Cucurbitacin R Reduces the Inflammation and Bone Damage Associated with Adjuvant Arthritis in Lewis Rats by Suppression of Tumor Necrosis Factor-α in T Lymphocytes and Macrophages

Abstract

The aim of this study was to investigate the effects of cucurbitacin R on an experimental model of adjuvant-induced arthritis in rats. The treatment of arthritic rats with cucurbitacin R (1 mg/kg p.o. daily) modified the evolution of the clinical symptoms, whereas the histopathology of paws demonstrated a reduction in the signs of arthritis. Compared with the control group, radiography of the tibiotarsal joints of cucurbitacin Rtreated rats showed a decrease in joint damage and soft tissue swelling of the footpad. The in vivo study of the expression of proinflammatory enzymes (nitric-oxide synthase-2 and cyclooxygenase-2) with the aid of the Western blot technique, and that of tumor necrosis factor-␣ (TNF-␣) and prostaglandin E 2 by means of enzyme-linked immunosorbent assays demonstrated a clear decrease in both the enzymes and the mediators in paw homogenates. The analysis for prostaglandin E 2 , nitric oxide, and TNF-␣ production in RAW 264.7 macrophages, as well as that for TNF-␣ in human lymphocytes, indicated a reduction of all mediators. The expression of cyclooxygenase-2 was not modified in RAW 264.7 macrophages, whereas the expression of nitric-oxide synthase-2 was clearly diminished. Moreover, cucurbitacin R was found to inhibit signal transducer and activator of transcription 3 activation in the lymphocytes of both healthy and arthritic men. These experimental data on the chronic model, together with previously reported activity on acute and subchronic experimental models, justify the antiinflammatory activity of cucurbitacin R and provide further evidence for the therapeutic potential of a group of natural products as anti-inflammatory agents.Arthritis is a chronic disease that affects several parts of the joints such as the cartilage, synovium, tendons, and muscles. Rheumatoid arthritis is a specific type of this disease characterized by chronic inflammation of the joints, with severe cartilage and bone damage. The precise causes are unknown, but genetics, infectious agents, environment, and hormonal effects have all been implicated. Treatments are focused on the reduction of pain, inflammation, and joint damage. The principal pharmacological agents are nonsteroidal anti-inflammatory drugs, disease-modifying antirheumatic drugs, glucocorticoids, and specific inhibitors of the mediator response such as the tumor necrosis factor-␣ (TNF-␣) antibody infliximab. Adjuvant arthritis is an experimental model unique to rats that is widely used for studying the physiology, biochemistry, and pharmacology of inflammation and also as a model of cell-mediated autoimmnune disease, human arthritis, and chronic pain. Different parameters can be evaluated, such as weight evolution, paw swelling, histology, immunohistochemistry, and radiographic evaluation (Taurog et al., 1988). The origin and development are complex, with the implication of different inflammatory cells and cytokines. Thus, when the inflammatory cells migrate into the joint space between bones, there is inflammation of the membranes and damage...

Activated kRas protects colon cancer cells from cucurbitacin-induced apoptosis: The role of p53 and p21

“…We have shown before that both cucurbitacins exert potent anti-inflammatory activity both in vitro and in vivo [2,3,5]. Here we examined their anti-tumorigenic activity in colon cancer cell lines, and compared their potency with CCI, a cucurbitacin with established anti-tumorigenic activity [11,30].…”

“…Indeed, cucurbitacins have been shown to have anti-inflammatory, analgesic as well as cytotoxic activity in vitro and in vivo [2,3]. Cayaponia tayuya (Cucurbitaceae) is a climbing lignified plant with a large tuber that has long been used in the folk medicines of Brazil, Peru, and Colombia as an antiinflammatory, antitumour and anti-rheumatic agent [4].…”

“…We recently isolated two cucurbitacins from the roots of Cayaponia tayuya, identified as 23, 24-dihydrocucurbitacin B (DHCB) and cucurbitacin R (CCR) [3]. We demonstrated the anti-inflammatory, anti-allergic and anti-arthritic activity of DHCB and CCR in vitro and in vivo, due to their ability to inhibit the expression of TNFα in lymphocytes and in macrophages, and to interfere with the activity of the nuclear factor NF-AT [2,5,6].…”

Effect of Solid Nanoparticle of Indomethacin on Therapy for Rheumatoid Arthritis in Adjuvant-Induced Arthritis Rat

“…The principal pharmacological agents are nonsteroidal anti-inflammatory drugs (NSAIDs), disease-modifying antirheumatic drugs, glucocorticoids and specific inhibitors of the mediator response. 2) It is well known, however, that these drugs have significant side effects. [3][4][5][6][7][8] Gastroenteropathy is the most common side effect among patients taking NSAIDs, and RA patients taking NSAIDs are more susceptible to NSAIDsinduced gastrointestinal lesions in comparison with other patients.…”

Excessive Interleukin 18 Relate the Aggravation of Indomethacin-Induced Intestinal Ulcerogenic Lesions in Adjuvant-Induced Arthritis Rat

“…The principal pharmacological agents are nonsteroidal anti-inflammatory drug (NSAIDs), glucocorticoids and specific inhibitors of the mediator response, disease-modifying antirheumatic drugs. 2) However, it is well known that these drugs have significant side effects. 3) In the patients taking NSAIDs, gastroenteropathy is known as the most common side effect.…”