• Archives of Pharmacal Research
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• 제28권7호
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• pp.848-853
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• 2005

Synurus deltoides was previously found to possess significant anti-inflammatory activity especially against chronic inflammation, and strong analgesic activity in vivo. In this study, new anti-inflammatory formulation containing S. deltoides extract as a major ingredient was prepared and in vivo activity was evaluated. The plausible action mechanism was also investigated. The new formulation (SAG) contains 1 part of S. deltoides extract, 0.9 part of Angelica gigas extract and 0.9 part of glucosamine sulfate (w/w). SAG inhibited dose-dependently edematic response of arachidonic acid (AA)- and 12-O-tetradecanoyl 13-acetate (TPA)-induced ear edema in mice, which is an animal model of acute inflammation. SAG showed 44.1 % inhibition of AA-induced ear edema at an oral dose of 50 mg/kg. In an animal model of chronic inflammation, SAG clearly reduced the edematic response of 7 -day model of multiple treatment of TPA (38.1 % inhibition at 200 mg/kg/day). Furthermore, SAG (50-800 mg/kg/day) as well as S. deltoides extract (285 mg/kg/day) significantly inhibited prostaglandin $E_2$ production from the skin lesion of the animals of 7-day model. These results were well correlated with in vitro finding that SAG as well as S. deltoides extract reduced cyclooxygenase (COX)-1- and COX-2-induced prostanoid production, measured in mouse bone marrow-derived mast cells. Therefore, these results suggest that SAG possesses anti-inflammatory activity in vivo against acute as well as chronic inflammatory animal models at least in part by inhibition of prostaglandin production through COX-1/COX-2 inhibition. And COX inhibition of SAG is possibly contributed by S. deltoides extract among the ingredients. Although the anti-inflammatory potencies of SAG were less than those of currently used anti-inflammatory drugs, this formulation may have beneficial effect on inflammatory disorders as a neutraceutical.

• 한국식품위생안전성학회지
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• 제29권4호
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• pp.383-390
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• 2014

The safety of a new natural plant composition (ADP) was assessed on the genotoxicity study and 14-day repeat dose toxicity study. ADP contains a mixed water extract obtained from the mixture of Phellodendron cortex (Phellodendron amurense) and Anemarrhena rhizoma (Anemarrhena asphodeloides), and poses the contractile properties mediated by alpha-adrenoceptor of the prostate and urethra as well as antioxidant and anti-inflammatory properties. In order to evaluate genetic safety, in vivo micronucleus test was performed in ICR mice orally administered with three dose levels of 1250, 2500, 5000 mg/kg body weight, and vehicle and positive control. In the 14 days study, Sprague-Dawley rats were treated with ADP at the dose levels of 500, 1000, 2000 mg/kg once a day, and clinical signs, body weights, hematology, serum biochemistry, necropsy findings and organ weights were monitored and examined. In experimental results, ADP treatment, compared with vehicle control, did not induce the micronucleated erythrocytes from mouse bone marrow. In the 14 days study, any significant and toxicological differences in all measurements of parameters were not observed in ADP treatment groups of animals, compared with vehicle treatment. The No-Observed-Adverse-Effect-Level (NOAEL) of ADP in the 14 days study was determined to be greater than 2000 mg/kg/day in both sexes.

• 한방재활의학과학회지
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• 제31권1호
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• pp.59-79
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• 2021

Objectives This study was performed to observe the genotoxic effect of the ChondroT. Methods To evaluate the genotoxicity of ChondroT, an experiment of bacterial reverse mutation test, in vitro mammalian chromosomal aberration test and mammalian erythrocyte micronucleus test in mouse was conducted. Results TA98, TA100 and TA1537 strains in the absence of metabolic activation system (S9 mix), the number of revertant colonies being greater than 2-fold of the respective negative control value. Both in -S9 mix and +S9 mix, the frequencies of aberration cells with structural aberration and numerical aberrations of chromosome were less than 5%. There was no increase of polychromatic erythrocyte with one or more micronuclei at any dose of test substance compared to the negative control group (p<0.05). Conclusions In TA98, TA100 and TA1537 strains in the absence of metabolic activation system (S9 mix), the number of revertant colonies was greater than 2-fold of the respective negative control value, showing positive results. ChondroT was considered to be non-clastogenic to Chinese hamster lung (CHL/IU) cells under the present experimental condition. and ChondroT was determined not to induce an increased frequency of micronuclei in the bone marrow cells of male ICR mice under the present experimental condition.

