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ABSTRACT: Physical protection of mucosa surface and reduction of inflammatory processes are currently considered the main strategies in the treatment and prevention of mucosal diseases. However, the majority of models used to verify the activity of new mucoprotective agents are based on limiting instrumental assessment or the sacrifice of experimental animals. In this study, for the first time, some in vitro experimental methods using Caco-2 cell line are proposed as predicting in vivo behaviour and action of mucoprotective agents. To this purpose, hyaluronic acid and natural polysaccharides for their bioadhesive activity, hydrocortisone and natural polyphenols as anti-inflammatory agents have been chosen. The obtained results demonstrated that the techniques (Con A/o-pd assay and Franz cell system) of mucoadhesive evaluation on Caco-2 cells are useful to compare the activity of each experimental sample and to assess the adhesion time to the mucosal cell surface. Moreover, the reduction of intercellular adhesion molecule-1 (ICAM-1) expression in Caco-2 cells can be considered directly correlated to the mucosal anti-inflammatory effect induced by the hydrocortisone and natural polyphenols. In conclusion, the study supported the use of Caco-2 cell as a model to compare and investigate the effect of different active substances on the mucosa and its diseases.
International journal of pharmaceutics 11/2011; 422(1-2):318-22. · 2.96 Impact Factor
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ABSTRACT: Chitosan is a natural polymer whose bioadhesive properties make it a useful material for filming over and protecting damaged or sensitive mucosae. Much effort has been expended to develop this employ, and new applications are in the offing. The aim of the present study was to optimize the synthesis under sonochemical conditions of water-soluble chitosan tetraalkylammonium salts and to assess the mucoadhesive properties of the resulting water-soluble cationic polyelectrolytes. Aqueous solutions of several tetralkylammonium chitosan derivatives, viz. N-trimethyl- (1), N-diethylmethyl- (2), N-carboxymethyl-(3) and N-[N,N-diethylaminomethyl(diethyldimethylene ammonium)(n)]methylchitosan (4) were tested along with the parent biopolymer and its citric acid salt (5), both at neutral and acidic pH. We used a published technique for evaluating in vitro bioadhesion to isolated buccal cells, a mucosal model that can predict bioadhesive behavior in vivo. Derivatives I and 4 gave the best results. (C) 2008 Elsevier B.V. All rights reserved.
International journal of pharmaceutics 01/2008; 362(1-2):88-92. · 2.96 Impact Factor
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ABSTRACT: Conventional medications in articular disease are often effective for symptom relief, but they can also cause significant side effects and do not slow the progression of the disease. Several natural substances have been shown to be effective as non-steroidal anti-inflammatory drugs at relieving the symptoms of osteoarthritis (OA), and preliminary evidence suggests that some of these compounds may exert a favourable influence on the course of the disease. In this study, we assay the anti-inflammatory/chondroprotective effect of some lyophilised extracts obtained from Opuntia ficus indica (L.) cladodes and of hyaluronic acid (HA) on the production of key molecules released during chronic inflammatory events such as nitric oxide (NO), glycosaminoglycans (GAGs), prostaglandins (PGE(2)) and reactive oxygen species (ROS) in human chondrocyte culture, stimulated with proinflammatory cytokine interleukin-1 beta (IL-1 beta). Further the antioxidant effect of these extracts was evaluated in vitro employing the bleaching of the stable 1,1-diphenyl-2-picrylhydrazyl radical (DPPH test). All the extracts tested in this study showed an interesting profile in active compounds. Particularly some of these extracts were characterized by polyphenolic and polysaccharidic species. In vitro results pointed out that the extracts of Opuntia ficus indica cladodes were able to contrast the harmful effects of IL-1 beta. Our data showed the protective effect of the extracts of Opuntia ficus indica cladodes in cartilage alteration, which appears greater than that elicited by hyaluronic acid (HA) commonly employed as visco-supplementation in the treatment of joint diseases.
