• 제목/요약/키워드: Matrix Metalloproteinase(MMP)

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Chondroprotective and Anti-inflammatory Effects of ChondroT, A New Complex Herbal Medication

  • Jung Up Park;WonWoo Lee
    • 한국자원식물학회:학술대회논문집
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    • 한국자원식물학회 2022년도 추계학술대회
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    • pp.103-103
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    • 2022
  • Ganghwaljetongyeum (GHJTY) is a complex herbal decoction comprising 18 plants; it is used to treat arthritis. In order to develop a new anti-arthritic herbal medication, we selected 5 out of 18 GHJTY plants by using bioinformatics analysis. The new medication, called ChondroT, comprised water extracts of Osterici Radix, Lonicerae Folium, Angelicae Gigantis Radix, Clematidis Radix, and Phellodendri Cortex. This study was designed to investigate its chondroprotective and anti-inflammatory effects to develop an anti-arthritic herb medicine. ChondroT was validated using a convenient and accurate high-performance liquid chromatography. photodiode array (HPLC-PDA) detection method for simultaneous determination of its seven reference components. The concentrations of the seven marker constituents were in the range of 0.81-5.46 mg/g. The chondroprotective effects were evaluated based on SW1353 chondrocytes and matrix metalloproteinase 1 (MMP1) expression. In addition, the anti-inflammatory effects of ChondroT were studied by Western blotting of pro-inflammatory enzymes and by enzyme-linked immunosorbent assay (ELISA) of inflammatory mediators in lipopolysaccharides (LPS)-induced RAW264.7 cells. ChondroT enhanced the growth of SW1353 chondrocytes and also significantly inhibited IL-1β-induced MMP-1 expression. However, ChondroT did not show any effects on the growth of HeLa and RAW264.7 cells. The expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) was induced by LPS in RAW264.7 cells, which was significantly decreased by pre-treatment with ChondroT. In addition, ChondroT reduced the activation of NF-κB and production of inflammatory mediators, such as IL-1β, IL-6, PGE2, and nitric oxide (NO) in LPS-induced RAW264.7 cells. These results show that ChondroT exerted a chondroprotective effect and demonstrated multi-target mechanisms related to inflammation and arthritis. In addition, the suppressive effect was greater than that exhibited by GHJTY, suggesting that ChondroT, a new complex herbal medication, has therapeutic potential for the treatment of arthritis.

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Avenanthramide-C Shows Potential to Alleviate Gingival Inflammation and Alveolar Bone Loss in Experimental Periodontitis

  • Su-Jin Kim;Se Hui Lee;Binh Do Quang;Thanh-Tam Tran;Young-Gwon Kim;Jun Ko;Weon-Young Choi;Sun Young Lee;Je-Hwang Ryu
    • Molecules and Cells
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    • 제46권10호
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    • pp.627-636
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    • 2023
  • Periodontal disease is a chronic inflammatory disease that leads to the gradual destruction of the supporting structures of the teeth including gums, periodontal ligaments, alveolar bone, and root cementum. Recently, interests in alleviating symptoms of periodontitis (PD) using natural compounds is increasing. Avenanthramide-C (Avn-C) is a polyphenol found only in oats. It is known to exhibit various biological properties. To date, the effect of Avn-C on PD pathogenesis has not been confirmed. Therefore, this study aimed to verify the protective effects of Avn-C on periodontal inflammation and subsequent alveolar bone erosion in vitro and in vivo. Upregulated expression of catabolic factors, such as matrix metalloproteinase 1 (MMP1), MMP3, interleukin (IL)-6, IL-8, and COX2 induced by lipopolysaccharide and proinflammatory cytokines, IL-1β, and tumor necrosis factor α (TNF-α), was dramatically decreased by Avn-C treatment in human gingival fibroblasts and periodontal ligament cells. Moreover, alveolar bone erosion in the ligature-induced PD mouse model was ameliorated by intra-gingival injection of Avn-C. Molecular mechanism studies revealed that the inhibitory effects of Avn-C on the upregulation of catabolic factors were mediated via ERK (extracellular signal-regulated kinase) and NF-κB pathway that was activated by IL-1β or p38 MAPK and JNK signaling that was activated by TNF-α, respectively. Based on this study, we recommend that Avn-C may be a new natural compound that can be applied to PD treatment.

