stilbenes and Osteoarthritis

stilbenes has been researched along with Osteoarthritis* in 26 studies

Reviews

3 review(s) available for stilbenes and Osteoarthritis

ArticleYear
Regulation of GSK-3 activity by curcumin, berberine and resveratrol: Potential effects on multiple diseases.
    Advances in biological regulation, 2017, Volume: 65

    Natural products or nutraceuticals promote anti-aging, anti-cancer and other health-enhancing effects. A key target of the effects of natural products may be the regulation of the PI3K/PTEN/Akt/mTORC1/GSK-3 pathway. This review will focus on the effects of curcumin (CUR), berberine (BBR) and resveratrol (RES), on the PI3K/PTEN/Akt/mTORC1/GSK-3 pathway, with a special focus on GSK-3. These natural products may regulate the pathway by multiple mechanisms including: reactive oxygen species (ROS), cytokine receptors, mirco-RNAs (miRs) and many others. CUR is present the root of turmeric (Curcuma longa). CUR is used in the treatment of many disorders, especially in those involving inflammatory processes which may contribute to abnormal proliferation and promote cancer growth. BBR is also isolated from various plants (Berberis coptis and others) and is used in traditional medicine to treat multiple diseases/conditions including: diabetes, hyperlipidemia, cancer and bacterial infections. RES is present in red grapes, other fruits and berries such as blueberries and raspberries. RES may have some anti-diabetic and anti-cancer effects. Understanding the effects of these natural products on the PI3K/PTEN/Akt/mTORC1/GSK-3 pathway may enhance their usage as anti-proliferative agent which may be beneficial for many health problems.

    Topics: Berberine; Cardiovascular Diseases; Curcumin; Gene Expression Regulation; Glycogen Synthase Kinase 3; Humans; Inflammation; Mechanistic Target of Rapamycin Complex 1; Neoplasms; Neurodegenerative Diseases; Osteoarthritis; Phosphatidylinositol 3-Kinases; Protective Agents; Proto-Oncogene Proteins c-akt; PTEN Phosphohydrolase; Resveratrol; Signal Transduction; Stilbenes

2017
Scientific evidence and rationale for the development of curcumin and resveratrol as nutraceutricals for joint health.
    International journal of molecular sciences, 2012, Volume: 13, Issue:4

    Interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α) are key cytokines that drive the production of inflammatory mediators and matrix-degrading enzymes in osteoarthritis (OA). These proinflammatory cytokines bind to their respective cell surface receptors and activate inflammatory signaling pathways culminating with the activation of nuclear factor κB (NF-κB), a transcription factor that can be triggered by a host of stress-related stimuli including, excessive mechanical stress and ECM degradation products. Once activated, NF-κB regulates the expression of many cytokines, chemokines, adhesion molecules, inflammatory mediators, and several matrix-degrading enzymes. Therefore, proinflammatory cytokines, their cell surface receptors, NF-κB and downstream signaling pathways are therapeutic targets in OA. This paper critically reviews the recent literature and outlines the potential prophylactic properties of plant-derived phytochemicals such as curcumin and resveratrol for targeting NF-κB signaling and inflammation in OA to determine whether these phytochemicals can be used as functional foods.

    Topics: Angiogenesis Inhibitors; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Cartilage, Articular; Chondrocytes; Curcumin; Humans; Inflammation; Interleukin-1beta; Joints; Osteoarthritis; Phytochemicals; Phytotherapy; Resveratrol; Stilbenes; Transcription Factor RelA; Tumor Necrosis Factor-alpha

2012
Dietary polyphenols and mechanisms of osteoarthritis.
    The Journal of nutritional biochemistry, 2012, Volume: 23, Issue:11

    Osteoarthritis is a condition caused in part by injury, loss of cartilage structure and function, and an imbalance in inflammatory and anti-inflammatory pathways. It primarily affects the articular cartilage and subchondral bone of synovial joints and results in joint failure, leading to pain upon weight bearing including walking and standing. There is no cure for osteoarthritis, as it is very difficult to restore the cartilage once it is destroyed. The goals of treatment are to relieve pain, maintain or improve joint mobility, increase the strength of the joints and minimize the disabling effects of the disease. Recent studies have shown an association between dietary polyphenols and the prevention of osteoarthritis-related musculoskeletal inflammation. This review discusses the effects of commonly consumed polyphenols, including curcumin, epigallocatechin gallate and green tea extract, resveratrol, nobiletin and citrus fruits, pomegranate, as well as genistein and soy protein, on osteoarthritis with an emphasis on molecular antiosteoarthritic mechanisms.

    Topics: Cartilage, Articular; Catechin; Citrus; Curcumin; Flavones; Genistein; Humans; Lythraceae; Osteoarthritis; Plant Extracts; Polyphenols; Resveratrol; Stilbenes

2012

Trials

2 trial(s) available for stilbenes and Osteoarthritis

ArticleYear
Resveratrol supplementation reduces pain experience by postmenopausal women.
    Menopause (New York, N.Y.), 2017, Volume: 24, Issue:8

    Pain is a common complaint among postmenopausal women. It has been postulated that vascular dysfunction caused by estrogen decline at menopause plays a key role in the initiation and progression of degradative joint disease, namely age-related osteoarthritis. We evaluated whether supplementation with resveratrol, a phytoestrogen, could improve aspects of well-being such as chronic pain that is commonly experienced by postmenopausal women.. A 14-week randomized, double-blind, placebo-controlled intervention with trans-resveratrol (75 mg, twice daily) was conducted in 80 healthy postmenopausal women. Aspects of well-being, including pain, menopausal symptoms, sleep quality, depressive symptoms, mood states, and quality of life were assessed by Short form-36 at baseline and at the end of treatment. Rating scales were averaged to provide a composite score representing overall well-being. Cerebral vasodilator responsiveness to hypercapnia was also assessed as a surrogate marker for cerebrovascular function.. Compared with placebo treatment, there was a significant reduction in pain and an improvement in total well-being after resveratrol supplementation. Both benefits, including measures of quality of life, correlated with improvements in cerebrovascular function.. Our preliminary findings indicate potential for resveratrol treatment to reduce chronic pain in age-related osteoarthritis. Resveratrol consumption may also boost perceptions of well-being in postmenopausal women. Further investigation to elucidate underlying mechanisms is warranted.

