• 한방재활의학과학회지
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• 제25권2호
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• pp.15-35
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• 2015

Objectives This study was performed to investigate the effects of Bujasasim-tang ethanol extract (BST) on oxidative stress, inflammation and osteoarthritic rat model. Methods To ensure safety of BST, heavy metal levels were measured and cytotoxicity test was done. In vitro, To evaluate antioxidative effects of BST, total phenolic contents, 1,1-diphenyl-2-picryl-hydrazyl (DPPH), 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) scavenging activity, reactive oxygen species (ROS) levels were measured. Also, to evaluate anti-inflammatory effects of BST treated group, total nitric oxide (NO) and pro-inflammatory cytokines (IL-$1{\beta}$, IL-6, TNF-${\alpha}$) levels were measured in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. In vivo, We injected MIA $50{\mu}l$ (60 mg/ml) into knee joints of rats to induce osteoarthritis. Rats were divided into total 3 groups (normal, control, BST treated group, each n=7). Normal group was not treated at all without inducing osteoarthritis and taken normal diet. Control group was induced osteoarthritis by MIA and taken with 2 ml of distilled water once a day for 4 weeks. BST treated group was induced osteoarthritis by MIA and taken BST 2 ml (200 mg/kg/mouse) once a day for 4 weeks. We evaluated dynamic weight bearing with the Incapacitance Test Meter. At the end of experiment, the rats were sacrificed to observe the functions of liver and kidney, changes of WBC, neutrophil, lymphocyte, monocyte levels in blood, to evaluate the levels of pro-inflammatory cytokines, tissue inhibitor of metallopreteinases-1 (TIMP-1), matrix metalloproteinase-9 (MMP-9), prostaglandin $E_2$ ($PGE_2$), leukotriene $B_4$ ($LTB_4$) within serum. We observed change of articular structures by Hematoxylin & Eosin (H&E), safranin-O staining method and measured amount of cartilage by micro CT-arthrography. Statistical analysis was done by unpaired student's t-test with significance level at p<0.05 in SPSS 11.0 for windows. Results 1. Safety of the BST was identified. 2. AST, ALT, BUN, creatinine levels of BST treated group were within normal limit. In vitro, 1. DPPH and ABTS free radical scavenging activities of BST showed dose-dependent increase. 2. ROS production were significantly decreased. 3. Total nitric oxide (NO) and IL-$1{\beta}$ production were decreased. 4. IL-6 and TNF-${\alpha}$ production were significantly decreased. In vivo, 1. Weight bearing ability was significantly increased. 2. WBC, neutrophil, lymphocyte, monocyte levels in blood were decreased. 3. IL-$1{\beta}$ and TNF-${\alpha}$ levels in serum were significantly decreased. and the IL-6 level was decreased. 4. TIMP-1, MMP-9, $LTB_4$, $PGE_2$ levels in serum were significantly decreased. 5. Cartilage volume of BST treated group was significantly increased. Also changes of cartilage, synovial membrane, fibrous tissue were suppressed. Conclusions The results obtained in this study Bujasasim-tang have effects of antioxidative, anti-inflammatory, relieve pain and protection of cartilage. Therefore we expect that Bujasasim-tang is effective treatment for osteoarthritis.

• Korean Journal of Acupuncture
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• 제26권1호
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• pp.125-137
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• 2009

Objectives : We studied anti-allergic effects of Cinnamomi Ramulus(CR) herbal acupuncture and Cinnamomi Ramulus extract. Methods : In vivo, animals were herbal-acupunctured with CR at both ST36s three times for 5 days. Then, we induced active systemic anaphylatic shock using compound 48/80 in ICR mice, and passive cutaneous anaphylaxis using anti-DNP IgE in Sprague Dawley rat. In vitro, we measured cell viability, ${\beta}$ -hexosaminidase release and the expressions of IL-4, TNF-${\alpha}$ and COX-2 mRNA in RBL-2H3 cells after treatment of various concentrations of CR extract. Results : In vivo, CR herbal acupuncture pretreatments at both ST36s inhibited compound 48/80-induced active systemic anaphylatic shock. Passive cutaneous anaphylaxis was inhibited by CR herbal acupuncture pretreatments at both ST36s and optional points. In vitro, CR extract treatments did not affect on cell viability and inhibited ${\beta}$-hexosaminidase release. CR extract treatments also decreased the expressions of IL-4, TNF-${\alpha}$ and COX-2 mRNA in RBL-2H3 cells. Conclusions : These results suggest that CR herbal acupuncture and CR extract should be beneficial in the inhibition of allergic inflammatory response.

