Preparation and characterization of alginate/silver/nicotinamide nanocomposites for treating diabetic wounds.

Silver/Alginate/Nicotinamide nanoparticles composite (Ag/ALG/Nic) was prepared and used for the first time to fabricate wound dressing material. Sodium alginate (ALG) was used as reducing and stabilizing agents for preparation of silver nanoparticles (Ag-NPs). Effect of concentrations of alginate (ALG) on the particle size of silver were studied and confirmed by different techniques like UV/vis spectroscopy, transmission electron microscope (TEM) and dynamic light scattering (DLS). Nonwoven viscous fabrics were used as a carrier for silver/alginate/nanoparticles composite by impregnated the nonwoven fabrics as per the padding-curing technique. Nicotinamide (Nic) as anti-inflammatory drug was entrapped into Ag-NPS/ALG/nonwoven fabrics. Scanning electron microscope and energy dispersive x-ray (SEM-EDX) were used to evaluate the presence of Ag/ALG/Nic nanoparticles composite anchored the nonwoven fabrics. The antibacterial activity of the Ag/ALG/Nic wound dressing material was evaluated against Escherichia coli (E. coli) and Staphylococcus Aureus (St. Aureus). The wound healing and histological studied were evaluated by using burn diabetic rat animals.

Flavonoid constituents, cytotoxic and antioxidant activities of Gleditsia triacanthos L. leaves.

Gleditsia triacanthos L. is a deciduous tree belonging to the family Fabaceae. It possesses important biological activities as anti-mutagenic, anticancer, cytotoxic and treating rheumatoid arthritis. The total ethanol extract (EtOHE) and successive extracts (petroleum ether, chloroform, ethyl acetate, and aqueous ethanol) were prepared from the leaves. Eight flavone glycosides and two flavone aglycones named vicenin-I (1), vitexin (2), isovitexin (3), orientin (4), isoorientin (5), luteolin-7-O-ß-glucopyranoside (6), luteolin-7-O-ß-galactopyranoside (7), apigenin-7-O-ß-glucopyranoside (8), luteolin (9) and apigenin (10) were isolated from the aqueous ethanol extract of G. triacanthos L. leaves. Potent cytotoxic activity of the EtOHE extract was observed against the liver (IC50 = 1.68 µg), breast (IC50 = 0.74 µg), cervix (IC50 = 1.28 µg), larynx (IC50 = 0.67 µg) and colon (IC50 = 2.50 µg) cancer cell lines. Cytotoxic activity of compounds 2, 4, 6 and 8 against, the liver, breast and colon cancer cell lines was also proved. Evaluation of the in-vivo antioxidant activity of the EtOHE and successive extracts revealed that the highest activity was exhibited by 100 mg of EtOHE (97.89% potency) as compared with vitamin E (100% potency). Compound 6 showed 91.8% free radical scavenging activity.

Water soluble polysaccharides extracted from Pterocladia capillacea and Dictyopteris membranacea and their biological activities.

Cold and hot water extracts (CWE, HWE) of both the red alga Pterocladia capillacea (P. capillacea) and the brown alga Dictyopteris membranacea (D. membranacea) were studied for their polysaccharide contents. In both (CWE) and (HWE) extracts. Relatively higher yields were obtained in case of P. capillacea pillacea (2.87 and 6.46%, respectively). The polysaccharide contents of the CWE hydrolyzate of both studied algae analyzed by HPLC were found to be enriched with glucuronic acid, arabinose and glucose, whereas, HWE hydrolyzate were found to be rich in glucuronic acid and fructose. The polysaccharide contents of the CWE and HWE extracts of (D. membranacea) showed appreciable antimicrobial activity in addition to a moderate antitumor activity against HELA (Cervix carcinoma cell line) at IC50 = 9.83 µg/dl, respectively. Whereas the polysaccharide contents of the CWE and HWE extracts of (P. capillacea) exhibited a promising anticoagulant activity.

A new flavonol glycoside and biological activities of Adenanthera pavonina L. leaves.