    Topics: Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Dietary Supplements; Double-Blind Method; Female; Humans; Middle Aged; Osteoarthritis; Pain; Pain Measurement; Phytoestrogens; Postmenopause; Resveratrol; Stilbenes; Treatment Outcome

2017
A randomized, controlled trial of the effects of resveratrol administration in performance horses with lameness localized to the distal tarsal joints.
    Journal of the American Veterinary Medical Association, 2016, Sep-15, Volume: 249, Issue:6

    OBJECTIVE To determine the effect of resveratrol administration in performance horses with lameness localized to the distal tarsal joints. DESIGN Randomized, blinded, placebo-controlled clinical trial. ANIMALS 45 client-owned horses with lameness localized to the distal tarsal joints. PROCEDURES All horses received injections of triamcinolone acetonide in the centrodistal and tarsometatarsal joints of both hind limbs. A placebo or a supplement containing resveratrol was fed twice daily by owners for 4 months. Primary outcomes were horse performance as determined by rider opinion (better, worse, or the same) and change in lameness severity from the enrollment examination. RESULTS Complete data were obtained for 21 horses that received resveratrol and 20 that received the placebo. Percentage of riders who reported that the horse's performance was better, compared with worse or the same, was significantly higher for the resveratrol group than for the placebo group after 2 (20/21 [95%] vs 14/20 [70%]) and 4 (18/21 [86%] vs 10/20 [50%]) months. The change in A1:A2 ratio between the enrollment and 4-month recheck examinations was significantly better for horses in the resveratrol versus placebo group. However, subjective lameness scores and degree of asymmetry of pelvis movement did not differ between groups. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that in performance horses with lameness localized to the distal tarsal joints, injection of triamcinolone in the centrodistal and tarsometatarsal joints of both hind limbs followed by oral supplementation with resveratrol for 4 months resulted in reduced lameness, compared with triamcinolone injection and supplementation with a placebo.

    Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Double-Blind Method; Female; Gait; Hindlimb; Horse Diseases; Horses; Injections, Intra-Articular; Lameness, Animal; Male; Osteoarthritis; Physical Conditioning, Animal; Resveratrol; Stilbenes; Tarsal Joints; Treatment Outcome

2016

Other Studies

21 other study(ies) available for stilbenes and Osteoarthritis

ArticleYear
Chondroprotective and anti-inflammatory effects of amurensin H by regulating TLR4/Syk/NF-κB signals.
    Journal of cellular and molecular medicine, 2020, Volume: 24, Issue:2

    The low-grade, chronic inflammation initiated by TLR4-triggered innate immune responses has a central role on early osteoarthritis. Amurensin H is a resveratrol dimer with anti-inflammatory and anti-apoptotic effects, while its effects on TLR-4 signals to inhibit osteoarthritis are still unclear. In the present study, treatment with amurensin H for 2 weeks in monosodium iodoacetate-induced mice significantly slows down cartilage degeneration and inflammation using macroscopic evaluation, haematoxylin and eosin (HE) staining and micro-magnetic resonance imaging. In IL-1β-stimulated rat chondrocytes, amurensin H suppresses the production of inflammatory mediators including nitric oxide, IL-6, IL-17, PGE2 and TNF-α using Greiss and ELISA assay. Amurensin H inhibits matrix degradation via decreasing levels of MMP-9 and MMP-13 using Western blot assay, promotes synthesis of type II collagen and glycosaminoglycan using immunostaining and safranin O staining, respectively. Amurensin H inhibits intracellular and mitochondrial reactive oxygen species (ROS) generation, and mitochondrial membrane depolarization using DCFH-DA, MitoSOX Red and JC-1 assay as well. IL-1β stimulates TLR4 activation and Syk phosphorylation in chondrocytes, while amurensin H inhibits TLR4/Syk signals and downstream p65 phosphorylation and translocation in a time and dose-dependent manner. Together, these results suggest that amurensin H exerts chondroprotective effects by attenuating oxidative stress, inflammation and matrix degradation via the TLR4/Syk/NF-κB pathway.

    Topics: Animals; Anti-Inflammatory Agents; Benzofurans; Chondrocytes; Disease Models, Animal; Disease Progression; Extracellular Matrix; Inflammation Mediators; Interleukin-1beta; Iodoacetates; Mice; Models, Biological; NF-kappa B; Osteoarthritis; Oxidative Stress; Phosphorylation; Protective Agents; Protein Transport; Rats, Sprague-Dawley; Reactive Oxygen Species; Signal Transduction; Stilbenes; Syk Kinase; Toll-Like Receptor 4; Transcription Factor RelA

2020
Isorhapontigenin Suppresses Interleukin-1β-Induced Inflammation and Cartilage Matrix Damage in Rat Chondrocytes.
    Inflammation, 2019, Volume: 42, Issue:6

    Osteoarthritis (OA) is a common cause of joint pain and physical disability in the elderly. It is highly associated with local inflammatory reactions and cartilage degradation. Isorhapontigenin (ISO), a natural compound existing in various plants, has shown prominent anti-inflammatory and anti-oxidative properties in several inflammatory diseases. However, the effects of ISO on OA remain to be elucidated. Here, we investigated the effects of ISO on interleukin-1β (IL-1β)-treated rat chondrocytes and cartilage explants. Our results revealed that ISO could suppress the IL-1β-induced elevated levels of nitric oxide (NO), inducible nitric oxide synthase (iNOS), prostaglandin E2 (PGE2), and cyclooxygenase-2 (COX2). Besides, ISO could also inhibit the IL-1β-induced up-regulation of cartilage matrix catabolic enzymes such as matrix metalloproteinases (MMPs) and aggrecanase-2 (ADAMTS5). Moreover, the IL-1β-induced downregulation of collagen II and aggrecan could be reversed by ISO. Furthermore, ISO prevented rat cartilage explant damage induced by IL-1β. Mechanistically, ISO worked partly by suppressing mitogen-activated protein kinase (MAPK)-associated ERK and p38 pathways. Taken together, our study indicated the anti-inflammatory potential of ISO on IL-1β-treated rat chondrocytes, providing a new idea for OA treatment.

