Protective potential effects of fucoidan in hepatic cold ischemia-rerfusion injury in rats.

The necessity to increase the efficiency of organ preservation has pushed physicians to consider the use of pharmacological additives in preservation solutions to minimize ischemia reperfusion injury. Here, we evaluated the effect of fucoidan, sulfated polysaccharide from brown seaweed, as an additive to IGL-1 (Institut Georges Lopez) preservation solution. Livers from Wistar rats were preserved for 24 h at 4 °C in IGL-1 solution, enriched or not with fucoidan (100 mg/L). Thereafter, they were subjected to reperfusion (2 h, at 37 °C) using an isolated perfused rat liver model. The addition of fucoidan to IGL-1 solution reduced hepatic injury (AST, ALT) and improved liver function compared to IGL-1 solution without fucoidan. In addition, we noted a significant increase in the phosphorylation of AMPK, AKT protein kinase and GSK3-ß, leading to a reduction in VDAC phosphorylation, as well as a reduction in apoptosis (caspase 3), mitochondrial damage, oxidative stress and endoplasmic reticulum (ER) stress markers. Furthermore, ERK1/2 and P38 MAPKs phosphorylation significantly decreased after supplementation of IGL-1 solution with fucoidan. In conclusion, the supplementation of IGL-1 solution with fucoidan maintained liver graft integrity and function through the prevention of the ER stress, oxidative stress and mitochondrial dysfunction. Fucoidan could be considered as potential natural therapeutic agent to alleviate graft injury.

Characterization of sulfated polysaccharide from Laurencia obtusa and its apoptotic, gastroprotective and antioxidant activities.

This study was designed to characterize the physico-chemical properties of the sulfated polysaccharide (SP) isolated from the red alga Laurencia obtusa and to evaluate its apoptotic, gastroprotective and antioxidant activities. The different macromolecular characteristics of SP were determined by size exclusion chromatography combined with multi-angle laser light-scattering detection (SEC-MALLS), Fourier transform infrared spectroscopy (FTIR) analysis and nuclear magnetic resonance spectroscopy (1H NMR and 13C NMR). The native molecular weight of the extracted polysaccharide is high (≥336,900 g·mol-1). It showed high amounts of sulfated groups (28.2%) and low levels of proteins. It was found to be a potent inducer of apoptosis on acute monocytic leukaemia THP-1cell lines with EC50 value of 53 µg·mL-1. Furthermore, a significant gastroprotective effect (p < 0.01) was also observed with a gastric ulcer inhibition of 63.44%, 78.42% and 82.15% at the doses 25, 50 and 100 mg·kg-1, respectively. In addition, SP significantly increased glutathione levels (GSH) and decreased the concentration of thiobarbituric acid-reactive substances (TBARS) in EtOH/HCl-damaged gastric mucosa in rats; it also exhibited an important antioxidant activity in vitro. Therefore, SP, derived from the red alga Laurencia obtusa, may have a potential therapeutic effect against acute myeloid leukaemia and a beneficial potential as gastroprotective and antioxidant natural product.

Anti-inflammatory activity and gastroprotective effect of Hertia cheirifolia L. roots extract.

ETHNOPHARMACOLOGICAL RELEVANCE: Hertia cheirifolia L. is used traditionally to treat rheumatic pains and known as a medicinal plant having several pharmaceutical and biological activities. The present study evaluated in vivo the anti-inflammatory and gastroprotective effects of the methanolic extract from H. cheirifolia L. MATERIALS AND METHODS: Reverse phase high-performance liquid chromatography (RP-HPLC) was performed to identify various chemical components of the plant extract. Anti-inflammatory and gastroprotective activities were assessed on carrageenan-induced paw edema and HCl/ethanol-induced gastric lesions in rats, respectively. RESULTS: (RP-HPLC) analysis indicated that coumarin is the abundant component in the extract (53.80%). Intraperitoneal administration of the methanolic extract at different doses showed interesting activities in rats in a dose-dependent manner. At 100 mg/kg, this extract showed the highest acute anti-inflammatory activity and an important inhibition of gastric lesions with inhibition percentage of 79.41% and 88.53%, respectively. CONCLUSION: Altogether, the results of this study reveal the anti-inflammatory and gastroprotective effects of H. cheirifolia extract and promote the traditional use of this plant in the treatment of different pain and inflammatory diseases.

Optimized extraction of pectin-like polysaccharide from Suaeda fruticosa leaves: Characterization, antioxidant, anti-inflammatory and analgesic activities.

