• Title/Summary/Keyword: $LTB_4$

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Effect of Cheongawongagam Extract on the Ovariectomized Rat Model of Osteoporosis (청아원가감 추출물이 난소적출로 유발된 흰쥐의 골다공증 모델이 미치는 영향)

  • Yun, Gee Won;Lee, Hyun
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.34 no.1
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    • pp.14-23
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    • 2020
  • This study was conducted to evaluate the efficacy of Cheongawongagam on osteoporosis rat. A total of 35 rats were divided into seven groups; Normal control(SD-Nr), experimental control group(OVX-CTL), positive control group(OVX-17β-E2) and herb extracts group[Eucommia ulmoides(OVX-EU-E), Juglandis semen(OVX-JR-SE), Acanthopanax senticosus(OVX-AS-E) extract and Cheongawongagam extracts(OVX-JAEG-E)]. All control group, and herb extracts group were ovariectomized. After the 3 weeks recovery period, herb extract group were orally administered 200 mg / kg of the EU-E, JR-SE, AS-E and JAEG-E for 12 weeks. In the OVX-CTL, 17β-estradiol(E2) was administered subcutaneously on the back of the rats at a dose of 0.03 ug/sc. Their body weight, serum total cholesterol, triglyceride, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), Leukotriene B4 (LTB4), calcium (Ca), estradiol, osteocalcin, and deoxypyridinoline (DPD) concentration were measured. Also, we investigated mRNA expression of inflammatory cytokine, MMP-2, MMP-9, and bone tissue. As a result, total cholesterol was significantly decreased in the OVX-AS-E and OVX-JAEG-E. ALP was significantly increased and osteocalcin, DPD was significantly decreased in OVX-JAEG-E. The expression of inflammatory mediators (TNF-α, IL-1β, LTB4, COX-2, NOS-2), inflammatory cytokines IL-1β and MMP-9 mRNA were significantly decreased in OVX-JAEG-E. Histologic examination of the femur showed that bone mineral density, and bone mass were increased and bone marrow were decreased in the OVX-JAEG-E group. The above experiment shows that cheongawongagam extract were effective in the prevention and treatment of osteoporosis.

A COMPARATIVE STUDY ON THE ARACHIDONIC ACID METABOLITES IN HUMAN INFLAMMATORY DENTAL PULP AND PERIODONTAL TISSUES (사람의 염증성 치수와 치주조직에서 Arachidonic acid 대사산물에 대한 비교연구)

  • Son, Ho-Hyun;Kim, Hyung-Seop;Chang, Kee-Wan
    • Restorative Dentistry and Endodontics
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    • v.16 no.2
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    • pp.165-173
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    • 1991
  • The purpose of the present study was to measure and compare the arachidonic acid metabolites in diseased periodontal tissue and vital pulp tissue of the tooth, and to investigate the relationship between periodontal and pulp disease. Diseased periodontal tissue of periodontally involved human teeth and vital pulp tissue from the same teeth which were intact with no periapical lesions were obtained. Each periodontal and pulp tissue homogenates from the same tooth were incubated with $^{14}C$ - arachidonic acid. Lipid solvent extracts were separated by thin layer chromatography to be analyzed by autoradiography and TLC analyzer. 1. The conversion into $TXB_2$, 6 - keto - $PGF_{1a}$ and $PGE_2$, and unidentified metabolite in pulp tissue were less than that in diseased periodontal tissue(P<0.05). 2. Biosynthetic levels of $TXB_2$, unidentified metabolite, 6 - keto - $PGF_{1a}$ and HETEs were not satistically significant between diseased periodontal tissue and pulp tissue. $LTB_4$ was measured highly in pulp tissue(P<0.1). 3. The percentage of each metabolite to the total converted metabolites were not statistically significant between diseased periodontal tissue and pulp tissue. But the percentage of $LTB_4$ in pulp tissue was higher than that in diseased periodontal tissue(P<0.05). 4. The relative amounts of the total metabolites formed in lipoxygenase pathway to those formed in cyclo - oxygenase pathway were 6 fold in diseased periodontal tissue and 12 fold in pulp tissue. But there was no statistical significance between diseased periodontal tissue and pulp tissue(P>0.05).