    Topics: Animals; Anti-Inflammatory Agents; Cartilage; Chondrocytes; Inflammation; Interleukin-1beta; Matrix Metalloproteinases; Mitogen-Activated Protein Kinases; Osteoarthritis; Rats; Stilbenes

2019
Topical delivery of 3,5,4'-trimethoxy-trans-stilbene-loaded microemulsion-based hydrogel for the treatment of osteoarthritis in a rabbit model.
    Drug delivery and translational research, 2019, Volume: 9, Issue:1

    The aim of this study was to develop a microemulsion-based hydrogel (MBH) formulation of 3,5,4'-trimethoxy-trans-stilbene (BTM) as topical delivery system for the treatment of osteoarthritis (OA). The pseudo-ternary phase diagrams were constructed to optimize the microemulsion (ME) formulation. The ME formulation containing 18.8% Cremopher EL35 (surfactant), 9.4% Transcutol HP (co-surfactant), 3.1% LABRAFIL M 1944 CS (oil), and 68.7% water was selected. The obtained BTM-loaded ME (BTM-ME) had a spherical morphology (17.5 ± 1.4 nm), with polydispersity index (PDI) value of 0.068 ± 0.016 and zeta potential of - 11.8 ± 0.5 mV, and was converted into BTM-loaded MBH (BTM-MBH) using Carbopol 940. Ex vivo skin permeation study showed that both ME and MBH formulations significantly enhanced the amount of BTM permeated. The cumulative amount of BTM permeated after 12 h (Q

    Topics: Acrylic Resins; Administration, Cutaneous; Administration, Oral; Animals; Cytokines; Disease Models, Animal; Emulsions; Gene Expression Regulation; Hydrogels; Male; Osteoarthritis; Papain; Rabbits; Stilbenes

2019
Resveratrol ameliorates inflammatory damage and protects against osteoarthritis in a rat model of osteoarthritis.
    Molecular medicine reports, 2018, Volume: 17, Issue:1

    Resveratrol is a non‑flavonoid polyphenol compound with a stilbene structure. As a type of phytoalexin produced under stress in plants, it improves the plant's resistance against pathogens and environment deterioration, and performs important functions beneficial to human health, such as anti‑cancer, anti‑oxidation, regulating blood lipid levels and prolonging life span. The effects of resveratrol were examined in a rat model of osteoarthritis (OA) and observed to ameliorate inflammatory damage and protect against OA. In the present study, resveratrol significantly inhibited the induction of clinical scores in rats with OA. Resveratrol inhibited tumor necrosis factor‑α, interleukin (IL)‑1β, IL‑6 and IL‑18 expression levels, and decreased caspase‑3/9 activity in rats with OA. Inducible nitric oxide synthase, nuclear factor (NF)‑κB, phosphorylated‑(p)‑AMP‑activated protein kinase and sirtuin 1 protein expression were significantly suppressed and heme oxygenase 1 (HO‑1) and nuclear factor erythroid 2‑related factor 2 (Nrf‑2) protein expression was stimulated in rats with OA treated with resveratrol. The current results indicate that resveratrol ameliorates inflammatory damage and protects against OA in a rat model of OA via NF‑κB and HO‑1/Nrf‑2 signaling.

    Topics: Adenylate Kinase; Animals; Anti-Inflammatory Agents, Non-Steroidal; Caspase 3; Caspase 9; Drug Evaluation, Preclinical; Enzyme Induction; Gene Expression; Heme Oxygenase-1; Male; Malondialdehyde; NF-E2-Related Factor 2; NF-kappa B; Nitric Oxide Synthase Type II; Osteoarthritis; Rats, Wistar; Resveratrol; Sirtuin 1; Stilbenes; Superoxide Dismutase

2018
Polydatin inhibits the IL-1β-induced inflammatory response in human osteoarthritic chondrocytes by activating the Nrf2 signaling pathway and ameliorates murine osteoarthritis.
    Food & function, 2018, Mar-01, Volume: 9, Issue:3

    Osteoarthritis (OA), which is characterized by progressive degradation of the articular cartilage, is the most prevalent form of human arthritis. Accumulating evidence has shown that polydatin (PD) exerts special biological functions in a variety of diseases. However, whether it protects against OA development has remained unknown. Here, we investigated the anti-inflammatory and chondroprotective effects of PD on interleukin (IL)-1β-induced human osteoarthritic chondrocytes and in the surgical destabilization of medial meniscus mouse (DMM) OA models. In vitro, PD treatment completely suppressed the over-production of pro-inflammatory mediators, including prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), nitric oxide (NO), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and IL-6 in IL-1β-induced human OA chondrocytes. Moreover, PD exerted a suppressive effect on the expression of matrix-degrading proteases, including matrix metalloproteinase 13 (MMP13) and thrombospondin motifs 5 (ADAMTS-5), which leads to the degradation of the extracellular matrix (ECM). Meanwhile, specific inhibition of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) level by short-interfering RNA (siRNA) strongly reversed the anti-inflammatory and chondroprotective effects of PD in human OA chondrocytes. The protective effects of PD were also observed in vivo. In conclusion, our studies demonstrate that PD holds novel therapeutic potential for the development of OA.