Box-Behnken design (BBD) was performed via ultrasound-assisted system to optimize extraction yield and total antioxidant ability of polysaccharides from Suaeda fruticosa. Three independent variables were studied: temperature, time and pH with optimal settings 90 °C, 37 min and 2.9, respectively. Under these settings, isolation yield and total antioxidant activity were 34.0% and 31.8 mg ascorbic acid equivalent/g material, respectively. Furthermore, preliminary structure study was carried out using UV-vis analysis, Fourier transform infrared spectroscopy (FT-IR) and Nuclear magnetic resonance (1D (1H, 13C NMR) and 2D (1H, 1H COSY, 1H/13C HSQC)) methods Size exclusion chromatography (SEC) determination revealed that polysaccharide extracted had an average molecular weight of 240 kDa. Chemical composition analyses showed that extracted polysaccharide was a pectin-like polysaccharide with uronic acid content (47.5%) and neutral monosaccharides (52.5%) constituted mainly of arabinose, mannose, galactose, rhamnose, glucose and xylose in the molar percentage of 48.63%, 5.85%, 29.42%, 7.96%, 6.54% and 1.60%, respectively. This sugar composition was typical of that of a galactoarabinan. Importantly, the optimum polysaccharide possesses significant potentials in antioxidant activity effect. Moreover, pharmacological investigation of extracted polysaccharide revealed a good anti-inflammatory effect and interesting peripheral as well as central antinociceptive activities.

Pharmacological activities of the organic extracts and fatty acid composition of the petroleum ether extract from Haplophyllum tuberculatum leaves.

ETHNOPHARMACOLOGICAL RELEVANCE: Haplophyllum tuberculatum is used in traditional medicine to treat many disorders including inflammation and pain. The aim of this study is to investigate the organic extracts from H. tuberculatum leaves against inflammation, gastric ulcer and pain. MATERIALS AND METHODS: Acute toxicity was studied in vivo to determine the toxic doses of the organic extracts. Anti-inflammatory activity was also evaluated in vivo using carrageenan-induced paw edema in Wistar rats. Gastroprotective activity was tested using the HCl/ethanol-induced gastric ulcer test in rats. Peripheral and central analgesic activities were assessed using the acetic acid-induced writhing test and the hot-plate method, respectively. The chemical composition of the fatty acids in the petroleum ether (PE) extract was determined with GC-MS. RESULTS: At 25, 50 and 100mg/kg PE extract was the most active against inflammation. Percentages inhibition 5h after carrageenan-injection were 51.12; 86.71% and 96.92%, respectively. The same extract at 100mg/kg showed good analgesic activities using the acetic acid-induced writhing test and the hot-plate method. The chloroform, ethyl acetate (EtOAc) and butanolic (n-BuOH) extracts exhibited strong anti-inflammatory, gastroprotective and analgesic activities at 100mg/kg. The GC-FID analysis revealed that the PE extract was rich in γ-linolenic acid (45.50%) followed by palmitic acid (18.48%), linoleic acid (10.73%), erucic acid (4.72), stearic acid (3.96%) and oleic acid (2.57%). CONCLUSION: The results of the present study support the traditional use of the leaves of H. tuberculatum and may possibly serve as prospective material for further development of safe new phytochemical anti-inflammatory, gastroprotective and/or analgesic agents.

Phytochemical Analysis and Evaluation of the Antioxidant, Anti-Inflammatory, and Antinociceptive Potential of Phlorotannin-Rich Fractions from Three Mediterranean Brown Seaweeds.

Phlorotannins, phenolic compounds produced exclusively by seaweeds, have been reported to possess various pharmacological properties. However, there have been few works on these compounds from Mediterranean seaweeds. In this study, we investigated the phytochemical analysis and pharmacological potential of phlorotannin-rich fractions from three brown seaweeds collected along the Tunisia coast: Cystoseira sedoides (PHT-SED), Cladostephus spongeosis (PHT-CLAD), and Padina pavonica (PHT-PAD). Phytochemical determinations showed considerable differences in total phenolic content (TPC) and phlorotannin content (PHT). The highest TPC level (26.45 mg PGE/g dry material (Dm)) and PHT level (873.14 µg PGE/g Dm) were observed in C. sedoides. The antioxidant properties of these three fractions assessed by three different methods indicated that C. sedoides displayed the highest total antioxidant activity among the three species (71.30 mg GAE/g Dm), as well as the free radical scavenging activity with the lowest IC50 value in both DPPH (27.7 µg/mL) and ABTS (19.1 µg/mL) assays. Furthermore, the pharmacological screening of the anti-inflammatory potential of these fractions using in vivo models, in comparison to reference drugs, established a remarkable activity of PHT-SED at the dose of 100 mg/kg; the inhibition percentages of ear edema in mice model and paw edema in rats model were of 82.55 and 81.08%, respectively. The content of malondialdehyde (MDA) in liver tissues has been quantified, and PHT-SED was found to remarkably increase the lipid peroxidation in rat liver tissues. In addition, in two pain mice models, PHT-SED displayed a profound antinociceptive activity at 100 mg/kg and has proved a better analgesic activity when used in combination with the opioid drug, tramadol.

