Rat Paw Edema Model Research Articles

Evaluation of analgesic and anti-inflammatory activity of ibuprofen and duloxetine in animal models

Background: Several antidepressants are currently being used as analgesic in neuropathic pain, but their effect on inflammatory pain is not clear. Few studies have shown that duloxetine also has anti-inflammatory effect along with its antinociceptive activity. Aims and Objectives: The present study was designed to explore the effect of duloxetine on experimentally induced pain and inflammation in animal models. Materials and Methods: The albino Wistar rats of either sex were randomly divided into four groups, i.e., control and ibuprofen, with six animals in each group. Analgesia was assessed by hot plate method in rats. Paw edema model in rats after induction with 0.1 mL of 1% carrageenan was used to assess the anti-inflammatory activity. Chronic anti-inflammatory activity was assessed by cotton pellet-induced granuloma. The results obtained were analyzed by analysis of variance followed by Tukey HSD post hoc test. Results: There was a statistically significant increase in reaction time at all time points compared to control in all treatment groups (ibuprofen and duloxetine) in the hot plate methods. Duloxetine (10 mg/kg) is superior to ibuprofen at every time point as shown by increase in mean reaction time. Duloxetine has also shown significant anti-inflammatory effects compared to control. Ibuprofen was found to cause statistically significant decrease in paw size compared to both control and duloxetine in carrageenan-induced rat paw edema. The anti-inflammatory effect of duloxetine was not significant compared to ibuprofen as seen in cotton pellet-induced granuloma. Conclusion: The present study showed analgesic and anti-inflammatory effect of duloxetine in dose-dependent matter. Thus, duloxetine may fit to be an agent offering analgesic and anti-inflammatory along with its antidepressant activity.

In vivo Antiinflammatory Potential of Leaf Extracts of Acacia auriculiformis Benth.

The prime objective of the present study was to evaluate the probable in vivo antiinflammatory potential of various extracts of the leaves of Acacia auriculiformis Benth. using carrageenan and formalin-induced inflammation in the rats. Thereafter gas chromatography-mass spectrometry analysis of the bioactive extract was performed to identify the compounds responsible for the antiinflammatory activity. The in vitro antioxidant potential was determined through 2,2-diphenyl-1-picrylhydrazyl scavenging assay, hydrogen peroxide scavenging assay and reducing power assay. Overall butanol and methanol leaf extracts showed significant antioxidant free radical scavenging activity. The methanol and petroleum ether leaf extracts at a dose of 400 mg/kg showed the highest percent inhibition of 84.88 and 82.12, respectively in the carrageenan-induced rat paw edema model, whereas, in formalin-induced rat paw edema model the chloroform and methanol leaf extracts showed the highest percent inhibition of 65.68 and 63.34 at a dose of 400 mg/kg, respectively. In both the antiinflammatory models, indomethacin (standard, 40 mg/kg) was used for comparison with test extracts. The gas chromatography-mass spectrometry analysis of bioactive butanol and methanol extracts showed the presence of compounds like sterols (stigmasterol, β-sitosterol and γ-sitosterol) and phenolic compounds (phenol, 2,4-bis(1,1-dimethylethyl),2,4-ditert-butylphenol), which could be responsible for the pharmacological activities observed. These in vitro and in vivo studies indicated that the antiinflammatory and antioxidant potential of the methanol leaf extract of Acacia auriculiformis Benth. could due to the presence of high phenolic and sterol content.

Anti-inflammatory effect of Śirīṣāvaleha prepared by two liquid media on carrageenan induced rat paw oedema model