    Topics: Animals; Anti-Inflammatory Agents; Chondrocytes; Glucosides; Humans; Interleukin-1beta; Interleukin-6; Male; Mice; Mice, Inbred C57BL; NF-E2-Related Factor 2; NF-kappa B; Nitric Oxide; Nitric Oxide Synthase Type II; Osteoarthritis; Signal Transduction; Stilbenes

2018
In Vitro and In Vivo Anti-Osteoarthritis Effects of 2,3,5,4'-Tetrahydroxystilbene-2-O-β-d-Glucoside from Polygonum Multiflorum.
    Molecules (Basel, Switzerland), 2018, Mar-03, Volume: 23, Issue:3

    Topics: Animals; Anti-Inflammatory Agents; Chondrocytes; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Dinoprostone; Edema; Gene Expression Regulation; Glucosides; Hindlimb; Iodoacetic Acid; Lipopolysaccharides; Male; Matrix Metalloproteinase 13; Mice; Nitric Oxide; Nitric Oxide Synthase Type II; Osteoarthritis; Polygonum; Primary Cell Culture; Rats; RAW 264.7 Cells; Stilbenes

2018
Engineered Coiled-Coil Protein for Delivery of Inverse Agonist for Osteoarthritis.
    Biomacromolecules, 2018, 05-14, Volume: 19, Issue:5

    Osteoarthritis (OA) results from degenerative and abnormal function of joints, with localized biochemistry playing a critical role in its onset and progression. As high levels of all- trans retinoic acid (ATRA) in synovial fluid have been identified as a contributive factor to OA, the synthesis of de novo antagonists for retinoic acid receptors (RARs) has been exploited to interrupt the mechanism of ATRA action. BMS493, a pan-RAR inverse agonist, has been reported as an effective inhibitor of ATRA signaling pathway; however, it is unstable and rapidly degrades under physiological conditions. We employed an engineered cartilage oligomeric matrix protein coiled-coil (C

    Topics: Amino Acid Motifs; Benzoates; Cells, Cultured; Chondrocytes; Drug Carriers; Humans; Interleukin-1beta; Matrix Metalloproteinase 13; Nanofibers; Osteoarthritis; Peptides; Receptors, Retinoic Acid; Stilbenes

2018
IL-6 in Osteoarthritis: Effects of Pine Stilbenoids.
    Molecules (Basel, Switzerland), 2018, Dec-29, Volume: 24, Issue:1

    Interleukin-6 (IL-6) is involved in the pathogenesis of various inflammatory diseases, like rheumatoid arthritis (RA). In the present study, we investigated the role of IL-6 in osteoarthritis (OA) patients and the effects of the stilbenoids monomethyl pinosylvin and pinosylvin on the expression of the cartilage matrix components aggrecan and collagen II and the inflammatory cytokine IL-6 in human OA chondrocytes. Synovial fluid and plasma samples were obtained from 100 patients with severe OA [BMI 29.7 (8.3) kg/m², age 72 (14) years, median (IQR); 62/38 females/males] undergoing total knee replacement surgery. IL-6 and matrix metalloproteinase (MMP) concentrations in synovial fluid and plasma were measured by immunoassay. The effects of pinosylvin on the expression of IL-6, aggrecan, and collagen II were studied in primary cultures of human OA chondrocytes. IL-6 levels in synovial fluid from OA patients [119.8 (193.5) pg/mL, median (IQR)] were significantly increased as compared to the plasma levels [3.1 (2.7) pg/mL, median (IQR)] and IL-6 levels in synovial fluid were associated with MMPs and radiographic disease severity. Natural stilbenoids monomethyl pinosylvin and pinosylvin increased aggrecan expression and suppressed IL-6 production in OA chondrocytes. The results propose that IL-6 is produced within OA joints and has an important role in the pathogenesis of OA. Stilbenoid compounds monomethyl pinosylvin and pinosylvin appeared to have disease-modifying potential in OA chondrocytes.

    Topics: Aged; Aged, 80 and over; Anti-Inflammatory Agents; Biomarkers; Cartilage, Articular; Cell Line; Cells, Cultured; Chondrocytes; Collagen; Cytokines; Female; Gene Expression; Humans; Inflammation Mediators; Interleukin-6; Male; Matrix Metalloproteinases; Middle Aged; NF-kappa B; Osteoarthritis; Pinus; Plant Extracts; Resveratrol; Severity of Illness Index; Stilbenes; Synovial Fluid

2018
Pterostilbene inhibits inflammation and ROS production in chondrocytes by activating Nrf2 pathway.
    Oncotarget, 2017, Jun-27, Volume: 8, Issue:26

    Pterostilbene has been reported as a potential drug to inhibit oxidative stress and inflammation. However, the effect of pterostilbene on chondrocytes and osteoarthritis remains to be elucidated. We sought to investigate whether pterostilbene could protect chondrocytes from inflammation and ROS production through factor erythroid 2-related factor 2 (Nrf2) activation. The pterostilbene toxicity on chondrocytes collected from cartilages of Sprague-Dawley rats was assessed by CCK-8 test. Immunofluorescence and Western blotting explored the nuclear translocation of Nrf2. Nrf2 expression was silenced by siRNA to evaluate the involvement of Nrf2 in the effect of pterostilbene on chondrocytes. Finally, osteoarthritis model was established by the transection of anterior cruciate ligament and partial medial meniscectomy in rats, and then these rats received pterostilbene 30 mg/kg, daily, p.o. for 8 weeks. Histology and immunohistochemistry were used to assess histopathological change and Nrf2 expression in cartilage. Nuclear translocation of Nrf2 was stimulated by pterostilbene without cellular toxicity. Pterostilbene inhibited the level of COX-2, iNOS, PGE2, and NO, as well as the mitochondrial and total intracellular ROS production induced by IL-1β in chondrocytes, partially reversed by the Nrf2 silencing. Pterostilbene prevented cartilage degeneration and promoted the nuclear translocation of Nrf2 in cartilage. These results suggest that pterostilbene could inhibit the IL-1β-induced inflammation and ROS production in chondrocytes by stimulating the nuclear translocation of Nrf2.

