Chondroitin sulfate inhibits lipopolysaccharide-induced inflammation in rat astrocytes by preventing nuclear factor kappa B activation

Cañas, Noelia; Gorina, Roser; Planas, Anna M.; Vergés, Josep; Montell, E.; Garcı́a, Antonio G.; López, Manuela G.

doi:10.1016/j.neuroscience.2010.02.069

Cited by 41 publications

(25 citation statements)

References 46 publications

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“…NF-κB activation requires three key steps including degradation of IκBα, nuclear translocation of NF-κB p65 and DNA binding of the NF-κB complex [20]. Numerous anti-inflammatory agents have been found to regulate NF-κB activation by interfering with one or more of these steps [21][22][23][24]. In this study, we found that ginsenoside Rb1 inhibited IκBα degradation, as well as decreased levels of p65 protein in the nucleus of IL-1β-induced SW1353 cells.…”

Section: Discussionmentioning

confidence: 61%

Ginsenoside Rb1 Reduces Nitric Oxide Production via Inhibition of Nuclear Factor-κB Activation in Interleukin-1β- Stimulated SW1353 Chondrosarcoma Cells

Jia¹,

Chen²,

Li³

et al. 2014

Trop. J. Pharm Res

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Section: Discussionmentioning

confidence: 61%

Ginsenoside Rb1 Reduces Nitric Oxide Production via Inhibition of Nuclear Factor-κB Activation in Interleukin-1β- Stimulated SW1353 Chondrosarcoma Cells

Jia¹,

Chen²,

Li³

et al. 2014

Trop. J. Pharm Res

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“…Нейропротективными свойствами обладают и ди-сахариды N-ацетилглюкозамина и глюкуроновой кислоты, образующиеся при метаболизме ХС [28,29].…”

Section: молекулярные эффекты хондрогарда при остеоартрите и грыжах мunclassified

“…Поступая внутрь оболочеч-ной ветви, ХС купируют провоспалительные реакции. Кроме того, в СМЖ поступают дисахариды N-ацетилглю-козамина и глюкуроновой кислоты, образующиеся при метаболизме ХС, которые также оказывают нейропротек-тивное действие [29].…”

Section: молекулярные эффекты хондрогарда при остеоартрите и грыжах мunclassified

Molecular effects of chondroguard in osteoarthritis and herniated discs

Лила¹,

Gromova

Torshin

et al. 2017

RJTAO

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Nevrologiya, neiropsikhiatriya, psikhosomatika = Neurology, neuropsychiatry, psychosomatics. 2017;9(3):88-97. DOI: http://dx.doi.org/10.14412/20749(3):88-97. DOI: http://dx.doi.org/10.14412/ -27119(3):88-97. DOI: http://dx.doi.org/10.14412/ -2017 Молекулярные эффекты хондрогарда при остеоартрите и грыжах межпозвоночного диска Основу гомеостаза межпозвоночного диска составляет баланс образующих его компонентов. Нарушения крово-снабжения, повышенная интенсивность системного воспа-ления, дефицит гиалуроновой кислоты, глюкозамина суль-фата (ГС) и хондроитина сульфата (ХС) приводят к дегене-ративным изменениям позвоночника [1]. Формирование грыжи межпозвоночного диска сопровождается резким бо-левым синдромом, стойкими неврологическим выпадения-ми двигательных и чувствительных функций. Операции по удалению грыжи не останавливают дегенеративный про-цесс и не исключают образования повторных грыж. В каче-стве консервативной терапии грыж межпозвоночного диска обсуждается поддержка метаболизма соединительной ткани хряща (хондропротекция) с использованием таких молеку-лярных компонентов соединительной ткани, как ХС. Пос-ледние вырабатываются хондроцитами и являются цент-ральным компонентом «гелевой основы» хряща, связок, мышц, кости, синовиальной жидкости. Молекулы ХС пред-ставляют собой полимеры, состоящие из длинных полиса-харидов, содержащих повторяющиеся дисахаридные еди-ницы (рис. 1, а). Каждая из таких единиц включает N-аце-тилглюкозамин и D-глюкуроновую кислоту и может суль-фатироваться (образовывать сложный эфир с анионом сер-ной кислоты). ХС отличаются по длине, характеризуемой числом полимеризации (n, число повторов дисахаридных единиц: n=20-200) и степени сульфатирования, что обусло-вливает различия в молекулярной массе ХС. Поэтому более уместно говорить о хондроитина сульфатах. С фармаколо-гической точки зрения, ХС являются хондропротекторами и способствуют активной регенерации хряща; ХС повыша-ют эластичность и механическую прочность хряща, сухожи-лий, обеспечивают гидратацию и накопление гиалуроновой кислоты и противовоспалительных цитокинов в хряще и синовии [2][3][4][5][6][7].

