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Osteoarthritis (OA), an age-related degenerative disease, is characterized by progressive degradation of the articular cartilage. There is increasing evidence that nobiletin (NOB) exerts special biological functions in a variety of diseases. However, whether it protects against OA remains unknown. In this study, we investigated the anti-inflammatory and chondroprotective effects of NOB on IL-1β-induced human OA chondrocytes and in the surgical DMM mice OA models. In vitro, NOB treatment completely suppressed the overproduction of pro-inflammatory mediators, including PGE2, NO, COX-2, iNOS, TNF-α and IL-6 in IL-1β-induced human OA chondrocytes. Moreover, NOB exerted a potent inhibitory effect on the expression of MMP-13 and ADAMTS-5 as well as the degradation of aggrecan and collagen-II, which leads to the degradation of the extracellular matrix. Furthermore, NOB dramatically suppressed the IL-1β-stimulated phosphorylation of PI3K/Akt and activation of NF-κB in human OA chondrocytes. In addition, treatment with NOB not only prevented the destruction of cartilage and the thickening of subchondral bone but also relieved synovitis in mice OA models. In conclusion, our study suggests that NOB holds novel therapeutic potential for the treatment of OA.
This article was published in the following journal.
Name: Food & function
Oxaliplatin is one of the most common chemotherapy drugs for colorectal cancer (CRC), but its application is greatly limited owing to the drug resistance. Nobiletin is a natural flavonoid isolated fro...
Nobiletin (3',4',5,6,7,8-hexamethoxyflavone), a dietary polymethoxylated flavonoid found in Citrus fruits, was reported to exhibit protective activity against ischemia/reperfusion (I/R). However, the ...
Oxidative stress-induced vascular endothelial cell (VEC) injury is a major mechanism in the initiation and development of atherosclerosis. Lunasin, a soybean-derived 43-aa peptide, has been previously...
Nobiletin has protective effects on cardiovascular diseases, but the mechanism is not clear. In this study, we examined whether nobiletin affects the expression of miR-590/LPL and its relative effects...
Phosphatidylinositol 3-kinases (PI3Ks) are crucial coordinators of intracellular signalling in response to the extracellular stimulators. Hyperactivation of PI3K signalling cascades is one among the m...
This is a single center prospective imaging study investigating the utility of hyperpolarized C-13 pyruvate as a Biomarker of PI3K/mTOR pathway inhibition in patients with advanced solid t...
The purpose of this signal seeking study is to determine whether treatment with BKM120 demonstrates sufficient efficacy in select pathway-activated solid tumors and/or hematologic malignan...
It is known that after application of MK-3475 activated PD -1 negatively regulates the activation of T cells through suppression of the path of PI3K / Akt. This study will identify the ef...
The underlying hypothesis of the synergistic activity of octreotide and everolimus is based on the combination of a) a direct action of everolimus over mTOR (mammalian target of rapamycin)...
The purpose of this study is to delineate the effects of preoperative oral carbohydrate on immediate postoperative insulin resistance (PIR) in patients undergoing elective open colorectal ...
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activa
Wnt proteins are a large family of secreted glycoproteins that play essential roles in EMBRYONIC AND FETAL DEVELOPMENT, and tissue maintenance. They bind to FRIZZLED RECEPTORS and act as PARACRINE PROTEIN FACTORS to initiate a variety of SIGNAL TRANSDUCTION PATHWAYS. The canonical Wnt signaling pathway stabilizes the transcriptional coactivator BETA CATENIN.
A suppressor of cytokine signaling protein that consists of an N-terminal kinase-inhibitory region, a central SH2 DOMAIN, a characteristic C-terminal SOCS box (a 40-amino acid motif, which functions to recruit E3 UBIQUITIN-PROTEIN LIGASE COMPLEXES). SOCS1 functions as a negative regulator of CYTOKINES that signal through the JANUS KINASES-STAT 3 TRANSCRIPTION FACTOR (JAK/STAT3) pathway by inhibiting the activity of JANUS KINASES.
Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly.
An inhibitory smad protein that associates with TRANSFORMING GROWTH FACTOR BETA RECEPTORS and BONE MORPHOGENETIC PROTEIN RECEPTORS. It negatively regulates SIGNAL TRANSDUCTION PATHWAYS by inhibiting PHOSPHORYLATION of RECEPTOR-REGULATED SMAD PROTEINS.
Arthritis is by definition the inflammation of one or more joints, characterized by swelling, pain, warmth, redness and diminished range of joint movement (Oxford Medical Dictionary). There are many different types; Noninflammatory; Osteoarthritis, N...
Biological therapy involves the use of living organisms, substances derived from living organisms, or laboratory-produced versions of such substances to treat disease. Some biological therapies for cancer use vaccines or bacteria to stimulate the body&rs...