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Anti-Inflammatory Effect of Anemarrhenae Rhizoma 80% Ethanol Extract in RAW 264.7 cells (RAW 264.7 세포에서 지모(知母) 80% 에탄올 추출물의 항염증 효과)

  • LEE, Young Keun;KIM, Cheong Taek;CHOI, Hak Joo
    • The Korea Journal of Herbology
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    • v.32 no.3
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    • pp.97-103
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    • 2017
  • Objective : According to recent studies, Anemarrhenae Rhizoma has anti-inflammatory activities of DW extract, but it hasn't not yet conducted to evaluate inflammatory factors about 80% ethanol extract. Therefore, The aim of this study is to investigate the various effects of individual or combined 80% ethanol extract of Anemarrhenae Rhizoma on cell viability and various anti-inflammatory factors. Methods : Anemarrhenae Rhizoma extract was prepared with 80% ethanol. MTT assay, ELISA, and Luminex were performed in LPS-activated RAW 264.7 cell line to measure cytotoxicity, Nitric oxide (NO), cyclooxygenase-2 (COX-2), prostaglandin E2 ($PGE_2$), Leukotriene B4 ($LTB_4$), and cytokines ($IL-1{\beta}$, IL-6, and $TNF-{\alpha}$), respectively. Results : At concentration of $200{\mu}g/m{\ell}$ Anemarrhenae Rhizoma extract, cytotoxicity was observed in RAW 264.7 cells. However, at concentration less than $100{\mu}g/m{\ell}$ of Anemarrhenae Rhizoma, cytotoxicity was not observed in RAW 264.7 cells. All concentration of Anemarrhenae Rhizoma extract showed no difference of NO, and $IL-1{\beta}$level in RAW 264.7 cells compared with control group. In contrast, at concentration of $100{\mu}g/m{\ell}$ Anemarrhenae Rhizoma extract significantly inhibited LPS-induced production of COX-2, PGE2, and $LTB_4$ level in RAW 264.7 cells. In addition, the production of proinflammatory cytokines (IL-6, $TNF-{\alpha}$) in LPS-induced RAW 264.7 cells was significantly decreased at concentration of all or 10, and $100{\mu}g/m{\ell}$, respectively. Conclusion : These findings demonstrate that Anemarrhenae Rhizoma has inhibitory effect on inflammatory mediators in LPS-activated RAW 264.7 cells showing possible developed as a raw material for new therapeutics to ease the symptoms related with inflammatory.

EFFECTS OF INHIBITORY DRUGS ON THE ARACHIDONIC ACID METABOLISM OF PERIODONTAL TISSUE (치은 Arachidonic acid 대사산물의 억제약물에 관한 실험적 연구)

