금은화, 연교, 포공영 혼합물의 항염증 작용에 관한 연구

최강민 ( Kang Min Choi ),전주현 ( Ju Hyun Jeon ),김은석 ( Eun Seok Kim ),성기정 ( Ki Jung Sung ),김영일 ( Young Il Kim ) 대전대학교 한의학연구소 2021 혜화의학회지 Vol.30 No.1

Objective : The purpose of this study is to investigate the inflammatory-control effects of Cheonghyeol-antidote complex(Lonicera japonica Thunberg, Forsythia viridissima Lindley, and Taraxacum platycarpum H. Dahlstedt complex, CHA) in LPS-induced RAW264.7 cell and mouse inflammation models. Method : For in vitro and in vivo experiment, Indicators such as cell viability, mRNA expression level(iNOS, IL-6, IL-1β, COX-2, TNF-a), Inflammatory factor production(NO, IL-6, IL-1β, TNF-a), and protein phosphorylation level(ERK, JNK, p38) were analyzed. For in vivo experiment, Indicators such as mRNA expression level(iNOS, IL-6, IL-1β, COX-2, TNF-a), Inflammatory factor production(IL-6, IL-1β, TNF-a), protein phosphorylation level(ERK, JNK, p38) and immune cell(white blood cell, lymphocyte) were analyzed. Results : 1. In vitro experiment In cell viability of CHA, CHA showed cell viability below 90% at concentrations of 400 μg / ml or more. In mRNA expression level, IL-6 and IL-1β showed a significant decrease at all concentrations except 25 μg / ml concentration, and iNOS, COX-2, and TNF-a showed a significant decrease at all concentrations of CHA compared to the control group. In inflammatory factor production, NO and TNF-a showed a significant decrease at all concentrations except 25 μg / ml concentration of CHA, and IL-1β showed a significant decrease at 100, 200 μg / ml concentration of CHA compared to the control group. IL-6 showed a significant decrease at all concentration of CHA compared to the control group. In protein phosphorylation level, ERK and p38 showed a significant decrease at all concentrations except 25 μg / ml concentration of CHA and JNK showed a significant decrease at all concentrations of CHA compared to control group. 2. In vivo experiment In mRNA expression level, iNOS, COX-2 and TNF-a showed a significant decrease in all administration groups of CHA compared to the control group. In Inflammatory factor production, IL-6, IL-1β and TNF-a showed a significant decrease in all the administration groups of CHA. In protein phosphorylation level, ERK, JNK, and p38 showed a significant decrease in all the administration groups of CHA. In the immune cells, leukocytes and lymphocytes showed a significant decrease in all the administration groups of CHA. Conclusions : This study shows that CHA has antioxidant and inflammatory-control effects on LPS-induced RAW264.7 cells. It is hoped that further research will be conducted on the individual mechanisms of Lonicera japonica Thunberg, Forsythia viridissima Lindley, and Taraxacum platycarpum H. Dahlstedt.

Hair-Loss Preventing Effect of Grateloupia elliptica

( Jung Il Kang ),( Sang Cheol Kim ),( Sang Chul Han ),( Hye Jin Hong ),( You Jin Jeon ),( Bo Ra Kim ),( Young Sang Koh ),( Eun Sook Yoo ),( Hee Kyoung Kang ) 한국응용약물학회 2012 Biomolecules & Therapeutics(구 응용약물학회지) Vol.20 No.1

This study was conducted to evaluate the effect of Grateloupia elliptica, a seaweed native to Jeju Island, Korea, on the prevention of hair loss. When immortalized rat vibrissa dermal papilla cells were treated with extract of G. elliptica, the proliferation of dermal papilla cells significantly increased. In addition, the G. elliptica extract significantly inhibited the activity of 5α-reductase, which converts testosterone to dihydrotestosterone (DHT), a main cause of androgenetic alopecia. On the other hand, the G. elliptica extract promoted PGE2 production in HaCaT cells in a dose-dependent manner. The G. elliptica extract exhibited particularly high inhibitory effect on LPS-stimulated IL-12, IL-6, and TNF-α production in lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells. The G. elliptica extract also showed inhibitory activity against Pityrosporum ovale, a main cause of dandruff. These results suggest that G. elliptica extract has the potential to treat alopecia via the proliferation of dermal papilla, 5α-reductase inhibition, increase of PGE2 production, decrease of LPS-stimulated pro-inflammatory cytokines and inhibitory activity against Pityrosporum ovale.