Adenanthera pavonina is a plant belonging to family Fabaceae. The 95% ethanol extract (EtOH) of the dried powdered leaves of the plant and successive extracts with solvents of increasing polarities were prepared. Fractionation of the successive aqueous EtOH extract on polyamide column and purification of the isolated compounds on Sephadex LH20 led to the isolation of a new methoxy flavonol glycoside named as quercetin 3-O-α-dirhamnopyranosyl-(1‴ → 2″,1″″ → 6″)-ß-glucopyranoside-4'-methoxy (1), as well as kaempferol-3-O-α-dirhamnopyranosyl-(1‴ → 2″,1″″ → 6″)-ß-glucopyranoside (2), isovitexin (3), quercetin-3-O-rhamnopyranosyl(1‴ → 4″)-ß-glucopyranoside (4), quercetin-3-O-ß-glucopranoside-4'-O-rhamnopyranoside (5), kaempferol-3-O-α-rhamnopyranosyl(1‴ → 2″)-ß-glucopyranoside (6), quercetin-3-O-rhamnopyranosyl(1‴ → 2″)-ß-glucopyranoside (7), quercetin-3-O-ß-glucopyranoside (8), kaempferol (9) and quercetin (10). Structures of the isolated compounds were established by spectroscopic analysis. Antioxidant activities of EtOH extract, successive extracts and compounds 1 and 2 were evaluated. The ethyl acetate (EtOAc) extract and EtOH extract showed 62.67% and 49.30% free radical scavenging activity, respectively. Cytotoxic activities of the EtOH extract and compounds (1) and (2) were evaluated. The EtOH extract showed a significant cytotoxic activity against Hep G-2 (IC50 = 2.50 µg) as compared with cisplatin (IC50>10 µg).

The effect of antidepressant drugs on thioacetamide-induced oxidative stress.

OBJECTIVE: The aim of the present study was to investigate the effect of the serotonin selective reuptake inhibitors (SSRIs) fluoxetine and sertraline and the tricyclic drug imipramine on oxidative stress in the brain and liver caused by thioacetamide in rats. MATERIALS AND METHODS: Drugs were administered orally once daily at doses of 10 and 20 mg/kg for two weeks prior to intraperitoneal injection of thioacetamide (300 mg/kg). Rats were euthanized 24 h after thioacetamide. Reduced glutathione (GSH), malondialdehyde (MDA) and nitric oxide were measured in brain and liver. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) were measured in serum and histopathological evaluation of liver injury was performed. RESULTS: The administration of thioacetamide increased MDA by 151.8% and 161.2%, increased nitric oxide by 57.2% and 63.9% and decreased GSH by -40.6% and -67% in the brain and liver, respectively. Thioacetamide markedly increased serum ALT, AST and ALP by 277.8, 80.8 and 121%, respectively. In the brain, MDA was decreased in rats treated with fluoxetine or sertraline. The level of GSH increased by fluoxetine and by the higher dose of sertraline. Nitric oxide in brain was unchanged by fluoxetine, but increased after sertraline at 20 mg/kg. Brain MDA was increased by imipramine, which also decreased brain nitrite level. In the liver, fluoxetine or sertraline treatment increased GSH and nitrite levels. MDA was also increased by either drug. The drugs markedly decreased ALT, but increased ALP in serum. Meanwhile, imipramine decreased liver nitric oxide levels (at the lower dose only -32.9%), markedly increased hepatic GSH, but did not change MDA level. Serum ALT decreased by imipramine (but AST and ALP showed no change). Histopathological and histochemical examinations indicated that thioacetamide-induced liver injury was not decreased after treatment with the antidepressant drugs. CONCLUSIONS: In thioacetamide-treated rats, pretreatment with the SSRIs drugs fluoxetine and sertraline is associated with decreased lipid peroxidation in brain; liver peroxidation, however, is increased. Imipramine displayed opposite effects. The thioacetamide-induced hepatic damage was not reduced by fluoxetine, sertraline or imipramine.  

Cerebrolysin attenuates cerebral and hepatic injury due to lipopolysaccharide in rats.

