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.

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>

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.

<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>

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.

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>

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>

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.

저강도 초음파 및 레이저를 이용한 장관골 불유합의 치료

전인호,오창욱,김성중,경희수,박일형,박병철,인주철,여준영 대한골절학회 2003 대한골절학회지 Vol.16 No.2

목 적: 저강도 초음파는 인체 및 동물 실험에서 골조직에 낮은 미세한 물리적 압력을 가하여 골절의 치유에 유리한 영향을 주고, 레이저 (LASER)는 심부 조직에 혈류를 증가시키고, 세포 내 잠재된 에너지를 증가시키는 것으로 알려져 있다. 이에 저자들은 임상적으로 확진된 장관골 붕류합의 치료에 있어 펄스형 저강도 초음파와 레이저를 적용하고 그 효용성을 알아보고자 하였다. 대상 및 방법: 초음파/레이저의 치료 효과를 비교하기 위하여 장관골 불유합으로 확진된 16예 중 8예는 연구군으로 골이식술 후 저강도 초음파와 레이저 치료를 추가하였고 대조군 8예에 대해선 일반적인 골이식술만 시행하여 조사하였다. 남자가 11예, 여자가 5예, 평균 연령은 41.7세 (19~62세)였고, 불유합 부위는 대퇴골이 10예, 경골이 6예였다. 첫 수상으로 인한 골절 후 초음파/레이저 치료까지 시간(골절 연력)은 평균 502일이었다. 결 과: 8예의 연구군에서는 완전 골유합이 6예에서 이루어졌으며 유합까지의 시간은 평균 141일 (101~202일)로 나타난 반면, 8례ㅢ 대조군에서는 5예에서 골유합이 이루어졌고, 유합까지의 시간은 평균 240일 (183~283일)이었다. 결 론: 저강도 초음파/레이져 골절 치료기가 반복된 수술로 인한 난치성 장관골 불유합의 치료에 있어 골이식술과 함께 사용될 경우 긍정적인 효과가 있었고, 특히 최초 가골 형성에 있어 대조군에 비해 그 시간을 줄일 수 있었따. Purpose: Low-intensity, pulsed ultrasound (LIPUS) has demonstrated a stimulation and acceleration of the normal fracture-repair process in cellular bases as well in animal and human models. In this study, the adjunctive effect of LIPUS and LASER was investigated in established nonunion of the long bones. Materials and Methods: Study group consisted of eight patients to whom conventional bone graft and adjunctive LIPUS and LASER was applied. On the other hands, eight patients in the control group underwent bone graft only. Eleven men and five women were included in this study and the average age of the patients was 41.7 years (range, 19~62 years). Six of the tibias and ten of the femurs met the criteria for established nonunion. The average fracture age, the post-fracture period before the start of LIPUS/LASER treatment, was 502 days. Results: Seven of the ten nonunions who were treated by LIPUS and LASER healed completely in an average treatment time of 141 days (range, 101~202 days) and otherwise, in control group, five of the eight nonunions healed completely, in 240 days (range 183~283 days). Conclusion: This clinical study showed a positive effect of LIPUS and LASER on the rate of osseous repair, especially accelerated time to initial callus cortical bridging compared to that of conventional treatment.