NLRC4 Inflammasome-Mediated Regulation of Eosinophilic Functions

  • Ilgin Akkaya;Ece Oylumlu;Irem Ozel;Goksu Uzel;Lubeyne Durmus;Ceren Ciraci
    • IMMUNE NETWORK
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    • 제21권6호
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    • pp.42.1-42.20
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    • 2021
  • Eosinophils play critical roles in the maintenance of homeostasis in innate and adaptive immunity. Although primarily known for their roles in parasitic infections and the development of Th2 cell responses, eosinophils also play complex roles in other immune responses ranging from anti-inflammation to defense against viral and bacterial infections. However, the contributions of pattern recognition receptors in general, and NOD-like receptors (NLRs) in particular, to eosinophil involvement in these immune responses remain relatively underappreciated. Our in vivo studies demonstrated that NLRC4 deficient mice had a decreased number of eosinophils and impaired Th2 responses after induction of an allergic airway disease model. Our in vitro data, utilizing human eosinophilic EoL-1 cells, suggested that TLR2 induction markedly induced pro-inflammatory responses and inflammasome forming NLRC4 and NLRP3. Moreover, activation by their specific ligands resulted in caspase-1 cleavage and mature IL-1β secretion. Interestingly, Th2 responses such as secretion of IL-5 and IL-13 decreased after transfection of EoL-1 cells with short interfering RNAs targeting human NLRC4. Specific induction of NLRC4 with PAM3CSK4 and flagellin upregulated the expression of IL-5 receptor and expression of Fc epsilon receptors (FcεR1α, FcεR2). Strikingly, activation of the NLRC4 inflammasome also promoted expression of the costimulatory receptor CD80 as well as expression of immunoregulatory receptors PD-L1 and Siglec-8. Concomitant with NLRC4 upregulation, we found an increase in expression and activation of matrix metalloproteinase (MMP)-9, but not MMP-2. Collectively, our results present new potential roles of NLRC4 in mediating a variety of eosinopilic functions.

Shedding; towards a new paradigm of syndecan function in cancer

  • Choi, So-Joong;Lee, Ha-Won;Choi, Jung-Ran;Oh, Eok-Soo
    • BMB Reports
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    • 제43권5호
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    • pp.305-310
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    • 2010
  • Syndecans, cell surface heparansulfate proteoglycans, have been proposed to act as cell surface receptors and/or coreceptors to play critical roles in multiple cellular functions. However, recent reports suggest that the function of syndecans can be further extended through shedding, a cleavage of extracellular domain. Shedding constitutes an additional level for controlling the function of syndecans, providing a means to attenuate and/or regulate amplitude and duration of syndecan signals by modulating the activity of syndecans as cell surface receptors. Whether these remaining cleavage products are still capable of functioning as cell surface receptors to efficiently transduce signals inside of cells is not clear. However, shedding transforms cell surface receptor syndecans into soluble forms, which, like growth factors, may act as novel ligands to induce cellular responses by association with other cell surface receptors. It is becoming interestingly evident that shed syndecans also contribute significantly to syndecan functions in cancer biology. This review presents current knowledge about syndecan shedding and its functional significance, particularly in the context of cancer.

Macrophage inhibitory cytokine-1 transactivates ErbB family receptors via the activation of Src in SK-BR-3 human breast cancer cells

  • Park, Yun-Jung;Lee, Han-Soo;Lee, Jeong-Hyung
    • BMB Reports
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    • 제43권2호
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    • pp.91-96
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    • 2010
  • The function of macrophage inhibitory cytokine-1 (MIC-1) in cancer remains controversial, and its signaling pathways remain poorly understood. In this study, we demonstrate that MIC-1 induces the transactivation of EGFR, ErbB2, and ErbB3 through the activation of c-Src in SK-BR-3 breast cells. MIC-1 induced significant phosphorylation of EGFR at Tyr845, ErbB2 at Tyr877, and ErbB3 at Tyr1289 as well as Akt and p38, Erk1/2, and JNK mitogen-activated protein kinases (MAPKs). Treatment of SK-BR-3 cells with MIC-1 increased the phosphorylation level of Src at Tyr416, and induced invasiveness of those cells. Inhibition of c-Src activity resulted in the complete abolition of MIC-1-induced phosphorylation of the EGFR, ErbB2, and ErbB3, as well as invasiveness and matrix metalloproteinase (MMP)-9 expression in SK-BR-3 cells. Collectively, these results show that MIC-1 may participate in the malignant progression of certain cancer cells through the activation of c-Src, which in turn may transactivate ErbB-family receptors.