비만 쥐의 식이제한과 유산소운동이 시상하부의 염증, 식욕억제 Neuropeptide 및 하루식이섭취량에 미치는 영향

박상용(Park, Sang-Yong),전용균(Jeon, Yong-Kyun),최재일(Choi, Jae-Il) 한국체육과학회 2017 한국체육과학회지 Vol.26 No.1

This study was conducted to investigate the effects of calorie restriction and aerobic exercise on expression of appetite suppression neuropeptide, inflammation factors in hypothalamus and daily feed intake of obese mouse. Obesity was induced in C57BL/6 male mice (n=60) by high-fat diet, which were divided into six experimental groups, control group (CG), high-fat diet group (HDG), normal diet group (NDG), normal diet and aerobic exercise group (NDEG), calorie restriction group (CRG), calorie restriction and aerobic exercise group (CREG). Calorie restriction and/or aerobic exercise of 12 weeks were treated, and as a result of analysis of dependent variables, the following conclusion was induced. After completion of experiment, CREG was shown to be effective in weight reduction compared with other groups. and average daily feed intake was shown less after completion of experiment than high-fat diet group (HDG), normal diet group (NDG) and calorie restriction group (CRG). Also, as manifestation of IL-6 in the hypothalamus was shown significantly higher compared with other groups. the affirmative effect in synaptic transmission of signal related to appetite suppression and energy consumption by increase of IL-6 in the hypothalamus due to aerobic exercise was confirmed. On the contrary, although, in HDG, concentration of leptin expression levels in the hypothalamus were shown significantly lower, leptin resistance may be confirmed. and TNF-α expression level was shown significantly more than other groups. As a result, by IL-6 in the hypothalamus as reaction to aerobic exercise and calorie restriction in treatment with leptin resistance in obesity, the effect of weight reduction was confirmed.

Thymol attenuates the worsening of atopic dermatitis induced by <i>Staphylococcus aureus</i> membrane vesicles

Kwon, Hyo Il,Jeong, Na Hee,Jun, So Hyun,Son, Joo Hee,Kim, Shukho,Jeon, Hyejin,Kang, Sun Chul,Kim, Sang Hyun,Lee, Je Chul Elsevier 2018 INTERNATIONAL IMMUNOPHARMACOLOGY Vol.59 No.-

<P><B>Abstract</B></P> <P> <I>Staphylococcus aureus</I> membrane vesicles (MVs) aggravate atopic dermatitis (AD) through the delivery of bacterial effector molecules to host cells and the stimulation of inflammatory responses. This study investigated the inhibitory effect of thymol, a phenolic monoterpene found in essential oils derived from plants, on the worsening of AD induced by <I>S. aureus</I> MVs both <I>in vitro</I> and <I>in vivo</I>. The sub-minimal inhibitory concentrations of thymol disrupted <I>S. aureus</I> MVs. Intact <I>S. aureus</I> MVs induced the expression of pro-inflammatory cytokine (interleukin (IL)-1β, IL-6, and tumor necrosis factor-α) and chemokine (IL-8 and monocyte chemoattractant protein-1) genes in cultured keratinocytes, whereas thymol-treated <I>S. aureus</I> MVs did not stimulate the expression of these genes. Topical application of thymol-treated <I>S. aureus</I> MVs or treatment with thymol after intact <I>S. aureus</I> MVs to AD-like skin lesions diminished the pathology of AD. This included decreases in epidermal/dermal thickness and infiltration of eosinophils/mast cells, and inhibited expression of pro-inflammatory cytokine and chemokine genes in mouse AD model. Moreover, thymol significantly suppressed the Th1, Th2, and Th17-mediated inflammatory responses in AD-like skin lesions induced by <I>S. aureus</I> MVs, and reduced the serum levels of immunoglobulin (Ig) G2a, mite-specific IgE, and total IgE. In summary, thymol disrupts <I>S. aureus</I> MVs and suppresses inflammatory responses in AD-like skin lesions aggravated by <I>S. aureus</I> MVs. Our results suggest that thymol is a possible candidate for the management of AD aggravation induced by <I>S. aureus</I> colonization or infection in the lesions.</P> <P><B>Highlights</B></P> <P> <UL> <LI> The subMICs of thymol disrupt <I>S. aureus</I> membrane vesicles (MVs). </LI> <LI> Thymol-treated <I>S. aureus</I> MVs do not induce inflammatory responses in keratinocytes. </LI> <LI> Thymol inhibits worsening of AD-like lesions induced by <I>S. aureus</I> MVs. </LI> </UL> </P>

