Suppression of Transglutaminase-2 is Involved in Anti-Inflammatory Actions of Glucosamine in 12-OTetradecanoylphorbol-13-Acetate-Induced Skin Inflammation

( Mi Kyung Park ),( Sun A Cho ),( Hye Ja Lee ),( Eun Ji Lee ),( June Hee Kang ),( You Lee Kim ),( Hyun Ji Kim ),( Seung Hyun Oh ),( Changsun Choi ),( Ho Lee ),( Soo Youl Kim ),( Chang Hoon Lee ) 한국응용약물학회 2012 Biomolecules & Therapeutics(구 응용약물학회지) Vol.20 No.4

Glucosamine (GS) is well known for the treatment of infl ammation. However, the mechanism and effi cacy of GS for skin infl ammation are unclear. The aim of this study was to evaluate the effects and mechanism of GS in the mouse 12-O-tetradecanoyl 13-acetate (TPA)-induced ear edema model. TPA-induced ear edema was evoked in ICR or transglutaminase 2 (Tgase-2) (-/-) mice. GS was administered orally (10-100 mg/kg) or topically (0.5-2.0 w/v %) prior to TPA treatment. Orally administered GS at 10 mg/kg showed a 76 or 57% reduction in ear weight or myeloperoxidase, respectively, and a decreased expression of cyclooxygenase- 2 (COX-2), NF-κB and Tgase-2 in TPA-induced ear edema by western blot and immunohistochemistry. Role of Tgase-2 in TPA ear edema is examined using Tgase-2 (-/-) mice and TPA did not induce COX-2 expression in ear of Tgase-2 (-/-) mice. These observations suggested that Tgase-2 is involved in TPA-induced COX-2 expression in the infl amed ear of mice and antiinfl ammatory effects of glucosamine is mediated through suppression of Tgase-2 in TPA ear edema.

Anti-inflammatory Effects of KOTMIN13: A Mixed Herbal Medicine in LPS-stimulated RAW 264.7 Cells and Mouse Edema Models

Lee, Eujin,Kim, Sun-Gun,Park, Na-Young,Park, Hyo-Hyun,Jeong, Kyu-Tae,Choi, Jongkeun,Lee, In-Hae,Lee, Hwadong,Lee, Eunkyung Medknow PublicationsMedia Pvt Ltd 2017 Pharmacognosy magazine Vol.13 No.50

<P><B>Background:</B></P><P>A Korean herbal medicine, KOTMIN13, composed of <I>Inula japonica</I> Thunberg, <I>Trichosanthes kirilowii Maximowicz</I> var. <I>japonica kitamura</I>, <I>Peucedanum praeruptorum</I> Dunn, and <I>Allium macrostemon</I> Bge, has been used for anti-allergic and anti-asthmatic treatment in oriental clinics, but its activity has not been investigated.</P><P><B>Materials and Methods:</B></P><P>To evaluate the anti-inflammatory activity of KOTMIN13 for <I>in vitro</I> study, LPS-stimulated RAW 264.7 cells were used to induce the production and expression of inflammatory mediators and its mechanisms. 12-<I>O</I>-Tetradecanoylphorobol-13 aceate (TPA)-induced ear edema and carrageenan-induced paw edema models were also used to evaluate the effect of KOTMIN13 on acute inflammation <I>in vivo</I>.</P><P><B>Results:</B></P><P>KOTMIN13 reduced the release of inflammatory mediators [nitric oxide, prostaglandin E2, interleukin (IL)-1β, and IL-6] and the protein expression of inducible nitric oxide synthase and cyclooxygenase-2 in LPS-stimulated RAW 264.7 cells. Mechanism studies showed the attenuation of LPS-induced NF-κB activation by KOTMIN13 via IκBα degradation abrogation and a subsequent decrease in nuclear p65 levels. Activation of mitogen-activated protein kinases (ERK, JNK, and p38) was also suppressed. Furthermore, KOTMIN13 ameliorated the development of TPA-induced ear edema and carrageenan-induced paw edema in acute inflammatory edema mouse models.</P><P><B>Conclusion:</B></P><P>Our study demonstrates that KOTMIN13 inhibits inflammatory mediators through the inhibitions of NF-κB and MAPK activities in LPS-induced RAW 264.7 cells, as well as acute inflammation in edema models, indicating that KOTMIN13 is an effective suppressor for anti-inflammatory activities.</P><P><B>SUMMARY</B></P><P><P>KOTMIN13 decrease the production of No, PGE<SUB>2</SUB>, and proinflammatory cytokine (TNF-∝, IL-1β,IL-6).</P><P>KOTMIN13 Suppressed the degradation of NF-kβ and IKβα and the phosorylation of MAP Kinases.</P><P>Topical application of KOTMIN13 reduced mouse ear edema.</P><P>Oral administration of KOTMIN13 decreased carrageenan-induced paw edema.</P></P> >[FIG OMISSION]</BR><P><B>Abbreviations used:</B> NO: nitric oxide; PGE2: prostaglandin E2; iNOS: inducible NO synthase; COX-2: cyclooxygenase-2; TNF-α: tumor necrosis factor-α; IL: interleukin; NF-κB: nuclear factor kappaB; MAPK: mitogen-activated protein kinases; ERK: extracellular signal regulated kinase; JNK: c-jun N terminal kinase; TPA: 12-O-tetradecanoylphorbol-13-acetate</P>

