Edema Test In Rats Research Articles

Investigation of Chemical Compounds and Evaluation of Toxicity, Antibacterial, and Anti-Inflammatory Activities of Three Selected Essential Oils and Their Mixtures with Moroccan Thyme Honey.

Throughout history, honey has been used to treat various diseases. The present work examined and assessed the in vivo anti-inflammatory potential of Moroccan thyme honey and its association with essential oils from three selected plants: Origanum vulgare L.; Mentha spicata L.; Eucalyptus globulus L. The chemical composition of the essential oils was studied, and preliminary toxicity, in vitro anti-inflammatory, and antibacterial tests were conducted. Then the anti-inflammatory effect was determined by applying carrageenan and an experimental trauma-induced paw edema test in rats. The essential oils were rich in phytochemicals and showed significant antibacterial activity against four selected ATCC bacterial strains. The results revealed the significant anti-inflammatory potential of honey and mixtures with essential oils and indicated higher efficiency of mixtures compared to honey alone. It can be concluded that the mixtures of honey and essential oils have advantageous anti-inflammatory effects and may be used for treating different types of inflammation in humans after certain clinical trials.

Sanguinarine-Chelerythrine Fraction of Coptis chinensis Exerts Anti-inflammatory Activity in Carrageenan Paw Oedema Test in Rats and Reveals Reduced Gastrotoxicity.

Inflammatory diseases are a common therapeutic problem and nonsteroidal anti-inflammatory drugs are not deprived of side effects, of which ulcerogenic activity is one of the most frequent. The aim of the study was to evaluate the anti-inflammatory activity of the sanguinarine-chelerythrine (SC) fraction of Coptis chinensis and its influence on the integrity of gastric mucosa. The study was conducted on sixty male rats randomly divided into six experimental groups: two control groups (a negative control group CON and a positive control group CAR); three groups receiving an investigational fraction of C. chinensis (1, 5, 10 mg/kg i.g.) named SC1, SC5, and SC10, respectively; and a group receiving indomethacin (IND) (10 mg/kg i.g.) as a reference drug. In all animals, the carrageenan-induced paw oedema was measured; PGE2 release, TNFα production, and MMP-9 concentration in inflamed tissue were determined. Additionally, the macroscopic and microscopic damage of gastric mucosa was evaluated. Administration of SC dose-dependently inhibited the second phase of carrageenan rat paw oedema and PGE2 release, decreased the production of TNFα, and reduced the concentration of MMP-9, and the efficacy of the highest dose was comparable to the effect of IND. Contrary to IND, no gastrotoxic activity of SC was detected. The investigated sanguinarine-chelerythrine fraction of C. chinensis seems to be a promising candidate for further research on new anti-inflammatory and analgesic drugs characterized with a safer gastric profile compared to existing NSAIDs.

Novel 1,3,4-Oxadiazole Derivatives of Pyrrolo[3,4-d]Pyridazinone Exert Anti-Inflammatory Activity without Acute Gastrotoxicity in the Carrageenan-Induced Rat Paw Edema Test.

Background and PurposeDue to the risk of gastrointestinal damage and various tissue toxicity associated with non-steroidal anti-inflammatory drugs (NSAIDs) use, investigating new anti-inflammatory agents with efficacy comparable to that of NSAIDs but reduced toxicity is still a major challenge and a clinical need. Based on our previous study, new 1,3,4-oxadiazole derivatives of pyrrolo[3,4-d]pyridazinone, especially 6-butyl-3,5,7-trimethyl-1-[[4-[[4-(4-nitrophenyl)piperazin-1-yl]methyl]-5-thioxo-1,3,4-oxadiazol-2-yl]methoxy]pyrrolo[3,4-d]pyridazin-4-one and 6-butyl-1-[[4-[[4-(4-chlorophenyl)-4-hydroxy-1-piperidyl]methyl]-2-thioxo-1,3,4-oxadiazol-5-yl]methoxy]-3,5,7-trimethyl-pyrrolo[3,4-d]pyridazin-4-one (hereafter referred to as the compounds 10b and 13b, respectively) seem to be promising anti-inflammatory agents. This study aimed to elucidate the effects of these two new derivatives on the course of experimental rat inflammation, liver and kidney function, and gastric mucosa.MethodsThe anti-inflammatory effect of compounds 10b and 13b was evaluated using the carrageenan-induced paw edema test in rats. The increase in paw volume (paw edema), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α) and myeloperoxidase (MPO) levels, histological alterations, and inflammatory cell infiltration in paw tissue were determined. Serum alanine transaminase (ALT) and aspartate transaminase (AST) activities, serum urea and creatinine levels, as well as changes in gastric mucosa, were measured as indicators of hepatic, renal, and gastric toxicity.ResultsPretreatment with both novel derivatives at 10 mg/kg and 20 mg/kg doses reduced paw edema, counteracted the increased PGE2 and TNF-α levels, reduced the influx of inflammatory cells, and decreased histopathological alterations in paw tissue. Compound 13b at a dose of 20 mg/kg was more effective than indomethacin in reversing the increased TNF-α levels and reducing the influx of inflammatory cells. Only compound 13b at all studied doses (5, 10, or 20 mg/kg) counteracted the increased MPO level in paw tissue. Both compounds neither caused alterations in ALT, AST, urea, creatinine parameters nor gastric mucosal lesions.ConclusionNew compounds exert an anti-inflammatory effect, presumably via inhibiting inflammatory mediators release and inflammatory cell infiltration. Moreover, both possess a more favorable benefit–risk profile than indomethacin, especially compound 13b.