UVB로 손상된 피부 섬유아세포에서 쌍별귀뚜라미 메탄올 추출물의 보호효과 (Protective Effect of Gryllus Bimaculatus Methanol Extract on UVB-induced Photoaging in Human Skin Fibroblasts)

  • 정택영;유명남;허희진;양진우;정헌상;이준수
    • 한국식생활문화학회지
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    • 제35권5호
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    • pp.478-482
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    • 2020
  • We evaluated the protective effects of cricket methanol extract (CME) on ultra-violet B (UVB)-induced photoaging in human skin fibroblasts. The fibroblast cells were treated with 10, 50, and 100 ㎍/mL of CME for 24 h, and then exposed to UVB (30 mJ/㎠). CME showed a dose-dependent cytoprotective effect without any observable cytotoxicity. CME reduced UVB-induced production of reactive oxygen species (ROS) by 34.4, 34.9, 40.6% at concentrations of 10, 50, 100 ㎍/mL respectively. CME inhibited the release of matrix metalloproteinase (MMP) 1 and 3. Furthermore, CME also reduced UVB-induced collagen degradation in the fibroblast cells. Taken together, our data suggests that CME has a significant protective effect on UVB-induced photoaging of the skin. This benefit occurs through multiple mechanisms. The results also suggest a potential role for CME as an ingredient in anti-photoaging cosmetic products in the future.

차조기추출물에 의한 염증성 cytokine 생성억제 및 진통작용에 관한 연구 (Effect on Inflammatory-cytokines Production Inhibition and Analgesic Activity of Perilla Frutescens Extracts)

  • 김시나;이은정;이현지;남경숙;김희석;황성완;황성연
    • 동의생리병리학회지
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    • 제20권2호
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    • pp.414-419
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    • 2006
  • Prostaglandins biosynthesis and nitric oxide production have been implicated in the process of inflammation and osteoarthritis. And nitric oxide (NO) activated the MMPs responsible for PG degradation in articular chondrocytes. Therefore, we have studied the effects on anti-inflammation and analgesic by ethyl acetate fraction from 70% ethanol extract of Perilla Frutescens (EPF). EPF inhibited LPS plus inflammation-cytokines-induced proteoglycan (PG) degradation, matrix-metalloproteinase (MMP-2,9) expression in rabbit articular chondrocytes. Also, EPF have inhibitory effects on LPS or LPS plus inflammation cytokines-induced nitric oxide (NO) and PGE2 production in mouse macrophage andrabbit articular chondrocytes. These results suggest that EPF decreases PGE2, iNOS, MMPs activity and PG degradation in mouse macrophage and/or rabbit articular chondrocytes. In vivo, EPF was shown to have inhibitory effects on acetic acid-induced pain. The herbal extract with this profile, may have utility in the treatment of osteoarthritis.

생강나무 잎 및 가지 추출물의 생리활성 (Physiological Activities of Leaf and Twig Extracts from Lindera obtusiloba Blume)

  • 홍주헌
    • 한국식품조리과학회지
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    • 제29권5호
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    • pp.573-580
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    • 2013
  • We investigated the physiological activities of extracts from Lindera obtusiloba Blume leaf and twig (LLW: water extract from Lindera obtusiloba Blume leaf, LLE: 50% ethanol extract from Lindera obtusiloba Blume leaf, LTW: water extract from Lindera obtusiloba Blume twig, LTE: 50% ethanol extract from Lindera obtusiloba Blume twig). Total polyphenol and total flavonoid contents of LTE were 445.38 mg/g and 302.09 mg/g, respectively. The electron donating ability (95.38%) of LTE was higher than that of the LLE (93.76%), LTW (88.09%), and LLW (82.06%). The oxygen radical absorbance capacity of extracts were improved with 50% ethanol condition, rather than hot water. Superoxide radical scavenging activity and FRAP activity of the extracts were improved with an increase of treatment concentration. All the extracts($1,000{\mu}g/mL$) stimulated a production of nitric oxide (NO) in macrophage RAW264.7 cells. In particular, the NO stimulating activity of LTE was superior to that of LLE, LTW, and LLW. The antitumor activity of LTE ($500{\mu}g/mL$) in A549, HeLa and SNU719 was 55.63%, 83.87% and 68.11%, respectively. The UVB-induced MMP-1 production in HS68 cells was suppressed by the treatment of LTE (88.28%), LLE (83.96%), LTW (80.59%) and LLW (76.08%).