Journal of Ethnopharmacology 06/2007; 111(2):315-21. · 3.01 Impact Factor
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ABSTRACT: The present work was aimed at evaluating the in vitro effects of a lyophilized extract of wine (JW-E) obtained from Jacquez grapes (Vitis aestivalis-cinereaxVitis vinifera grapes) on the production of key molecules released in inflammatory disease utilising interleukin-1beta (IL-1beta) activated chondrocytes. The extract contains large amounts of phenolic components, in particular some flavonoids (flavan-3-ols, also known as catechins) and proanthocyanidins, as hydroxycinnamic acids and anthocyanins, that possess several biological features such as antiinflammatory and antioxidant effects and a "radical scavenger" activity too. In this study, we assayed the effect of JW-E on the production of key molecules released during chronic inflammatory events as nitric oxide (NO), prostaglandins E(2) (PGE(2)) and reactive oxygen species (ROS) in human chondrocytes culture, stimulated with proinflammatory cytokine interleukin-1beta. The JW-E proved to possess good ability against the harmfull effects of IL-1beta. Our data showed the protective effects of JW-E in cartilage alteration, that appears greater than that elicited by indomethacin, a not steroidal antiinflammatory drug (NSAID), commonly employed in joint diseases.
Phytomedicine 08/2006; 13(7):522-6. · 3.27 Impact Factor
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ABSTRACT: In traditional medicine extracts of polysaccharide-containing plants are widely employed for the treatment of skin and epithelium wounds and of mucous membrane irritation. The extracts of Opuntia ficus-indica cladodes are used in folk medicine for their antiulcer and wound-healing activities. The present study describes the wound-healing potential of two lyophilized polysaccharide extracts obtained from O. ficus-indica (L.) cladodes applied on large full-thickness wounds in the rat. When topically applied for 6 days, polysaccharides with a molecular weight (MW)>10(4)Da from O. ficus-indica cladodes induce a beneficial effect on cutaneous repair in this experimental model; in particular the topical application of O. ficus-indica extracts on skin lesions accelerates the reepithelization and remodelling phases, also by affecting cell-matrix interactions and by modulating laminin deposition. Furthermore, the wound-healing effect is more marked for polysaccharides with a MW ranging 10(4)-10(6)Da than for those with MW>10(6)Da, leading us to suppose that the fine structure of these polysaccharides and thus their particular hygroscopic, rheologic and viscoelastic properties may be essential for the wound-healing promoter activity observed.
Phytomedicine 05/2006; 13(5):352-8. · 3.27 Impact Factor
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ABSTRACT: The aim of the present study was to evaluate the in vitro chondroprotective effects of the lyophilised methanolic extract from flowering buds of Capparis Spinosa L (LECS). This plant, common to the Mediterranean basin, has been used by the traditional medicine for its diuretic and antihypertensive effects and also in certain pathological conditions related to uncontrolled lipid peroxidation. The extract contains many constituents, in particular some flavonoids (kaempferol and quercetin derivatives) and hydrocinammic acids with several known biological effects such as the anti-inflammatory and the antioxidant ones. In this study, we assayed the effect of LECS on human chondrocytes cultures stimulated by proinflammatory cytokine interleukin-1beta (IL-1beta) and we determined the production of key molecules released during chronic inflammatory events (nitric oxide, glycosaminoglycans, prostaglandins and reactive oxygen species). We observed that LECS was able to counteract the harmful effects induced by IL-1beta. This protection appeared to be greater than that elicited by indomethacin, which is usually employed in joint diseases. Since LECS possess a chondroprotective effect, it might be used in the management of cartilage damage during the inflammatory processes.
Life Sciences 10/2005; 77(20):2479-88. · 2.53 Impact Factor
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ABSTRACT: Thiocolchicoside, a semi-synthetic derivative of colchicoside, is used in topical formulations for its anti-inflammatory and muscle-relaxant properties. The objective of this study was to evaluate the effect of a (propylene glycol diperlagonate) DPPG and (propylene glycol) PG mixture present in an innovative foam formulation (Miotens) on the flux of thiocolchicoside through excised human skin. Furthermore, the in vitro permeation behaviour of this new formulation (Miotens foam) was compared to another commercial product (Muscoril ointment) and to a control gel formulation (thiogel), both enhancer free. The best permeation profile was obtained from the foam formulation (Miotens) which was able to increase the thiocolchicoside flux about three fold compared to control formulation (thiogel) and about two fold compared to the commercial formulation Muscoril ointment.