ОЦЕНКА АНАЛЬГЕТИЧЕСКОЙ И ПРОТИВОВОСПАЛИТЕЛЬНОЙ АКТИВНОСТИ АДДУКТА 1-ГИДРОКСИ-1,1-ЭТИЛИДЕНДИФОСФОНОВОЙ КИСЛОТЫ И БИС(2-ПИРИДИЛ-1,2,4-ТРИАЗОЛИЛ-3)ПРОПАНА ПРИ КУРСОВОМ ВВЕДЕНИИ У САМЦОВ КРЫС

The article presents the results of evaluation of analgesic and anti-inflammatory activity of the adduct of 1-hydroxy-1,1-ethylidendiphosphonic acid and bis(2-pyridyl-1,2,4-triazolyl-3)propane (HEA+BPP) in male rats with a 21-day course administration. The aim of the study was to evaluate analgesic and anti-inflammatory activity in male rats with 21-day course administration of HEA+BPP course administration with 21-day course administration. The animals were divided into 7 groups of 10 individuals. Analgesic activity of HEA+BPP was tested on 40 males, and anti – inflammatory activity was tested on 30 others. In studies of analgesic activity of HEA+BPP, males of one group were control and received intraperitoneal injections of 0.2 ml of saline solution every day at 10.00 for 21 days, the others groups received 0.2 ml of intraperitoneal injections of HEA+BPP at doses of 5, 50 and 100 mg/kg at the same time for 21 days. In analgesic studies, groups of animals were similarly formed, when testing the anti-inflammatory effect of HEA+BPP, only without injecting a dose of 100 mg/kg. HEA+BPP synthesized at the Department of General and inorganic chemistry of the faculty of biology and chemistry of the Tauride Academy (structural division) of the V. I. Vernadsky Crimean Federal University. The chemical purity of HEA+BPP was at least 98 %. The analgesic activity of HEA+BPP was evaluated by the parameters of pain sensitivity of animals in the background and 1 hour after intraperitoneal injections on the 1st, 6th, 10th, 14th and 21st days of the experiment in the models of acute pain stress «tail-flick», Randall-Sellitto and «hot plate». Before the tail-flick and Randall-Sellitto tests were performed, the animals were placed in special rat retainers after injection. The anti-inflammatory activity of HEA+BPP was evaluated in the formalin paw edema test in rats. Acute inflammatory response was reproduced by subplantar injection of 0.1 ml of 2 % formalin solution in the form of an aqueous solution into the left hind leg of a rat, and then the value of limb edema was measured using the method of water plethysmometry on the 10th and 21st days of course administration of HEA+BPP in doses of 5 and 50 mg/kg. The data are presented as mean and standard error mean, statistical analysis performed using the software packages StatSoft/STATISTICA 8 and Graph Pad Prism 7.0. The significance of differences between groups was determined using one-way analysis of variance (ANOVA) with post hoc test Tukey and non-parametric criterion of multiple comparisons of Dunn, according to official methodological recommendations on statistical treatment of the results of preclinical studies of medicines, given in the literature. During course administration to male rats of HEA+BPP for 21 days in the dose range from 5 to 100 mg / kg, it was found that this compound mainly demonstrates effectiveness as an analgesic with a single injection, only for mechanical pain, this substance is effective with a course administration at a dose of 5 mg/kg: The «tail-flick» test showed, that using of HEA+BPP as an analgesic involved in the spinal mechanism of pain sensitivity regulation is advisable in doses of 5, 50 and 100 mg/kg only with a single injection: latent period of the reaction discharge of the tail increased relative to control at a dose of 5 mg/kg on the 1st day of administration of HEA+BPP by 32.7 % (p≤0.05), at a dose of 50 mg/kg on the 1st and 21st days of administration – by 40 % (p≤0.01) and 67.1 % (p≤0.001) and at a dose of 100 mg/kg on the 1st day of administration – by 80.0 % (p≤0.01), respectively. At a dose of 5 mg/kg on the 10th day of administration, on the contrary, was discovered algogenic effect of HEA+BPP (latent period of the reaction discharge of the tail was significantly decreased relative to control by 24.1 % (p≤0.01). In the test of Randall-Selitto the efficiency of single use HEA+BPP as an analgesic in mechanical pain at doses of 50 and 100 mg/kg (pain threshold was significantly increased relative to control at 25.2 % (p≤0.01) and 80 % (p≤0.01), and in course administration only at a dose of 5 mg/kg (pain threshold was significantly increased relative to control at 55.3 % (p≤0.001), 72.5 % (p≤0.001) and 49.6 % (p≤0.01) on the 6th, 14th and 21st day of the course introduction). The «hot plate» test shows the feasibility of only a single use of HEA+BPP as an analgesic in doses of 5 and 50 mg/kg, since these effects were unstable and unstable when administered on a course basis. The «formalin test» revealed the inflammatory and exudative effect of HEA+BPP at a dose of 5 mg/kg, in which HEA+BPP on the 21st day of administration increased the formalin edema of the rat paw by 70.9 % (p≤0.01).