<i>In vivo</i> genotoxicity evaluation of lung cells from Fischer 344 rats following 28 days of inhalation exposure to MWCNTs, plus 28 days and 90 days post-exposure

Kim, Jin Sik,Sung, Jae Hyuck,Choi, Byung Gil,Ryu, Hyeon Yeol,Song, Kyung Seuk,Shin, Jae Hoon,Lee, Jong Seong,Hwang, Joo Hwan,Lee, Ji Hyun,Lee, Gun Ho,Jeon, Kisoo,Ahn, Kang Ho,Yu, Il Je Informa Healthcare 2014 INHALATION TOXICOLOGY Vol. No.

<P>Despite their useful physico-chemical properties, carbon nanotubes (CNTs) continue to cause concern over occupational and human health due to their structural similarity to asbestos. Thus, to evaluate the toxic and genotoxic effect of multi-wall carbon nanotubes (MWCNTs) on lung cells <I>in vivo</I>, eight-week-old rats were divided into four groups (each group = 25 animals), a fresh air control (0 mg/m<SUP>3</SUP>), low (0.17 mg/m<SUP>3</SUP>), middle (0.49 mg/m<SUP>3</SUP>), and high (0.96 mg/m<SUP>3</SUP>) dose group, and exposed to MWCNTs <I>via</I> nose-only inhalation 6 h per day, 5 days per week for 28 days. The count median length and geometric standard deviation for the MWCNTs determined by TEM were 330.18 and 1.72 nm, respectively, and the MWCNT diameters ranged from 10 to 15 nm. Lung cells were isolated from five male and five female rats in each group on day 0, day 28 (only from males) and day 90 following the 28-day exposure. The total number of animals used was 15 male and 10 female rats for each concentration group. To determine the genotoxicity of the MWCNTs, a single cell gel electrophoresis assay (Comet assay) was conducted on the rat lung cells. As a result of the exposure, the olive tail moments were found to be significantly higher (<I>p</I> < 0.05) in the male and female rats from all the exposed groups when compared with the fresh air control. In addition, the high-dose exposed male and middle and high-dose exposed female rats retained DNA damage, even 90 days post-exposure (<I>p</I> < 0.05). To investigate the mode of genotoxicity, the intracellular reactive oxygen species (ROS) levels and inflammatory cytokine levels (TNF-α, TGF- β, IL-1, IL-2, IL-4, IL-5, IL-10, IL-12 and IFN-γ) were also measured. For the male rats, the H<SUB>2</SUB>O<SUB>2</SUB> levels were significantly higher in the middle (0 days post-exposure) and high- (0 days and 28 days post-exposure) dose groups (<I>p</I> < 0.05). Conversely, the female rats showed no changes in the H<SUB>2</SUB>O<SUB>2</SUB> levels. The inflammatory cytokine levels in the bronchoalveolar lavage (BAL) fluid did not show any statistically significant difference. Interestingly, the short-length MWCNTs deposited in the lung cells were persistent at 90 days post-exposure. Thus, exposing lung cells to MWCNTs with a short tube length may induce genotoxicity.</P>

Antiviral and anti-inflammatory activity of budesonide against human rhinovirus infection mediated via autophagy activation

Kim, Seong-Ryeol,Song, Jae-Hyoung,Ahn, Jae-Hee,Lee, Geun-Shik,Ahn, Huijeong,Yoon, Sung-il,Kang, Seung Goo,Kim, Pyeung-Hyeun,Jeon, Sang-Min,Choi, Eun-Ji,Shin, Sooyoung,Cha, Younggil,Cho, Sungchan,Kim, Elsevier 2018 Antiviral research Vol.151 No.-