    Topics: Animals; Cartilage; Cell Survival; Cells, Cultured; Chondrocytes; Cyclooxygenase 2; Immunohistochemistry; Inflammation; Interleukin-1beta; Male; NF-E2-Related Factor 2; Nitric Oxide Synthase Type II; Nitrites; Osteoarthritis; Protein Transport; Rats; Reactive Oxygen Species; RNA, Small Interfering; Signal Transduction; Stilbenes

2017
Beneficial effect of resveratrol on phenotypic features and activity of osteoarthritic osteoblasts.
    Arthritis research & therapy, 2017, 06-30, Volume: 19, Issue:1

    Osteoarthritis (OA) is a complex disease, which affects multiple tissues, namely the subchondral bone, articular cartilage and synovial membrane. Alterations of the subchondral bone include an increased, yet under mineralized osteoid matrix, abnormal osteoblast cell phenotype including elevated alkaline phosphatase (ALP) activity, increased release of osteocalcin (OC) and transforming growth factor β-1 (TGF-β1). Previous studies have demonstrated an inhibition of the canonical Wnt signaling (cWnt) pathway in OA osteoblasts (Ob). As resveratrol (RSV) has been shown to upregulate the Wnt signaling pathway in different cell systems, we hypothesized that RSV could be beneficial for OA Ob.. We prepared primary human Ob using the subchondral bone plate of tibial plateaus of OA patients undergoing total knee arthroplasty, or tibial plateaus of normal individuals at autopsy. Sirtuin 1 (Sirt1) expression in normal and OA subchondral bone tissue was evaluated by immunohistochemical analysis. Expression of genes was evaluated by qRT-PCR and protein production by western blot analysis. ALP activity and osteocalcin secretion were evaluated respectively with substrate hydrolysis and enzyme immunoassay. Mineralization levels were evaluated with alizarin red staining. Wnt/β-catenin signaling was evaluated by target gene expression using the TOPflash TCF/lef luciferase reporter assay and intracellular signaling using β-catenin levels in western blot analysis. Extracellular signal-regulated kinase (Erk)1/2 and the Smad1/5/8 pathways were evaluated by western blot analysis.. Sirt1 expression and production were reduced in OA subchondral bone tissue compared to normal tissue. RSV upregulated Sirt1 and its activity, and reduced the expression of leptin. RSV increased Erk1/2 phosphorylation in OA Ob; however, it had no effect on Smad 1/5/8 phosphorylation. RSV had little effect on cell proliferation and only slightly affected the Bax/Bcl2 ratio. The expression of Runx2/Cbfa1 and peroxisome proliferator-activated receptor (PPAR)γ were not affected by increasing doses of RSV. The endogenous increased ALP activity and OC release observed in OA Ob compared to normal Ob were partly corrected only for ALP at high RSV levels but not for OC release. In contrast, RSV increased the mineralization of OA Ob. Moreover, whereas Wnt3a stimulates the Wnt/β-catenin pathway in these cells, RSV further increased the response to Wnt3a.. These data indicate that RSV promotes Sirt1 levels, inhibits the endogenous expression of leptin by OA osteoblasts and can promote the Wnt/β-catenin and Erk1/2 signaling pathways, which are altered in these cells.

    Topics: Aged; Animals; Anti-Inflammatory Agents, Non-Steroidal; Cell Line; Cells, Cultured; Dose-Response Relationship, Drug; Female; Humans; Male; Mice; Middle Aged; Osteoarthritis; Osteoblasts; Phenotype; Resveratrol; Sirtuin 1; Stilbenes; Treatment Outcome

2017
Local intra-articular injection of resveratrol delays cartilage degeneration in C57BL/6 mice by inducing autophagy via AMPK/mTOR pathway.
    Journal of pharmacological sciences, 2017, Volume: 134, Issue:3

    Autophagy is an essential cellular homeostasis mechanism that was found to be compromised in aging and osteoarthritis (OA) cartilage. Previous studies showed that resveratrol can effectively regulate autophagy in other cells. The purpose of this study was to determine whether the chondroprotective effect of resveratrol was related to chondrocyte autophagy and to elucidate underlying mechanisms. OA model was induced by destabilization of the medial meniscus (DMM) in 10-week-old male mice. OA mice were treated with resveratrol with/without 3-MA for 8 weeks beginning 4 weeks after surgery. The local intra-articular injection of resveratrol delayed articular cartilage degradation in DMM-induced OA by OARSI scoring systems and Safranin O-fast green. Resveratrol treatment increased Unc-51-like kinase1, Beclin1, microtubule-associated protein light chain 3, hypoxia inducible factor-1α, phosphorylated AMPK, collagen-2A1, Aggrecan expressions, but decreased hypoxia inducible factor-2α, phosphorylated mTOR, matrix metalloproteinases13 and a disintegrin and metalloproteinase with thrombospondin motifs 5 expressions. The effects of resveratrol were obviously blunted by 3-MA except HIF and AMPK. These findings indicate that resveratrol intra-articular injection delayed articular cartilage degeneration and promoted chondrocyte autophagy in an experimental model of surgical DMM-induced OA, in part via balancing HIF-1α and HIF-2α expressions and thereby regulating AMPK/mTOR signaling pathway.

    Topics: AMP-Activated Protein Kinases; Animals; Autophagy; Cartilage; Chondrocytes; Disease Models, Animal; Hypoxia-Inducible Factor 1, alpha Subunit; Injections, Intra-Articular; Male; Mice, Inbred C57BL; Osteoarthritis; Resveratrol; Signal Transduction; Stilbenes; TOR Serine-Threonine Kinases

2017
Piceatannol inhibits the IL-1β-induced inflammatory response in human osteoarthritic chondrocytes and ameliorates osteoarthritis in mice by activating Nrf2.
    Food & function, 2017, Nov-15, Volume: 8, Issue:11

    Topics: Animals; Chondrocytes; Cyclooxygenase 2; Drugs, Chinese Herbal; Euphorbia; Heme Oxygenase-1; Humans; Interleukin-1beta; Male; Mice; Mice, Inbred C57BL; NF-E2-Related Factor 2; NF-kappa B; Nitric Oxide; Osteoarthritis; Stilbenes

2017
Resveratrol inhibits the IL-1β-induced expression of MMP-13 and IL-6 in human articular chondrocytes via TLR4/MyD88-dependent and -independent signaling cascades.
    International journal of molecular medicine, 2017, Volume: 39, Issue:3