Anti-inflammatory Effects of Enzymatic Extract from Ecklonia cava on TPA-induced Ear Skin Edema

Ginnae Ahn,Eunjin Park,Dae Seung Kim,You-Jin Jeon,Taekyun Shin,Jae Woo Park,Ho-Chun Woo,Ki-Wan Lee,Youngheun Jee 한국식품과학회 2008 Food Science and Biotechnology Vol.17 No.4

Anti-inflammatory potential of the enzymatic extract prepared by Kojizyme (ECK), a component of brown seaweeds Ecklonia cava (Alariaceae, Phaeophyta) in vivo was investigated. For the application of mouse ear edema model, 12-O-tetradecanoylphorbol acetate (TPA) was used, a topical inducer of a long-lasting inflammatory response. Our results demonstrated that ECK inhibited ear edema when topically applied to mouse ear skin. In histological evaluation, the inhibition activity of ECK on TPA-induced inflammation is similar to that of dexamethasone, although less strong. In addition, the mRNA expression levels of IL-1β, IFN-γ, TNF-α, and cyclooxygenase-2 (COX2) and the immunoreactivity to inducible nitric oxide synthase (iNOS) and COX2 expressed mainly in inflammatory cells were down-regulated by ECK. These results indicate that ECK has anti-inflammatory effects through the inhibition of Th1 cytokines and 2 inducers of inflammation in TPA-induced ear skin edema.

Topical Anti-inflammatory Activity of Dianemycin Isolated from Streptomyces sp. MT 2705-4

Lee, Song-Jin,Kim, Hyun-Pyo,Park, Byung-Keun,Ahn, Soon-Cheol,Lee, Hyun-Sun,Ahn, Jong-Seog The Pharmaceutical Society of Korea 1997 Archives of Pharmacal Research Vol.20 No.4

In order to develop new anti-inflammatory agents having different action mechanisms compared with nonsteroidal and steroidal anti-inflammatory drugs, the culture broths of various actinomycetes isolated from soil were screened using an in vivo mouse ear edma assay and one strain (Streptomyces sp. MT 2705-4: KCTC 8651 P) was selected. Activity-guided purification led to the isolation of a polyether compound, dianemycin. Topically, dianemycin showed a potent anti-inflammatory activity in mouse ear edema induced by croton-oil or arachidonic acid.$ED_{50}$value of dianemycin was found to be 0.8 mg,/ear compared to 0.4 mg/ear of prednisolone in croton-oil ear edema. However, dianemycin did not show the inhibitory activity in UV-erythema and delayed hypersensitivity reaction. These results indicate that dianemycin is a potential topical anti-inflammatory agent.

