manner. In addition, the EUC root extract reduced phosphorylation of mitogen-activated protein kinases and protein kinase B, which is upstream of NF-${\kappa}B$. The EUC root extract also reduced the degradation of inhibitory kappa B. These results indicate that EUC root extract exerts anti-inflammatory effects, which are mediated by inhibition of iNOS expression and the NF-${\kappa}B$ pathway.

• Molecules and Cells
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• v.41 no.7
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• pp.653-664
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• 2018

The RNA-binding protein tristetraprolin (TTP) binds to adenosine-uridine AU-rich elements in the 3'-untranslated region of messenger RNAs and facilitates rapid degradation of the target mRNAs. Therefore, it regulates the expression of multiple cancer and immunity-associated transcripts. Furthermore, a lack of TTP in cancer cells influences cancer progression and predicts poor survival. Although the functions of TTP on cancer cells have previously been researched, the mechanism of TTP on the interaction between cancer cells with their micro-environment remains undiscovered. In this study, we admed to determine the role of cancer cell TTP during the interaction between tumor and immune cells, specifically regulatory T cells (Tregs). We evaluate the capability of TTP to modulate the antitumor immunity of GC and explored the underlying mechanism. The overexpression of TTP in GC cells dramatically increased peripheral blood mononuclear lymphocyte (PBML) -mediated cytotoxicity against GC cells. Increased cytotoxicity against TTP-overexpressed GC cells by PBMLs was determined by Treg development and infiltration. Surprisingly, we found the stabilization of programmed death-ligand 1 (PD-L1) mRNA was declining while TTP was elevated. The PD-L1 protein level was reduced in TTP-abundant GC cells. PD-L1 gas been found to play a pivotal role in Treg development and functional maintenance in immune system. Taken together, our results suggest the overexpression of TTP in GC cells not only affects cell survival and apoptosis but also increases PBMLs -mediated cytotoxicity against GC cells to decelerate tumor progression. Moreover, we identified PD-L1 as a critical TTP-regulated factor that contributes to inhibiting antitumor immunity.

• Journal of Microbiology and Biotechnology
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• v.30 no.9
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• pp.1412-1419
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• 2020

Human noroviruses (HuNoVs) are a leading cause of gastroenteritis outbreaks worldwide. However, the paucity of appropriate cell culture models for HuNoV replication has prevented developing effective anti-HuNoV therapies. In this study, first, the replication of the virus at various temperatures in different cells was compared, which showed that lowering the culture temperature from 37℃ significantly increased virus replication in Madin-Darby canine kidney (MDCK) cells. Second, the expression levels of autophagy-, immune-, and apoptosis-related genes at 30℃ and 37℃ were compared to explore factors affecting HuNoV replication. HuNoV cultured at 37℃ showed significantly increased autophagy-related genes (ATG5 and ATG7) and immune-related genes (IFNA, IFNB, ISG15, and NFKB) compared to mock. However, the virus cultured at 30℃ showed significantly decreased expression of autophagy-related genes (ATG5 and ATG7), but not significantly different major immune-related genes (IFNA, ISG15, and NFKB) compared to mock. Importantly, expression of the transcription factor FOXO1, which controls autophagy- and immune-related gene expression, was significantly lower at 30℃. Moreover, FOXO1 inhibition in temperature-optimized MDCK cells enhanced HuNoV replication, highlighting FOXO1 inhibition as an approach for successful virus replication. In the temperature-optimized cells, various HuNoV genotypes were successfully replicated, with GI.8 showing the highest replication levels followed by GII.1, GII.3, and GII.4. Furthermore, ultrastructural analysis of the infected cells revealed functional HuNoV replication at low temperature, with increased cellular apoptosis and decreased autophagic vacuoles. In conclusion, temperature-optimized MDCK cells can be used as a convenient culture model for HuNoV replication by inhibiting FOXO1 and providing adaptability to different genotypes.

• Journal of the Korean Society of Food Science and Nutrition
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• v.37 no.4
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• pp.477-484
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• 2008

For the effective use of the conger eel by-products, such as head and frame, Tang, which is the Korean-type soup, from conger eel by-products (TCEB) was developed and its food component characterization was compared with that of commercial Chueotang, loach Tang. According to the results of viable cells and coliform group of TCEB heated at $115^{\circ}C$ for various times, the reasonable $F_0$ value was 8 min. The proximate composition of TCEB was 90.7% for the moisture, 4.8% for the protein, 2.6% for the lipid, and 1.5% for the ash. The extractive-nitrogen content of TCEB was 243.1 mg/100 g, which was higher than that of commercial Chueotang, 208.0 mg/100 g. The total amino acid content of TCEB was 4,310 mg/100 g and its major amino acids were glutamic acid (637.3 mg/100 g, 14.8%), glycine (409.1 mg/100 g, 9.5%) and alanine (404.4 mg/100 g, 9.3%). TCEB was not felt in the sensual fish odor and its sensual taste was good. The health functional properties for health of TCEB were 1.29 as a PF (protection factor) for antioxidative activity and 39.4% for angiotensin Ⅰ converting enzyme (ACE) inhibiting activity.