Inhibitory Effects of Gamimahaenggamsuk-tang on RA-related Inflammatory Responses in Cultured Fibroblast-like Synoviocytes

  • Jo Jun;NamGung Uk;Kim Soo-Myung;Kang Tak-Lim;Kim Dong-Hee
    • 동의생리병리학회지
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    • 제19권6호
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    • pp.1647-1655
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    • 2005
  • Gamimahaenggamsuk-tang (GMHGST) is used for treatment of inflammatory diseases including rheumatoid arthritis (RA). Here, regulatory activity of GMHGST on RA-mediated inflammatory responses was investigated in cultured human fiDroblast-like synoviocytes (FLS), Levels of mRNAs encoding for inflammatory cytokines such as $IL-1{\beta}$, IL-6 and IL-8 and NOS-II enzyme, which had been induced by $TNF-{\alpha}$ and $IL-1{\beta}$ cotreatment, were decreased to the similar levels as those in cells treated with anti-inflammatory agent MTX. mRNA expressions of matrix metalloproteinase-3 (MMP-3) and tissue inhibitor of metalloproteinases (TIMPs) as well as intercellular adhesion molecule (ICAM) were also downregulated by increasing doses of GMHGST in activated FLS. Moreover, GMHGST appeared to protect cells by decreasing NO levels, and inhibited cell proliferation which had been induced by inflammatory stimulation by $TNF-{\alpha}$ and IL-1. These results suggest that GMHGST is effective as an inhibitory agent for regulating inflammatory responses in activated FLS.

천연물로부터의 항노화소재 개발: Triterpenoid계 식물성분인 Oleanolic acid의 항노화 효과

  • 남개원;이소희;김승훈;김수현;성대석;김수남;이병곤
    • 대한화장품학회지
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    • 제29권1호
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    • pp.27-44
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    • 2003
  • 전반적인 피부세포의 생리적 지능 자하로 인한 자연노화와 더불어, 여러 피부 스트레스 요인들이 다양하게 작용하여 발생하는 외인성노화를 방지하거나, 개선할 수 있는 항노화소재로서의 개발 가능성을 알아보기 위해, 예로부터 항염활성이 있다고 알려진 oleanolic acid(OA)를 포함한 ursolic acid(UA), betulin, betulinic acid(BA) 등의 triterpenoids가 어떻게 피부에서의 항노화 활성을 나타내는지를 알아보았다. 시험 결과, OA는 자외선에 의한 각질형성세포에서의 PGE$_2$ 생성과 섬유아세포(NHF)에 의한 matrix metalloproteinase-1(MMP-1) 분비를 억제하였다. 그리고, NHF의 procollagen 생성을 촉진하였으며, 이런 procollagen 생성촉진활성이 in vivo에서도 발현되는 것을 무모생쥐의 실험을 통해서 확인하였다. 또한 OA는 각질세포의 증식과 분화를 촉진하여 표피세포로 하여금 세라마이므와 필라그린 생성을 증가시키도록 하는 작용도 있음을 보여주었다. 더불어 실험한 UA, betulin, BA 들은 비록, betulin, BA의 경우 세포 독성이 다른 물질 들에 비해 높았고, UA가 각질세포의 분화를 오히려 억제하는 양상을 보이기는 했지만, 대부분의 기능은 OA와 유사하였다. 피부세포보호작용과 진피 기질물질에 대한 작용, 그리고, 표피의 장벽기능과 보습기능에 대해 시험한 본 연구는, 식물성분인 triterpenoids가 피부를 위한 항노화소재로서의 개발 가능성이 있음을 확인하는 계기가 되었고, 그 중에서도 OA가 보다 우수한 항노화 소재가 될 수 있음을 시사하고 있다.