stilbenes and Arthritis

Arthritis, an inflammation of the joints, is usually a chronic disease that results from dysregulation of pro-inflammatory cytokines (e.g. tumour necrosis factor and interleukin-1beta) and pro-inflammatory enzymes that mediate the production of prostaglandins (e.g. cyclooxygenase-2) and leukotrienes (e.g. lipooxygenase), together with the expression of adhesion molecules and matrix metalloproteinases, and hyperproliferation of synovial fibroblasts. All of these factors are regulated by the activation of the transcription factor nuclear factor-kappaB. Thus, agents that suppress the expression of tumour necrosis factor-alpha, interleukin-1beta, cyclooxygenase-2, lipooxygenase, matrix metalloproteinases or adhesion molecules, or suppress the activation of NF-kappaB, all have potential for the treatment of arthritis. Numerous agents derived from plants can suppress these cell signaling intermediates, including curcumin (from turmeric), resveratrol (red grapes, cranberries and peanuts), tea polyphenols, genistein (soy), quercetin (onions), silymarin (artichoke), guggulsterone (guggul), boswellic acid (salai guggul) and withanolides (ashwagandha). Indeed, several preclinical and clinical studies suggest that these agents have potential for arthritis treatment. Although gold compounds are no longer employed for the treatment of arthritis, the large number of inexpensive natural products that can modulate inflammatory responses, but lack side effects, constitute 'goldmines' for the treatment of arthritis.

Topics: Animals; Arthritis; Curcumin; Ergosterol; Humans; Phytotherapy; Plant Preparations; Pregnenediones; Resveratrol; Stilbenes; Triterpenes; Withania

Metalloproteinase-13 is the major type II collagenase that directly implicates cartilage matrix destruction. Metalloproteinase-13 is inducted and activated by interleukin-1β, which is a commonly observed proinflammatory cytokine in the joint cavity of arthritic patients. Depression of interleukin-1β function can inhibit metalloproteinase-13 expression and protect the cartilage extracellular matrix. In this study, resveratrol release microspheres were developed, and the direct function of the released resveratrol on the interleukin-1β was discussed. The resveratrol-loaded microspheres were fabricated using oil-in-water emulsion and solution-evaporation methods. The particle size and the encapsulation efficiency for the techniques, which used different fabrication conditions, were within 8.3-63.9 μm and 37%-82%, respectively. The effect of drug release lasted for more than 650 h in a PBS solution at 37℃. Human bone mesenchymal stem cells were chosen for cell experiments. Interleukin-1β was used to induce an inflammatory condition. The effect of sustained resveratrol release from the microspheres on the cells' gene expression was observed using the transwell co-culturing method. The results indicated that metalloproteinase-13 mRNA expression was upregulated after interleukin-1β induction. The released resveratrol directly inhibited the function of interleukin-1β and thus downregulated metalloproteinase-13 mRNA expression. Moreover, the upregulation of Col2, aggrecan and Sox9 mRNA expressions, which are major chondrocyte markers, was observed after resveratrol was released into the culture medium. Resveratrol was observed to maintain the cells' chondrogenic gene expression when subject to the inflammation condition. The sustained released resveratrol inhibited interleukin-1β-inducted metalloproteinase-13 activation and promoted chondrocyte differentiation. This drug-loading microsphere is a promising candidate for arthritis therapy.

Topics: Antioxidants; Arthritis; Cell Differentiation; Cell Proliferation; Cell Survival; Cells, Cultured; Chondrocytes; Coculture Techniques; Drug Carriers; Drug Delivery Systems; Humans; Inflammation; Interleukin-1beta; Lactic Acid; Matrix Metalloproteinase 13; Matrix Metalloproteinase 8; Mesenchymal Stem Cells; Microspheres; Particle Size; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Resveratrol; SOX9 Transcription Factor; Stilbenes