Pharmacological evaluation of analgesic, anti-inflammatory and antipyretic activities of ethanolic extract of Indigofera argentea Burm. f.

Ethnopharmacological relevanceIndigofera argentea Burm. f.; commonly known as neel, jantari, hathio; is traditionally used for the treatment of headache, fever, inflammation and body pain. Local communities also used this plant for the treatment of malaria, jaundice, vertigo and gastric disorders. Aim of the studyThis study is aimed to evaluate the toxicity and possible analgesic, anti-inflammatory and antipyretic activities of the ethanolic crude extract of Indigofera argentea (IaCr) to support its use in folk medicine and to screen the phytochemical constituents and antioxidant activity. Materials and methodsAqueous ethanolic (30:70) extract of whole plant of Indigofera argentea (IaCr) was prepared and phytochemical study was performed by preliminary methods followed by HPLC and DPPH method. In vivo experiments were performed in Wistar albino rats including hot plate, tail immersion, formalin and capsaicin-induced pain tests in rats and acetic acid-induced writhing test in mice. Anti-inflammatory activity was assessed by using in vitro human red blood cell (HRBC) membrane stabilization and carrageenan-induced rat paw edema test, while antipyretic activity was evaluated by Brewer’s yeast-induced pyrexia test. ResultsThe crude extract of Indigofera argentea confirmed the presence of flavonoids, glycosides, alkaloids, saponins and tannins as soluble ethanolic constituents in preliminary study. The maximum quantity of gallic acid equivalent (GAE) phenolics, and quercetin equivalent (QE) flavonoid content found was 81 ± 2 mg GAE/g and 56 ± 1.4 mg QE/g of extract respectively. Quantification based on HPLC exposed the presence of phenols and flavonoids, quercetin, gallic acid, caffeic acid, chlorogenic acid, benzoic acid, ferulic acid and coumaric acid. In vivo experiments revealed significant P < 0.05) dose-dependent inhibition in hot plate, tail immersion and capsaicin-induced pain test. IaCr showed significant inhibition of pain latency against both phases in formalin test and considerably decreased the number of writhes caused by acetic acid at the doses of 30, 100 and 300 mg/kg. In the in vitro anti-inflammatory (HRBC) assay, IaCr showed good membrane stability with maximum percentage hemolysis inhibition of 49.29% while in carrageenan-induced paw edema test in rats the IaCr showed significant anti-inflammatory action in a dose-dependent fashion. Statistical significant reduction in rectal temperature was observed at the doses of 100 and 300 mg/kg in yeast-induced pyrexia test in rats. ConclusionThe results of the experimental studies proved the analgesic, anti-inflammatory and antipyretic activities of Indigofera argentea and supported the traditional use of this plant.

In vivo anti-inflammatory response and bioactive compounds' profile of polyphenolic extracts from edible Argan oil (Argania spinosaL.),obtained by two extraction methods.

The present work examined and assessed the in vivo anti-inflammatory effect of polyphenolic extracts from Moroccan edible Argan oils (Argania spinosaL.), extracted by two extraction processes: Hand pressing and mechanical pressing. Chemical properties, such as acidity, peroxide index, ultraviolet indices, total polyphenols composition, fatty acid composition, tocopherol composition, phenolic profiling, and sterol composition were studied. Then, the anti-inflammatory potential was determined by applying carrageenan, an induced paw edema test in rats. The results revealed an anti-inflammatory effect of edible Argan oil and indicated a higher efficiency of hand-pressed oil compared to mechanical-pressed oil, supporting its traditional use in human health, related to pain and inflammations. The chemical composition of these oils was evaluated, and total polyphenols, tocopherol composition, and some phenolic compounds were found highly concentrated in the hand-pressed oil. PRACTICAL APPLICATIONS: The present study highlights and compares the in vivo anti-inflammatory effect of polyphenolic compounds, extracted from Argan oil by two processes (hand and mechanical extraction). The study demonstrated the better quality of hand-pressed oil over mechanically pressed, supporting the traditional uses of this oil in treating several inflammations and pain-related situations. Moreover, the edible Argan oil may be introduced as a regular diet and food ingredient.