This study aimed to investigate the effect of cerebrolysin on oxidative stress in the brain and liver during systemic inflammation. Rats were intraperitoneally challenged with a single subseptic dose of lipopolysaccharide (LPS; 300 µg/kg) without or with cerebrolysin at doses of 21.5, 43 or 86 mg/kg. After 4 h, rats were euthanized and the brain and liver tissues were subjected to biochemical and histopathological analyses. Cerebrolysin revealed inhibitory effects on the elevation of lipid peroxidation and nitric oxide induced by LPS. In contrast, the decrease in reduced glutathione level and paraoxonase activity induced by LPS was attenuated by an injection of cerebrolysin in a dose-dependent manner. Moreover, cerebrolysin reduced LPS-induced activation of brain NF-κB and reversed LPS-induced decline of brain butyrylcholinesterase and acetylcholinesterase activities in a dose-dependent manner. Histopathological analyses revealed that neuronal damage and liver necrosis induced by LPS were ameliorated by cerebrolysin dose-dependently. Cerebrolysin treatment dose-dependently attenuated LPS-induced expressions in cyclooxygenase 2, inducible nitric oxide synthase, and caspase-3 in the cortex or striatum as well as the liver. These results suggest that cerebrolysin treatment might have beneficial therapeutic effects in cerebral inflammation. Cerebrolysin might also prove of value in liver disease and this possibility requires further exploration.

Effect of trazodone and nefazodone on hepatic injury induced by carbon tetrachloride.

The present study aimed to evaluate the effect of the serotonin antagonists and reuptake inhibitors trazodone and nefazodone on liver injury induced by treatment with carbon tetrachloride (CCl(4)) in rats. Liver damage was induced in rats by oral administration of CCl(4) (2.8 mL/kg in olive oil). Nefazodone (5, 10, or 20 mg/kg), trazodone (5, 10, or 20 mg/kg), silymarin (25 mg/kg), or saline (control) was orally administered once daily in association with CCl(4) and for one week thereafter. Liver damage was assessed by determining serum enzyme activities and hepatic histopathology. In CCl(4)-treated rats, treatment with trazodone (5, 10, 20 mg/ kg), reduced serum alanine aminotransferase (ALT) levels by 24, 38.6, and 49.3%. Serum aspartate aminotransferase (AST) levels were decreased by 18.1, 37.9, and 42.2%, and alkaline phosphatase (ALP) levels decreased by 25.7, 32.6, and 39.7%, respectively. Nefazodone (5, 10, 20 mg/kg) in a dose-dependent manner reduced the elevation of ALT levels by 15.6, 36.5, and 45.9%, AST levels by 16.7, 17.3, and 43%, and ALP by 30.5, 37.5, and 42.9%, respectively. Silymarin treatment reduced the levels of ALT, AST, and ALP by 56.1-62.8, 56.0-64.0, and 50.1-58.2%, respectively. The administration of CCl(4) decreased levels of reduced glutathione in blood compared to the vehicle-treated group. In CCl(4)-treated rats, reduced glutathione levels increased after trazodone in a dose-dependent manner. Reduced glutathione was increased by nefazodone at concentrations of 5 and 10 mg/kg, but not after 20 mg/kg nefazodone. Reduced glutathione levels were increased by the administration of silymarin to near normal values. The administration of CCl(4) resulted in a marked increase in nitric oxide levels in serum (the concentrations of nitrite/nitrate) as compared to the control group. Treatment with trazodone or nefazodone caused a dose-dependent decrease in serum nitric oxide levels compared with the CCl(4) control group. Histopathological and histomorphometric examinations also indicated that CCl(4)-induced liver injury was less severe in trazodone and nefazodone-treated groups than in the CCl(4) control groups. Metabolic perturbations caused by CCl(4) in the form of decreased intracellular protein and mucopolysaccharide content in hepatocytes were improved by treatment with trazodone and nefazodone. It is concluded that administration of serotonin antagonists and reuptake inhibitors trazodone and nefazodone is associated with a reduction in experimental liver injury induced by CCl(4).