Resveratrol (RSV) was first isolated in 1940 from the roots of white hellebore (Veratrum grandiflorum (Maxim. ex Miq) O. Loes) and in 1963 from the roots of Japanese knotweed (Polygonum cuspidatum Siebold & Zucc.). These species have been used traditionally to treat arthritis, gout or inflammation. RSV (3,5,4-trihydroxystilbene) is a polyphenolic phytoalexin compound found in various plants, such as grape vines, berries, peanuts, seeds and roots; the highest concentration is in the skin of red grapes. This component of red wine has potent anti-inflammatory properties and may reduce the side effects of non-steroidal anti-inflammatory drugs that are currently used for pain amelioration in osteoarthritis (OA). In early degeneration of articular cartilage, which may lead to OA there is a loss of the tensile properties, indicative of damage to the fibrillar network. Damage to this fibrillar meshwork, made up of primarily collagen type II (90-95%), may be a critical event in the pathology of many arthritides, due in part to the very slow rate of collagen turnover within the cartilage. Collagen type II is the pre-dominant protein of the cartilage middle zone matrix mainly responsible for tensile strength of articular cartilage. The aim of the study was to investigate the effects of RSV on the expression of collagen type II from the superficial and middle zone chondrocytes of porcine articular cartilage.. Porcine articular chondrocytes were isolated from the superficial and middle zone of articular cartilage, cultured as monolayers in serum-free chemically defined medium for four days. Effects of RSV on porcine articular chondrocytes were studied by assessing expression of collagen type II mRNA by RT-PCR and protein levels of collagen type II by ELISA; as well as localisation of collagen type II on cartilage tissue sections using immunohistochemistry.. RSV significantly stimulated the expression of collagen type II at the mRNA and protein levels in the superficial and middle zone. Immunohistochemistry revealed that collagen type II was present along the whole cartilage tissue sections. The staining was strong in the superficial zone, mild in the middle zone and less around hypertrophic chondrocytes in the deep zone. Histological analysis confirmed that cartilage slices were obtained from specific articular cartilage zones.. This study revealed the importance of RSV in the regulation of collagen type II protein in different zones of articular cartilage.

Topics: Animals; Arthritis; Cartilage, Articular; Chondrocytes; Collagen Type II; Immunohistochemistry; Resveratrol; RNA, Messenger; Stilbenes; Swine

Vitis thunbergii Sieb. and Zucc. var. taiwaniana Lu is an endemic plant in Taiwan used as a dietary supplement for bone health. In this study, human chondrocytes were induced to produce COX-2, MMP-3, -13, and PGE(2) by LPS. An (18)F-FDG microPET imaging system was used to evaluate the anti-inflammatory arthritic effects in vivo. Six stilbenes, resveratrol (1), (+)-ε-viniferin (2), ampelopsin C (3), ampelopsin A (4), (-)-vitisin B (5), and (+)-vitisin A (6), were isolated from the stem part of V. thunbergii, which displayed the strongest PGE(2) inhibition. Among these compounds, 1 significantly decreased COX-2 activity, PGE(2), MMP-3, and -13 production in vitro, and (18)F-FDG uptake and serum PGE(2) in rabbits in vivo. Anti-inflammatory effects were enhanced through the combined usage of 1 and other oligostilbenes. Taken together, the synergistic effects of 1 and oligostilbenes resulted in stem part extracts with lower 1 content displaying the better anti-inflammatory arthritis effects.

Topics: Anti-Inflammatory Agents; Arthritis; Humans; Lipopolysaccharides; Magnetic Resonance Spectroscopy; Resveratrol; Spectrometry, Mass, Electrospray Ionization; Stilbenes; Vitis

In an extensive analysis of the antiviral and interferon-induction structure-activity relationship of 6-arylpyrimidinones we found that modifications at positions 1-4 of the pyrimidine ring resulted in a loss of activity. However, we uncovered interesting hypotensive and antiinflammatory activity with a series of N-substituted analogues, the results of which we report herein.

Topics: Animals; Anti-Inflammatory Agents; Antiviral Agents; Arthritis; Diuresis; Dose-Response Relationship, Drug; Female; Furosemide; Guanethidine; Heart; Hydrochlorothiazide; Hypotension; Male; Methylation; Natriuresis; Phenylacetates; Potassium; Pyrimidinones; Rats; Rats, Inbred Strains; Stilbenes; Structure-Activity Relationship; Tamoxifen