Effects of Aralia continentalis and Angelica biserrata on Inflammatory Response in Lipopolysaccharide-Induced RAW 264.7 Macrophages and Phorbol Ester-induced Ear Edema

Cheon, Myeong-Sook,Yoon, Tae-Sook,Yasukawa, Ken,Yu, So-Yeon,Kim, Seung-Ju,Choi, Go-Ya,Moon, Byeong-Cheol,Lee, A-Yeong,Choo, Byung-Kil,Kim, Ho-Kyoung The Korean Society for Applied Biological Chemistr 2009 Applied Biological Chemistry (Appl Biol Chem) Vol.52 No.2

The roots of both Aralia continentalis and Angelica biserrata, known as 'Dokwhal' in Korea, have been used widely as a traditional oriental medicine to treat inflammation and thrombosis. However, the pharmacological differences between A. continentalis and A. biserrata have not been fully established. In the present study, we investigated and compared the inhibitory effects of 70% ethanolic extracts of A. continentalis (ACE) and A. biserrata (ABE) on the production of inflammatory mediators and secondary swelling from chemically induced ear edema. In RAW264.7 macrophages, both ACE and ABE significantly inhibited the release of nitric oxide, prostaglandin $E_2$, interlukin-lbeta, and tumor necrosis factor-alpha in a dose dependent manner. In addition, the swelling from TPA-induced edema in mouse ears was reduced by ACE and ABE. Overall, ACE showed stronger activities than ABE in vitro and in vivo. Our results indicate that A. continentalis roots possess stronger anti-inflammatory activity than A. biserrata roots.

Effects of Aralia continentalis and Angelica biserrata on Inflammatory Response in Lipopolysaccharide-Induced RAW 264.7 Macrophages and Phorbol Ester-induced Ear Edema

Myeong Sook Cheon,윤태숙,Seung Ju Kim,Goya Choi,문병철,A-Yeong Lee,Byung Kil Choo,Ho Kyoung Kim,So Yeon Yu,Ken Yasukawa 한국응용생명화학회 2009 Journal of Applied Biological Chemistry (J. Appl. Vol.52 No.2

The roots of both Aralia continentalis and Angelica biserrata, known as ‘Dokwhal’ in Korea, have been used widely as a traditional oriental medicine to treat inflammation and thrombosis. However, the pharmacological differences between A. continentalis and A. biserrata have not been fully established. In the present study, we investigated and compared the inhibitory effects of 70% ethanolic extracts of A. continentalis (ACE) and A. biserrata (ABE) on the production of inflammatory mediators and secondary swelling from chemically induced ear edema. In RAW264.7 macrophages, both ACE and ABE significantly inhibited the release of nitric oxide, prostaglandin E2, interlukin-1beta, and tumor necrosis factor-alpha in a dose dependent manner. In addition, the swelling from TPA-induced edema in mouse ears was reduced by ACE and ABE. Overall, ACE showed stronger activities than ABE in vitro and in vivo. Our results indicate that A. continentalis roots possess stronger anti-inflammatory activity than A. biserrata roots.

Ginsenoside Rg3 attenuates skin disorders via down-regulation of MDM2/HIF1a signaling pathway

Na-Ra Han,Seong-Gyu Ko,Phil-Dong Moon,Hi-Joon Park 고려인삼학회 2021 Journal of Ginseng Research Vol.45 No.5

Background: Thymic stromal lymphopoietin (TSLP) acts as a master switch for inflammatory responses. Ginsenoside Rg3 (Rg3) which is an active ingredient of Panax ginseng Meyer (Araliaceae) is known to possess various therapeutic effects. However, a modulatory effect of Rg3 on TSLP expression in the inflammatory responses remains poorly understood. Methods: We investigated antiinflammatory effects of Rg3 on an in vitro model using HMC-1 cells stimulated by PMA plus calcium ionophore (PMACI), as well as an in vivo model using PMA-induced mouse ear edema. TSLP and vascular endothelial growth factor (VEGF) levels were detected using enzyme-linked immunosorbent assay or real-time PCR analysis. Murine double minute 2 (MDM2) and hypoxia-inducible factor 1α (HIF1α) expression levels were detected using Western blot analysis. Results: Rg3 treatment restrained the production and mRNA expression levels of TSLP and VEGF in activated HMC-1 cells. Rg3 down-regulated the MDM2 expression level increased by PMACI stimulation. The HIF1α expression level was also reduced by Rg3 in activated HMC-1 cells. In addition, Rg3-administered mice showed the decreased redness and ear thickness in PMA-irritated ear edema. Rg3 inhibited the TSLP and VEGF levels in the serum and ear tissue homogenate. Moreover, the MDM2 and HIF1α expression levels in the ear tissue homogenate were suppressed by Rg3. Conclusion: Taken together, the current study identifies new mechanistic evidence about MDM2/HIF1a pathway in the antiinflammatory effect of Rg3, providing a new effective therapeutic strategy for the treatment of skin inflammatory diseases.

