Abderrahman Bouraoui

Screening of analgesic and anti-inflammatory activities of Citrullus colocynthis from southern Tunisia

ETHNOPHARMACOLOGICAL RELEVANCE Inflammations and immune-related diseases such as rheumatoid arthritis are growing global concerns. Most of the drugs from plants which have become important in modern medicine had a folklore origin and are traditional in systems of medicine. Citrullus colocynthis Schrad. (cucurbitaceae), endemic in Southern Tunisia, is used in folk medicine to treat many inflammation diseases. AIM OF STUDY To evaluate the acute toxicity of different parts of Citrullus colocynthis and then to screen the analgesic and anti-inflammatory activities of aqueous extracts from roots and stems of the plant and from fruits and seeds at different maturation stages. MATERIALS AND METHODS After identification and acute toxicity assay Citrullus colocynthis Schrad. aqueous extracts were screened for analgesic and anti-inflammatory activities using, respectively, the acetic acid writhing test in mice and the carrageenan-induced paw edema assay in rats. RESULTS All extracts displayed analgesic and anti-inflammatory activities at different doses without inducing acute toxicity. Topic results were obtained with immature fruits followed by seeds. The stem and root extracts were shown to possess the less significant inhibitory activity against analgesic and anti-inflammatory models. CONCLUSIONS Based on this study, we confirmed that Citrullus colocynthis Schrad. is a potentially useful drug suitable for further evaluation for rheumatoid arthritis, and its folk medicinal use as an analgesic and anti-inflammatory agents is validated.

Synthesis and pharmacological profile of 6-methyl-3-isopropyl-2H-1,2-benzothiazin-4(3H)-one 1,1-dioxide derivatives: non-steroidal anti-inflammatory agents with reduced ulcerogenic effects in the rat.

The new anti-inflammatory agents 6-methyl-3-isopropyl-2H-1,2-benzothiazin-4(3H)-one 1,1-dioxide 6a and its analogues 6b-f were synthesized from L-valine. All compounds were characterized by physical, chemical and spectral studies. Preliminary pharmacological evaluation of the resulting products showed that compounds 6a-f (5-20 mg/kg, i.p.) are active anti-inflammatory agents in carrageenan-induced rat paw oedema assay in albino rats, and their effects are comparable to that of piroxicam (5 mg/kg, i.p.), used as a reference drug. The nature of the substituents on the sulfonamide nitrogen and those on position three had a pronounced effect on the anti-inflammatory activity. Studies of structure-activity relationships have led to selection of compound 2,6-dimethyl-3-isopropyl-1,2-benzothiazin-3,4-diol 1,1-dioxide 6 f which exhibited the most potent activity (61.7% inhibition at 5 mg/kg, i.p. and ED(50)=4.5 mg/kg, i.p.). Comparison of the gastrointestinal safety of compounds 6a-f with that of piroxicam showed a far better tolerability for our products. This comparison was based on the ulcer index and the pH of gastric content.

Evaluation of antiproliferative and anti-inflammatory activities of methanol extract and its fractions from the Mediterranean sponge

BackgroundWithout doubt, natural products have been, and still are, the cornerstone of the health care armamentarium. Of all natural sources, the marine environment is clearly the last great frontier for pharmaceutical and medical research.MethodsThis work progresses in the direction of identifying component(s) from the Mediterranean sponge, Spongia officinalis with pharmacological activities. In the present study we investigated the efficacy of methanol extract and its semi-purified fractions (F2, F3) from Spongia officinalis for their in vivo anti-inflammatory activity using the carrageenan-induced paw edema in rats and their in vitro antiproliferative effects by their potential cytotoxic activity using the MTT colorimetric method and clonogenic inhibition against three human cancer cell lines (A549, lung cell carcinoma, HCT15, colon cell carcinoma and MCF7, breast adenocarcinoma).ResultsThe fractions F2 and F3 showed interesting anti-inflammatory and antiproliferative activities in a dose dependent manner.ConclusionsThe present study indicates that the methanolic extrac and its fractions from Spongia officinalis are a significant source of compounds with the antiproliferative and anti-inflammatory activities, and this may be useful for developing potential chemopreventive substances.