    The natural polyphenolic compound, resveratrol, has been shown to exhibit anti-osteoarthritic activity. Therefore it is hypothesized that resveratrol may serve as a nutritional supplement to counteract osteoarthritis (OA). However, the mechanisms responsible for these anti-osteoarthritic effects have not yet been fully elucidated. The aim of this study was to determine whether the biological effects of resveratrol against interleukin (IL)-1β‑induced inflammation in human articular chondrocytes involved both Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)-dependent and -independent signaling pathways. Human articular chondrocytes derived from patients with OA were stimulated with IL-1β, and then co-treated with resveratrol. Cell viability was subsequently evaluated by MTS assays, and the concentrations of matrix metalloproteinase (MMP)-13 and the pro-inflammatory factor, IL-6, were detected in culture supernatants using ELISA. The mRNA and protein levels of downstream mediators of TLR4/MyD88-dependent and -independent signaling pathways were also assayed by RT-qPCR and western blot analysis, respectively. Our results revealed that resveratrol prevented the IL-1β-induced reduction in cell viability. Furthermore, stimulation of the chondrocytes with IL-1β resulted in a significant upregulation of TLR4 and downstream targets of both TLR4/MyD88-dependent and -independent signaling pathways that are associated with the synthesis of MMP-13 and IL-6. Correspondingly, IL-1β-induced catabolic and inflammatory responses were effectively reversed by resveratrol. Taken together, these data suggest that resveratrol exerted protective effects against matrix degradation and inflammation in OA-affected chondrocytes by inhibiting both TLR4/MyD88-dependent and -independent signaling pathways. Thus, resveratrol represents a potential treatment for OA and warrants further investigation.

    Topics: Aged; Biomarkers; Cell Survival; Chondrocytes; Gene Expression; Humans; Interleukin-1beta; Interleukin-6; Matrix Metalloproteinase 13; Middle Aged; Myeloid Differentiation Factor 88; Osteoarthritis; Phenotype; Resveratrol; Signal Transduction; Stilbenes; Toll-Like Receptor 4

2017
Oral Administration of Resveratrol Alleviates Osteoarthritis Pathology in C57BL/6J Mice Model Induced by a High-Fat Diet.
    Mediators of inflammation, 2017, Volume: 2017

    Topics: Administration, Oral; Animals; Anti-Inflammatory Agents; Blotting, Western; Diet, High-Fat; Enzyme-Linked Immunosorbent Assay; Inflammation; Male; Mice; Mice, Inbred C57BL; Obesity; Osteoarthritis; Resveratrol; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; Stilbenes

2017
Oral Resveratrol Prevents Osteoarthritis Progression in C57BL/6J Mice Fed a High-Fat Diet.
    Nutrients, 2016, Apr-20, Volume: 8, Issue:4

    The effects of resveratrol on osteoarthritis (OA) pathogenesis have been demonstrated in vitro and in animal models employing intra-articular injections. However, the potential for oral resveratrol supplements to mediate protective effects on OA have not been examined. Therefore, the aim of the present study was to investigate the potential anti-OA effects of oral resveratrol on mice fed a high-fat diet (HFD). C57BL/6J male mice were fed either a standard diet or a HFD, and a subset of the latter also received varying doses of resveratrol. Twelve weeks later, all of the animals were sacrificed and knee joints were evaluated with histological, immunohistochemical, and TUNEL analyses. Mice that received a HFD had significantly greater body weights than the control mice and also exhibited features consistent with knee OA. The mice that received a HFD in combination with low, intermediate, or high doses of resveratrol were only slightly heavier than the control mice at the end of 12 weeks. Quantitative histological assessments indicated that resveratrol treatment partly recovered joint structure in the mice that received a HFD, while high doses of resveratrol prevented the degradation of type II collagen into C-telopeptide of type II collagen (CTX-II) and retained type II collagen expression in cartilage. Furthermore, TUNEL analyses revealed a reduction in chondrocyte apoptosis in the resveratrol-treated mice compared with the HFD mice. Thus, oral resveratrol appears to exert anti-OA effects in a mouse model of HFD-induced OA, thereby highlighting the potential preventive and therapeutic value of administering resveratrol for obesity-associated OA.

    Topics: Administration, Oral; Animals; Anti-Inflammatory Agents; Apoptosis; Cartilage, Articular; Chondrocytes; Collagen Type II; Dietary Fats; Dose-Response Relationship, Drug; Gene Expression Regulation; Male; Mice; Mice, Inbred C57BL; Osteoarthritis; Random Allocation; Resveratrol; Stilbenes

2016
Resveratrol, a natural antioxidant, protects monosodium iodoacetate-induced osteoarthritic pain in rats.
    Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 2016, Volume: 83

    Osteoarthritis (OA) is a chronic progressive joint disease characterized by advanced joint pain, subchondral bone sclerosis and articular cartilage degeneration. Resveratrol has been shown to have anti-inflammatory, cardioprotective and antioxidant properties and to inhibit platelet aggregation and coagulation. However, the effects of resveratrol on OA have not been examined. In this study, we investigate the protective effects of resveratrol on monosodium iodoacetate (MIA)-induced OA through inhibition of cyclooxygenase (COX-2) and inducible nitric oxide synthase (iNOS) signaling pathway in a rat model.. A single intra-articular injection of MIA was injected into rats for the induction of OA. The mechanical, heat and cold hyperalgesia were measured at days 0, 7 and 14. The serum and synovial fluid levels of IL-1β, IL-10 and TNF-α and osteocalcin were measured by enzyme-linked immunosorbent assay. The mRNA and protein expressions of IL-1β, IL-10, TNF-α, Il-6, MMP-13 and COX-2 and iNOS were determined by RT-PCR and western blot, respectively. Osteoarthritic lesion in the knee joint was evaluated by histological analysis.. MIA-injected rats treated with resveratrol at a dose of either 5 or 10mg/kg body weight were significantly reduced hyperalgesia of mechanical, heat and cold and increased the vertical and horizontal movements. Subsequently, MIA-injected rats increased serum and synovial fluid levels of IL-1β, IL-10, IL-6, TNF-α, MMP-13 and osteoclastic activity marker, osteocalcin and its articular cartilage mRNA and protein expressions. Further, MIA-injected rats increased COX-2 and iNOS mRNA and protein expressions were decreased by resveratrol. The protective effect of resveratrol was comparable to a reference drug, etoricoxib. The cartilage damage induced by MIA were attenuated by resveratrol.. Taken together, resveratrol has the potential to improve MIA-induced cartilage damage by inhibiting the levels and expressions of inflammatory mediators suggesting that resveratrol may be a potential therapeutic agent for OA.