<P>Human rhinovirus (HRV) infection causes more than 80% of all common colds and is associated with severe complications in patients with asthma and chronic obstructive pulmonary disease. To identify antiviral drug against HRV infection, we screened 800 FDA-approved drugs and found budesonide as one of the possible drug candidates. Budesonide is a corticosteroid, which is commonly used to prevent exacerbation of asthma and symptoms of common cold. Budesonide specifically protects host cells from cytotoxicity following HRV infection, which depend on the expression of glucocorticoid receptor. Intranasal administration of budesonide lowered the pulmonary HRV load and the levels of IL-1 beta cytokine leading to decreased lung inflammation. Budesonide regulates IL-1 beta production following HRV infection independent of inflammasome activation. Instead, budesonide induces mitochondrial reactive oxygen species followed by activation of autophagy. Further, the inhibition of autophagy following chloroquine or bafilomycin Al treatment reduced the anti-viral effect of budesonide against HRV, suggesting that the antiviral activity of budesonide was mediated via autophagy. The results suggest that budesonide represents a promising antiviral and anti-inflammatory drug candidate for the treatment of human rhinovirus infection.</P>

Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF)의 첨가가 생쥐 수정란의 발생과 착상관련 유전자 발현에 미치는 영향

김동훈,고덕성,이회창,이호준,강희규,김태전,박원일,김세웅,Kim, Dong-Hoon,Ko, Duck-Sung,Lee, Hoi-Chang,Lee, Ho-Joon,Kang, Hee-Gyoo,Kim, Tai-Jeon,Park, Won-Il,Kim, Seung-Samuel 대한생식의학회 2002 Clinical and Experimental Reproductive Medicine Vol.29 No.2

Objective : The purpose of the current series of experiments were to assess the effect of GM-CSF, as a medium supplement, on the development of mouse embryos and the expression of LIF and IL-1? mRNA. Materials and Methods: Mouse 2-cell embryos were collected from the oviducts of 6 weeks old ICR mice at 48 hours after hCG injection. Embryos were cultured in P-1 medium supplemented with mouse GM-CSF (0, 1, 5, 10 ng/ml). The embryo development to blastocysts and hatching blastocysts was assessed and the cell number in blastocyst was also examined. Using RT-PCR, the expressions of LIF and IL-1? mRNA in blastocyst were evaluated in the GM-CSF supplemented group and control group. Results: In mouse, the addition of GM-CSF increased the percentage of blastocysts (65.5%, 68.6%, 73.0% and 76.1% for control and 1, 5 and 10 ng/ml, respectively), and increased the proportion of hatching blastocysts (35.2%, 36.4%, 43.2% and 53.0% for control and 1, 5 and 10 ng/ml, respectively). The mean cell numbers in blastocyst were significantly increased in GM-CSF supplemented groups compared to control group. LIF and IL-1? expression in blastocyst were significantly higher in GM-CSF supplemented group than in control group. Conclusion: The results of experiment by mouse embryos showed beneficial effects of GM-CSF as a medium supplement. Furthermore, the addition of GM-CSF significantly increased the expression of LIF and IL-1? in mouse embryos. These results suggest that GM-CSF might be a important molecule in embryo implantation.

Cell source-dependent <i>in vivo</i> immunosuppressive properties of mesenchymal stem cells derived from the bone marrow and synovial fluid of minipigs

Lee, Won-Jae,Hah, Young-Sool,Ock, Sun-A.,Lee, Jae-Hoon,Jeon, Ryong-Hoon,Park, Ji-Sung,Lee, Sang-Il,Rho, Na-Young,Rho, Gyu-Jin,Lee, Sung-Lim Elsevier 2015 Experimental cell research Vol.333 No.2

