• Tuberculosis and Respiratory Diseases
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• 제39권4호
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• pp.304-309
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• 1992

연구배경 : 폐포대식세포에서 아라카돈산 대사산물의 생성을 자극하는 일부 인자에 의해서 지속적인 자극시 이와같은 자극으로 인해 생산된 아라키돈산 대사산물이 만성적인 기관지 수축과 섬유화, 계속되는 독성 산소기의 분비를 통하여 잘환의 진행을 항진시키게 된다고 알려져 있고 또한 폐가 외부 물질에 만성적으로 폭로됨으로 인한 질환은 진폐증이 그 대표적인 예라고 할 수 있다. 그러으로 대식세포나 호중구 또는 섬유모세포에서 생산하는 prostaglandin이나 leukotriene등 대사산물의 측정을 통하여 진폐증의 질환의 진행정도를 파악하려는 노력이 계속되고 있으나 아직 명백한 결론을 얻지 못하고 있다. 본 연구는 시험관내에서 폐포대식세포를 유리규산으로 자극시 아라키돈산 대사산물의 측정을 통하여 섬유화 과정에 미치는 prostaglandin $E_2$와 leukotriene $B_4$의 영향을 연구하기 위하여 시행되었다. 방법 : 쥐의 폐포대식세포를 유리규산분진, 자연산 석탄 분진, Lipopolysaccharide, calcium ionophore과 같은 자극제와 같이 배양하고 24, 48시 간후 방사선 동위원소를 이용하여 $PGE_2$와 $LTB_4$를 측정하였다. 결과 : 1) 정상 흰쥐의 폐포대식세포에서 $PGE_2$는 유리규산 자극시 48시간에서 무자극군에 비하여 유의한 감소를 보였다. 2) 실험규폐증군의 폐포대식세포에서 유리된 $PGE_2$는 유리규산 및 자연산 석탄분진으로 자극시 48시간에서 무자극군에 비하여 유의하게 감소하였다. 3) 정상 흰쥐의 폐포대식세포에서 $LTB_4$는 유리규산 자극후 24시간 및 48시간, 그리고 자연산 석탄분진으로 자극시 48시간에서 무자극군에 비하여 유의한 증가를 보였다. 4) 실험 규폐증의 폐포대식세포에서 유리된 $LTB_4$는 유리규산 및 자연산 석탄분진 자극시 장시간 및 48시간에서 무자극군에 비하여 모두 유의하게 증가하였다. 결론 : 본 실험 결과 시험관에서 유리규산과 자연산 석탄분진에 폐포대식세포가 폭로시 폐에 염증반응을 항진시킬 수 있는 방향으로 아라키돈산 대사가 이루어짐을 알았고 이와갈은 아라키돈산 대사의 변화가 진폐증의 병태생리에 중요한 인자로서 작용할 가능성이 있다고 하겠다.

• 대한한의학회지
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• 제34권1호
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• pp.116-135
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• 2013

Objectives: This study was intended to clarify how Jakyakkamchobuja-tang (hereinafter referred to JKBT) affects mice of C57BL/10 whose osteoarthritis was induced by papain. Methods: Osteoarthritis was induced in mice by injecting papain in the knee joint. Mice were divided into 4 groups (n=6). The normal group were not treated at all whereas the control group (OAC-control) were induced for osteoarthritis by papain and oral medicated with 200 ul of physiological saline per day. The positive comparison group (OAC-$Joins^{(R)}$) were injected with papain and after 7 days, 100 mg/kg of $Joins^{(R)}$ were medicated with 200 ul of physiological saline mixed. The experimental group (OAC-JKBT) were injected with papain and after 7 days were medicated with 400 mg/kg of JKBT mixed with 200 ul of physiological saline. OAC-$Joins^{(R)}$ and OAC-JKBT were oral medicated for each substance for a total of 4 weeks, once per day. After experiments (from 1 week after injection of papain to 4 weeks elapsed), the function of liver and kidney, inflammation cytokine values within serum, degree of revelation for inflammation cytokine genes, immune cells within blood, metabolism of arachidonic acid and amount of cartilage were measured and histopathological variations for knee joint structures were observed. Results: Functions of liver and kidney were not affected. IL-$1{\beta}$ (interleukin-$1{\beta}$), MCP-1 (monocyte chemoattractant protein-1) and TNF-${\alpha}$ (tumor necrosis factor-${\alpha}$) were significantly reduced and IL-6 (interleukin-6) was also reduced but not significantly. After analyzing inflammation cytokine in joints with mRNA (messenger ribonucleic acid), revelation of IL-6, TNF-${\alpha}$, COX-2 (cyclooxygenase-2) and iNOS-II (inducible nitric oxide synthase-II) were all significantly reduced. Revelation of IL-$1{\beta}$ gene was also reduced but not significantly. Neutrophil for WBC (white blood cell) within serum was significantly reduced; monocyte was also reduced but not significantly. PGE2 (prostaglandin E2), TXB2 (thromboxane B2) were significantly reduced and LTB4 (leukotriene B4) was also reduced but not significantly. Destruction of cartilage on micro CT (computed tomography)-arthrography was reduced but had no significant differences. In terms of histopathology, infiltration of inflammation, proliferation of synovial membrane, subsidence of cartilage and bone due to penetration of excessive formation of synovial cell and destruction of cartilage were small (H&E (hematoxylin and eosin), safranine O staining). Conclusions: Based on these results, Jakyakkamchobuja-tang (JKBT) is believed to be useful for suppressing the progress of osteoarthritis and its treatments because of its anti-inflammatory effects and alleviation of pain with histopathological effective efficacy.