    Topics: Animals; Antioxidants; Cartilage, Articular; Cyclooxygenase 2; Cytokines; Extremities; Hyperalgesia; Iodoacetates; Male; Nitric Oxide Synthase Type II; Osteoarthritis; Pain; Rats, Sprague-Dawley; Resveratrol; RNA, Messenger; Stilbenes; Synovial Fluid

2016
Intra-articular resveratrol injection prevents osteoarthritis progression in a mouse model by activating SIRT1 and thereby silencing HIF-2α.
    Journal of orthopaedic research : official publication of the Orthopaedic Research Society, 2015, Volume: 33, Issue:7

    We investigated the feasibility of the intra-articular injection of resveratrol for preventing the progression of existing cartilage degeneration in a mouse model of osteoarthritis (OA). The effects of resveratrol on the expression of silent information regulator 2 type 1 (SIRT1), hypoxia-inducible factor-2α (HIF-2α) and catabolic factors in OA cartilage was explored. OA was induced in the mouse knee via destabilization of the medial meniscus (DMM). Resveratrol was injected weekly into the operated knee beginning 4 weeks after surgery. The OA phenotype was evaluated via histological and immunohistochemical analyses at 8 weeks after DMM. Western blot analysis was performed to identify whether resveratrol modulated the interleukin (IL)-1β-induced expression of HIF-2α in human chondrocytes. Histologically, resveratrol treatment preserved the structural homeostasis of the articular cartilage and the subchondral bone. Following resveratrol injection, the expression of collagen type II was retained, but the expression of inducible nitric oxide synthase and matrix metalloproteinase-13 was reduced in OA cartilage. Moreover, the administration of resveratrol significantly induced the activation of SIRT1 and the inhibition of HIF-2α expression in mouse OA cartilage and in IL-1β-treated human chondrocytes. These findings indicate that the intra-articular injection of resveratrol significantly prevents the destruction of OA cartilage by activating SIRT1 and thereby suppressing the expression of HIF-2α and catabolic factors.

    Topics: Animals; Antioxidants; Basic Helix-Loop-Helix Transcription Factors; Cartilage, Articular; Collagen Type II; Drug Evaluation, Preclinical; Injections, Intra-Articular; Male; Matrix Metalloproteinase 13; Mice, Inbred C57BL; Nitric Oxide Synthase Type II; Osteoarthritis; Phytotherapy; Random Allocation; Resveratrol; Sirtuin 1; Stilbenes

2015
Resveratrol inhibits interleukin 1β-mediated inducible nitric oxide synthase expression in articular chondrocytes by activating SIRT1 and thereby suppressing nuclear factor-κB activity.
    European journal of pharmacology, 2012, Jan-15, Volume: 674, Issue:2-3

    In chondrocytes, resveratrol, a natural SIRT1 activator, exerts an anti-inflammatory response via inhibition of nuclear factor kappaB (NF-κB). Given that SIRT1 inhibits the transactivation potential of NF-κB by deacetylating acetylated lysines in p65, the NF-κB subunit, we investigated the effects of resveratrol-activated SIRT1 on articular chondrocytes. We found that when chondrocytes were stimulated with interleukin 1β (IL-1β), the time- and dose-dependent expression of inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production was suppressed by resveratrol. Resveratrol-activated SIRT1 mediated this suppression. SIRT1 suppressed not only the nuclear translocation of NF-κB but also the acetylation of p65. Furthermore, acetylated Lys310 in p65, which must be present for transactivation activity, was the immediate downstream target of SIRT1. Therefore, SIRT1 protects against the inflammatory response induced by IL-1β in articular chondrocytes. Resveratrol, as an activator of SIRT1, merits consideration as a therapeutic agent in the treatment and prevention of osteoarthritis.

    Topics: Active Transport, Cell Nucleus; Animals; Cell Nucleus; Chondrocytes; DNA; Gene Expression Regulation, Enzymologic; Interleukin-1beta; Joints; Nitric Oxide; Nitric Oxide Synthase Type II; Osteoarthritis; Rats; Rats, Wistar; Resveratrol; Signal Transduction; Sirtuin 1; Stilbenes; Transcription Factor RelA; Transcriptional Activation

2012
Resveratrol suppresses interleukin-1beta-induced inflammatory signaling and apoptosis in human articular chondrocytes: potential for use as a novel nutraceutical for the treatment of osteoarthritis.
    Biochemical pharmacology, 2008, Dec-01, Volume: 76, Issue:11

    Osteoarthritis is an inflammatory disease of load-bearing synovial joints that is currently treated with drugs that exhibit numerous side effects and are only temporarily effective on pain, the main symptom of the disease. Consequently, there is an acute need for novel, safe and more effective chemotherapeutic agents for the treatment of osteoarthritis and related arthritic diseases. Resveratrol is a phytoalexin stilbene produced naturally by plants including red grapes, peanuts and various berries. Recent research in various cell models has demonstrated that resveratrol is safe and has potent anti-inflammatory properties. However, its potential for treating arthritic conditions has not been explored. In this study we provide experimental evidence that resveratrol inhibits the expression of VEGF, MMP-3, MMP-9 and COX-2 in human articular chondrocytes stimulated with the pro-inflammatory cytokine IL-1beta. Since these gene products are regulated by the transcription factor NF-kappaB, we investigated the effects of resveratrol on IL-1beta-induced NF-kappaB signaling pathway. Resveratrol, like N-Ac-Leu-Leu-norleucinal (ALLN) suppressed IL-1beta-induced proteasome function and the degradation of IkappaBalpha (an inhibitor of NF-kappaB) without affecting IkappaBalpha kinase activation, IkappaBalpha-phosphorylation or IkappaBalpha-ubiquitination which suppressed nuclear translocation of the p65 subunit of NF-kappaB and its phosphorylation. Furthermore, we observed that resveratrol as well as ALLN inhibited IL-1beta-induced apoptosis, caspase-3 activation and PARP cleavage in human articular chondrocytes. In summary, our results suggest that resveratrol suppresses apoptosis and inflammatory signaling through its actions on the NF-kappaB pathway in human chondrocytes. We propose that resveratrol should be explored further for the prophylactic treatment of osteoarthritis in humans and companion animals.