<P><B>Abstract</B></P> <P>The <I>in vitro</I> differentiation and immunosuppressive capacity of mesenchymal stem cells (MSCs) derived from synovial fluid (SF-MSCs) and bone marrow extract (BM-MSCs) in an isogenic background of minipigs were comparatively analyzed in a collagen-induced arthritis (CIA) mouse model of rheumatoid arthritis (RA). The proliferation capacity and expression of pluripotent transcription factors (Oct3/4 and Sox2) were significantly (<I>P</I><0.05) higher in SF-MSCs than in BM-MSCs. The differentiation capacity of SF-MSCs into adipocytes, osteocytes and neurocytes was significantly (<I>P</I><0.05) lower than that of BM-MSCs, and the differentiation capacity of SF-MSCs into chondrocytes was significantly (<I>P</I><0.05) higher than that of BM-MSCs. Systemic injection of BM- and SF-MSCs significantly (<I>P</I><0.05) ameliorated the clinical symptoms of CIA mice, with SF-MSCs having significantly (<I>P</I><0.05) higher clinical and histopathological recovery scores than BM-MSCs. Furthermore, the immunosuppressive properties of SF-MSCs in CIA mice were associated with increased levels of the anti-inflammatory cytokine interleukin (IL)-10, and decreased levels of the pro-inflammatory cytokine IL-1β and osteoclast-related sRANKL. In conclusion, SF-MSCs exhibited eminent pluripotency and differentiation capacity into chondrocytes, addition to substantial <I>in vivo</I> immunosuppressive capacity by elevating IL-10 and reducing IL-1β levels in CIA mice.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Immunosuppressive capacity of BM-, SM-, and SF-MSCs was evaluated in an RA model. </LI> <LI> Proliferation, pluripotency and chondrogenic differentiation capacity were higher in SF-MSCs. </LI> <LI> SF-MSCs exhibited improved therapeutic effects than BM-MSCs. </LI> <LI> SF-MSCs may have applications as immunosuppressive therapy in autoimmune diseases. </LI> </UL> </P>

Cyclohexane에 의한 흰쥐의 폐독성

전태원,이상일,윤종국 대한의생명과학회 2000 Journal of biomedical laboratory sciences Vol.6 No.4

Cyclohexane에 의한 생체장기의 독성을 검토할 목적으로 휜쥐에 체중 kg당 1.56 g의cyclohexane을 복강으로 1일 1회 2일 간격으로 4회 투여한 다음 24시간 후에 처치하여 각 장기 (간,신장, 비장, 심장, 소장, 위 및 폐)의 체중 당 장기무게 (%)와 조직세포중 glucose-6-phosphatase (G6Pase) 활성변동을 측정한 결과, 실험군의 체중 당 폐무게가 대조군에 비하여 현저하게 증가 (p<0,001)하였고 이와는 반대로 G6pase 활성은 유의한 (p<0.001) 감소를 나타내었다. 그러나 폐를 제의한 장기에서는 별다른 차이를 볼 수 없었다. 이러한 결과는 cyclohexane이 주로 폐조직에 독작용을 야기시킨다는 것을 시사해 주고 있으며, 폐조직에서 malondialdehyde 함량이 대조군에 비하여 유의하게 (p<0.05) 증가된 것이 이를 뒷받침 해 주고 있다. 한편, cytochrome P450에 의해 나타나는 aniline hydroxylase활성은 폐조직이 간조직에 비하여 대단히 낮았으며, alcohol dehydrogenase (ADH) 활성 역시 간조직 보다 현저하게 낮게 나타났다. 그리고 cyclohexane투여로 인하여 ADH 활성은 간 및 폐조직 모두에서 증가하였으나 간조직에서 더욱민감한 반응을 나타내었다. 이상 실험결과를 종합해 볼 때, cyclohexane은 폐조직에 주로 독성을 나타 내며 이는 간조직에서 대사된 cyclohexane의 독성 중간대사산물인 cyclohexanone이 혈류를 통해 폐조직에 분포되어 나타난 결과로 사료된다. In order to search the target organ of cylclohexane toxicity, the rats were intraperitoneally treated with cyclohexane (1.56 g/kg of body wt.) four times every other day. In the increasing rate of organ weight per body weight (%) in cyclohexane-treated animals, the lung was highest among the liver, spleen small intestine, stomach, heart and kidney. And in the decreasing rate of glucose-6-phosphatase (G-6-Pase) activity in each organ that of lung was also highest among all organs. Lung MDA content was significantly increased (p<0.05) by the cyclohexane treatment. On the other hand, microsomal aniline hydroxylase activity in lung tissue both of control and cyclohexane-treated rats was greatly low as could be scarcely measured, but that in liver possessing high activity was significantly increased (p<0.05) in cyclohexane-treated rat compared with control. Alcohol dehydrogenase activity in lung was markedly higher than that of liver and the latter was significantly (p<0.05) increased by the cyclohexane treatment. In conclusion, cyclohexane treatment to the rats showed mainly lung toxicity and it may be responsible far cyclohexanon, cyclohexane metabolite, distributed from liver.