• 한국식품영양학회지
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• 제32권3호
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• pp.246-250
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• 2019

Nelumbo nucifera Gaertn has been usedas a traditional remedy and food source in South Korea. It promotes gastrointestinal function and controls blood pressures. Nelumbo nucifera Gaertn water extracts supplement at 5, 10, 50, 100, 250, 500, $1,000{\mu}g/mL$ after a 48 h pre-treatment with the mitogen (ConA or LPS) increased the mouse splenocytes proliferation. Water extract supplement also increased the cytokine production ($IL-1{\beta}$, $TNF-{\alpha}$ and $IFN-{\gamma}$), measured by a cytokine ELISA kit. For the result of in vitro study, the proliferation of splenocytes and cytokine production activated by peritoneal macrophages increased when water extracts were supplemented in the range of $50{\sim}500{\mu}L/mL$ concentration. Specifically, the levels of the splenocytes proliferation, $IL-1{\beta}$, $TNF-{\alpha}$ and $IFN-{\gamma}$ were the highest at $250{\mu}L/mL$ concentration. This in vitro study suggestedthat supplementation with Nelumbo nucifera Gaertn water extracts may enhance the immune function by regulating the splenocyte proliferation and enhancing the cytokine production activating macrophage in vitro.

• 대한한방부인과학회지
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• 제26권1호
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• pp.41-58
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• 2013

Objectives: The object of this study was to observe the in vitro anti-bacterial and anti-inflammatory effects of three single aqueous herbal extracts(Trichosanthes Semen, Gardeniae Fructus, and Angelicae Dahuricae Radix), traditionally used for treating various gynecological diseases including mastitis in Korea, against Staphylococcus aureus and lipopolysaccharide(LPS)-activated Raw 264.7 cells. Methods: Anti-bacterial activities of three single aqueous herbal extracts against S. aureus were detected using standard agar microdilution methods. In addition, the effects on the cell viability, $PGE_2$, NO, TNF-${\alpha}$, IL-$1{\beta}$ and IL-6 productions of LPS activated Raw 264.7 cells. The anti-bacterial and anti-inflammatory effects were compared with lincomycin and piroxicam, respectively in the present study. Results: MIC of three single aqueous herbal extracts against S. aureus were detected as over 25, $4.063{\pm}2.096$ and $1.641{\pm}0.972$ mg/ml, respectively. MIC of lincomycin was detected as $0.469{\pm}0.297{\mu}g/ml$ at same conditions. In addition, $ED_{50}$ against LPS-induced cell viabilities and cytokine releases of three single aqueous herbal extracts were as follows - cell viability: 7.635, 13.761, 6.986 mg/ml, NO production : 4.808, 22.015, 2.949 mg/ml, $PGE_2$ production : 3.040, 4.312, 0.821 mg/ml, TNF-${\alpha}$ production : 9.563, 54.931, 1.240 mg/ml, IL-$1{\beta}$ production : 1.362, 1.801, 0.534 mg/ml, IL-6 production : 0.371, 0.797, 0.202 mg/ml, respectively. $ED_{50}$ of piroxicam against LPS-induced cell viabilities, NO, $PGE_2$, TNF-${\alpha}$, IL-$1{\beta}$ and IL-6 were detected as 35.179, 6.552, 1.162, 7.273, 7.101 and 5.044 ${\mu}g/ml$, respectively at same conditions. Conclusions: The results of the study showed anti-bacterial effects against S. aureus in the order of Gardeniae Fructus and Angelicae Dahuricae Radix aqueous extracts, except for Trichosanthes Semen. They also showed anti-inflammatory effects against LPS-activated Raw 264.7 cells in the order of Angelicae Dahuricae Radix, Trichosanthes Semen, and Gardeniae Fructus aqueous extracts. These three herbs are expected to be great substitutes to reduce side-effect of lincomycin and piroxicam, if the amount of those three single aqueous herbal extracts is adjusted appropriately.

• 동의생리병리학회지
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• 제25권6호
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• pp.982-988
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• 2011