Anti-Inflammatory and Analgesic Effects of Pyeongwisan on LPS-Stimulated Murine Macrophages and Mouse Models of Acetic Acid-Induced Writhing Response and Xylene-Induced Ear Edema

Oh, You-Chang,Jeong, Yun Hee,Cho, Won-Kyung,Ha, Jeong-Ho,Gu, Min Jung,Ma, Jin Yeul MDPI 2015 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.16 No.1

<P>Pyeongwisan (PW) is an herbal medication used in traditional East Asian medicine to treat anorexia, abdominal distension, borborygmus and diarrhea caused by gastric catarrh, atony and dilatation. However, its effects on inflammation-related diseases are unknown. In this study, we investigated the biological effects of PW on lipopolysaccharide (LPS)-mediated inflammation in macrophages and on local inflammation <I>in vivo</I>. We investigated the biological effects of PW on the production of inflammatory mediators, pro-inflammatory cytokines and related products as well as the activation of nuclear factor kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs) in LPS-stimulated macrophages. Additionally, we evaluated the analgesic effect on the acetic acid-induced writhing response and the inhibitory activity on xylene-induced ear edema in mice. PW showed anti-inflammatory effects by inhibiting the production of nitric oxide (NO), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and interleukin-1β (IL-1β). In addition, PW strongly suppressed inducible nitric oxide synthase (iNOS), a NO synthesis enzyme, induced heme oxygenase-1 (HO-1) expression and inhibited NF-κB activation and MAPK phosphorylation. Also, PW suppressed TNF-α, IL-6 and IL-1β cytokine production in LPS-stimulated peritoneal macrophage cells. Furthermore, PW showed an analgesic effect on the writhing response and an inhibitory effect on mice ear edema. We demonstrated the anti-inflammatory effects and inhibitory mechanism in macrophages as well as inhibitory activity of PW <I>in vivo</I> for the first time. Our results suggest the potential value of PW as an inflammatory therapeutic agent developed from a natural substance.</P>

잔가시 물 추출물의 항염증 효과

김재영 ( Jae Young Kim ),이상목 ( Sang Mok Lee ),이한진 ( Han Jin Lee ),장문익 ( Moon Ik Chang ),강남숙 ( Nam Sook Kang ),김남선 ( Nam Sun Kim ),김희정 ( Hee Jung Kim ),조윤제 ( Yoon Jae Cho ),정지윤 ( Jiyoon Jeong ),김미경 ( Mee 한국응용생명화학회(구 한국농화학회) 2014 Journal of Applied Biological Chemistry (J. Appl. Vol.57 No.3