Influence of the uronic acid composition on the gastroprotective activity of alginates from three different genus of Tunisian brown algae.

Alginates from three genus of Tunisian brown algae were isolated and characterized by size exclusion chromatography and Solid-state NMR spectroscopy. Alginate from Padina pavonica (APP) had the highest molecular weight (Mw) with 147,000g/mol while it was 85,000g/mol for alginate from Cystoseira compressa (ACC) and 58,000g/mol for alginate from Dictyopteris membranaceae (ADM). The mannuronate (M) to guluronate (G) ratios were estimated from spectral deconvolution of the 13C CP/MAS spectra and the results has shown that all the extracts are mannuronic acid-rich alginates with M/G ratio increased in the order ADM - ACC - APP. An interesting gastroprotective effect was observed for the extracts; ADM and ACC exhibited the highest inhibition of gastric lesions, at 50mg/kg, with 83.41% and 75.39% respectively. Otherwise, it has been shown that the gastroprotective effect of alginates depends mainly on their uronic acid composition.

Physico-chemical characterization and pharmacological activities of polysaccharides from Opuntia microdasys var. rufida cladodes.

The aim of this study is to isolate pectin from peel (WNPE) and pulp (WNPU) of Opuntia microdasys var. rufida's (OMR) cladodes and to characterize these polysaccharides by size exclusion (SEC/MALS/VD/DRI), gas chromatography coupled to mass spectrometer (GC-MS), nuclear magnetic resonance (1H NMR), and Fourier transform infrared spectroscopy (FTIR) analysis. The polysaccharides were extracted in neutral aqueous media followed by ethanol precipitation and dialysis. Both WNPE and WNPU are mainly composed of uronic acids and some neutral sugars such as arabinose, galactose, rhamnose and mannose. Their molecular weight range from 2,180,000 and 4,920,000g/mol. The in-vivo pharmacological activities (anti-inflammatory, analgesic and gastroprotective activities) have been performed. The extracted pectin (50-100mg/kg, i.p. (intraperitoneal)) inhibited, in a dose-related manner, both carrageenan-induced paw edema in rats and Xylene-induced ear edema in mice. A dose-dependent action was obtained against chemical (writhing test) and thermic (hot plate test) stimuli, respectively, with doses of 50 and 100mg/kg. Moreover, a considerable gastroprotective effect was observed with these two biopolymers, the gastric ulcer was attenuated until 67.67% for WNPE and 81.93% for WNPU, at the dose of 100mg/kg.

Microwave-assisted extraction and pharmacological evaluation of polysaccharides from Posidonia oceanica.

Microwave-assisted extraction was employed for the isolation of polysaccharides from Posidonia oceanica (PPO). The extracting parameters were optimized adopting response surface methodology. The highest polysaccharide yield (2.55 ± 0.09%), which is in concordance with the predicted value (2.76%), was obtained under the following conditions: extraction time 60 s, liquid-solid ratio of 50:1 (mL/g) and power of 800 W. This polysaccharide, with molecular weight of 524 KDa, characterized by gas chromatography-mass spectrometry showed that PPO was mainly composed of galactose, glucose, and arabinose with molar percentages 25.38, 24.37, and 21.64%, respectively. The pharmacological evaluation of PPO using animal models at the dose of 100 mg/kg indicated a significant anti-inflammatory activity with a percentage of inhibition of edema of 54.65% and a significant antinociceptive activity with 78.91% inhibition of writhing for peripheral analgesic activity and an increase in the hot plate reaction time for central analgesic activity.

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.

Evaluation of the Genotoxicity and Cytotoxicity of Semipurified Fractions from the Mediterranean Brown Algae, Dictyopteris membranacea.