Analgesic and antiinflammatory activities of the essential oil from Artemisia sieberi Besser

The analgesic activity of Artemisia sieberi oil was assessed by acetic acid-induced writhing test and Eddy’s hot plate method; while the acute anti-inflammatory effect was investigated by inflammatory paw edema test in rats. The administration rout of the essential oil, standard drugs and the vehicle used in all assays was intraperitoneal injection. The 1 and 2.5 mg/kg doses of the studied oil significantly decreased the number of acetic acid-induced writhes in mice. The dose of 1 mg/kg of the oil also exhibited a central analgesic effect as evidenced by a significant increase in reaction time at several time points after 15 min treatment in the hot plate method. In addition, the 1 mg/kg dose of the oil significantly reduced carrageenan induced paw edema in rats at the first hour of the test by 72.7% inhibition and lasted to the third hour of the test by 74.3% inhibition found to be very close to that of the standard drug, diclofenac sodium (50 mg/kg). The major components of the oil were characterized as camphor (31.2%) and 1,8-cineole (20.0%). The results suggest that A. sieberi essential oil has a significant effect against acute inflammation and has central and peripheral anti-nociceptive effects.

The Effects of Two Nitric Oxide Donors in Acute Inflammation in Rats Experimental data

We aimed to investigate the effects of two nitric oxide donors in acute inflammation in rats. The experiment was carried out on white Wistar rats, randomly distributed in 4 groups of 5 animals each; the substances were administered intraperitoneally as follows: Group 1 (SS): saline solution 0.1mL/100 g body weight (control); Group 2 (IND): indometacin 150 mg/kg body weight; Group 3 (NEB): nebivolol 1 mg/kg body weight; Group 4 (GSNO): S-nitroso-glutathione 1 mg/kg body weight. An experimental model of acute hind paw inflammation with carrageenan was used for the researches. The influence of the nitric oxide donors on blood parameters, specific inflammatory and immune markers was evaluated 24 h, respectively 72 hours after the injection of irritant agent. The experimental protocol was implemented according to the recommendations of our University Committee for Research and Ethical Issues. The administration of nitric oxide donors nebivolol and S-nitroso-glutathione was accompanied by a substantial diminution of paw edema, as well as by an important decrease in the percent of lymphocytes, a reduction of interleukin 6 and tumor necrosis factor alpha values. The effects of nebivolol were more accentuated than of S-nitroso-glutathione, but less intense than of indomethacin in the experiment. The treatment with nebivolol and S-nitroso-glutathione produced anti-inflammatory effects on local acute inflammation in the carrageenan-induced paw edema test in rats.

Design, Synthesis, Characterization, QSAR, Docking, Anti-inflammatory and Analgesic Evaluation of Some New Phthalazinediones.

phthalazine derivatives were reported to possess anticonvulsant , cardiotonic , antibacterial, analgesic , anti-inflammatory, and anti-microbial activity. In the current study, we applied the QSAR for prediction of newly phthalazinediones incorporating thioamide moiety aiming to reach a more potent anti-inflammatory and Analgesic agent. Phthalazinediones 10-15 have been synthesized through condensation of dibenzobarallene 3 with thiosemicarbazides 4-8. One equation was predicted using quantitative structure activity relationship (QSAR) and regression analysis for the anti-inflammatory activity with a regression correlation (R) close to unity. The docking studies were performed to investigate the biological trends of the organic compounds (thiol form) against cyclooxygenas- 2 enzyme, which is a responsible inflammation mediator by using Molgro Virtual Docker (MVD) software. The anti-inflammatory activity and analgesic effect of the thioamides 10-15 were determined by collagen II-adjuvant induced paw edema test in rats. Compounds 10, 11, 12, and 14, exhibited promising anti-inflammatory activity. Furthermore, in the pain scoring, compounds 10, 11 and 12 were found to be more effective than piroxicam and the order of the analgesic effect of the investigated compounds is as followed 14 >12 > 10 > 11 > 15. It is clear from the foregoing that the compound 14 is a promising compound if future pharmacological detailed studies. This is consistent with what has been predictable equation 1 in this study.

