• 동의생리병리학회지
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• 제33권2호
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• pp.109-115
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• 2019

Aster Yomena (AY) has been used in traditional medicine to treat diseases such as obesity, hyperlipidemia, atherosclerosis, diabetes and osteoarthritis. However, protective effect of AY on acute pancreatitis (AP) has not been reported. The present study examined the anti-inflammatory effects of an ethanol extract of AY on cerulein-induced AP. AP was induced in mice by intraperitoneally injecting cerulein ($50{\mu}g/kg$) hourly for 6 times. 70% ethanol extract of AY (0.1, 0.2, and 0.5 g/kg) was orally administered for 1 week before acute pancreatitis induction. The mouse was killed at 6 hours after the final cerulein injection. The pancreas and lung were rapidly removed for histological examination and myeloperoxidase (MPO) assay. Blood samples were taken to determine serum amylase and lipase activity. In addition real-time reverse transcription-polymerase chain reaction (RT-PCR) was also performed to investigate mRNA expression of proinflammatory cytokines such as $TNF-{\alpha}$. $IL-1{\beta}$, and IL-6. Administration of AY significantly ameliorated pancreatic weight to body weight ratio, histological damages and MPO activity during AP. In addition, AY inhibited the serum amylase and lipase activity during AP. Also, mRNA expression of $TNF-{\alpha}$, $IL-1{\beta}$ and IL-6 were inhibited by AY against AP. Our results revealed that pre-treatment of AY reduces the severity of cerulein-induced AP. Therefore, AY may have a protective effect drug against AP.

• Fisheries and Aquatic Sciences
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• 제24권4호
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• pp.153-162
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• 2021

In this study, a fish metabolic accelerator (a combination of butaphosphan and cyanocobalamin [BPC]) was injected into the muscle of the olive flounder, Paralichthys olivaceus, to investigate its effect on immunity and stress in fish maintained at low temperatures. A single dose of BPC was injected (100 mg/kg body weight) into the olive flounder, and its immunity and stress were observed after one and two weeks. Immunity tests revealed the presence of lysozyme (LZM), nitroblue tetrazolium (NBT), myeloperoxidase (MPO), anti-protease (AP), glutathione peroxidase (GPx), and total immunoglobulin (TIg). BPC injection was found to increase immunity activity compared to the control group. In particular, there was significantly high GPx activity. There was similarly high activity for MPO and GPx in the first week following the injection, followed by significant differences between the BPC-injected and control groups in the second week. There was a reduced low water-temperature stress response in the BPC-injected fish, as evidenced by the cortisol and glucose levels of the control and BPC groups. Lower levels were also observed in the BPC group than the control group during the second week. Cortisol levels were significantly lower in the BPC group than the control group. Histological examinations were conducted in the first and second weeks after the intramuscular injection of the recommended BPC dose to confirm the safety of BPC in aquaculture. There were no abnormalities observed in any tissue samples. This study confirms that the injection of BPC is safe even when used in a culture situation. BPC helps relieve stress and improves non-specific immune responses (innate immunity) in the olive flounder.

• 대한의생명과학회지
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• 제27권3호
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• pp.142-153
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• 2021

Liver fibrosis is a wound-healing response to chronic liver injury, which is caused by the continuous and excess deposition of extracellular matrix (ECM). The aim of this study is to investigate whether Uncaria rhynchophylla water extract (UR) can ameliorate thioacetamide (TAA)-induced liver fibrosis. The liver fibrosis model was induced on C57BL/6 mice by intraperitoneal injection with TAA three times a week for 8 weeks. UR (200 mg/kg) or silymarin (50 mg/kg) was administered orally daily for 8 weeks. Biochemical analyses including AST, ALT, MPO, and Ammonia levels were measured in serum. In the mice liver tissues, western blot and histological staining were analyzed. As a result, UR dramatically reduced the levels in serum AST, ALT, MPO, and Ammonia levels. UR treatment regulated NADPH oxidase factors expression, and antioxidant enzymes except for GPx-1/2 were significantly increased via Nrf2 activation. Furthermore, pro-inflammatory mediators, such as COX-2 and iNOS were markedly suppressed through the inhibition of NF-κB activation. Expressions of ECM-related protein including α-SMA and Collagen I were noticeably decreased. The additional histological evaluation confirmed that hepatocyte damage and collagenous fiber accumulation were attenuated. Taken together, these data suggest that UR possessed hepatoprotective effects in TAA-induced liver fibrosis via the NF-κB inactivation and Nrf2 activation. Therefore, UR may act as a potential therapeutic drug against liver fibrosis.