Dictyopteris membranacea, a species of Mediterranean brown algae, is believed to have potential pharmacological and nutritional applications. However, such potentials only make sense when devoid of any adverse health consequences. The present study should be seen in this context. It aimed at evaluating the genotoxicity and cytoxicity of its organic extract (F0) and semi purified fractions (F4, F5, and F6). Extracts were tested using the bacterial Vitotox® test and micronucleus assay in different concentrations (from 1.25 µg/mL up to 100 µg/mL, depending on the test and the extract). Applied concentrations were based on a preliminary dose-finding test with the neutral red uptake assay. The results show that all extracts were not genotoxic in the presence or absence of a rat metabolic enzyme fraction (S9). This is encouraging and justifies further investigations on the therapeutic and other values of this algae. SUMMARY: Dictyopteris membranacea extracts and some of their semi purified fractions have important antibacterial properties.The organic extract (F0) and semi purified fractions (F4, F5, and F6) were not genotoxic according to the bacterial Vitotox test.They were also not genotoxic according to the micronucleus test in human C3A cells.Applied concentrations were based on the in-vitro neutral red uptake (NRU) test.

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

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.

Anti-inflammatory and analgesic activities with gastroprotective effect of semi-purified fractions and isolation of pure compounds from Mediterranean gorgonian Eunicella singularis.

OBJECTIVE: To explore anti-inflammatory activities of organic extract and its semi-purified fractions (ethanol, acetone, methanol/dichloromethane) from the Mediterranean gorgonian Eunicella singularis. METHODS: The anti-inflammatory and analgesic activities were evaluated, using the carrageenan-induced rat paw edema model and the acetic acid writhing test in mice. The gastroprotective activity was determined using HCl/EtOH induced gastric ulcers in rats. The purification and structure elucidation of compound(s) from the more effective fraction were determined by chromatographic and spectroscopic methods and in comparison with data reported in the literature. RESULTS: The fraction F-EtOH showed an important anti-inflammatory activity associated with significant analgesic and gastroprotective properties. The purification and structure elucidation of compound(s) from this fraction lead to the identification of one diterpenoid and four sterols. CONCLUSIONS: These results suggested that components from the active fraction can be used to treat various anti-inflammatory diseases.

Physico-chemical characterization and pharmacological evaluation of sulfated polysaccharides from three species of Mediterranean brown algae of the genus Cystoseira.

BACKGROUND: Seaweed polysaccharides are highly active natural substances having valuable applications. The present study was conducted to characterize the physico-chemical properties of sulphated polysaccharides from three Mediterranean brown seaweeds (Cystoseira sedoides, Cystoseira compressa and Cystoseira crinita) and to evaluate their anti-radical, anti-inflammatory and gastroprotective activities. METHODS: The different rates of neutral sugars, uronic acids, L-fucose and sulphate content were determined by colorimetric techniques. The different macromolecular characteristics of isolated fucoidans were identified by size exclusion chromatography equipped with a triple detection: multiangle light scattering, viscometer and differential refractive index detectors, (SEC/MALS/VD/DRI). Anti-inflammatory activity was evaluated, using the carrageenan-induced rat paw edema test in comparison to the references drugs Acetylsalicylate of Lysine and Diclofenac. The gastroprotective activity was determined using HCl/EtOH induced gastric ulcers in rats and to examine the antioxidant effect of fucoidans in the three species, the free radical scavenging activity was determined using 1,1-diphenyl-2-picrylhydrazyl. RESULTS: The pharmacological evaluation of the isolated fucoidans for their anti-inflammatory, and their gastroprotective effect established that these products from C. sedoides, C. compressa and C. crinita exhibited a significant anti-inflammatory activity at a dose of 50 mg/kg, i.p; the percentages of inhibition of the oedema were 51%, 57% and 58% respectively. And, at the same dose, these fucoidans from C. sedoides and C. compressa showed a significant decrease of the intensity of gastric mucosal damages compared to a control group by 68%, whereas, the fucoidan from C. crinita produced a less gastroprotective effect. Furthermore, the isolated fucoidans exhibited a radical scavenging activity. CONCLUSION: The comparative study of fucoidans isolated from three species of the genus Cystoseira showed that they have similar chemicals properties and relatives anti-radical, anti-inflammatory and gastroprotective activities which are found to be promising.