흰쥐에 Xylene 반복 투여가 Xylene의 대사에 미치는 영향

전태원,이혜자,윤종국,이상일,조현국 THE KOREAN SOCIETY FOR BIOMEDICAL LABORATORY SCIEN 1999 Journal of biomedical laboratory sciences Vol.5 No.1

실험동물에 xylene의 반복 투여가 이물질의 대사에 어떠한 영향을 미치는지를 알아보기 위하여 흰쥐에 m-xylene과 olive oil의 동량혼합액을 체중 100g당 0.25ml씩 2일 간격으로 1, 4, 8, 12 및 16회 복강으로 투여한 다음 마지막 투여 24시간 후에 처치하여 다음과 같은 결과를 얻었다. 요 중 m-methylhippuric acid 함량은 m-xylene 4회 투여군의 경우 1회 투여군에 비하여 약 56%의 유의한 증가를 보였으며 이후 12회 투여까지 유사한 결과를 나타내었으나 m-xylene 16회 투여시에는 xylene 1회 투여군 치와 유사한 치로 감소되었다. 그리고 간조직의 microsomal aniline hydroxylase와 alcohol dehydrogenase 활성은 m-xylene 12회 투여시 까지는 대체적으로 점진적인 증가를 보였으나 이후 16회 투여시에는 12회 투여군에 비하여 유의한 감소를 보였다. 또한 aldehyde dehydrogenase 활성은 m-xylene 투여 회수에 비례해서 전 실험기간 동안 감소되었으며 특히 16회 투여군에서 본 효소활성의 현저한 감소를 보였다. 한편 본 실험조건에서 투여기간에 따른 진자현미경적 미세구조의 변화는 초기에 활면소포체의 증식이 보이다가 16회 투여군에서는 활면소포체가 감소되고 조면소포체가 증가되었다. 이상 실험결과는 흰쥐에 있어서 xylene 투여 회수에 따라서 요 중 m-methylhippuric acid의 농도 변동이 초래되며 이는 효소단백 유도에 따른 xylene 대사효소 활성 변동에 기인된 결과로 생각된다. To evaluate the effect of repeated treatment of xylene on its metabolism, m-xylene (0.25ml of 50% in olive oil/100 g body weight) has been intraperitoneally given to the rats 1, 4, 8, 12 and 16 times every other day. m-Xylene was once more administered to the animals after 24 hrs since last injection of it. And then the animals were sacrificed after 24 hrs. Four times xylene treated rats showed the significantly elevated urinary m-methylhippuric acid, compared to those treated with the singe dose of m-xylene with the continued similiar high levels of urinary m-methylhippuric acid up to the animals pretreated 12 times and then those treated 16 times defined the significantly decreased urinary m-methylhippuric acid compared to those treated 12 times. On the other hand, hepatic aniline hydroxylase and alcohol dehydrogenase activities demonstrated a gradual increase from the first group to the 12 times xylene-treated animals, but those treated 16 times showed the significantly decreased value compared with the 12 times treated-group. And aldehyde dehydrogenase activities in rats treated with m-xylene 8, 12 or 16 times were significantly decreased compared to those pretreated one or four times. In the early stage of xylene administration, proliferation of SERs were seen whereas SERs were decreased and RERs were clearly increased in xylene-treated rats 16 times. These results indicate that the frequency of xylene injection may influence upon the changes in xylene metabolite, m-methylhippuric acid and it may be due to induction of xylene metabolizing enzymes.