• Korean Journal of Pharmacognosy
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• v.41 no.3
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• pp.216-220
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• 2010

Obesity is an important risk factor that significantly increases mortality and disease rates in the cardiovascular disease, diabetes, and various diseases. So far, the most powerful way to inhibit fat absorption is pancreatic lipase inhibitors. In this study, we investigated the anti-obesity effect of the extract of Juniperus rigida. Juniperus rigida extract (JRE) had a inhibitory effect on pancreatic lipase activity ($IC_{50}$=8.63 ${\mu}g$/ml). In in vivo oil-emulsion loading test, this extract also inhibited the intestinal fat absorption. In addition, we measured inhibitory effects of JRE on activity of phosphodiesterase (PDE) and hormone sensitive lipase (HSL) among the important enzymes associated with lipolysis. JRE strongly inhibited PDE activity ($IC_{50}$=4.56 ${\mu}g$/ml), whereas inhibitory effect on HSL activity was very weak compared with orlistat. As a result, JRE inhibited the absorption of fat by inhibiting the activity of pancreatic lipase and induced lipolysis through inhibition of PDE activity. Therefore, we suggest that Juniperus rigida may be a potential therapeutic agent improving obesity.

• Korean Journal of Microbiology
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• v.34 no.4
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• pp.188-193
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• 1998

The authors examined the variations of environmental factors, the distributions of cyanobacteria, heterotrophic bacteria, and microorganisms that inhibit the growth of Anabaena cylindrica according to development and extinction of cyanobacterial bloom at a site in Daechung Dam reservoir. And certified the relationship between each other. Water temperature variated in a typical pattern. pH and concentrations of dissolved oxygen and chlorophylla was high in bloom period, and lowered with the decline of bloom. Phosphorus played as a growth-limiting factor at this study site. Total nitrogen concentration increased during blooming period, which indicated that nitrogen has been fixed by aquatic organisms such as cyanobacteria. Cyanobacteria distributed from June 17, and such cyanobacterial species as Anabaena spp., Aphanizomenon spp., Microcystis spp., Oscillatoria spp. and Phormidium spp. was detected during study period. Anabaena spp. distributed relatively highly distributed from July 23 to September 22, and disappeared completely at September 29. Heterotrophic bacterial and cyanobacterial populations varied inverse-proportionally. There was a relevancy between the variations of Anabaena spp., heterotrophic bacteria, and microorganisms that inhibit the growth of Anabaena cylindrica. Microorganisms that inhibit the growth of Anabaena cylindrica distributed from early growth phase of Anabaena spp. population to immediately after the extinction of Anabaena spp. With the population of Anabaena cylindrica growth-inhibiting microorganisms decreasing, increases of heterotrophic bacterial population followed it. Thease results indicate that microorganisms have a part in the extinction of cyanobacterial bloom, especially at its destroying period.

• Journal of Korean Medical Science
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• v.33 no.53
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• pp.298.1-298.10
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• 2018

Background: The renal function of individuals is one of the reasons for the variations in therapeutic response to various drugs. Patients with renal impairment are often exposed to drug toxicity, even with drugs that are usually eliminated by hepatic metabolism. Previous study has reported an increased plasma concentration of indoxyl sulfate and decreased plasma concentration of $4{\beta}$-hydroxy (OH)-cholesterol in stable kidney transplant recipients, implicating indoxyl sulfate as a cytochrome P450 (CYP) inhibiting factor. In this study, we aimed to evaluate the impact of renal impairment severity-dependent accumulation of indoxyl sulfate on hepatic CYP3A activity using metabolic markers. Methods: Sixty-six subjects were enrolled in this study; based on estimated glomerular filtration rate (eGFR), they were classified as having mild, moderate, or severe renal impairment. The plasma concentration of indoxyl sulfate was quantified using liquid chromatography-mass spectrometry (LC-MS). Urinary and plasma markers ($6{\beta}$-OH-cortisol/cortisol, $6{\beta}$-OH-cortisone/cortisone, $4{\beta}$-OH-cholesterol) for hepatic CYP3A activity were quantified using gas chromatography-mass spectrometry (GC-MS). The total plasma concentration of cholesterol was measured using the enzymatic colorimetric assay to calculate the $4{\beta}$-OH-cholesterol/cholesterol ratio. The correlation between variables was assessed using Pearson's correlation test. Results: There was a significant negative correlation between MDRD eGFR and indoxyl sulfate levels. The levels of urinary $6{\beta}$-OH-cortisol/cortisol and $6{\beta}$-OH-cortisone/cortisone as well as plasma $4{\beta}$-OH-cholesterol and $4{\beta}$-OH-cholesterol/cholesterol were not correlated with MDRD eGFR and the plasma concentration of indoxyl sulfate. Conclusion: Hepatic CYP3A activity may not be affected by renal impairment-induced accumulation of plasma indoxyl sulfate.