본 연구에서는 LPS로 유도된 RAW 264.7 대식세포의 염증반응을 통해 잔가시 모자반 (S. micracanthum) 물 추출물의 항염증 활성을 알아보았다. 잔가시 모자반 물 추출물이 대식세포에 미치는 독성을 알아보기 위해 MTT assay를 시행했으며, NO 생성량을 비롯하여 TNF-α, IL-6 및 IL-1β와 같은 염증 매개성 사이토카인 분비량을 측정하기 위해 ELISA법을 사용하였다. 또한, immunoblotting을 통해 iNOS, COX-2 및 NF-κBp65 단백질 발현량을 알아보았다. 실험결과, 잔가시 모자반 물추출물이 대식세포에 미치는 독성은 보이지 않았으며, NO 및염증 매개성 사이토카인의 분비량이 농도 의존적으로 억제됨을 보였다. 특히, IL-1β 분비량이 50 μg/mL에서 50% 이상 저해됨을 보였다. 또한, iNOS, COX-2 및 NF-κB p65 단백질 발현량에서도 농도의존적인 감소를 보였다. 모자반 물 추출물을5, 000 mg/kg body weight까지 경구투여 한 후 2주 동안 관찰한 결과 경구독성을 보이지 않음을 확인하였다. 그 후, 동물실험을 통해 염증으로 인한 귀 부종의 두께를 측정한 결과, 가장 높은 처리 농도인 250 mg/kg body weight으로 경구투여하였을 때 prednisolone을 투여한 대조군과 유의적으로 비슷한수준까지 귀 부종이 완화됨을 보였다. 따라서 본 연구는 잔가시 모자반 물 추출물이 뛰어난 항염증 효과를 가지고 있음을나타내며, 향후 염증질환 치료제 개발에 잔가시 모자반 물 추출물이 이용될 수 있을 것으로 사료된다. The anti-inflammatory effect of Sargassum micracanthumwater extract (SMWE) was investigated using lipopolysaccharide(LPS)-induced inflammatory response in this study. The murinemacrophage cell line RAW 264.7 cells were used and MTT assaywas performed to measure the cell proliferation ability. Thesecretion of nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1β was measured in LPS-inducedRAW 264.7 cells by ELISA. The expression of inducible nitricoxide synthase (iNOS), cyclooxygenase-2 (COX-2), and nucleartranscription factor-kappa B p65 protein was studied by immunoblotting. The Balb/c mice were used for an acute toxicity test, andimprinting control region mice were purchased to evaluate acroton oil-induced ear edema. As a result, there was no cytotoxicityin the macrophage proliferation treated with SMWE compared tothe control. NO levels decreased with increasing concentration ofSMWE and were inhibited over 50%. Moreover, the secretion ofIL-6, TNF-α, and IL-1β was suppressed in a dose-dependentmanner, especially, IL-1β inhibition activity was over 50% at 50μg/mL. The formation of ear edema of mice was reduced at thehighest dose tested compared to that in the control. Moreover, inacute toxicity test, no moralities occurred in mice administered5, 000 mg/kg body weight of SMWE over 2 weeks observationperiod. These results suggested that SMWE may have significanteffects on inflammatory factors and be potential anti-inflammatorytherapeutic materials.

양파껍질 열수추출물의 in vitro 및 in vivo 항염증 효과

강보경(Bo-Kyeong Kang),김꽃봉우리(Koth-Bong-Woo-Ri Kim),안나경(Na-Kyung Ahn),최연욱(Yeon-Uk Choi),김민지(Min-ji Kim),박시우(Si-Woo Bark),박원민(Won-Min Pak),김보람(Bo-Ram Kim),박지혜(Ji-Hye Park),배난영(Nan-Young Bae),안동현(Dong-Hyun 한국생물공학회 2015 KSBB Journal Vol.30 No.4

Onion (Allium cepa) is one of the flavonoids-rich materials in human diet and onion peel, which is the onion byproducts, contains over 20 times more quercetin than the flesh. In this study, to examine the anti-inflammatory effects of onion peel hot water extract (OPHWE), the cell viability, nitric oxide (NO), pro-inflammatory cytokines, such as interluekin-6 (IL- 6), tumor necrosis factor-α (TNF-α), and IL-1β, were measured using the murine macrophage cell line RAW 264.7 cells. The Balb/c mice were used for an in vivo acute toxicity test and ICR mice were used for measurement of inhibition effects of croton oil-induced mouse ear edema. As a result, NO levels decreased in a dose-dependent manner. The production of IL-6, TNF-α, and IL-1β was suppressed by 38%, 41%, and 34% respectively, compared with that of the LPS only group, without any cytotoxicity. The edema formation in the ICR mouse ear was also reduced compared to that in control. Moreover, there were no mortalities occurred in mice administered 5,000 mg/kg body weight of OPHWE. These results suggest that OPHWE has considerable anti-inflammatory activities and can be regarded as a potent candidate material to treat inflammatory diseases.