• 대한상한금궤의학회지
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• 제13권1호
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• pp.21-44
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• 2021

Objective : This study aimed to assess the preventive effect of Bupleuri Radix aqueous extracts (BR) and red koji-fermented BR (fBR) in lipopolysaccharide (LPS)-induced acute lung injury in a rat model. Methods : Rats were administered 30, 60, or 120 mg/kg/day of fBR for 28 days before LPS treatments. All rats were sacrificed 5 h after LPS treatment (500 ㎍/head, intratracheal instillation). Body weights, lung weights, pulmonary transcapillary albumin transit, arterial gas parameters (pH, partial pressure [Pa] of O2, PaCO2), bronchoalveolar lavage fluid (BALF) protein, lactate dehydrogenase (LDH), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), total cell numbers, neutrophil/alveolar macrophage ratios, lung malondialdehyde (MDA), and myeloperoxidase (MPO) were measured. In addition, histopathological changes including the luminal surface of alveoli (LSA), thickness of alveolar septum, and number of polymorphonuclear neutrophils (PMNs) were checked. Results : LPS injection led to increases in lung weights, pulmonary transcapillary albumin transit, BALF protein, LDH, TNF-α and IL-1β contents, total cells, neutrophil and alveolar macrophage ratios, lung MDA, MPO, alveolar septum thickness, and PMNs, and decreases in PaCO2 and pH of arterial blood and LSA. However, these LPS-induced acute lung injuries were inhibited by pretreatment of 30, 60, and 120 mg/kg of fBR. The most favorable effects were seen with 30 mg/kg fBR as compared with 60 mg/kg of α-lipoic acid and BR. Conclusions : fBR showed preventive effects on LPS-induced acute lung injury, which resembles acute respiratory distress syndrome. The mechanisms of action were likely via antioxidant and anti-inflammatory means.

• 대한한방내과학회지
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• 제43권4호
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• pp.643-655
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• 2022

Objective: To investigate the protective effects of Haeganjeon on a thioacetamide (TAA)-induced liver fibrosis mouse model and to determine the Haegan-jeon signaling pathway. Methods: Mice were randomly divided into 4 groups: Normal group (Nor), TAA-induced liver fibrosis group (Con), TAA-induced liver fibrosis group administered 50 mg/kg silymarin (S50), TAA-induced liver fibrosis group administered 200 mg/kg Haegan-jeon (H200). The liver fibrosis mouse model was established by intraperitoneal injection with TAA three times a week for 8 weeks. During the 8 weeks, mice were orally administered silymarin and Haegan-jeon every day. At the end of the study, serum was collected to measure the levels of AST, ALT, ammonia, and myeloperoxidase (MPO). Liver tissue was harvested and analyzed by western blotting and Masson's trichrome staining. Results: Administration of Haegan-jeon suppressed the increase in serum levels of AST, ALT, ammonia, and MPO due to TAA-induced liver fibrosis. Compared to the Con group, the H200 group showed increases in antioxidant-related factors (Nrf2, HO-1, catalase, and GPx-1/2) and decreases in inflammatory-related factors (NF-κB p65, p-IκB-α, Cox-2, iNOS, TNF-α, and IL-1β) in western blots. The H200 treatment inhibited the expression of α-SMA and Collagen I. Conclusions: Haegan-jeon showed a hepatoprotective effect induced by activation of antioxidant-related factors, such as Nrf2, and it regulated the inflammation response by suppression of NF-κB.

• 대한본초학회지
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• 제33권2호
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• pp.45-52
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• 2018

Objectives : Smilacis Glabrae Rhizoma (SGR) has been used in traditional medicine for treating diseases related to inflammation and cancer. However, the protective effect of SGR has not been reported in the study of acute pancreatitis (AP). Therefore, this study was performed to evaluate the protective effects of SGR water extract on cerulein-induced AP. Methods : AP was induced by intraperitoneal injection of supramaximal concentrations of stable cholecystokinin analogue cerulein ($50{\mu}g/kg$) 6 times at intervals of one hour in mice. SGR water extract (0.01, 0.05, or 0.1 g/kg) was administrated intraperitoneally 1 h prior to the first injection of cerulein. The mice were sacrificed at 6 h after the final injection of cerulein. Pancreas and lung were rapidly removed for histochemical examination and myeloperoxidase (MPO) assay. In addition, polymerase chain reaction (PCR) was performed to examine mRNA levels of proinflammatory cytokines such as interleukin(IL)-6, $IL-1{\beta}$ and Tumor necrosis $factor(TNF)-{\alpha}$. Results : Administration of SGR water extract significantly inhibited pancreatic weight to body weight ratio. In addition, SGR treatment inhibited the histological damages and increase of MPO activity in both pancreas and lung during AP. Also, mRNA levels of IL-6 but not $IL-1{\beta}$and $TNF-{\alpha}$ were inhibited by SGR water extract against AP. Conclusion : Our results revealed that pre-treatment of SGR water extract reduces the severity of cerulein-induced AP. Therefore, this study suggest that SGR could be used as a drug or agent to prevent AP.