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“…[7][8][9] Although the biological activity varies for each GAG, a common feature is the presence of an anti-inflammatory effect. Several in vitro [10][11][12][13][14] and in vivo 15,16) studies have shown that HP, CS, and HA suppress the lipopolysaccharide (LPS)-induced production of inflammatory cytokines by inhibiting the activation of MyD88, p38 mitogen-activated protein kinase (MAPK), and nuclear factor-kappaB (NF-κB).Previously, we reported that glycol-split HP conjugated with D-erythro-sphingosine or aliphatic amines forms selfassembled nano-sized particles and strongly inhibits the production of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1β in LPSstimulated macrophages.17) The anti-inflammatory activity of the HP conjugates was greater than that of native HP. Since HP conjugates prevented phosphorylation of IL-1 receptorassociated kinase-1 (IRAK-1) and degradation of inhibitor of NF-κB (IκBα), its anti-inflammatory effect was concluded to occur via inhibition of the Toll-like receptor 4 (TLR4)-mediated MyD88-dependent NF-κB pathway.…”

mentioning

confidence: 99%

mentioning

confidence: 99%

Anti-inflammatory Effect of Self-assembling Glycol-Split Glycosaminoglycan-Stearylamine Conjugates in Lipopolysaccharide-Stimulated Macrophages

Yanamoto

Babazada

Sakai

et al. 2017

Biological & Pharmaceutical Bulletin

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Glycosaminoglycans (GAGs) play important roles in various biological processes such as cell adhesion and signal transduction, as well as promote anti-inflammatory activity. We previously revealed that glycolsplit heparin (HP)-aliphatic amine conjugates form self-assembled nanoparticles and suppress the production of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β in lipopolysaccharide (LPS)-stimulated macrophages much more strongly than native HP (J. Control. Release, 194, 2014, Babazada et al.). Considering that HP is not the only GAG to have anti-inflammatory activity, the present study was initiated to examine whether conjugation of GAGs with aliphatic amines is generally effective in their activity augmentation against LPS-stimulated macrophages. We newly synthesized the stearylamine conjugates of chondroitin sulfate (CS), hyaluronic acid (HA), and low-molecular-weight heparin (LH), and investigated the effect of the position and degree of sulfation and molecular weight of GAGs on their anti-inflammatory activity. All of the conjugates formed self-assembled nanoparticles in aqueous solution. The IC 50 value for suppression of TNF-α production from the macrophages was the smallest with the derivative of LH, followed by HP, CS, and HA. The degree of sulfation appeared to be important in determining their anti-inflammatory activity, which would correspond to previous results using the derivatives of siteselectively desulfated HP. Comparison of HP and LH derivatives revealed that fractionated smaller heparin has greater anti-inflammatory activity.Key words glycosaminoglycan; self-assembled nanoparticle; anti-inflammatory activity; Toll-like receptor 4; macrophage; structure-activity relationship Glycosaminoglycans (GAGs) are linear polysaccharides that play important roles in processes such as cell adhesion and signal transduction. 1) Heparin (HP) is one of the highly sulfated GAGs that consist of repeats of alternating uronic acid and D-glucosamine.2) HP is a well-known anticoagulant that activates antithrombin, leading to anticoagulation 3) ; moreover, it has a variety of additional biological effects such as antiangiogenesis and anti-inflammation. Chondroitin sulfate (CS), consisting of repeats of alternating D-glucuronic acid and N-acetyl-D-galactosamine, 2,4) is used clinically to reduce pain and improve articular function in patients with osteoporosis.5,6) Hyaluronic acid (HA) consists of repeats of alternating D-glucuronic acid and N-acetyl-D-glucosamine, but characteristically lacks sulfo groups. 2,4) HA has been used to protect synovial membranes and heal injuries. [7][8][9] Although the biological activity varies for each GAG, a common feature is the presence of an anti-inflammatory effect. Several in vitro [10][11][12][13][14] and in vivo 15,16) studies have shown that HP, CS, and HA suppress the lipopolysaccharide (LPS)-induced production of inflammatory cytokines by inhibiting the activation of MyD88, p38 mitogen-activated protein kinase (MAPK), an...

show abstract

Chondroitin sulfate inhibits lipopolysaccharide-induced inflammation in rat astrocytes by preventing nuclear factor kappa B activation

Cited by 41 publications

References 46 publications

Ginsenoside Rb1 Reduces Nitric Oxide Production via Inhibition of Nuclear Factor-κB Activation in Interleukin-1β- Stimulated SW1353 Chondrosarcoma Cells

Ginsenoside Rb1 Reduces Nitric Oxide Production via Inhibition of Nuclear Factor-κB Activation in Interleukin-1β- Stimulated SW1353 Chondrosarcoma Cells

Molecular effects of chondroguard in osteoarthritis and herniated discs

Anti-inflammatory Effect of Self-assembling Glycol-Split Glycosaminoglycan-Stearylamine Conjugates in Lipopolysaccharide-Stimulated Macrophages

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