Pharmazie 12/2002; 57(11):750-2. · 1.01 Impact Factor
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ABSTRACT: Polyoxyethylene esters of ketoprofen (1a-e), naproxen (2a-e) and diclofenac (3a-e) were tested in vitro to determine their stability in pH 7.4 phosphate buffer and in simulated gastric fluid (pH 2.0 buffer) and their susceptibility in undergoing enzymatic cleavage in human plasma. Furthermore their in vivo antiinflammatory and analgesic activity and GI toxicity were evaluated in rodents. All the prodrugs showed a good stability both in pH 7.4 phosphate buffer and in pH 2.0 buffer. They were readily hydrolyzed by human plasma and, for each group of prodrugs, no significant difference in hydrolysis rate was observed as the length of the oligoethylene chain increased. Esters 1a-e, 2a-e and 3a-e showed an anti-inflammatory activity (expressed as inhibition percent of carrageenan-induced edema in the rat) similar to that of their respective parent drug although at higher doses. The results obtained in the writhing test in mice demonstrated that all the prodrugs tested exhibited, following acute administration, a good analgesic effect. Furthermore these esters were significantly less irritating to the gastric mucosa, although administered at doses higher than the respective parent drug.
Pharmazie 09/2002; 57(8):552-5. · 1.01 Impact Factor
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ABSTRACT: Diabetes mellitus is associated with a high oxidative stress level, resulting from an imbalance between free radicals or reactive oxygen species production and the antioxidant systems. Inhibition of these oxidative processes by co-adjuvant therapy could therefore prevent, or at least delay, the onset and/or the development of long-term diabetic complications. Dietary supplementation with plant biophenols may be a successful strategy to decrease this risk of pathological complications. The Red Orange Complex (ROC) is a standardized red orange extract containing, as its main active principles, phenolic compounds (anthocyanins, flavanones and hydroxycinnamic acids) as well as ascorbic acid. The aim of the present preliminary study was to evaluate the effects of short-term (2 mo) dietary supplementation with ROC (50 mg/d, orally) on some serum non-invasive biomarkers of oxidative stress (total antioxidant status, or TAS, levels of thiol groups and levels of free radicals) in a group of 33 patients with Type 2 diabetes, in comparison with a group of 28 healthy volunteers. The results obtained demonstrate that in diabetic patients supplementation with ROC can improve blood levels of thiol groups on proteins (an indirect measurement of glutathione activity in serum); furthermore, it can elicit a marked decrease in serum free radical levels, in patients with high blood oxidative stress status. However, ROC supplementation appeared unable to modify serum TAS. Finally, the glycemic profile remained stable during the study period in all subjects, and no unpleasant side effects were reported. In conclusion, the treatment of diabetic patients with ROC might be of therapeutic benefit in order to protect against diabetes complications that are partially due to uncontrolled lipid oxidation. D
Diabetes, nutrition & metabolism 03/2002; 15(1):14-9.
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ABSTRACT: Novel polyoxyethylene esters of ketoprofen (1(a-e)), naproxen (2(a-e)) and diclofenac (3(a-e)) were synthesized and evaluated as potential dermal prodrugs of naproxen, ketoprofen and diclofenac. These esters were obtained by coupling these drugs with polyoxyethylene glycols by a succinic acid spacer. The aqueous solubilities, lipophilicities and hydrolysis rates of esters 1(a-e), 2(a-e) and 3(a-e) were determined in a buffered solution and in porcine esterase. The permeation of these prodrugs through excised human skin was studied in vitro. Furthermore we investigated the in vivo topical anti-inflammatory activity of esters 1(d), 2(e) and 3(e), which showed the best in vitro profile, evaluating the ability of these compounds to inhibit methyl nicotinate (MN)-induced skin erythema on healthy human volunteers. Esters 1(a-e), 2(a-e) and 3(a-e) showed good water stability and rapid enzymatic cleavage and their hydrolysis rates, both chemical and enzymatic, were not significantly affected by the length of the polyoxyethylenic chain used as promoiety. Concerning in vitro percutaneous absorption studies, only esters 1(d-e), 2(d-e) and 3(c-e) showed an increased flux through stratum corneum and epidermis membranes compared to their respective parent drugs. In vivo results showed an interesting delayed and sustained activity of esters 1(d) and 3(e) compared to the parent drugs. In conclusion polyoxyethylene glycols could prove to be suitable promoieties for ketoprofen, naproxen and diclofenac design since esters 1(d-e), 2(d-e) and 3(c-e) showed some requirements (chemical stability, enzymatic lability and an increased skin permeation) needed to obtain successful dermal prodrugs. Furthermore, was observed an appreciable and sustained in vivo topical anti-inflammatory activity of esters 1(d) and 3(e), compared to the parent drugs, using MN-induced erythema in human volunteers as inflammation model.