In vitro and in vivo assessment of meadowsweet (Filipendula ulmaria) as anti-inflammatory agent

Ethnopharmacological relevanceMeadowsweet (Filipendula ulmaria (L.) Maxim, Rosaceae) has been traditionally used in most European countries for the treatment of inflammatory diseases due to its antipyretic, analgesic, astringent, and anti-rheumatic properties. However, there is little scientific evidence on F. ulmaria anti-inflammatory effects regarding its impact on cyclooxygenases enzymatic activity and in vivo assessment of anti-inflammatory potential. This study aims to reveal the anti-inflammatory activity of methanolic extracts from the aerial parts (FUA) and roots (FUR) of F. ulmaria, both in in vitro and in vivo conditions. Materials and methodsThe characteristic phenolic compounds in F. ulmaria extracts were monitored via high performance thin layer chromatography (HPTLC). The in vitro anti-inflammatory activity of F. ulmaria extracts was evaluated using cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzyme assays, and an assay for determining COX-2 gene expression. The in vivo anti-inflammatory effect of F. ulmaria extracts was determined in two doses (100 and 200 mg/kg b.w.) with hot plate test and carrageenan-induced paw edema test in rats. Inflammation was also evaluated by histopathological and immunohistochemical analysis. ResultsFUA extract showed the presence of rutoside, spiraeoside, and isoquercitrin. Both F. ulmaria extracts at a concentration of 50μg/mL were able to inhibit COX-1 and -2 enzyme activities, whereby FUA extract (62.84% and 46.43% inhibition, respectively) was double as effective as the root extract (32.11% and 20.20%, respectively). Extracts hardly inhibited the level of COX-2 gene expression in THP-1 cells at a concentration of 25μg/mL (10.19% inhibition by FUA and 8.54% by FUR). In the hot plate test, both extracts in two doses (100 and 200mg/kg b.w.), exhibited an increase in latency time when compared with the control group (p<0.05). In the carrageenan-induced acute inflammation test, FUA at doses of 100 and 200mg/kg b.w., and FUR at 200mg/kg, were able to significantly reduce the mean maximal swelling of rat paw until 6h of treatment. Indomethacin, FUA, and FUR extracts significantly decreased inflammation score and this effect was more pronounced after 24h, compared to the control group (p<0.05). ConclusionsThe observed results of in vitro and, for the first time, in vivo anti-inflammatory activity of meadowsweet extracts, provide support of the traditional use of this plant in the treatment of different inflammatory conditions. Further investigation of the anti-inflammatory compounds could reveal the mechanism of anti-inflammatory action of these extracts.

IN VIVO AND IN VITRO IMMUNOMODULATORY AND ANTI-INFLAMMATORY EFFECTS OF TOTAL FLAVONOIDS OF ASTRAGALUS.

Background:Astragali Radix has long been used to improve immune function in traditional Chinese medicine. However, its main active components and potential immunomodulatory or anti-inflammatory activities have not been elucidated. In the present study, the immunomodulatory and anti-inflammatory activities of total flavonoids of Astragalus (TFA) isolated from Astragali Radix were evaluated by using in vivo animal models and in vitro cell models.Materials and Methods:The in vivo Immunomodulatory and anti-inflammatory activities of TFA were assessed by measuring macrophage phagocytic index, delayed type hypersensitivity, serum hemolysin level and immune organ index in mice, ear edema test in mice, paw edema test in rats, vascular permeability test in mice and granuloma test in rats. The in vitro Immunomodulatory and anti-inflammatory activities of TFA were assessed by examining its effect on cytokine and mediator production in un-stimulated and LPS-stimulated murine RAW 264.7 macrophages.Results:The results of in vivo experiments showed that TFA enhanced macrophage phagocytic index, delayed type hypersensitivity, serum hemolysin level and immune organ index in mice, and attenuated mouse ear edema, rat paw edema, mouse vascular permeability and rat granuloma formation. The results of in vitro experiments showed that TFA stimulated the production of NO and cytokine TNF-α, IL-Ιβ, IL-6 and IFN-γ in un-stimulated RAW 264.7 macrophages, and inhibited the overproduction of these inflammatory mediators in LPS-stimulated RAW 264.7 macrophages in a dose-dependent manner without exerting cytotoxicity.Conclusion:These results of this study indicate that TFA have potential immunostimulatory and anti-inflammatory effects.

Synthesis, Anti-inflammatory and Antibacterial Activities of Novel Pyrazolo[4,3-g]pteridines.