  • Han, Se-Hee;Oh, Kwi-Ok;Kim, Hyung-Seop
    • Journal of Periodontal and Implant Science
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    • v.23 no.2
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    • pp.243-259
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    • 1993
  • The bone resorbing activity of $PGE_2$ and elevated level of prostaglandins(PGs) and thromboxanes (TXs) in inflamed gingiva which are cyclooxygenase(C) metabolites have been well documented. Nonsteroidal anti-inflammatory drugs(NSAIDs) have been known to suppress gingival inflammation and bone resorption through the specific inhibitory action on the C pathway thereby decrease of various C metabolites. Recent studies provide unequivocal results that gingival tissue metabolizes arachidonic acid(AA) mainly through lipoxygenase(L) pathway. And the results of our previous experiments suggest that indomethacin may have inhibitory action on L as well as C. Thus we started this study to show the influences of several C inhibitors on the L activity at therapeutic and toxic dosage. Periodontal tissue samples were obtained from patients with advanced periodontitis and incubated with $^{14}C-AA(0.2{\mu}Ci)$ and various enzyme inhibitors. The tissue lipid extracts were separated by means of thin layer chromatography(TLC) and analyzed by means of autoradiography and TLC analyzer. Our results showed that aspirin inhibited C more selectively than L, however at higher concentration it also decreased HETEs production significantly. Indomethacin showed dose-dependent inhibition of L as well as C and all of the L metabolites were decreased to the same degree by high concentration of indomethacin. AA-861, which is an experimental tool of selective L inhibitor, showed inhibition of HETEs production but no effect on the production of $TXB_2$, PGs and $LTB_4$. Various propionic acid derivatives NSAIDs(ibuprofen, flurbiprofen, naproxen) showed the same patterns of effect on AA metabolism each other that was profound inhibition of PGs production, to the less degree HETEs and $TXB_2$ production, and of no effect on the $LTB_4$ production.

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Immune regulation effects of Gentianae Radix extract in LPS-induced acute inflammatory mice (LPS로 급성 염증을 유발한 동물에 대한 용담초 추출물의 면역조절 효과)

  • Lee, Hyo-Jung;Seung, Yoon-Cheol;Lee, Myung-Sun
    • The Korea Journal of Herbology
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    • v.33 no.2
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    • pp.79-84
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    • 2018
  • Objective : The immune enhance is the main focus of current society that to increase resistance to invasion by pathogenic species of bacteria in body, stimulate the immune system and possibly protect against cancer or inflammatory disease. The present study aimed to evaluate the effect of Gentianae Radix extract on immune regulation in a LPS-induced mice model of acute inflammation. Methods : Gentianae Radix extract was administered orally at doses of 200 mg/kg/day or 400 mg/kg/day for 2 weeks before a intraperitoneally injection of LPS (1 mg/kg of 0.9% saline). After LPS-intraperitoneal injection 3 hours, blood was collected by cardiac puncture under ether anaesthesia from all animals, for the immune regulate efficacy verification based on blood or serum biomarkers (i.e., immune cells, cytokine, $PGE_2$, ROS, and $LTB_4$) analysis. Results : Compared to the control mice, the Gentianae Radix extract treatments significantly increased the count of immune cells (i.e., wite blood cell, neutrophils, and monocyte), and significantly reduced the lymphocyte. In addition, the Gentianae Radix extract treatments significantly decreased the pro-inflammatory cytokine (i.e., $IL-1{\beta}$, IL-6, and $TNF-{\alpha}$), and significantly increased IL-10 of anti-inflammatory cytokine. Furthermore, the Gentianae Radix extracts treatments significantly increased the levels of $PGE_2$ and significantly decreased the levels of ROS, and $LTB_4$. Conclusions : The results indicate that Gentianae Radix extract alleviated acute inflammatory reaction though regulation of immune meditor. Thus, Gentianae Radix extract may raw material of development a health food and medicine option for the immune enhance.

Effects of Different Sources of Dietary n-3 Fatty Acids on Immune Response and Eicosanoids Production (급원이 다른 n-3 지방산이 흰쥐에서 면역반응과 Prostaglandin $E_2$ 및 Leukotriene $B_4$ 생성에 미치는 영향)