• 동의생리병리학회지
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• 제18권5호
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• pp.1494-1504
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• 2004

The present paper reports the effects of Hwaotang an atherosclerosis using a spontaneous experimental model, We have also investigated the pharmacological effect of Hwaotang on collagen- and ADP-induced blood platelet aggregation, thrombin-induced conversion of fibrinogen and fibrinolysis in in vitro experiments, and various effects on stimuli-induced superoxide generation in human neutrophils. Hwao-tang was shown to have inhibitory effect on collagen- and ADP-induced blood platelet aggregation, on thrombin-induced conversion of fibrinogen to fibrin and on the activity of plasminogen or plasmin. Hwao-tang also significantly inhibited fMLP-induced superoxide generation in a concentration-dependent manner, but not that induced by arachidonic acid. Hwao-tang inhibited neutrophil functions, including degranulation, superoxide generation, and leukotriene B4 production, without any effect on 5-lipoxygenase activity. In conclusion, the protection of extracts of Hwao-tang on the ischemic infarction induced artificially might be involved to their inhibition of thrombotic action. The results also indicate that Hwao-tang exerts the effects on superoxide generation related to the inhibition of neutrophil functions.

• 한국약용작물학회지
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• 제15권2호
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• pp.132-137
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• 2007

Inhibitory effect of Scutellaria baicalensis ethanol extracts (SR) on chemical mediator release and immunoglobulin (Ig) production from Sprague-Dawley rats originated cells as type I allergic reaction was examined. SR showed concentration-dependent inhibition on basal and concanavalin A (ConA)-stimulated Ig production. In the mesenteric lymph node lymphocytes, the inhibitory effect of SR on the IgE production in the presence of Con A was stronger than these on IgA and IgG production. Moreover, tumor necrosis factor-alpha $(TNF-{\alpha})$ production-inhibiting effect of SR in the presence ConA was observed. However, SR did not affect the production of $interferon-{\gamma}$. SR also inhibited histamine release from the peritoneal exudate cells stimulated with a calcium ionophore A23187. In the case of leukotriene B4, SR markedly inhibited it at the concentration of 100 mg/ml. From these results, ethanol extracts obtained from Scutellaria baicalensis may have an anti-allergic effect on the intestinal system of rats.

• 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.

• 생약학회지
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• 제30권4호
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• pp.377-383
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• 1999

The anti-asthmatic activities of the extract of Lonicera japonica (BuOH fraction) and its mode of action were investigated using several in vitro and in vivo models. Lonicera japonica was extracted with 30% ethanol (v/v) and successively partitioned into BuOH. The BuOH fraction reduced antigen-induced contraction of isolated trachea from sensitized guinea pigs in a concentration-dependent manner. The BuOH fraction also inhibited histamine release from rat peritoneal mast cells induced by antigen or calcium ionophore A23187 ($IC_{50}=0.26$ and 0.32mg/ml, respectively). Eosinophil infiltration into bronchoalveolar lavage fluids induced by aeroallergen challenge in passively sensitized guinea pigs was inhibited by the BuOH fraction at a dose of 800mg/kg (51.7%). In addition, the BuOH fraction inhibited leukotriene $B_4$ prodution in rat basophilic leukemia cells ($IC_{50}=0.42\;mg/ml$) as well as phosphodiesterase 4 (PDE4) isolated from rat brain ($IC_{50}=0.015\;mg/ml$). All results from this study strongly suggest that the BuOH fraction of Lonicera japonica may be useful in the treatment of asthma and its mode of action may be related with inhibition of both 5-lipoxygenase and PDE4 enzyme.