Formulation and evaluation of antihyperglycemic leaf extracts of Zizyphus spina-christi (L.) Willd.

This study deals with the formulation of antihyperglycemic leaf extracts of Zizyphus spina-christi (L.) Willd. A bioactivity guided fractionation of different leaf extracts [defatted ethanol 70% (a), butanol (b), ethanol 70% (c), ethyl acetate (d) and petroleum ether (e) extracts] revealed that extract (c) possessed the highest antihyperglycemic activity followed by (b) and (a). HPLC was adopted for standardization of the extract (c) based on evaluation of the major saponin christinin-A which was used as marker. The detection limit was 9.45 mg/ml for Christinin-A. Extracts (a), (b) and (c) were separately formulated in soft (S) and hard (H) gelatin capsules. Two different formulations (F1 and F2) were tried using different excipients suitable for oral drug delivery. Formula 1, used for soft gelatin capsules [(F1) Sa, Sb, Sc] Formula 2, used for hard gelatin capsules [(F2) - Ha, Hb, Hc]. The recovery rates of the samples of saponin were in the range 99.43-101.86% at 200, 800 microg/ml and 1200 microg/ml. Saponin release rates from different formulae were carried out using dissolution tester USP XXIV. The highest release was obtained from formulation Sc. The release of the extracts followed diffusion mechanism. The selected formula Sc exhibited highest anti-diabetic activity (P < 0.01) on acute and long-term administration and highest saponin release. This formula (Sc) contained poly-oxyethylene (20) cetyl ether (BC-20TX), PEG 400, PEG 6000, purified water, meglyol 810, ascorbic acid and 200 mg of extract (c).

Study of the analgesic, anti-inflammatory, and gastric effects of gabapentin.

Gabapentin, a drug used to treat neuropathic pain, was evaluated in models of acute nociceptive pain, in instances of haloperidol-induced catalepsy, carrageenan-induced paw edema, gastric lesions caused by indomethacin or ethanol, and gastric acid secretion in rats. Reaction time in a hot plate assay was delayed by gabapentin. The antinociceptive effect of the drug was produced with a dose of 12.5 mg/kg and a maximal increase in hot plate latency of 68% 1 h after drug administration was produced at 100 mg/kg. Gabapentin (25, 50 or 100 mg/kg) caused a significant rise in current threshold in a tail electrical stimulation test in mice, resulting in values of 20, 30, and 60.5% vs. control values, 1 h post-dosing. With the agent, the duration of paw licking following intraplantar capsaicin injection decreased in a dose-dependent manner. In contrast, gabapentin failed to have antinociceptive action in a mouse acetic-acidinduced writhing assay. The drug (12.5-50 mg/kg) increased the duration of catalepsy induced by haloperidol by 33.5, 47.4, and 53.2%, respectively. It had an anti-inflammatory effect at doses of 25 or 50 mg/kg. Gabapentin (12.5-50 mg/kg) reduced the number and severity of gastric mucosal lesions induced by subcutaneous indomethacin (20 mg/kg) or intragastric 96% ethanol, but at doses of 50 and 100 mg/kg it increased gastric acid secretion. In conclusion, gabapentin decreased thermal, electrical, and chemogenic pain but not visceral pain and had a gastric protective effect.

A laser doppler study of the effect of 2-alkylthio-4-ethyl-4-methyl-4,5 dihydro-1H-imidazolin-5-one oxime (oxime) on the ischaemic rat lower limb.