• Journal of Microbiology and Biotechnology
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• 제31권2호
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• pp.290-297
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• 2021

Leptolyngbya sp. KIOST-1 (LK1) is a newly isolated cyanobacterium that shows no obvious cytotoxicity and contains high protein content for both human and animal diets. However, only limited information is available on its toxic effects. The purpose of this study was to validate the safety of LK1 powder. Following Organisation for Economic Co-operation and Development (OECD) guidelines, a single-dose oral toxicity test in Sprague Dawley rats was performed. Genotoxicity was assessed using a bacterial reverse mutation test with Salmonella typhimurium (strains TA98, TA100, TA1535, and TA1537) and Escherichia coli WP2 uvrA, an in vitro mammalian chromosome aberration test using Chinese hamster lung cells, and an in vivo mammalian erythrocyte micronucleus test using Hsd:ICR (CD-1) SPF mouse bone marrow. After LK1 administration (2,500 mg/kg), there were no LK1-related body weight changes or necropsy findings. The reverse mutation test showed no increased reverse mutation upon exposure to 5,000 ㎍/plate of the LK1 powder, the maximum tested amount. The chromosome aberration test and micronucleus assay demonstrated no chromosomal abnormalities and genotoxicity, respectively, in the presence of the LK1 powder. The absence of physiological findings and genetic abnormalities suggests that LK1 powder is appropriate as a candidate biomass to be used as a safe food ingredient.

• 치위생과학회지
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• 제23권2호
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• pp.169-175
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• 2023

Background: Although microbial infection is direct cause of periodontal disease, various environmental factors influence the disease severity. Aging is considered a risk factor for oral diseases, with the prevalence of periodontal diseases increasing with age. Moreover, senescence-associated secretory phenotype (SASP) expressed in age-related diseases is a key marker of chronic inflammation and aging phenotypes. Therefore, this study aimed to understand the relevance of senescent cells to periodontal health and disease, investigate the possibility of regulating the expression of aging- and osteolysis-related factors in gingival fibroblasts, and investigate the effect of senescence induction in gingival fibroblasts on osteoclast differentiation in mouse bone marrow-derived macrophages (BMMs). Methods: After stimulation with 400 nM hydrogen peroxidase, human gingival fibroblasts (HGFs) were examined for senescence-associated β-galactosidase. Western blot and enzyme-linked immunosorbent assays were performed to assess the expression of SASP. Osteoclast formation was assessed in BMMs using a conditioned medium (CM) from hydrogen peroxide-stimulated HGFs. Osteoclastic differentiation was investigated using tartrate-resistant acid phosphatase (TRAP) staining and activity. Data analysis was performed using SPSS version 25.0. Results: The expression of senescence-related molecules, including p53, p16, and p21, and the expression of osteolytic factors, including IL-6, IL-8, and IL-17, were found to be significantly higher in the hydrogen peroxide-stimulated HGF than in the control group. Regarding the indirect effects of senescent gingival cells, the number of osteoclasts and TRAP activity increased according to the differentiation of BMM cultured in CM. Conclusion: Our results on the of between osteolytic factors and cellular senescence in gingival fibroblast cells helped to reveal evidence of pathological aging mechanisms. Furthermore, our results suggest that the development of novel therapies that target specific SASP factors could be an effective treatment strategy for periodontal disease.