• Journal of Nutrition and Health
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• 제34권8호
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• pp.896-904
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• 2001

Conjugated linoleic acid(CLA) is a group of positional and geometric isomers of linoleic acid(LA) and exhibits anticarcinogenic activity in multiple experimental animal models. Cis-9,trns-11(c9t11) and trans-10,cis-12(t10c12) CLA are the principal isomers found in foods. The present study was performed to determine whether CLA and the two isomers inhibits HT-29 cell proliferation and to assess whether such an effect was related to changes in secretion of eicosanoids. Cells were incubated in serum-free medium with various concentrations(0 to 20$\mu$M) of CLA or LA. CLA inhibited cell proliferation in a dose-dependent manner, with maximal inhibition(70 $\pm$ 1%) observed at 20$\mu$M concentration after 96 hours. However, LA had no effect at the same concentration range. To compare the ability of c9f11 and t10c12 to inhibit cell proliferation, cells were incubated with increasing concentrations(0 to 4$\mu$M) of these isomers. T10c12 inhibited cell proliferation in a dose-dependent manner. A 66 $\pm$ 2% decrease in cell number was observed within 96 hours after addition of 4$\mu$M t10c12. By contrast, c9t11 had no effect. The concentrations of CLA and the two isomers in the plasma membrane were increased when they were added to the incubation medium. However, they did not alter the levels of arachidonic acid in plasma membrane. To assess whether the proliferation inhibiting effect of CLA was related to changes in eicosanoid production, prostaglandin E$_2$(PGE$_2$) and leukotriene B$_4$(LTB$_4$) concentrations in conditioned media were estimated by a competitive enzyme immunoassay. Both CLA and t10c12 increased the production of materials reactive to PGE$_2$ and LTB$_4$ antibodies in a dose-dependent manner. By contrast, c9t11 had no effect. These results indicate that inhibition of HT-29 cell proliferation by CLA is attributed to the effect of the t10v12 isomer. The materials reactive to PGE$_2$ and LTB$_4$ antibodies may inhibit growth stimulatory effect of arachidonic acid-derived eicosanoids on HT-29 cell proliferation.

• 대한한의학회지
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• 제34권3호
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• pp.69-85
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• 2013

Objectives: This study investigated the anti-osteoarthritic effects of Kyejiinsam-tang (hereinafter referred to KIT) on the monosodium iodoacetate (MIA)-induced osteoarthritis rats. Methods: Anti-oxidative effects of KIT were measured by scavenging activities of DPPH, reactive oxygen species (ROS) and nitric oxide (NO). Scavenging activities of anti-oxidation in lipopolysaccharide (LPS)-treated RAW 264.7 cells were also measured for inhibitory effects against the production of inflammatory mediators (tumor necrosis factor-${\alpha}$, interleukin-$1{\beta}$, interleukin-6). Osteoarthritis was induced in rats by injecting MIA in the knee joint. Rats were divided into a total of 4 groups (n=6). The normal group were not treated at all without inducing osteoarthritis whereas the control group were induced for osteoarthritis by MIA and oral medicated physiological saline per day. The positive comparison group was injected with MIA and after 7 days, 2 mg/kg of Indomethacin. The experimental group was injected with MIA and after 7 days was medicated with 34 mg/kg of KIT. Indomethacin and KIT were orally-medicated for each substance a total of 4 weeks, once per day. Weight-bearing on hind legs was measured every week after MIA injection. At the end of the experiment (5 weeks after MIA injection), micro CT (computed tomography)-arthrography and histopathological examinations on the articular structures of knee joint were performed. The effect on inflammatory cytokines and immunological cells in synovial fluid was measured. Volume of cartilage was measured by micro CT-arthrography. Injury to synovial tissue was measured by H & E (hematoxylin and eosin), Safranin-O immunofluorescence. Results: 1. Cytotoxicity against hFCs was insignificant. 2. KIT showed the potent full term for DPPH. 1. NO was significantly reduced by KIT (at 100, $200{\mu}g/m{\ell}$) and ROS was also reduced, but not significantly, by KIT (at $200{\mu}g/m{\ell}$). 2. IL-6 and IL-$1{\beta}$ were significantly reduced by KIT (at 100, $200{\mu}g/m{\ell}$) and TNF-${\alpha}$ was also reduced, but not significantly, by KIT (at $200{\mu}g/m{\ell}$). 1. In hind legs weight-bearing measurement, level of weight increased. 2. Functions of liver and kidney were not affected. 3. IL-$1{\beta}$ was significantly reduced and TNF-${\alpha}$, IL-6 were also reduced but not significantly. 4. PGE2 (prostaglandin E2), LTB4 (leukotriene B4) were significantly reduced in the KIT group. 5. MMP-9 (matrix metalloproteinase-9), TIMP-1 (tissue inhibitor of metalloproteinases-1) and Osteocalcin were significantly reduced in the KIT group. 6. Destruction of cartilage on micro CT arthrography was reduced but had no significant differences. 7. Histopathologically, injury to synovial membrane of the KIT group was decreased and proteoglycan content of KIT group was increased. Conclusions: According to this study, Kyejiinsam-tang has inhibiting effect on the progression of arthritis in MIA-induced osteoarthritis rat. Kyejiinsam-tang has anti-oxidants and anti-inflammation effects, and is related to inhibiting the activity of inflammatory cytokine and injury of volume in cartilage.