European Journal of Pharmaceutical Sciences 10/2001; 14(2):123-34. · 3.21 Impact Factor
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ABSTRACT: Sedum telephium L. is a medicinal plant used in antiquity to cure many types of inflammatory skin diseases. The leaves (without the external cuticle), are used to promote healing and reduce skin inflammation and pain, and contain various components. We found two major components: flavonol glycosides and polysaccharides, with molecular weight between 13,000 and 13,500 Da. We evaluated the in-vitro antioxidant and in-vivo skin photoprotective effects of three lyophilized extracts obtained from the juice of S. telephium L. leaves: a total lyophilized juice, a lyophilized flavonolic fraction, and a lyophilized polysaccharidic fraction. Two in-vitro models were used: the bleaching of the stable 2,2-diphenyl-1-picrylhydrazyl (DPPH*) radical, and the protective effect against UV-induced peroxidation on phosphatidylcholine multilamellar vesicles, as model membranes. The antioxidant/radical scavenging activity of each lyophilized extract was also assessed in-vivo by determining their ability to reduce UVB-induced skin erythema (monitored by reflectance spectrophotometry) in healthy human volunteers. The findings of the in-vitro experiments clearly demonstrated that, unlike the lyophilized polysaccharidic fraction, the lyophilized flavonolic fraction and total lyophilized juice possess strong antioxidant/free radical scavenging properties, which are likely due to phenolic compounds. Consistent with these findings, gel formulations of both the total lyophilized juice and, to a greater degree, the lyophilized flavonolic fraction appeared to possess a strong protective effect against UV-induced skin erythema in-vivo, whereas the lyophilized polysaccharidic fraction was completely ineffective. The in-vitro and in-vivo results suggest that, both the total lyophilized juice and, in particular, the lyophilized flavonolic fraction, but not the lyophilized polysaccharidic fraction of S. telephium L. leaves, have photoprotective effects against UVB-induced skin damage.
Journal of Pharmacy and Pharmacology 11/2000; 52(10):1279-85. · 2.17 Impact Factor
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ABSTRACT: The aim of the present study was to evaluate the in vitro antioxidant and in vivo photoprotective activities of a lyophilized extract of Capparis spinosa L. (LECS) obtained by methanolic extraction from the flowering buds of this plant. For the in vitro experiments, LECS was tested employing three different models: (a). bleaching of the stable 1,1-diphenyl-2-picrylhydrazyl radical (DPPH test); (b). peroxidation, induced by the water-soluble radical initiator 2,2'-azobis(2-amidinopropane) hydrochloride, of mixed dipalmitoylphosphatidylcholine/linoleic acid unilamellar vesicles (LUVs) (LP-LUV test); and (c). UV-induced peroxidation of phosphatidylcholine multilamellar vesicles (UV-IP test). The in vivo antioxidant/radical scavenger activity was assessed by determining the ability of topically applied LECS to reduce UVB-induced skin erythema in healthy human volunteers. From the results obtained in in vitro and in vivo tests, LECS showed a significant antioxidant effect. Furthermore, by chromatographic fractionation and spectroscopic methods, we identified the major constituents of LECS, and particularly some flavonols (kaempferol and quercetin derivatives) and hydroxycinnamic acids (caffeic acid, ferulic acid, p-cumaric acid, and cinnamic acid).
Journal of cosmetic science 53(6):321-35. · 0.28 Impact Factor