• Journal of Veterinary Science
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• 제24권5호
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• pp.72.1-72.16
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• 2023

Background: Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) on the surface of Streptococcus dysgalactiae, coded with gapC, is a glycolytic enzyme that was reported to be a moonlighting protein and virulence factor. Objective: This study assessed GAPDH as a potential immunization candidate protein to prevent streptococcus infections. Methods: Mice were vaccinated subcutaneously with recombinant GAPDH and challenged with S. dysgalactiae in vivo. They were then evaluated using histological methods. rGAPDH of mouse bone marrow-derived dendritic cells (BMDCs) was evaluated using immunoblotting, reverse transcription quantitative polymerase chain reaction, and enzyme-linked immunosorbent assay methods. Results: Vaccination with rGAPDH improved the survival rates and decreased the bacterial burdens in the mammary glands compared to the control group. The mechanism by which rGAPDH vaccination protects against S. dysgalactiae was investigated. In vitro experiments showed that rGAPDH boosted the generation of interleukin-10 and tumor necrosis factor-α. Treatment of BMDCs with TAK-242, a toll-like receptor 4 inhibitor, or C29, a toll-like receptor 2 inhibitor, reduced cytokines substantially, suggesting that rGAPDH may be a potential ligand for both TLR2 and TLR4. Subsequent investigations showed that rGAPDH may activate the phosphorylation of MAPKs and nuclear factor-κB. Conclusions: GAPDH is a promising immunization candidate protein for targeting virulence and enhancing immune-mediated protection. Further investigations are warranted to understand the mechanisms underlying the activation of BMDCs by rGAPDH in a TLR2- and TLR4-dependent manner and the regulation of inflammatory cytokines contributing to mastitis pathogenesis.

• 한국자원식물학회:학술대회논문집
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• 한국자원식물학회 2021년도 춘계학술대회
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• pp.67-67
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• 2021

The genus Glycyrrhiza (Licorice) has been used as an oriental herbal medicine for a long time in Asian countries. Wongam (WG), which is Glycyrrhiza new variety, have been developed to improve limitation of licorice including low productivity, environmental restriction and insufficient components by Korea Rural Development Administration. To using WG as a herbal medicine, it is important to reveal the adverse effects in health. In this study, we evaluated the genotoxicity test of WG extract through in vitro bacterial reverse mutation (AMES) assay, in vitro chromosomal aberration assay and in vivo mouse bone marrow micronucleus assay. When compared with the control, WG extract with or without the S9 mix showed no genotoxicity in the AMES assay up to 5000 ㎍/plate and in the chromosomal aberration assay up to 1100 ㎍/ml. In micronucleus assay, no significant increase in the number of micronucleated polychromatic erythrocytes or in the mean ratio of polychromatic to total erythrocytes up to 5000 mg/kg/day for 2 days. The present study demonstrated that WG extract is safe and reliable herbal medicine since no detectable genotoxic effects at least under the conditions of this study.

• IMMUNE NETWORK
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• 제22권4호
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• pp.33.1-33.17
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• 2022

Suppressors of cytokine signaling (SOCS) have emerged as potential regulators of macrophage function. We have investigated mechanisms of SOCS3 action on type 2 macrophage (M2) differentiation induced by glucocorticoid using human monocytic cell lines and mouse bone marrow-derived macrophages. Treatment of THP1 monocytic cells with dexamethasone (Dex) induced ROS generation and M2 polarization promoting IL-10 and TGF-β production, while suppressing IL-1β, TNF-α and IL-6 production. SOCS3 over-expression reduced, whereas SOCS3 ablation enhanced IL-10 and TGF-β induction with concomitant regulation of ROS. As a mediator of M2 differentiation, glucocorticoid-induced leucine zipper (GILZ) was down-regulated by SOCS3 and up-regulated by shSOCS3. The induction of GILZ and IL-10 by Dex was dependent on ROS and p38 MAPK activity. Importantly, GILZ ablation led to the inhibition of ROS generation and anti-inflammatory cytokine induction by Dex. Moreover, GILZ knock-down negated the up-regulation of IL-10 production induced by shSOCS3 transduction. Our data suggest that SOCS3 targets ROS- and p38-dependent GILZ expression to suppress Dex-induced M2 polarization.