The potential vasodilator effect of the novel compound 2-alkylthio-4-ethyl-4-methyl-4,5 dihydro-1H-imidazolin-5-one oxime (oxime) was investigated in a model of lower limb ischaemia induced in rats by unilateral ligation of the right femoral artery using Laser Doppler Flowmetry. The effect of oxime was compared with that of isoprenaline or L-arginine. Test drugs were injected systemically into the femoral vein or applied locally on the planter surface of the rat hind paw. Serum level of nitrite (NO(2) (-)) and nitrate (NO(3) (-)) were measured by ELISA. Immediately after operative induction of right lower limb ischaemia, blood flow ratio (Right/Left limb ratio: BFR) decreased to 0.33-0.39 in different groups. The intravenous (i.v.) administration of oxime increased BFR in a dose-dependent manner. Compared with pre-drug BFR, oxime administered at doses of 0.064, 0.128 or 0.256 mg/kg increased BFR to 178.8, 328.9 and 705.9 %, respectively. Meanwhile, L-arginine given i.v. at 100 mg/kg increased BFR to 560 %. Isoprenaline given i.v. at 1 microg/kg increased BFR to 274.3 %, while isoprenaline combined with oxime (0.064 mg/kg) increased BFR to 402.7 %. Similarly, after topical application of oxime, BFR increased to 113.5, 261.1 and 433.3 %, respectively. L-arginine given at 1000 mg/kg increased BFR to 389.7 %. Isoprenaline given at 10 microg/kg increased BFR to 231.6 %, while isoprenaline administered in combination with oxime (0.064 mg/kg) increased BFR to 308.3 %. The concentration of NO in serum was significantly increased after systemic or topical administration of either 0.128 and 0.256 mg/kg oxime or 100 and 1,000 mg/kg L-arginine, respectively. It is concluded that systemic or topical oxime results in marked enhancement of blood flow in the rat ischaemic lower limb. This effect of oxime is likely to be mediated through the release of NO.

Phenolic compounds and bioactivity of leaves of Mayodendron igneum Kurz.

Four apigenin glycosides were isolated from the ethyl acetate extract of the leaves of Mayodendron igneum Fam.Bignoniaceae. They were identified as apigenin 7-O-glucoside; 6-methoxy apigenin-7-O-glucoside; 6-methoxy apigenin-7-O-rhamnoglucoside and 6-hydroxy apigenin-7-O-rhamnoglucoside. In addition an isoflavone glycoside was isolated, and identified as genistin 5,4'-methyl ether. Ethanol (80%) extract of Mayodendron igneum leaves exhibited significant anti-inflammatory and analgesic activities. LD(50) determination of the extract indicated the safety of the leaves of the plant.

Flavonoids, anti-inflammatory activity and cytotoxicity of Macfadyena unguis-cati L.

Ethyl acetate and ethanol extracts of unflowering aerial part of Macfadyena unguis-cati L. (Fam. Bignoniaceae) were found to be rich in phenolic compounds. From ethyl acetate extract, six flavonoids were identified, 8, methoxy, acacetin, 7-O glucoside; 6, methoxy apigenin 7-O glucoside; 4'-O methyl scutellarin, 6-O apiosyl galactoside; acacetin, 7-O glucosyl, 8-C rhamnosyl, 3-O-alpha arabinofuranoside; 4'-methyl, 6- methoxy kaempferol, 7-O, 8-C diglucoside and vicenin II were isolated, while 6, methoxy, acacetin 7-O glucoside; and quercitrin were isolated from ethanol extract. These compounds were characterized and identified by their physicochemical and spectral data. The crude ethanol extract exhibited significant anti-inflammatory activity (80.47%) and moderate cytotoxic activity against lung cell line.

Antiinflammatory flavonoids from Opuntia dillenii (Ker-Gawl) Haw. flowers growing in Egypt.

Opuntia dillenii (Ker-Gawl) Haw. (Family Cactaceae), is used in folk medicine as an antidiabetic and antiinflammatory. The antiinflammatory activity of the alcohol extracts of the flowers, fruits and stems was carried out using the carrageenan-induced rat paw oedema model. The analgesic effect of the same extracts was evaluated using electric current as a noxious stimulus. The alcohol extract of the flowers revealed the most potent antiinflammatory effect and a pronounced analgesic action at a dose of 200 mg/kg. Bioassay-guided fractionation of this extract using VLC followed by Sephadex and paper chromatography, afforded three flavonoid glycosides, namely, kaempferol 3-O-alpha-arabinoside, isorhamnetin-3-O-glucoside and isorhamnetin-3-O-rutinoside. Their identification was based on physical, chemical and spectroscopic data.