• Journal of Nutrition and Health
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• 제51권3호
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• pp.208-214
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• 2018

본 연구는 으뜸도라지추출물의 항알레르기 효과를 조사하기 위해 실시하였다. 으뜸도라지추출물 (50, 100 및 $200{\mu}g/mL$) 처리에 따른 RBL-2H3 비만세포의 세포독성을 조사한 결과 으뜸도라지추출물은 모든 농도에서 세포독성이 관찰되지 않았고, ${\beta}$-hexosaminidase assay를 통해 비만세포의 탈과립 억제능을 평가한 결과 재래종도라지추출물과 비교하여 ${\beta}$-hexosaminidase 억제능이 10배 뛰어남을 확인 하였다. 또한 으뜸도라지추출물은 RBL-2H3 비만세포에서 탈과립 후 유리되는 대표물질인 IL-4, $TNF-{\alpha}$, $PGE_2$ 및 $LTB_4$의 생성 분비를 현저히 감소시켰고, 이러한 효과는 재래종도라지와 비교하여 월등한 것으로 나타났다. 이상의 결과는 으뜸도라지추출물이 알레르기 반응을 효과적으로 억제함을 제시하며 향후 항알레르기 기능성 소재로 개발 가능성이 있음을 나타낸다.

• The Korean Journal of Physiology and Pharmacology
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• 제2권5호
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• pp.617-628
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• 1998

In order to understand the pathogenetic mechanism of adult respiratory distress syndrome (ARDS), the role of phospholipase A2 (PLA2) in association with oxidative stress was investigated in rats. $Interleukin-1{\alpha}\;(IL-1,\;50\;{\mu}g/rat)$ was used to induce acute lung injury by neutrophilic respiratory burst. Five hours after IL-1 insufflation into trachea, microvascular integrity was disrupted, and protein leakage into the alveolar lumen was followed. An infiltration of neutrophils was clearly observed after IL-1 treatment. It was the origin of the generation of oxygen radicals causing oxidative stress in the lung. IL-1 increased tumor necrosis factor (TNF) and cytokine-induced neutrophil chemoattractant (CINC) in the bronchoalveolar lavage fluid, but mepacrine, a PLA2 inhibitor, did not change the levels of these cytokines. Although IL-1 increased PLA2 activity time-dependently, mepacrine inhibited the activity almost completely. Activation of PLA2 elevated leukotriene C4 and B4 (LTC4 and LTB4), and 6-keto-prostaglandin $F2{\alpha}\;(6-keto-PGF2{\alpha})$ was consumed completely by respiratory burst induced by IL-1. Mepacrine did not alter these changes in the contents of lipid mediators. To estimate the functional changes of alveolar barrier during the oxidative stress, quantitative changes of pulmonary surfactant, activity of gamma glutamyltransferase (GGT), and ultrastructural changes were examined. IL-1 increased the level of phospholipid in the bronchoalveolar lavage (BAL) fluid, which seemed to be caused by abnormal, pathological release of lamellar bodies into the alveolar lumen. Mepacrine recovered the amount of surfactant up to control level. IL-1 decreased GGT activity, while mepacrine restored it. In ultrastructural study, when treated with IL-1, marked necroses of endothelial cells and type II pneumocytes were observed, while mepacrine inhibited these pathological changes. In histochemical electron microscopy, increased generation of oxidants was identified around neutrophils and in the cytoplasm of type II pneumocytes. Mepacrine reduced the generation of oxidants in the tissue produced by neutrophilic respiratory burst. In immunoelectron microscopic study, PLA2 was identified in the cytoplasm of the type II pneumocytes after IL-1 treatment, but mepacrine diminished PLA2 particles in the cytoplasm of the type II pneumocyte. Based on these experimental results, it is suggested that PLA2 plays a pivotal role in inducing acute lung injury mediated by IL-1 through the oxidative stress by neutrophils. By causing endothelial damage, functional changes of pulmonary surfactant and alveolar type I pneumocyte, oxidative stress disrupts microvascular integrity and alveolar barrier.