  • 김우경
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.26 no.4
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    • pp.697-703
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    • 1997
  • This study was planned to compare the effects of source of dietary n-3 fatty acids, i.e., tuna oil and perilla oil, on mitogenesis and production of prostaglandin E$_2$ and leukotriene B$_4$ in rats. Weaning male Sprague-Dawley rats were fed 3 different experimental diets for 4 weeks(Control: beef tallow 50% + sesame oil 50%, FO : beef tallow 50% + sesame oil 25% + tuna oil(27% docosahexaenoic acid) 25%, PO : beef tallow 50% + sesame oil 25% + perilla oil 25%). Food intakes were higher in FO group than in other groups, but body weight gains, food efficiency rates and weights of spleen were not different among groups. Proliferation of splenocyte to PWM(pokeweedmitogen) was higher in FO and PO group than control group. But there was no difference between FO and PO group. Response to ConA was not different among three groups. Serum PGE$_2$ levels were higher in control group than other groups. Serum LKB$_4$ levels were not different among groups. Therefore, it seemed that n-3 fatty acids increased the immune response by means of decreasing the PGE$_2$ production.

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Effects of Ketotifen on an Experimental Model of IgA Nephropathy (IgA 신증의 실험모델에서 케토티펜의 효과)

  • Do, Young-Sun;Soon, Eu-Jene;NamGoong, Mee-Kyung
    • Childhood Kidney Diseases
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    • v.13 no.2
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    • pp.153-160
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    • 2009
  • Purpose : The intestinal mucosal defect has been known as one of the pathogenicmechanisms of IgA nephropathy. Oral antigens usually induce the activation of Th2 cells and mast cells. These cells secrete cytokines IL-4, IL-5 and TGF-$\beta$, which increase IgA production. Although ketotifen (benzocycloheptathiophene) is an H1 antagonist and a mast cell membrane stabilizer, it could protect the gastrointestinal membrane through inhibiting the production of IL-4, IL-5, PGE2, and LTB4, and decreasing the activity of nitric oxide synthease. Therefore, we have investigated if ketotifen may protect the development of IgA nephropathy with an oral antigen. Methods : ICR mice were used as an animal model orally with Poliovax only [ketotifen (-)], the other group was given oral ketotifen [ketotifen (+)] in addition to Poliovax. Results : Mesangial IgA deposition developed in 11 out of the 18 mice in the ketotifen (-) group, while in three out of the nine mice in ketotifen (+) group. The mesangial change developed in 16 out of the 18 mice in the ketotifen (-) group, while in five out of the nine mice in the ketotifen (+) group. Serum IL-4 and IL-5 levels were not significantly lower in the latter group than in the former. Conclusion : According to the statistical results from the above, ketotifen therapy would be beneficial to reducing mesangial changes in IgA nephropathy.

Anti-inflammation and Anti-oxidation Effects of Gamikyejakjimo-tang Herbal Acupuncture on Pathologic Factor and MIA-induced Osteoarthritis Rat (가미계작지모탕약침(加味桂芍知母湯藥鍼)이 퇴행성관절염 병리인자 및 동물병태 모델에 미치는 영향)

  • Lee, Hyun-Jae;Park, Jung-Oh;Oh, Min-Seok
    • Journal of Korean Medicine Rehabilitation
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    • v.25 no.4
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    • pp.1-20
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    • 2015
  • Objectives This study was intended to clarify the anti-inflammation and anti-oxidation effects of gamikyejakjimo-tang herbal acupuncture (GKHA) for osteoarthritis. Methods Osteoarthritis was induced by injection of MIA into right knee joint cavities of rats. Rats were divided into a total of 4 groups (n=8). The 4 groups were normal group, control group, positive comparison group and expeimental group. Indomethacin and GKHA were medicated for a total of 4 weeks. After that, functions of liver and kidney by AST, ALT, creatinine, BUN, DPPH and ABTS free radical scavenging activity, ROS (reactive oxygen species) production, NO (Total Nitric oxide), IL-$1{\beta}$, IL-6, TNF-${\alpha}$ production, weight changes in the hind legs of MIA-induced osteoarthritis rat, serum PGE2, TIMP-1, MMP-2, MMP-9, LTB4, hs-CRP, and white blood cells, neutrophils, lymphocytes, monocytes were measured. The volume of cartilage was observed by micro CT arthrography. H&E and Safranin-O staining were used to examine the injury of synovial tissue. Results 1. In the hind leg weight bearing measurement, level of weight was increased. 2. AST, ALT, BUN, creatinine were decreased. 3. The production of total white blood cell was decreased, and the production of neutrophils, lymphocytes, monocytes were significantly decreased. 4. The production of NO, PGE2, TIMP-1, MMP-2, MMP-9, LTB4 were significantly decreased, and the production of hs-CRP was also decreased but with no significance. 5. The cartilage volume was significantly increased. 6. In H&E staining and Safranin-O staning, the cartilage cell appeared to be proliferated, and proteoglycans appeared to be increased. Conclusions Based on the results above, Gamikyejakjimo-tang Herbal Acupuncture has anti-oxidation and anti-inflammation effects, which leads to suppressing the underlying causes and the progression of osteoarthritis.

