Inhibiting the PI3K/AKT/NF-κB signal pathway with nobiletin for attenuating the development of osteoarthritis: in vitro and in vivo studies.

08:00 EDT 2nd April 2019 | BioPortfolio

Summary of "Inhibiting the PI3K/AKT/NF-κB signal pathway with nobiletin for attenuating the development of osteoarthritis: in vitro and in vivo studies."

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.


Journal Details

This article was published in the following journal.

Name: Food & function
ISSN: 2042-650X


DeepDyve research library

PubMed Articles [18275 Associated PubMed Articles listed on BioPortfolio]

Nobiletin sensitizes colorectal cancer cells to oxaliplatin by PI3K/Akt/MTOR pathway.

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 suppresses oxidative stress and apoptosis in H9c2 cardiomyocytes following hypoxia/reoxygenation injury.

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 ...

Lunasin attenuates oxidant-induced endothelial injury and inhibits atherosclerotic plaque progression in ApoE mice by up-regulating heme oxygenase-1 via PI3K/Akt/Nrf2/ARE pathway.

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 reduces LPL-mediated lipid accumulation and pro-inflammatory cytokine secretion through upregulation of miR-590 expression.

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...

The relation between PI3K/AKT signalling pathway and cancer.

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...

Clinical Trials [3562 Associated Clinical Trials listed on BioPortfolio]

Hyperpolarized C-13 Pyruvate as a Biomarker in Patients With Advanced Solid Tumor Malignancies

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...

BKM120 for Patients With PI3K-activated Tumors

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...

Evaluation Of The Treatment Effectiveness Of Glioblastoma / Gliosarcoma Through The Suppression Of The PI3K/Akt Pathway In Compared With MK-3475

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...

Phase II Study of Everolimus Combined With Octreotide LAR to Treat Advanced GI NET

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 Effect of the Preoperative Oral Carbohydrate Attenuating Immediate Postoperative Insulin Resistance on PI3K Dependent Signaling Pathway

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 ...

Medical and Biotech [MESH] Definitions

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.


Quick Search


DeepDyve research library

Relevant Topics

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
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...

Searches Linking to this Article