Anti-inflammatory, anti-proliferative and anti-oxidant activities of organic extracts from the Mediterranean seaweed, Cystoseira crinita

This study was conducted to evaluate the anti-inflammatory, the anti-proliferative, total phenolic content (TPC) and the anti-oxidant activity of the chloroformic (CHCl 3 ), the ethyl acetate (AcOEt) and the methanolic (MeOH) extracts of Cystoseira crinita . These extracts were assayed on carrageenan induced rat paw oedema assay. They exhibited significant anti-inflammatory activity in a dose dependent manner. The anti-proliferative activity of organic extracts of C. crinita was evaluated on cancer cell lines (A549, MCF7 and HCT15) by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. CHCl 3 and AcOEt extracts showed important anti-proliferative activity against both HCT15 and MCF7 cell lines. Organic extracts of C. crinita showed important TPC. Moreover, they exhibited significant radical scavenging activity and displayed the highest reducing power. Organic extracts of C. crinita might be used as a significant potential source of natural compounds with anti-inflammatory, anti-proliferative and anti-oxidant activity. It could have a promising role in future medicine. Key words : Cystoseira crinita, anti-inflammatory, anti-proliferative, 2,2-diphenyl-1- picrylhydrazyl radical scavenging activity, total polyphenol content.

Anti-inflammatory and antiproliferative activities of crude extract and its fractions of the defensive secretion from the Mediterranean sponge, Spongia officinalis

The fact that conventional and newly emerging treatment procedures like chemotherapy, catalytic therapy, photodynamic therapy, and radiotherapy have not succeeded in reversing the outcome of many cancers alternative treatment options has been explored. This study documents the identification of component(s) from the Mediterranean sponge, Spongia officinalis that have anti‐inflammatory and antiproliferative activities. In the present study we investigated the efficacy of a crude extract and its semi‐purified fractions (F1–F3) of the defensive secretion from Spongia officinalis for in vivo anti‐inflammatory activity using the carrageenan‐induced paw edema assay in rats and their in vitro antiproliferative effects against three human cancer cell lines (A549, lung cell carcinoma; HCT15, colon cell carcinoma; and MCF7, breast adenocarcinoma). Among the series, the crude extract exhibited interesting anti‐inflammatory activity associated with significant growth and concentration‐related colony inhibitory effects against the three cell lines. The fractions F2 and F3 showed, respectively, interesting anti‐inflammatory and antiproliferative activities in a dose‐dependent manner. The purification and the determination of chemical structures of compounds of these active fractions are under investigation. Drug Dev Res 71: 412–418, 2010.

Anti‐Inflammatory and Antiproliferative Activities of Organic Fractions from the Mediterranean Brown Seaweed, Cystoseira Compressa

Strategy, Management and Health Policy Enabling Technology, Genomics, Proteomics Preclinical Research Preclinical Development Toxicology, Formulation Drug Delivery, Pharmacokinetics Clinical Development Phases I‐III Regulatory, Quality, Manufacturing Postmarketing Phase IV

Parallel synthesis and anti-inflammatory activity of cyclic peptides cyclosquamosin D and Met-cherimolacyclopeptide B and their analogs

We report the parallel synthesis of two natural cyclopeptides, isolated from the seeds of Annona squamosa, cyclosquamosin D (A1), and Met-cherimolacyclopeptide B (B) and their analogs. All of the compounds were screened for anti-inflammatory activity by evaluating their inhibitory effects on the production of pro-inflammatory cytokines using the lipopolysaccharide stimulated macrophage J774A.1 cell line. Compounds having significant anti-inflammatory activity in suppressing the secretion of IL-6 and TNF-α have been identified, some of which exhibit activity superior to that observed with the natural products.