A novel series of 6-substituted pyrazolo[3,4-g]pteridines 2-9 and pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pteridin-2(3H)-one (thione) 10 and 11 was synthesized using the starting compound 3,7-dimethyl-1-phenylpyrazolo[4',3':5,6]pyrazino[2,3-d][1,3]oxazin-5(1H)-one 2. The structure of the newly synthesized compounds was elucidated by IR, (1)H-NMR, (13)C-NMR, mass spectroscopy and elemental analyses. The anti-inflammatory activity of all the newly synthesized compounds was evaluated using the carrageenan-induced paw oedema test in rats using indomethacin as the reference drug. Compound 11 and the two derivatives 7f and 8b were the most active compounds, showing an activity comparable to indomethacin. Also, the synthesized compounds were evaluated for their antibacterial activity against Gram-positive bacteria (Staphylococcus aureus and Bacillus cereus) and Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa) using chloramphenicol as control. The pyrazolotriazolopteridin-2-thione 11, 6-hydroxyethyl- 6a, 6-(4-nitrophenyl)-7g, and 6-(phenylamino) 8b derivatives were found to be the most active compounds against the Gram-positive species. None of them showed any activity against Gram-negative species.

Evaluation of in vitro and in vivo anti-inflammatory and toxicity studies of methanolic extract of Rumex vesicarius Linn

Rumex vesicarius L. belongs to the family polygonaceae and is popularly known as “bladder dock”. It is a green vegetable traditionally used as an important plant to cure many diseases. In the present study the methanol extract of Rumex vesicarius L. was evaluated for its toxicity and potential in vitro and in vivo anti-inflammatory activity. The extract at different concentration from 100 to 2000 mg/kg bw was used to evaluate the toxicity on albino rat. For evaluating the in vivo anti-inflammatory activity, carrageenan induced edema test in rats were done at the dose 100 mg/kg bw and 200 mg/kg bw. The biochemical, hematological and histopathological studies were also estimated as supportive studies. Effect of methanol extract on protein denaturation and HRBC membrane were estimated to detect invitro anti-inflammatory activity. Acute toxicity and short term toxicity studies revealed that the methanol extract of Rumex vesicarius L. is nontoxic at the studied concentration. The appropriate dose range for preclinical study was found to be 100 mg/kg bw and 200 mg/kg bw. Oral administration of the extract at the dose of 100 and 200 mg/kg bw exhibited dose dependent and significant anti-inflammatory activity in carrageenan induced edema rats. The hematological and biochemical parameters were found normal. Invitro anti-inflammatory studies showed dose dependent activity with the IC50 value of 476.06 μg/ml and 491.355 μg/ml for inhibition of protein denaturation and stabilization of HRBC membrane respectively. Hence present investigation established some pharmacological evidences to support the folklore claim that Rumex vesicarius L. is used as anti-inflammatory agent.

Anti-inflammatory effect of sea-buckthorn fruit in vivo

Fruits of Hippophae rhamnoides L. has recently become a popular medicinal and nutritional herbal drug due to its beneficial constituents, mainly the high concentration of vitamin C, flavonoids, phytosterols, and carotenoids. Sea-buckthorn has been used in traditional medicine for treatment of asthma, skin diseases, gastric ulcers and lung disorders [1]. Preparations of the fruit are used nowadays in Hungary to treat allergic symptoms. To support traditional uses of sea-buckthorn berry we have investigated the in vivo anti-inflammatory effect of different extracts of the fruits and their active constituents were investigated by bioactivity-guided isolation. Aqueous and methanol extracts of the whole fruit and methanol extracts of different parts of the berries (peel, pulp, seeds) were tested on induced paw oedema test in rats. The 70% methanol peel extract was found to be the most potent, and it was further examined in different acute inflammation models induced by carrageenan, histamine, dextran, bradykinin, serotonine and by 48/80 substance to approach the mechanism of action. The extract inhibited only the 48/80 induced inflammation. The peel extract was subjected to liquid-liquid partitioning to yield chloroform, ethyl acetate, n-butanol and water soluble fractions. Only the chloroform soluble fraction was found to be active in 48/80-induced paw oedema test. The chloroform fraction was subjected then to vacuum liquid chromatography resulting 7 subfractions. In the most active subfraction high amounts of oleanolic acid (31%) and ursolic acid (19%) were detected. Both triterpenes display anti-inflammatory activity in 48/80-induced paw oedema test. Our results suggest that oleanolic acid and ursolic acid may be responsible unequivocally for the anti-allergic effect of the sea-buckthorn fruit peel extract due to their membrane stabilising effect.