This research seeks a basis for developing new anti-inflammatory medicine by investigating Cornus Walteri extract for its anti-inflammatory effects. After the injection of LPS in to rats with Cornus Walteri extract, its anti-inflammatory effects were compared among the treatment groups. The plasma concentration of IL-$1{\beta}$, IL-6 and TNF-${\alpha}$ peaked at 5h after LPS injection, and the values of the Cornus Walteri extract groups were lower than those of the control group. In the increment of concentration of these cytokines at 2h and 5h after LPS injection, the Cornus Walteri groups were lower than that of control group. The plasma concentration of IL-10 peaked at 5h after LPS injection, and the values of the Cornus Walteri extract groups were higher than those of the control group. In the increment of cytokines concentration at 2h and 5h after LPS injection, the Cornus Walteri groups were higher than that of control group. Liver cytokines measurement was done at 5h after LPS injection. The concentration of liver IL-$1{\beta}$ and IL-6 in the Cornus Walteri groups was lower than that of the control group. The concentrations of liver TNF-${\alpha}$, and IL-10 showed no significant differences among all the treatment groups. In the studies of lipopolysaccharide-exposed Raw 264.7 cells, the concentration of IL-$1{\beta}$, IL-6 and TNF-${\alpha}$ in the lipopolysaccharide-exposed cells groups was higher than that of control group (normal group). However, in lipopolysaccharide-exposed cells groups, they showed lower values than those of control group and these values showed a tendency to decrease in the Cornus Walteri groups. The concentration of IL-10 in the lipopolysaccharide-exposed cells groups was higher than that of control group (normal group), and among the lipopolysaccharide-exposed cells groups, all Cornus Walteri extract groups showed higher values than single lipopolysaccharide-exposed cells groups. This studies have shown that in vitro and in vivo Cornus Walteri extracts are significantly more sensitive to inflammatory cytokines and LPS induced lethality. We conclude that the Cornus Walteri extracts have an functional material for inflammatory activities.

• 한국임상수의학회지
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• 제26권5호
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• pp.408-412
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• 2009

The Artemisia capillaris THUNB is a perennial herb that belongs to the family Compositae spp. and probably the most common plant among the various herbal folk remedies being used in the treatment of abdominal pain, hepatitis, chronic liver disease, jaundice and coughing in Korea. This experiment was conducted to investigate the effects of Artemisia capillaris extracts on the amounts of splenocytes-derived cytokine ($TNF-{\alpha},\;IL-1{\beta}$ and IL-10). In in vivo experimental tests using 210 ICR mice with Hepa-1c1c7 or sarcoma 180 cancer line, splenocytes derived cytokine contents were significantly (p < 0.05) reduced in the Hepa-1c1c7 and Sarcoma 180 inoculated vehicle controls, HP and SP, compared to those of the intact vehicle control on both the $28^{th}$ day and the $42^{nd}$ day, respectively. However, these decreases of $TNF-{\alpha},\;IL-1{\beta}$ and IL-10 levels induced by tumor inoculations were significantly (p < 0.01, p < 0.05) inhibited by mACH (Artemisia capillaris methanol extracts) treatment regardless of the type of experiments and tumor cells inoculated. The results suggest that Artemisia capillaris methanol extracts have prominent anti-inflammation effects on the cancer cell lines Hepa-1c1c7 and Sarcoma 180.

• 대한한방내과학회지
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• 제30권3호
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• pp.495-509
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• 2009

Objective : Membranous nephropathy(MN) is an organ-specific autoimmune disease and a relatively common cause of nephrotic syndrome in adults worldwide. But treatment of MN is not defined. This study was to evaluate the effects of Acasia Catechu extract(ACE) on the MN induced by cBSA in mice. Methods : Mice were divided into 4 groups. The normal group was injected with a saline solution. The control group was treated with cBSA(10 mg/kg i.p.) only. The third group was treated with cBSA (10 mg/kg i.p.) and ACE (250 mg/kg, p.o.). The fourth group was treated with cBSA (10mg/kg i.p.) and ACE (500mg/kg, p.o.). After cBSA and ACE treatment for 6 weeks, we measured change of body weight, 24hrs proteinuria, serum albumin, total cholesterol, triglyceride, BUN, creatinine, TNF-$\alpha$, IL-6, IL-$1{\beta}$, IFN-$\gamma$, IgA, IgM and IgG levels. The morphologic changes of renal glomeruli were also observed with a light microscope. Results : The levels of 24 hrs proteinuria, total cholesterol, triglyceride, IgG, IgM, IgA, TNF-$\alpha$, IL-6, IL-$1{\beta}$, IFN-$\gamma$ significantly decreased in both ACE groups. The level of albumin significantly increased in both ACE groups. The mRNA expression of IL-$1{\beta}$ in splenocytes considerably decreased in the ACE-500 group. In histological findings of kidney tissue, thickening of GBM decreased in both ACE groups. Conclusions : This study shows that ACE might be effective for treatment of MN. More clinical data and studies are to be done for efficient application.

• International Journal of Oral Biology
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• 제42권1호
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• pp.33-38
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• 2017