• Journal of Veterinary Science
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• 제25권3호
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• pp.35.1-35.13
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• 2024

Importance: Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis characterized by inflammation within the central nervous system. However, inflammation in non-neuronal tissues, including the lungs, has not been fully evaluated. Objective: This study evaluated the inflammatory response in lungs of EAE mice by immunohistochemistry and histochemistry. Methods: Eight adult C57BL/6 mice were injected with myelin oligodendrocyte glycoprotein_35-55 to induce the EAE. Lungs and spinal cords were sampled from the experimental mice at the time of sacrifice and used for the western blotting, histochemistry, and immunohistochemistry. Results: Histopathological examination revealed inflammatory lesions in the lungs of EAE mice, characterized by infiltration of myeloperoxidase (MPO)- and galectin-3-positive cells, as determined by immunohistochemistry. Increased numbers of collagen fibers in the lungs of EAE mice were confirmed by histopathological analysis. Western blotting revealed significantly elevated level of osteopontin (OPN), cluster of differentiation 44 (CD44), MPO and galectin-3 in the lungs of EAE mice compared with normal controls (p < 0.05). Immunohistochemical analysis revealed both OPN and CD44 in ionized calcium-binding adapter molecule 1-positive macrophages within the lungs of EAE mice. Conclusions and Relevance: Taken together, these findings suggest that the increased OPN level in lungs of EAE mice led to inflammation; concurrent increases in proinflammatory factors (OPN and galectin-3) caused pulmonary impairment.

• Tuberculosis and Respiratory Diseases
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• 제61권4호
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• pp.374-383
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• 2006

연구배경: 급성폐손상에서 활성산소종에 의한 산화 손상은 주요한 역할을 한다. Ethyl pyruvate (EP) 는 체내에서 생성되는 pyruvate의 유도체로 항산화 및 항염증 효과가 있음이 알려졌다. 저자들은 리포다당질에 의한 급성폐손상 모델에서 EP가 염증반응에 미치는 영향을 연구하고자 하였다. 방 법: 5주 령의 BALB/c 생쥐를 이용하여 리포다당질을 기관 내로 투여하여 급성폐손상을 유도하였다. 대조군, LPS군, EP+LPS군, LPS+EP군으로 나누어 기관지폐포세척액에서 TNF-$\alpha$, IL-6 및 myeloperoxidase (MPO)의 활성을, 폐조직에서 급성폐손상 지수와 NF-$\kappa$B의 농도를 측정하였다. 결 과: EP+LPS군에서 TNF-$\alpha$ 및 IL-6의 농도는 LPS군과 비교하여 감소하였고 (p<0.05) 이들 염증성 시토카인의 농도의 변화는 NF-$\kappa$B의 농도의 변화와 상관 관계를 보였다 (p<0.01). 급성폐손상 지수는 EP+LPS군 및 LPS+EP군에서 LPS군과 비교하여 낮았고 (p<0.05) MPO활성은 EP+LPS군에서 LPS군에 비해 낮았다 (p<0.05). 결 론: EP는 LPS로 인한 급성폐손상에 있어서 예방 및 치료 효과가 있는 것으로 판단된다.

• Journal of Chest Surgery
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• 제42권1호
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• pp.1-8
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• 2009