Anti-inflammatory and analgesic activities with gastroprotective effect of semi-purified fractions and isolation of pure compounds from Mediterranean gorgonianEunicella singularis

Objective:To explore anti-inflammatory activities of organic extract and its semi-purified fractions (ethanol, acetone, methanol/dichloromethane) from the Mediterranean gorgonian Eunicella singularis.Methods:The anti-inflammatory and analgesic activities were evaluated, using the carrageenan-induced rat paw edema model and the acetic acid writhing test in mice. The gastroprotective activity was determined using HCl/EtOH induced gastric ulcers in rats. The purification and structure elucidation of compound(s) from the more effective fraction were determined by chromatographic and spectroscopic methods and in comparison with data reported in the literature.Results: The fraction F-EtOH showed an important anti-inflammatory activity associated with significant analgesic and gastroprotective properties. The purification and structure elucidation of compound(s) from this fraction lead to the identification of one diterpenoid and four sterols.Conclusions: These results suggested that components from the active fraction can be used to treat various anti-inflammatory diseases.

Pharmacological evaluation of the semi-purified fractions from the soft coral Eunicella singularis and isolation of pure compounds.

BACKGROUND: Gorgonians of the genus Eunicella are known for possessing a wide range of pharmacological activities such as antiproliferative and antibacterial effect. The aim of this study was to evaluate the anti-inflammatory and gastroprotective effect of the organic extract and its semi-purified fractions from the white gorgonian Eunicella singularis and the isolation and identification of pure compound(s) from the more effective fraction. METHODS: Anti-inflammatory activity was evaluated, using the carrageenan-induced rat paw edema test and in comparison to the reference drug Acetylsalicylate of Lysine. The gastroprotective activity was determined using HCl/EtOH induced gastric ulcers in rats. The purification of compound(s) from the more effective fraction was done by two chromatographic methods (HPLC and MPLC). The structure elucidation was determined by extensive spectroscopic analysis (1H and 13C NMR, COSY, HMBC, HMQC and NOESY) and by comparison with data reported in the literature. RESULTS: The evaluation of the anti-inflammatory activity of different fractions from Eunicella singularis showed in a dependent dose manner an important anti-inflammatory activity of the ethanol fraction, the percentage of inhibition of edema, 3 h after carrageenan injection was 66.12%, more effective than the reference drug (56.32%). In addition, this ethanolic fraction showed an interesting gastroprotective effect compared to the reference drugs, ranitidine and omeprazol. The percentage of inhibition of gastric ulcer induced by HCl/ethanol in rats was 70.27%. The percentage of the reference drugs (ranitidine and omeprazol) were 65 and 87.53%, respectively. The purification and structure elucidation of compound(s) from this ethanolic fraction were leading to the isolation of five sterols: cholesterol (5α-cholest-5-en-3ß-ol) (1); ergosterol (ergosta-5,22-dien-3ß-ol) (2); stigmasterol (24-ethylcholesta-5,22-dien-3b-ol) (3); 5α,8α-epidioxyergosta 6,22-dien-3ß-ol (4) and 3ß-hydroxy-5α,8α-epidioxyergosta-6-ene (5); and one diterpenoid: palmonine D (6). CONCLUSION: Based on data presented here, we concluded that diterpenoids and sterols detected in the ethanolic fraction can be responsible for its pharmacological activity.

Antioxidant, Anti-inflammatory and Antiproliferative Effects of Aqueous Extracts of Three Mediterranean Brown Seaweeds of the Genus Cystoseira.

Seaweeds have caused an emerging interest in the biomedical area, mainly due to their contents of bioactive substances which show great potential as anti-inflammatory, anti-microbial, anti-viral and anti-tumoral drugs. Despite the diversity in quality and quantity of the Mediterranean Tunisian coast flora, with its large contains of marine organisms and seaweeds, most of them have not yet been investigated for pharmacological and biological activities. Antioxidant, anti-inflammatory and antiproliferative effects of the aqueous extracts (AQ) of three brown seaweed respectively, Cystoseira crinita (AQ-C cri), Cystoseira sedoides (AQ-C sed) and Cystoseira compressa (AQ-C com) were investigated. Antioxidant activity was evaluated using the DPPH assay. Total phenolic contents were measured using Folin-Ciocalteu method. The anti-inflammatory activity of these extracts was determined in-vivo, using carrageenan induced rat paw oedema assay. The antiproliferative activity was studied on normal cells (MDCK and rat fibroblast) and cancer (A549, MCF7 and HCT15) cell lines by the ability of the cells to metabolically reduce MTT formazan dyes, in comparison to a reference drug the Cisplatin. Results demonstrated that AQ-C cri, AQ-C sed and AQ-C com extracts exhibited significant radical scavenging activity. AQ-C com extract had the highest total phenolic content. AQ-C cri, AQ-C sed and AQ-C com extracts exhibited significant anti-inflammatory activity in a dose dependent manner by comparison to reference drugs. Moreover, AQ-C cri, AQ-C sed and AQ-C com extracts showed an important antiproliferative activity against both Human tumor cell lines HCT15 and MCF7. These pharmacological efficacies of these AQ- extracts of Cystoseira were positively correlated with their total phenol content and their good antioxidant activity. The purification and the determination of chemical structures of compounds of these active aqueous extracts are under investigation. It could have a promising role in the future medicine and nutrition when used as drug or food additive.