Background: Periodontitis is an inflammatory disease characterized by the breakdown of tooth-supporting tissues, leading to tooth loss. Aggregatibacter actinomycetemcomitans are major etiologic bacterium causing aggressive periodontitis. Ursodeoxycholic acid (UDCA), a hydrophilic gall bladder acid, has been used as an effective drug for various diseases related to immunity. The aim of this study was to investigate the effect of UDCA on the inflammatory response induced by A. actinomycetemcomitans. Methods: A human acute monocytic leukemia cell line (THP-1) was differentiated to macrophage- like cells by treatment with phorbol 12-mystristate 13-acetate (PMA) and used for all experiments. The cytotoxic effect of UDCA was examined by MTT assay. THP-1 cells were pretreated with UDCA for 30 min before A. actinomycetemcomitans infection and the culture supernatant was analyzed for various cytokine production by ELISA. The effect of UDCA on bacterial growth was examined by measuring optical densities using a spectrophotometer. Results: UDCA showed no cytotoxic effect on THP-1 cells, up to $80{\mu}M$ Ed highlight: Please confirm technical meaning. UDCA pretreatment inhibited the A. actinomycetemcomitans-induced $IL-1{\beta}$, $TNF-{\alpha}$, and IL-17A secretion in a dose-dependent manner. UDCA also inhibited IL-21 production at $60{\mu}M$. The production of IL-12 and IL-4 was not influenced by A. actinomycetemcomitans infection. Conclusion: These findings indicate that UDCA inhibits the production of inflammatory cytokines involved in innate and Th17 immune responses in A. actinomycetemcomitans-infected THP-1- derived macrophages, which suggests its possible use for the control of aggressive periodontitis.

• Tuberculosis and Respiratory Diseases
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• 제69권5호
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• pp.337-347
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• 2010

Background: Transglutaminase-2 (TG-2) has been reported to play an important role in the process of fibrosis. However, TG-2 studies on fibroproliferation of acute lung injury (ALI) are absent. The purpose of this study was to investigate the role of TG-2 in the fibroproliferation of lipopolysaccharide (LPS)-induced ALI. Methods: The male C57BL/6 mice of 5 weeks age were divided into 3 groups; control group (n=30) in which $50{\mu}L$ of saline was given intratracheally (IT), LPS group (n=30) in which LPS 0.5 mg/kg/$50{\mu}L$ of saline was given IT, and LPS+Cyst group treated with intraperitoneal 200 mg/kg of cystamine, competitive inhibitor of TG-2, after induction of ALI by LPS. TG-2 activity and nuclear factor $(NF)-{\kappa}B$ were measured in lung tissue homogenate. Tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-$1{\beta}$, IL-6, myeloperoxidase (MPO), and transforming growth factor (TGF)-${\beta}1$ were measured using bronchoalveolar lavage fluids. Histopathologic ALI score and Mallory's phosphotunistic acid hematoxylin (PTAH) for collagen and fibronectin deposition were performed. Results: The TG-2 activities in the LPS group were significantly higher than the control and LPS+Cyst groups (p<0.05). The TNF-${\alpha}$ and IL-$1{\beta}$ concentrations and $NF-{\kappa}B$ activity were lower in the LPS+Cyst group than the LPS group (p<0.05). The LPS+Cyst group showed lower MPO, ALI score, TGF-${\beta}1$ concentration, and Mallory's PTAH stain than the LPS group, but the differences were not significant (p>0.05). Conclusion: Inhibition of TG-2 activity in the LPS-induced ALI prevented early inflammatory parameters, but had limited effects on late ALI and fibroproliferative parameters.

• 한국식품과학회지
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• 제50권4호
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• pp.444-450
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• 2018

본 연구는 꿀벌 꽃가루 추출물(BPW)의 면역 활성에 관하여 알아보기 위하여, 선천면역계의 대표적인 수지상세포와 후천면역계의 대표적인 비장세포에 BPW를 처리 하여 면역세포의 활성능을 관찰하였다. 수지상 세포에 BPW를 처리하여 세포 생존율, 산화질소(II)와 사이토카인($TNF-{\alpha}$, IL-6과 $IL-1{\beta}$) 분비능과 세포 표면분자를 관찰 하였다. 세포 생존율은 수지상 세포에 BPW를 처리하였을 때, 세포 독성을 일으키지 않았으며 주요 면역 활성 인자인 산화질소(II) 분비능을 관찰한 결과, 농도 의존적으로 증가하는 것을 확인하였다. 또한 사이토카인의 분비능을 관찰한 결과, $TNF-{\alpha}$, IL-6과 $IL-1{\beta}$의 함량이 농도 의존적으로 증가하는 것으로 관찰되었다. 또한 활성화된 면역세포의 세포 표면에서 발현되는 CD80과 CD86의 발현과 항원제시에 밀접한 관련이 있는 MHC class I, II의 발현이 유의적으로 증가하는 것으로 관찰되었다. 또한 후천면역에서 중요한 역할을 수행하는 면역 T 세포가 다량 분포하는 지라 세포를 분리하여 BPW를 처리 하였을 때 Th1 세포가 분비하는 사이토카인의 함량이 농도 의존적으로 증가되는 것으로 나타났다. 이러한 결과로 미루어 볼 때 BPW는 선천면역뿐만 아니라 후천면역에 관여하는 다양한 면역세포의 활성화에 직간접적으로 관여하는 것으로 사료된다.