    Topics: Apoptosis; Blotting, Western; Cartilage, Articular; Cell Nucleus; Cells, Cultured; Chondrocytes; Dietary Supplements; Dose-Response Relationship, Drug; Extracellular Matrix; Humans; Inflammation Mediators; Interleukin-1beta; Microscopy, Electron, Transmission; NF-kappa B; Osteoarthritis; Protein Transport; Resveratrol; Signal Transduction; Stilbenes

2008
The antioxidant resveratrol protects against chondrocyte apoptosis via effects on mitochondrial polarization and ATP production.
    Arthritis and rheumatism, 2008, Volume: 58, Issue:9

    To determine the effects of the antioxidant resveratrol on the functions of human chondrocytes in osteoarthritis (OA).. Chondrocytes and cartilage explants were isolated from OA patients undergoing knee replacement surgery. Effects of resveratrol in the presence or absence of interleukin-1beta (IL-1beta) stimulation were assessed by measurement of prostaglandin E(2) (PGE(2)) and leukotriene B(4) (LTB(4)) synthesis, cyclooxygenase (COX) activity, matrix metalloproteinase (MMP) expression, and proteoglycan production. To explore the mechanisms of action of resveratrol, its effects on mitochondrial function and apoptosis were examined by assessing mitochondrial membrane potential, ATP levels, cytochrome c release, and annexin V staining.. Resveratrol inhibited both spontaneous and IL-1beta-induced PGE(2) production by >20% (P < 0.05) and by 80% (P < 0.001), respectively; similarly, LTB(4) production was reduced by >50% (P < 0.05). The production of PGE(2) was inhibited via a 70-90% suppression of COX-2 expression and enzyme activity (P < 0.05). Resveratrol also promoted anabolic effects in OA explant cultures, by elevating proteoglycan synthesis and decreasing production of MMPs 1, 3, and 13. Pretreatment of OA chondrocytes with resveratrol blocked mitochondrial membrane depolarization, loss of mitochondrial biomass, and IL-1beta-induced ATP depletion. Similarly, IL-1beta-mediated induction of the apoptotic markers cytochrome c and annexin V was also inhibited by resveratrol. Exogenous addition of PGE(2) abolished the protective effects of resveratrol on mitochondrial membrane integrity, ATP levels, expression of apoptotic markers, and DNA fragmentation.. Resveratrol protects against IL-1beta-induced catabolic effects and prevents chondrocyte apoptosis via its inhibition of mitochondrial membrane depolarization and ATP depletion. These beneficial effects of resveratrol are due, in part, to its capacity to inhibit COX-2-derived PGE(2) synthesis. Resveratrol may therefore protect against oxidant injury and apoptosis, which are main features of progressive OA.

    Topics: Adenosine Triphosphate; Analysis of Variance; Annexin A5; Antioxidants; Apoptosis; Blotting, Western; Cartilage; Chondrocytes; Cyclooxygenase 2; Cytochromes c; Dinoprostone; DNA Fragmentation; Dose-Response Relationship, Drug; Enzyme-Linked Immunosorbent Assay; Humans; Interleukin-1beta; Leukotriene B4; Matrix Metalloproteinases; Membrane Potential, Mitochondrial; Mitochondria; Osteoarthritis; Proteoglycans; Resveratrol; Reverse Transcriptase Polymerase Chain Reaction; Stilbenes

2008
Effect of resveratrol in experimental osteoarthritis in rabbits.
    Inflammation research : official journal of the European Histamine Research Society ... [et al.], 2005, Volume: 54, Issue:4

    Resveratrol (trans-3,4',5-trihydroxystilbene) is a phytoalexin found in high concentration in the skins of grapes and red wines which has been shown to have antiinflammatory, anticancerogen and antioxidant properties. Resveratrol is a potent and specific inhibitor of nuclear factor kappa B (NF-kappaB). Resveratrol also inhibits COX-2 gene expression and enzyme activity. We aimed to determine the in vivo effects of intra-articular injections of resveratrol on cartilage and synovium in an experimental osteoarthritis (OA) model in rabbits.. As OA model, rabbits underwent unilateral anterior cruciate ligament transection (ACLT). Five weeks after test group was injected with 10 microMol/kg resveratrol in dimethylsulphoxide (DMSO) in the knees once daily for two weeks and as the control group at the same time DMSO was injected into the knees. All rabbits were killed one week after the last injection. Cartilage tissue and synovium were evaluated with a histological scoring system.. Histological evaluation of cartilage tissue by H&E staining revealed a significantly reduced average cartilage tissue destruction score of 1.7 in the resveratrol group versus 2.8 in the control group (p = 0.016). Loss of matrix proteoglycan content in cartilage was also much lower, as determined by safranin O staining. Scores of synovial inflammation didn't show difference between groups (1.3 vs 2.2; p = 0.057).. A characteristic parameter in arthritis is the progressive loss of articular cartilage. This study suggests that intraarticular injections of resveratrol starting at the onset of disease may protect cartilage against the development of experimentally induced OA.

    Topics: Animals; Cartilage; Disease Models, Animal; Inflammation; Osteoarthritis; Rabbits; Resveratrol; Stilbenes

2005