• 동의생리병리학회지
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• 제17권3호
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• pp.605-610
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• 2003

인삼, 호장근, 상산 등에서 분리한 성분들이 HL60, HL-60, Jurkat, Molt-4에 대한 억제작용이 있는 것으로 조사되었고, 익모초의 Leonunrine, 대청엽의 Indirubin, 천문동의 Aspargus polysaccharideA.B.C.D, 백합의 Colchicnamile, 익모초의 Lenunrine, 산두근, 자초근 추출물이 여러유형의 백혈병 환자에 대한 백혈병 억제효과가 있는 것으로 조사되었으며, mouse의 P388, L1210, L615, L120, S-180 등에 항 백혈병 효과가 있는 것으로는 완화, 로회, 원지, 오수유, 파두, 뇌공등, 석산, 백출, 단삼, 산약, 목단피, 청대, 감초, 당귀에서 분리한 성분들이 있으며 백굴채, 마전자, 가시오가피, 천초 추출물들이 동물실험에서 항암작용이 있는 것으로 조사되었다. 또 천연물에서 분리한 성분이 항백혈병 작용이 있는것으로는 ginsenoside Ro, ginseonoside Rh2, Emodin, Yuanhuacine, Aleemodin, phorbocdiester, Triptolide, Homolycorine, Atractylol, Colchicnamile, Paeonol, 당귀다당체, Aspargus polysaccharideABCD, Indirubin, Leonunrine, Acinosohic acid, Trichosanthin, G2 132, Schizandrin, allicin, Indirubin, cmdiumlactone chuanxiongol, 18A glycyrrhetic acid, Kansuiphorin A, 13 oxyingenol Kansuiphorin B 등이 조사되었고, 추출물이 항 백혈병 작용이 있는 것으로는 원지, 오수유, 백굴채, 대황, 산두근, 마전자, 가시오가피, 천초 등이 조사되었다.

• 한국식품영양과학회지
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• 제43권1호
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• pp.9-15
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• 2014

간장 중에 존재하는 새로운 생물활성 성분을 규명하기 위해 일본식으로 제조된 시판 간장(CSP-0)과 우리나라 전통방식으로 제조된 재래식 간장으로부터 다당(KTSP-0)을 분리하여 장관면역 활성에 대하여 비교, 검토하였다. Peyer's patch 세포를 이용한 in vitro 실험에서 간장 유래 다당인 CSP-0와 KTSP-0는 IL-6 생산 자극활성을 증가시켰지만 KTSP-0가 CSP-0보다 상대적으로 높게 나타났다. 또한 KTSP-0는 모든 농도에서 대조군에 비해 IgA 생산능을 유의적으로 증가시켰으나, 시판 간장 유래 다당인 CSP-0의 경우 IgA 생산증가에 큰 영향을 미치지 않은 것으로 나타났다. Peyer's patch를 경유한 골수세포 증식능에서 KTSP-0는 100 ${\mu}g/mL$의 농도에서 대조군에 비해 높은 장관면역 활성을 나타냈으며, CSP-0는 골수세포 증식능이 거의 없는 것으로 확인되었다. 간장 유래 다당에 의한 in vivo 장관면역 활성을 관찰하기 위해 0.0, 0.5, 1.0 및 5.0 mg/mouse의 농도로 30일간 경구 투여하고 Peyer's patch 세포에 의한 IgA 생산능을 측정한 결과, CSP-0와 KTSP-0를 경구 투여한 mouse 군에서 농도 의존적으로 우수한 IgA 생산 증진활성을 보였으며 분변 중에 존재하는 IgA 함량을 증가시켰다. Peyer's patch 세포에 의한 IL-6 생산능을 측정한 결과, CSP-0 및 KTSP-0를 투여한 mouse의 Peyer's patch 세포들은 대조군에 비해 모두 IL-6의 생산능을 증진시켰으나 동일 투여 농도에서 KTSP-0의 효과가 더 우수하였다. 또한 KTSP-0의 경구 투여는 혈청 내 IL-6를 높게 증가시키는 반면 CSP-0는 IL-6 생산에 영향을 미치지 않는 것으로 확인되었다. 이러한 결과를 토대로 본 연구를 통해 시판 간장보다 전통 재래식 간장이 높은 장관면역 활성 효과를 가지고 있는 것으로 확인되었으며, 이는 간장 제조 원료 및 제조과정과 발효에 관여하는 미생물의 차이에서 기인된 것으로 생각된다.