Bioactivity screening of five Centaurea species and in vivo anti-inflammatory activity of C. athoa

Context: Centaurea L. (Asteraceae) species used as herbal remedies in Turkish traditional medicine have shown several biological properties.Objective: Extracts obtained from the aerial parts of Centaurea aphrodisea Boiss., Centaurea athoa DC., Centaurea hyalolepis Boiss., Centaurea iberica Trev. and Centaurea polyclada DC. were evaluated for their antioxidant, cytotoxic and anti-inflammatory activities.Materials and methods: Extracts of Centaurea species were tested for their antioxidant activity in the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS) screening assays and for in vitro anti-inflammatory activity by Nf-κB and iNOS inhibition assays. The extracts were tested for their in vitro cytotoxicities against a panel of human solid tumor cell lines (SK-MEL: malignant melanoma, KB: oral epidermal carcinoma, BT-549: breast ductal carcinoma and SK-OV-3: ovary carcinoma) as well as non-cancerous kidney fibroblast (Vero) and kidney epithelial cells (LLC-PK1) by Neutral Red assay. In vivo anti-inflammatory activity of C. athoa was evaluated by the carrageenan-induced paw edema test in rats.Results: Antioxidant activities were observed for methanol extracts of plants. C. polyclada had the strongest effect on BT-549, KB and SK-OV-3 cell lines (30, 33 and 47 µg/ml, respectively). Nf-κB inhibition of chloroform extract of C. athoa was determined equivalent to positive control parthenolide (IC50: 6 µg/ml). This extract also showed anti-inflammatory activity by the carrageenan-induced paw edema test in rats, in all hours at a dose of 50 mg/kg compared to the control group.Discussion and conclusion: C. athoa is suggested to be a potential source of lead compounds for inflammatory diseases due to the significant in vitro and in vivo anti-inflammatory results.

Synthesis, Analgesic and Anti-inflammatory Activities of 3- Ethyl-2-substituted Amino-3H-quinazolin-4-ones

Purpose: To synthesize a series of novel 3-ethyl-2-substituted amino-quinazolin-4(3H)-ones and evaluate them for their analgesic and anti-inflammatory activities. Methods : The compounds, 3-ethyl-2-substituted amino-quinazolin-4(3H)-ones, were synthesized by reacting the amino group of 3-ethyl-2-hydrazino quinazolin-4(3H)-one with a variety of aldehydes and ketones. The synthesized compounds were characterized by Fourier transform infrared (FTIR), protonnuclear magnetic resonance spectroscopy (1H-NMR) and mass spectrometry. The purity of the compounds was determined by elemental analysis. Test for analgesic activity was performed by tail-flick technique using Wistar albino mice while anti-inflammatory activity was evaluated by carrageenaninduced paw oedema test in rats. Diclofenac sodium was used as positive control for both analgesic and anti-inflammatory activities. Results: The compound, 3-ethyl-2-(cyclohexylidene-hydrazino)-3H-quinazolin-4-one (AS1), emerged as the active analgesic (activity, 63.89 %) and anti-inflammatory (activity, 60.00 %) compound of the series, and compared well with the reference standard, diclofenac sodium, which exbited analgesic and anti-inflammatory activities of 62.04 and 65.11 %, respectively Conclusion : The compound (AS1) can serve as a lead molecule for further development to a clinically useful novel class of analgesic and anti-inflammatory agents. Keywords : Quinazoline, Analgesic, Anti-inflammatory, Synthesis

EVALUATION OF POLYHERBAL FORMULATION FOR ANTI-INFLAMMATORY ACTIVITY IN CARRAGEENAN INDUCED PAW OEDEMA MODEL IN RATS

Dazzle Capsule, a Poly herbal formulation is marketed i n management of Arthritis and joint - musculo skeletal pain . In this study, safety and efficacy of this polyherbal formulation was investigated in whi ch it wa s being proved safe for use via acute toxicity study and e fficacy was being evaluated by carrageenan - induced rat paw o edema test in rats in order to explore its anti - inflammatory activity at the dose level of 90 and 180 mg/kg, p.o , comp ared with In domethacin (10 mg/kg, p.o.) . It showed an highly significant reduction in o edema (p<0.001). Indomethacin inhibited o edema by 30.054 % and 36.216 % at 2 and 3 h r after carrageenan injection, respectively. The inhibitory effect of Dazzle Capsule began at 2 h r or later after carrageenan injection depending upon the administered dose. Low doses of Dazzle Capsule ( 90 mg/kg) gave highly significant inhibitory effects of 37.894 - 39.378% , and higher doses (180 mg/kg) caused highly significant inhibition of 19.125 - 30 % . The reduction of o edema by Indomethacin and Dazzle Capsule at 2 h r or more after carrageenan injection suggest ed that both compounds produce anti - inflammatory effects in the second phase of o edema, indicating inhibition of prostaglandin synthesis. Hence , i t was concluded that, Dazzle Capsule is having potent anti - inflammatory activity yet safe polyherbal formulation for use in arthritis management .