Synthesis and pharmacological evaluation of pyrazolopyrimidopyrimidine derivatives: anti-inflammatory agents with gastroprotective effect in rats.

We report the synthesis of new anti-inflammatory 1,7-dihydropyrazolo[3',4':4,5]pyrimido[1,6-a]pyrimidine 5 from aminocyanopyrazole. All compounds were characterized by physical, chemical and spectral studies. Preliminary pharmacological evaluation of the resulting products showed that compounds 5a, b, f (50-100 mg/kg, i.p) are active anti-inflammatory agents in carrageenan-induced rat paw oedema assay, and their effects are comparable to that of acetylsalicylic-lysine (300 mg/kg, i.p.), used as a reference drug. The nature of substituent (Y, R3) had a pronounced effect on the anti-inflammatory activity. Studies of structure-activity relationships have led to selection of compound ethyl-3,5-dimethyl-7-imino-N1-phenyl-1,7-dihydropyrazolo[3',4':4,5]pyrimido[1,6-a]pyrimidine-6-carboxylate, 5f which exhibited the most potent anti-inflammatory activity. In addition, the compounds 5a, b, f showed a significant gastroprotective effect against HCl/EtOH-induced gastric ulcer.

Antimalarial and cytotoxic activities of chiral triamines.

Chiral triamine antimalarial compounds have been identified following the screening of mixture-based positional scanning libraries made up of 31,320 compounds against P. falciparum. The library, namely N-methyl triamine (TPI 762) was generated following exhaustive reduction of resin-bound acylated dipeptides. Using the PSCL approach, individual compounds were rapidly identified which were only 10 times less active than the standard drugs chloroquine (CQ) and Artemisinin (Artes).

Evaluation of antiproliferative and antioxidant activities of the organic extract and its polar fractions from the Mediterranean gorgonian Eunicella singularis.

The present study was conducted to evaluate the antiproliferative and antioxidant activities of organic extract and its polar fractions from Eunicella singularis (Esper 1794). Organic extract and two fractions of E. singularis (F2 and F3) were screened for the presence of phenolic compounds, terpenoids and glycosides. The antiproliferative activity of E. singularis organic extract and its polar fractions was evaluated on human cancer cell lines (A549, lung cell carcinoma; HCT15, colon cell carcinoma and MCF7, breast adenocarcinoma), using the MTT colorimetric method and clonogenic assay, as well as the antioxidant activity, using the stable radical 1,1-diphenyl-2-picrylhydrazyl (DPPH), and the FRAP assays. The fractions F2 and F3 showed significant total phenolic content (40 and 35.72mg gallic-acid equivalent/g dried sample), respectively, and important antiproliferative properties against the cancer cell lines. The IC50 values, ranged from 36 to 274µg/ml for A549; 93 to 426µg/ml for HCT15; and 52 to 225µg/ml for MCF7 and in the clonogenic inhibition assay from 18 to 134µg/ml for A549; 43 to 357µg/ml for HCT15; and 17 to 160µg/ml for MCF7. Using the DPPH method, the fraction F2 exhibited the strongest radical scavenging activity, with IC50 0.08mg/ml, which approaches the activity of the powerful antioxidant standard, ascorbic acid (IC50=0.064mg/ml). The reducing power of the samples was in the following order: F2>organic extract>F3. These results suggest that E. singularis fractions might be used as a potential source of natural antioxidant and antitumor agents. The purification and determination of the chemical structures of compounds in these active fractions are under investigation. The results could provide a compound(s) with a promising role in future medicines.