• Fisheries and Aquatic Sciences
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• v.24 no.4
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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.

• Biomolecules & Therapeutics
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• v.29 no.5
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• pp.536-544
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• 2021

5-amino salicylic acid (5-ASA) is a standard therapy for the treatment of mild to moderate forms of inflammatory bowel diseases (IBD) whereas more severe forms involve the use of steroids and immunosuppressive drugs. Hyaluronic acid (HA) is a naturally occurring non-sulfated glycosaminoglycan that has shown epithelium protective effects in experimental colitis recently. In this study, both 5-ASA (30 mg/kg) and HA (15 mg/kg or 30 mg/kg) were administered rectally and investigated for their potential complementary therapeutic effects in moderate or severe murine colitis models. Intrarectal treatment of moderate and severe colitis with 5-ASA alone or HA alone at a dose of 30 mg/kg led to a significant decrease in clinical activity and histology scores, myeloperoxidase activity (MPO), TNF-α, IL-6 and IL-1β in colitis mice compared to untreated animals. The combination of HA (30 mg/kg) and 5-ASA in severe colitis led to a significant improvement of colitis compared to 5-ASA alone. Combined rectal therapy with HA and 5-ASA could be a treatment alternative for severe cases of IBD as it was the only treatment tested that was not significantly different from the healthy control group. This study further underlines the benefit of searching for yet unexplored drug combinations that show therapeutic potential in IBD without the need of designing completely new drug entities.

• 대한상한금궤의학회지
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• v.13 no.1
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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.

• Journal of Microbiology and Biotechnology
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• v.32 no.7
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• pp.835-843
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• 2022

Deinococcus radiodurans is an extremophilic bacterium that can thrive in harsh environments. This property can be attributed to its unique metabolites that possess strong antioxidants and other pharmacological properties. To determine the potential of D. radiodurans R1 lysate (DeinoLys) as a pharmacological candidate for inflammatory bowel disease (IBD), we investigated the antiinflammatory activity of DeinoLys in bone marrow-derived dendritic cells (BMDCs) and a colitis mice model. Lipopolysaccharide (LPS)-stimulated BMDCs treated with DeinoLys exhibited alterations in their phenotypic and functional properties by changing into tolerogenic DCs, including strongly inhibited proinflammatory cytokines (TNF-α and IL-12p70) and surface molecule expression and activated DC-induced T cell proliferation/activation with high IL-10 production. These phenotypic and functional changes in BMDCs induced by DeinoLys in the presence of LPS were abrogated by IL-10 neutralization. Furthermore, oral administration of DeinoLys significantly reduced clinical symptoms against dextran sulfate sodium-induced colitis, including body weight loss, disease activity index, histological severity in colon tissue, and lower myeloperoxidase level in mice. Our results establish DeinoLys as a potential anti-inflammatory candidate for IBD therapy.

• Journal of Korean Medicine Rehabilitation
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• v.32 no.1
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• pp.1-19
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• 2022

Objectives This study aims to evaluate the wound healing effects of oral administered hot water extracts of Korean black ginseng (KBG). Methods 40 C57BL/6 mice were divided into five groups; normal, control, vitamin E 200 mg/kg, KBG 100 mg/kg, KBG 200 mg/kg, each n=8. Skin wounds were made in the back of all mice except normal group using biopsy punches. Wounds were observed on days 7 and 14 after injury. The anti-oxidant and inflammatory protein levels were evaluated using western blotting. Skin tissue was analyzed by hematoxylin & eosin and Masson's trichrome staining method. Results KBG significantly accelerated reducing wound area. KBG significantly decreased myeloperoxidase activity. KBG significantly decreased oxidative stress factors such as NADPH oxidase-4 and p22^phox and increased antioxidant enzymes including nuclear factor erythroid 2-related factor2, kelch-like ECH-associated protein-1, heme oxygenase-1, superoxide dismutase, catalase and glutathione peroxidase-1/2. Moreover, KBG significantly decreased inflammation factors including nuclear factor-κB, phosphorylated inhibitor of κBα, cyclooxygenase-2, inducible nitric oxide synthase, tumor necrosis factor-α and interleukin (IL)-6 and increased anti-inflammation cytokine such as IL-4 and IL-10. In addition, KBG significantly increased tight junction proteins including claudin-1, claudin-3, claudin-4. In histopathologic, KBG made the epithelium thin and uniform, and accelerated the remodeling of collagen. Conclusions The results suggest that KBG has healing effects on skin wound in mice by anti-inflammatory and antioxidant activity.

• The Journal of Internal Korean Medicine
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• v.43 no.4
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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.