Synthesis, Anti-Inflammatory, and Ulcerogenicity Studies of Novel Substituted and Fused Pyrazolo[3,4-d]pyrimidin-4-ones

In the present investigation, some new pyrazolo[3,4-d]pyrimidin-4(5H)-one derivatives (7–12) as well as fused pyrazolo[3′,4′:4,5]pyrimido[1,2-b]pyridazin-4(1H)-one (14–16) and 7,8,9,10-tetrahydropyrazolo[3′,4′:4,5]pyrimido[1,2-b]-cinnolin-4(1H)-one (17) ring systems were synthesized using the starting compound 5-amino-6-methyl-1-phenyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one (5). The structures of the newly synthesized compounds were elucidated by IR, 1H NMR, 13C NMR, mass spectroscopy, and elemental analysis. The theoretical calculation of their lipophilicity as C log P was performed. The anti-inflammatory activity of all newly synthesized compounds was evaluated using the carrageenan-induced paw edema test in rats using indomethacin as the reference drug. Ulcer indices for the most active compounds were calculated. Seven compounds (10b, 11a–f) showed consistently good anti-inflammatory activity. In particular, 5-{[4-(4-bromophenyl)-3-(4-chlorophenyl)-1,3-thiazol-2(3H)-ylidene]amino}-6-methyl-1-phenyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one (11e) and its 3,4-bis(4-chlorophenyl) analog (11f) were found to be the most effective among the other derivatives, showing activity comparable to that of indomethacin with minimal ulcerogenic effects. Correlation of the biological data of the active compounds with their theoretically calculated C log P values revealed that lipophilicity influences the biological response.

Computer simulation of the in vitro and in vivo anti-inflammatory activities of dihydropyrimidines acid derivatives through the inhibition of cyclooxygenase-2

Simulation of virtually designed 20 compounds as COX-2 inhibitors using molecular modelling of protein–ligand interactions to predict drug structure–activity relationship was performed in this study. A synthetic route with a rational chemical approach to (E)-2-oxo-(thio)-4-substituted phenyl-6-styryl-1,2,3,4-tetrahydro-pyrimidine-5-caboxylic acid was designed and demonstrated. A comparative analysis of antimetabolite drug and corresponding metabolites (virtually designed compounds) provided a better understanding of rational drug design. COX-1(pdb entry: 1eqg) and COX-2(pdb entry: 6cox) enzymes docked with novel ligands were evaluated for binding energies. Lead optimization was performed by computational simulation: methoxy-substituted analogues displayed the highest negative ligand–protein-binding energies. These results prompted us to evaluate in vivo anti-inflammatory activity by carrageenan-induced paw oedema test in rats at a dose of 100 mg/kg. Ibuprofen was administered as standard drug. Lead compounds having significant activity were tested for in vitro cyclooxygenase isoenzyme inhibition assay and found to be more selective towards COX-2 as indicated by COX-2 selective index. The objective of our research is to accept the challenge of discovery of new drug. To ensure the desired target specificity and potency, bioavailability and lack of toxicity, our approach stems out lead generation from virtual screening to their synthesis and ends up with biological assays.

Evaluation of anti-inflammatory and antioxidant potential of the kernel root of Xylocarpus mekongensis (Lamk.) M. Roem

Anti-inflammatory and antioxidant activities of the crude ethanolic extract of the kernel root of Xylocarpus mekongenesis (Lamk.) M. Roem. (Meliaceae) was evaluated in different methods. The extract showed significant anti-inflammatory activity in carrageenan-induced oedema test in rats showing 69.42 % reduction in the paw volume (P < 0.01) comparable to that produced by the standard drug indomethacin (70.25 %) at 24 h when the extract was fed at the dose of 400 mg/kg body weight. The percentage inhibition of the oedema paw volume was statistically significant (p < 0.05) when compared with the indomethacin treated animals at 0.5, 1, 2, 4 and 6 h. The extract exhibited IC50 value 4.78 μg/ml in DPPH free radical scavenging activity test that was found to be very significant and comparable to that of the standard antioxidants ascorbic acid and BHA (1.9372 and 4.81 μg/ml) respectively. In nitric oxide radical scavenging test, the IC50 value was also found fairly significant 57.37 μg/ml when compared to standard ascorbic acid (36.81 μg/ml). In reducing power test, the maximum absorbance of the same extract was observed as 1.923 at 100 μg/ml and that of ascorbic acid and BHA were 2.8111 and 1.0314 respectively. The extract showed highest antioxidant capacity at 100 μg/ml concentration expressed as equivalents of ascorbic acid (1.44). The total phenolic content of the extract was also found quite high (342.15 ± 0.92 mg/g of gallic acid equivalent). Therefore, the results of this study suggest the probable anti-inflammatory and antioxidant activities of the ethanolic extract of X. mekongenesis kernel root and justify its use in traditional medicines.