Two new cucurbitacin glucosides, opercurins A and B, from the Brazilian folk medicine "Buchinha" (Luffa operculata).
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The structures of two new cucurbitacin glucosides designated opercurins A (1) and B (2), isolated from the fruit of Luffa operculata, have been confirmed by extensive spectroscopic investigation. (+info)
Cucurbitacin R reduces the inflammation and bone damage associated with adjuvant arthritis in lewis rats by suppression of tumor necrosis factor-alpha in T lymphocytes and macrophages.
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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 R-treated 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-alpha (TNF-alpha) 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-alpha production in RAW 264.7 macrophages, as well as that for TNF-alpha 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 anti-inflammatory activity of cucurbitacin R and provide further evidence for the therapeutic potential of a group of natural products as anti-inflammatory agents. (+info)
Polymeric micelles for the solubilization and delivery of STAT3 inhibitor cucurbitacins in solid tumors.
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Poly(ethylene oxide)-block-poly(epsilon-caprolactone) (PEO-b-PCL) and newly developed poly(ethylene oxide)-block-poly(alpha-benzyl carboxylate epsilon-caprolactone) (PEO-b-PBCL) micelles were evaluated for the solubilization and delivery of cucurbitacin I and B, poorly water soluble inhibitors of signal transducer and activator of transcription 3 (STAT3). Encapsulation of cucurbitacins in PEO-b-PCL and PEO-b-PBCL by co-solvent evaporation technique resulted in polymeric micelles <90 nm in diameter. The aqueous solubility of both derivatives increased from less than 0.05 mg/mL in the absence of the copolymer to around 0.30-0.44 and 0.65-0.68 mg/mL in the presence of 5000-5000 and 5000-24,000 PEO-b-PCL micelles, respectively. Maximum cucurbitacin solubilization was achieved with PEO-b-PBCL micelles for both derivatives. PEO-b-PCL micelles having longer PCL block were found to be more efficient in sustaining the rate of release for cucurbitacins. The anti-cancer and STAT3 inhibitory activity of polymeric micellar cucurbitacins were comparable with free drugs in B16.F10 melanoma cell line in vitro. Intratumoral injection of 1 mg/kg/day cucurbitacin I resulted in the regression of established B16.F10 mouse melanoma tumors in vivo. In comparison to free cucurbitacin I, PEO-b-PBCL micellar cucurbitacin I was found to provide comparable anti-cancer effects against B16.F10 tumors and limit drug levels in animal serum while maintaining high drug levels in tumor following intratumoral administration. The results indicate the potential of polymeric micelles as suitable vehicles for the delivery of cucurbitacin- I and B. (+info)
Evaluation of the purified fraction of Wilbrandia (c.f.) verticillata for antitumour activity.
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Cucurbitacins are known to produce cytotoxic and anticancer activities. Two novel norcucurbitacin glucosides (Wv1 and Wv2) have recently been isolated from a purified fraction obtained from the rhizome of Wilbrandia verticillata. The present study evaluates the cytotoxic and antitumour activities of these norcucurbitacins. We have found a regular cytotoxicity in KB cells (Cy50 = 12 micrograms/ml) as well as a significant inhibition in the Walker 256 carcinosarcoma growth (approximately 75%). (+info)
Differential regulation of STAT family members by glycogen synthase kinase-3.
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Cucurbitacin IIa: a novel class of anti-cancer drug inducing non-reversible actin aggregation and inhibiting survivin independent of JAK2/STAT3 phosphorylation.
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