The Experimental Study on Antioxidant, Anti-inflammatory, Antipruritic and Antibacterial Effects of the Banchong-san (BCS) (반총산의 항산화, 항염증, 항소양증, 항균효능에 관한 실험 연구)

  • Cho, Eun-Jin;Jo, Seong-Hui;Yang, Seung-Jeong
    • The Journal of Korean Obstetrics and Gynecology
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    • v.34 no.3
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    • pp.29-48
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    • 2021
  • Objectives: Banchong-san (BCS) is a herbal formula composed of 13 korean medicinal herbs and is traditionally used to treat inflammatory diseases and pain. The object of this study was to research the antioxidant, anti-inflammatory, antipruritic and antimicrobial effects of the BCS in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Methods: In this experiment, effects of BCS on the following four were measured as follows: (1) Anti-oxidative effects were evaluated by 1,1-diphenyl-2-picryl-hydrazyl (DPPH) Radical scavenging activity, 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) Radical scavenging activity. (2) Anti-inflammatory effects were evaluated by the production amount of Reactive oxygen species (ROS), Nitric oxide (NO), Interleukin-1β (IL-1β), Interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), Prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2)(the previous two are "mRNA"), extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinases (p38), inhibitor of nuclear factor kappa B (IκBα), nuclear factor kappa B (NF-κB) (the previous five are "Protein") in LPS-Stimulated RAW 264.7 cells. (3)Antipruritic effects were evaluated by the production amount of histamine, Leukotriene B4 (LTB4), LeukotrieneC4 (LTC4) Levels in phorbol 12-myristate 13-acetate(PMA)/ionomycin-stimulated MC/9 mast cell. (4) Anti-microbial effects were evaluated by the growth suppression of Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Aspergillus niger. Results: The following results were obtained through each measurement: (1) DPPH Radical Scavenging Activity, ABTS Radical Scavenging Activity evoked a significant concentration-dependent increase. (2) ROS, NO, IL-1β, IL-6, TNF-α, PGE2 production amount, iNOS, COX-2 mRNA expression were significantly reduced in the BCS extraction group compared with the control group and significantly decreased the amount of ERK, JNK, p38, NF-κB Protein expression. The amount of IκB-α Protein Expression have increased significantly. (3) The amounts of histamine, LTB4, LTC4 were significantly decreased. (4) The antibacterial efficacy, BCS inhibited the growth of Escherichia coli, Pseudomonas aeruginosa at concentrations of 5 ㎍/ml, but did not suppress the growth of staphylococcus aureus and aspergillus niger. Conclusions: The experimental results show that BCS has anti-oxidant, anti-inflammatory, antipruritic and antimicrobial properties.

Effects of Bujasasim-tang Ethanol Extract on Oxidative Stress, Inflammation and Osteoarthritic Rat Model (부자사심탕(附子瀉心湯)이 산화적 손상, 염증 및 골관절염 병태모델에 미치는 영향)

  • Woo, Chang-Hoon;Oh, Min-Seok
    • Journal of Korean Medicine Rehabilitation
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    • v.25 no.2
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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.