The chondroprotective effects of ferulic acid on hydrogen peroxide-stimulated chondrocytes: Inhibition of hydrogen peroxide-induced pro-inflammatory cytokines and metalloproteinase gene expression at the mRNA level
The objective of the study is to evaluate the effect of ferulic acid (FA), an antioxidant from the Chinese herb Dong-Gui [Chinese angelica, Angelica sinensis (Oliv.) Diels], on the regulation of various genes in hydrogen peroxide-stimulated porcine chondrocytes at the mRNA level.
The effect of FA and the effective concentration of FA on porcine chondrocytes was evaluated by the lactate dehydrogenase, WST-1, crystal violet assay, and a chemical luminescence assay. Gene expression in hydrogen peroxide-stimulated chondrocytes either pre- or post-treated with FA was evaluated by real-time PCR.
Chondrocytes pre-treated with 40 microM FA decreased the hydrogen peroxide-induced interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), and MMP-1 and partially restored SOX9 gene expression. Post-treatment with 40 microM FA also decreased the expression of MMP-1 and MMP-13.
FA decreased the hydrogen peroxide-induced IL-1beta, TNF-alpha, MMP-1 and MMP-13 and increased SOX9 gene expression. These findings suggest that FA may prove to be important in the treatment of osteoarthritis. Further research is needed.
"Furthermore, NO can inhibit the synthesis of collagens and proteoglycans and can increase MMP activity in chondrocytes . Pathologic changes include the decreased synthesis of ECM proteins, and the local accumulation of destructive enzymes was observed in H2O2-stimulated chondrocytes . Drugs for the treatment of degenerative diseases of articular joints may be developed by increasing the synthesis of ECM molecules such as type II collagen and SOX9 and by inhibiting destructive enzymes such as MMPs . "
[Show abstract][Hide abstract] ABSTRACT: The abnormal maturation and ossification of articular chondrocytes play a central role in the pathogenesis of osteoarthritis (OA). Inhibiting the enzymatic degradation of the extracellular matrix and maintaining the cellular phenotype are two of the major goals of interest in managing OA. Ginseng is frequently taken orally, as a crude substance, as a traditional medicine in Asian countries. Ginsenoside Rb1, a major component of ginseng that contains an aglycone with a dammarane skeleton, has been reported to exhibit various biological activities, including anti-inflammatory and anti-tumor effects. However, a chondroprotective effect of ginsenoside Rb1 related to OA has not yet been reported. The purpose of this study was to demonstrate the chondroprotective effect of ginsenoside Rb1 on the regulation of pro-inflammatory factors and chondrogenic genes. Cultured rat articular chondrocytes were treated with 100 μM ginsenoside Rb1 and/or 500 μM hydrogen peroxide (H2O2) and assessed for viability, reactive oxygen species production, nitric oxide (NO) release, and chondrogenic gene expression. Ginsenoside Rb1 treatment resulted in reductions in the levels of pro-inflammatory cytokine and NO in H2O2-treated chondrocytes. The expression levels of chondrogenic genes, such as type II collagen and SOX9, were increased in the presence of ginsenoside Rb1, whereas the expression levels of inflammatory genes related to chondrocytes, such as MMP1 and MMP13, were reduced by approximately 50%. These results suggest that ginsenoside Rb1 has potential for use as a therapeutic agent in OA patients.
Journal of ginseng research 04/2012; 36(2):161-168. DOI:10.5142/jgr.2012.36.2.161 · 2.82 Impact Factor
"On the other hand, one of our previous studies suggested that increased oxidative DNA damage in GO patients was correlated with their clinical evolution, especially the inflammation activity . In addition, it has been pointed out that H2O2 can induce gene expression of pro-inflammatory cytokines such as IL-1β and TNF-α , which play a crucial role in the development of GO . Taken together, we suggest that the increase in oxidative stress play a role in the pathogenesis of GO, especially in the inflammatory process. "
[Show abstract][Hide abstract] ABSTRACT: To investigate whether orbital fibroblasts from patients with Graves' ophthalmopathy (GO) are more responsive to oxidative stress. Lipid peroxidation, oxidative DNA damage, reactive oxygen species (ROS) contents and activities of antioxidant enzymes were measured in cultured orbital fibroblasts from GO patients and age-matched normal controls in response to 200 μM hydrogen peroxide (H(2)O(2)). GO fibroblasts had increased basal levels of malondialdehyde (MDA), 8-hydroxy 2'-deoxyguanosine, superoxide anions, H(2)O(2), and manganese-dependent superoxide dismutase (Mn-SOD) activity, as well as decreased glutathione peroxidase (GPx) activity and the ratio between reduced (GSH) and oxidized glutathione (GSSG) compared with the orbital fibroblasts from normal subjects. After treatment of the cells with 200 μM H(2)O(2), the amplitude of increase in the intracellular levels of MDA (63% versus 26%), H(2)O(2) (24% versus 13%) and Mn-SOD activity (48% versus 23%) was exaggerated in GO fibroblasts compared with normal controls, respectively. In addition, treatment of GO fibroblasts with 200 μM H(2)O(2) led to a dramatic reduction of catalase activity (-59% versus -29%), GPx activity (-56% versus -13%), and GSH/GSSG ratio (-49% versus -21%), respectively.
Elevated ROS and redox imbalance in GO orbital fibroblasts were exacerbated by H(2)O(2) as a result of exhaustion of GSH and compromise of antioxidant enzymes. Hypersensitivity to oxidative stress of GO orbital fibroblasts may play a role in the pathogenesis of GO.
[Show abstract][Hide abstract] ABSTRACT: This review focuses on various strategies that enable the crosslinking and post-crosslinking of polymers, excluding crosslinking obtained by radiation (e.g., X-ray, UV, etc.) and that at high temperature. The review is divided into two main parts: systems enabling crosslinking at room temperature and those for which crosslinking occurs at intermediate temperatures (<150 ◦C). In the first part, various key functional groups can be used, such as (i) carboxylic acid involving reactions with compounds that bear carbodiimide or aziridine functions; (ii) acetoacetyl groups (with isocyanate, activated alkenes, aldehyde, amine functions); (iii) reactions involving activated amines with carbonyl functions (aldehydes, ketones, etc.); (iv) species bearing acetals as pH-sensitive crosslinking agents since they are stable in basic medium but they can self react under acidic conditions; (v) acrylamide functions which are able to self-crosslink; (vi) crosslinking agents able to react with water (such as species that bear a poly(alkoxy)silane for sol–gel process) and derivatives containing isocyanate functions and (vii) systems that require oxygen, for example polymers bearing double bonds, boranes for generating hydroperoxides and acetylenic functions which undergo acetylenic coupling. The second series of systems, used at higher temperatures (yet below 150 ◦C) involving the following key functions: (i) carboxylic acid that react with oxazoline, or epoxide function where specific catalysts are necessary; (ii) alcohols reacting with protected urethanes, azlactones and methylol amide (for coating applications); (iii) azetidines (obtained from a cyclic amine onto an activated double bond) which selfcrosslink; (iv) reversible Diels–Alder reaction (such as furane/bismaleimide reaction), and (v) Huisgen reactions between azido and triple bond. Various examples are presented, along with a discussion of their properties and applications.
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