• The Korea Journal of Herbology
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• v.29 no.1
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• pp.19-26
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• 2014

Objectives : This study was performed in order to evaluate the effects of Salviae Miltiorrhizae Radix (SMR) water extract against the cerebral hemorrhage and the blood-brain barrier (BBB) impairment in the intracerebral hemorrhage (ICH). Method : ICH was induced by the stereotaxic intrastriatal injection of bacterial collagenase type IV in Sprague-Dawley rats. SMR was orally given three times every 20 hours during 3 days after the ICH induction. Hematoma volume, water content of brain tissue and volume of evans blue leakage were examined. Myeloperoxidase (MPO) positive neutrophils and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) were observed with immunofluorescence labeling and confocal microscope. Results : SMR significantly reduced the hematoma volume of the ICH-induced rat brain. SMR significantly reduced the water content of brain tissue of the ICH-induced rat brain. SMR reduced the percentage of the evans blue leakage around the hematoma on the caudate putamen compared to the ICH group, especially on the cerebral cortex. SMR significantly reduced the volume of the evans blue leakage level in the peri-hematoma regions of the ICH-induced rat brain. SMR significantly reduced MPO positive neutrophils in the peri-hematoma regions of the ICH-induced rat brain. SMR reduced the TNF-${\alpha}$ expression in peri-hematoma regions of the ICH-induced rat brain. TNF-${\alpha}$ immuno-labeled cells were coincided with MPO immuno-labeled neutrophils in peri-hematoma regions of the ICH-induced rat brain. Conclusion : These results suggest that SMR plays a protective role against the blood-brain barrier impairment in the ICH through suppression of inflammation in the rat brain tissues.

• The Korea Journal of Herbology
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• v.33 no.2
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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.

• The Korea Journal of Herbology
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• v.29 no.2
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• pp.33-38
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• 2014

Objectives : Inflammation is mediated by cellular components, such as leukocytes and microglia, and molecular components, including cytokines, extracellular proteases, and reactive oxygen species. Cnidium Rhizoma effects the anti-inflammatory, antioxidant, suppression of the microglia activation and protection of the nerve cell injury. For this reason, we investigated the anti-inflammatory effects of water extracts of Cnidium Rhizoma on intracerebral hemorrhage (ICH). Method : ICH was induced by the stereotaxic intracerebral injection of bacterial collagenase type IV (0.23 $U/{\mu}{\ell}$, 0.1 ${\mu}{\ell}/min$) in Sprague-Dawley rats. We orally administrated once 3 hours after ICH, then 2 times at 24-hour intervals the water extracts of Cnidium Rhizoma (500 mg/kg), myeloperoxidase (MPO) was observed by using immunofluorescense and expression of inducible nitric oxide synthase (iNOS), tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and microglia were observed by using immunohistochemistry. Results : Infiltration of MPO expressing neutrophil, expression of iNOS and TNF-${\alpha}$ and activated microglia were significantly reduced in peri-hematoma of the rats fed with water extracts of Cnidium Rhizoma. Conclusion : These results demonstrated that water extracts of Cnidium Rhizoma suppressed an inflammatory reaction through inhibition of MPO, iNOS and TNF-${\alpha}$ positive cell and activated microglia number in peri-hematoma of ICH-induced rats.

• Journal of Veterinary Science
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• v.21 no.4
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• pp.61.1-61.16
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• 2020

Background: Panax notoginseng saponins (PNS) are bioactive substances extracted from P. notoginseng that are widely used to treat cardiovascular and cerebrovascular diseases and interstitial diseases. PNS have the functions of scavenging free radicals, anti-inflammation, improving blood supply for tissue and so on. Objectives: The aim of this study was to investigate the effects of PNS on the oxidative stress of immune cells induced by porcine circovirus 2 (PCV2) infection in vitro and in vivo. Methods: Using an oxidative stress model of PCV2 infection in a porcine lung cell line (3D4/2 cells) and mice, the levels of nitric oxide (NO), reactive oxygen species (ROS), total glutathione (T-GSH), reduced glutathione (GSH), and oxidized glutathione (GSSG) and the activities of xanthine oxidase (XOD), myeloperoxidase (MPO) and inducible nitric oxide synthetase (iNOS) were determined to evaluate the regulatory effects of PNS on oxidative stress. Results: PNS treatment significantly reduced the levels of NO and ROS, the content of GSSG and the activities of XOD, MPO, and iNOS (p < 0.05), while significantly increasing GSH and the ratio of GSH/GSSG in infected 3D4/2 cells (p < 0.05).Similarly, in the in vivo study, PNS treatment significantly decreased the level of ROS in spleen lymphocytes of infected mice (p < 0.05), increased the levels of GSH and T-GSH (p < 0.05), significantly decreased the GSSG level (p < 0.05), and decreased the activities of XOD, MPO, and iNOS. Conclusions: PNS could regulate the oxidative stress of immune cells induced by PCV2 infection in vitro and in vivo.