In vitro immunomodulatory activity and in vivo anti-inflammatory and analgesic potential with gastroprotective effect of the Mediterranean red alga Laurencia obtusa

Abstract Context: Red algae have been recognized as a rich natural source of compounds possessing interesting biological and pharmacological activities. Objective: This work investigates anti-inflammatory, analgesic and gastroprotective activities of MeOH/CH2Cl2 crude extract and its fractions F1 (50% MeOH) and F2 (80% MeOH) from the whole alga plant Laurencia obtusa Hudson (Rhodomelaceae). Materials and methods: Anti-inflammatory activity was evaluated in vitro using cytometric bead array (CBA) technology to follow up the secretion of tumour necrosis factor alpha (TNF-α) in lipopolysaccharide activated THP-1 monocytic cells at doses of 10–250 μg/mL and in vivo using carrageenan-induced paw oedema in Wistar rats at doses of 25, 50, 100 and 200 mg/kg. Crude extract and fractions were tested at the doses of 25, 50, 100 and 200 mg/kg for peripheral and central analgesic activity by acetic acid-induced writhing test and hot-plate method, respectively, in Swiss albino mice. Gastroprotective activity was evaluated using HCl/ethanol-induced gastric ulcer test in rats at doses of 25, 50, 100 and 200 mg/kg. Results: Crude extract, F1 and F2 showed an interesting inhibition of TNF-α secretion with IC50 values of 25, 52 and 24 μg/mL, respectively, and a significant anti-inflammatory activity in vivo (p <  0.01), 3 h after carrageenan injection, the oedema inhibition was 55.37%, 52.18% and 62.86%, respectively, at the dose of 100 mg/kg. Furthermore, they showed a significant peripheral analgesic activity with 53.79%, 55.92% and 57.37% (p <  0.01) of writhing inhibition, respectively. However, no significant activity was found in the hot-plate test. An interesting gastroprotective effect was observed with crude extract and its fractions F1 and F2 with a gastric ulcer inhibition of 65.48%, 77.42% and 81.29%, respectively, at the dose of 50 mg/kg. Discussion and conclusion: These results suggest that L. obtusa might be used as a potential source of natural anti-inflammatory and analgesic agents with gastroprotective effect.

Synthesis of new 3-substituted-2H-1,2-naphthothiazin-4(3H)-one 1,1-dioxides via directed ortho-metalation reaction

Abstract The reaction of compounds 6a – i , readily available from α-amino acids, with an excess of lithium diisopropylamide, leads to new 3-substituted-2 H -1,2-naphthothiazin-4(3 H )-one 1,1-dioxides 7a – i , with yields ranging between 21 and 70%. The key steps are: the naphthylsulfonyl ortho-deprotonation based on the directed ortho-metalation reaction followed by a regiospecific intramolecular cyclisation reaction. Lithiation–deuteration experiments carried out on the naphthylsulfonamides 8 and 9 using n -BuLi and LDA demonstrated the regioselectivity of the deprotonation of the H-3 over the H-1 one of the naphthalene ring.

Physico-chemical characterization and pharmacological activities of sulfated polysaccharide from sea urchin, Paracentrotus lividus

Sulfated polysaccharide (SP) from the eggs of sea urchin Paracentrotus lividus, extracted by papain digestion, was characterized by size exclusion chromatography coupling on-line with light scattering and viscosity detectors (SEC/MALS/VD/DRI), gas chromatography coupled to mass spectrometer (GC-MS), and Fourier transform infrared spectroscopy (FTIR) analysis. The native molecular mass of the extracted polysaccharide is high (≥22 000 KDa) and it is composed mainly of arabinose, accompanied by other monosaccharides (mostly galactose, glucose and fucose), significant amounts of uronic acids (18.4%) and relatively high proportions of sulfate (22.4%). The pharmacological evaluation of SP showed a significant in vivo anti-inflammatory activity (p<0.001), 3h after injection, the edema inhibition was 75.8% at the dose of 100mg/Kg; a significant peripheral analgesic activity (p<0.001), with 64.9% of writhing inhibition, and a significant increase in the hot plate reaction time in mice indicating central analgesic activity. In addition, an interesting gastroprotective effect was observed with this polysaccharide; the gastric ulcer inhibition was 69.7%, at the dose of 100mg/Kg.