배경: 패혈증에 동반된 급성호흡곤란증후군의 병태생리는 내독소에 의해 유발된 급성폐손상이다. 이 연구에서 우리는 내독소로 인해 유발된 급성 폐손상에서 moxifloxacin의 영향을 알아보고자 하였다. 대상 및 방법: 백서를 대조군(C), 내독소처리군(L), 내독소-moxifloxacin처리군(L-M)으로 나누었다. 대장균의 내독소를 기관 내 분무하여 급성폐손상을 유발하였고 L-M군에서는 내독소 분무 30분 후 moxifloxacin을 투여하였다. 내독소 투여 5시간 후 폐질량/체중비, 폐세척액 내의 단백함량, 폐세척액 내의 호중구 수, 폐장 내 myeloperoxidase (MPO) 활성도, 폐장 내 malondialdehyde (MDA) 함량을 측정하였고, 폐장 내 세포질형 $phospholipaseA_2$ ($cPLA_2$)와 분비형 $phospholipaseA_2$ ($sPLA_2$)의 발현을 관찰하고 광학현미경을 이용하여 형태학적인 분석을 시행하였다. 결과: 폐질량/체중비, 폐세척액 내의 단백함량, 폐세척액 내의 호중구 수, 폐장 내 myeloperoxidase (MPO) 활성도, 폐장 내 malondialdehyde (MDA) 함량은 L군에서 대조군 보다 유의하게 증가되어 있었고, L-M군은 L군보다 의미있게 낮은 것으로 나타났다. L군에서 $cPLA_2$와 $sPLA_2$의 발현은 증가되어 있었고 L-M군에서는 $cPLA_2$의 발현이 감소되어 있었다. 그러나 L-M군에서 $sPLA_2$의 발현은 L군과 차이가 없었다. 형태학적 분석으로 L군에서 많은 염증성 소견들을 관찰할 수 있었으나 L-M군에서는 관찰할 수 없었다. 결론: 내독소에 의해 유발된 급성폐손상의 많은 염증성 변화들이 moxifloxacin처리에 의해 소멸됨을 관찰할 수 있었다.

• Tuberculosis and Respiratory Diseases
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• 제62권4호
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• pp.299-307
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• 2007

배경: HMGB1은 염증반응의 후기에 분비되는 중요한 염증유발물질 중 하나이다. 본 연구에서는 기존에 염증유발물질로 잘 알려진 LPS와 새롭게 염증유발물질로 관심을 받고 있는 HMGB1의 염증유발작용을 생체 외 및 생체 내 실험을 통해 비교하고자 하였다. 또한 HMGB1의 자극에 의한 IL-8 promoter region의 활성화에 중요한 역할을 수행하는 전사인자들을 확인하고자 하였다. 방법: RAW264.7 세포에 LPS(100 ng/ml) 또는 HMGB1(500 ng/ml)을 투여하고 각각 0, 2, 4, 8, 12 그리고 24시간 뒤에 세포상층액의 $TNF-{\alpha}$, MIP-2 그리고 $IL-1{\beta}$의 농도를 ELISA법으로 측정하였다. 생쥐의 복강에 LPS(5 mg/kg) 또는 HMGB1(2.5 mg/kg)을 주입하여 급성폐손상을 유발한 후에 폐의 사이토카인의 발현과 MPO 활성도를 측정하였다(LPS는 4시간 뒤, HMGB1은 24 시간 뒤). IL-8 promoter 부위에 있는 NF-IL6, $NF-{\kappa}B$ 그리고 AP-1에 대한 결합부위에 대해 돌연변이를 일으킨 후에 각각의 돌연변이체를 pIL-6luc에 결합시킨 뒤 RAW264.7 세포에 삽입하였다. 이 세포들을 36시간 배양한 후에 HMGB1(500 ng/ml)으로 자극하고, 한 시간 뒤에 세포를 녹인 후 luciferase 활성도를 측정하였다. 결과: LPS 투여 후에 RAW264.7 세포 배양상층액의 $TNF-{\alpha}$농도는 24시간 뒤에, MIP-2 농도는 8시간 뒤에 최고치를 보였다. 한편 HMGB1 투여 후에는 $TNF-{\alpha}$와 MIP-2 농도 모두 24시간 뒤에 최고치를 나타내었다. LPS 복강 내 투여 후 4시간 뒤에 생쥐의 폐의 $TNF-{\alpha}$, MIP-2 그리고 $IL-1{\beta}$의 농도는 대조군에 비해 현저히 증가하였으나, HMGB1 복강 내 투여 후 24시간 뒤에 생쥐의 폐에서는 $IL-1{\beta}$의 농도만 약간 증가하였다. MPO 활성도는 LPS와 HMGB1 투여 후에 모두 증가하였으며, LPS 투여 후가 더 의미있게 증가하였다. $NF-{\kappa}B$ 돌연변이체와 AP-1 돌연변이체에서 luciferase 활성도가 의미있게 감소하였다. 결론: 이상의 결과를 살펴볼 때 HMGB1은 염증유발효과는 LPS에 비해 강도가 떨어지나 지속시간은 오래 계속되는 것으로 보이며, HMGB1에 의한 IL-8의 활성화에 $NF-{\kappa}B$ 뿐만 아니라 AP-1도 중요한 역할을 수행하는 것으로 판단된다.