Background: Steroidal and non-steroidal anti-inflammatory agents have several limitations, due to which people are moving towards use of traditional medicines. Considering this, the current attempt is aimed to evaluate in vivo anti-inflammatory effect of a poly-herbal formulation Śirīṣāvaleha prepared in presence of water and Kanji (sour gruel). Kanji is anticipated to bring extraction of more principles from the raw drugs and may improve therapeutic attributes of the drug. Considering this, Kanji was used as a liquid medium for preparation of Śirīṣāvaleha and was evaluated for anti-inflammatory activity in comparison to Śirīṣāvaleha prepared with water. Materials and Methods: The activity was screened in carrageenan induced rat paw oedema model in albino rats. The raw materials were collected; authenticated and trial formulations were prepared by following standard classical guidelines. Randomly selected animals were divided into four groups of six animals each. The test drugs were administered orally at a dose of 1.8 g/kg for five days. Phenylbutazone was used as standard anti-inflammatory drug for comparison. Results: Results showed the presence of pronounced anti-inflammatory activity in Śirīṣāvaleha prepared with water (SW) followed by Śirīṣāvaleha prepared with Kanji (SK). Conclusion: Study shows that both samples of Śirīṣāvaleha have anti-inflammatory effect.

Evaluation of Anti-inflammatory Activity of Capparis decidua Edgew. StemEvaluation of Anti-inflammatory Activity of Capparis decidua Edgew. Stem

Capparis decidua Edgew. belonging to the family Capparidaceae is a bushy shrub or small tree growing throughout the dry areas of India and other parts of the world. It is commonly known as ‘Kair’. Various parts of the plant are used traditionally in rheumatism, arthritis, gout and other inflammatory disorders. Therefore the present study was aimed at evaluation of antiinflammatory activity of the stems of the plant. Three extracts, viz. aqueous extract, alcoholic extract and hydro-alcoholic extract of the stem (at a dose of 500 mg/kg) were studied for anti-inflammatory activity by using carrageenan-induced rat paw edema model. The percentage inhibition of edema was calculated and compared with Indomethacine as a standard drug. Results revealed that all the extracts show significant inhibition of carrageenan-induced rat paw edema, the aqueous extract exhibiting the highest anti-inflammatory activity as compared to other extracts. The present investigation supports the traditional use of the plant in inflammatory diseases.

Eco-friendly synthesis, characterization, in vitro and in vivo anti-inflammatory activity of silver nanoparticle-mediated <em>Selaginella myosurus</em> aqueous extract

IntroductionThere is emerging interest in medicinal plants in the biomedical field, due to their multitude of chemicals which show anti-inflammatory, antimicrobial, antiviral, or antitumoral potential. Research on medicinal plants has shown that nanotechnology could offer new solutions in the quality control, delivery aspects, or in sustaining herbal biological activities. This work reports on the preparation and characterization of silver nanoparticle-mediated Selaginella myosurus plant extract.MethodsUltraviolet-visible spectroscopy, Fourier transform infrared spectroscopy, powder X-ray diffraction, energy dispersive X-ray spectroscopy, high-resolution scanning electron microscopy, high-resolution transmission electron microscopy, and selected area electron diffraction have been used to characterize the prepared silver nanoparticles. The synthetic stability was studied by varying concentrations and pH of reactants. Egg albumin denaturation and carrageenan-induced rat paw edema model were used to ascertain the anti-inflammation.ResultsUltraviolet-visible spectroscopy gave plasmon resonance ranging between 420 and 480 nm while Fourier transform infrared spectroscopy proved nano interface functionalized with organics. The powder X-ray diffraction pattern is in agreement with silver and silver chloride nanoparticles of crystallite size 33.7 nm and 44.2 nm for silver and silver chloride, respectively. Energy dispersive X-ray spectroscopy enables elemental characterization of the particles consisting of silver and silver chloride among main elements. Spherical silver grain of 58.81 nm average size has been depicted with high-resolution scanning electron microscopy and high-resolution transmission electron microscopy. Inhibitions of 99% and 60% were obtained in vitro and in vivo, respectively.ConclusionThe albumin denaturation and carrageenan-induced rat hind paw edema model to assess the anti-inflammatory potential of generated nanoparticles suggests that the silver nanoparticles may act as reducing/inhibiting agents on the release of acute inflammatory mediators. Hence, this work clearly demonstrated that silver nanoparticles mediated-Selaginella myosurus could be considered as a potential source for anti-inflammatory drugs.

EVALUATION OF ANTI-ASTHMATIC ACTIVITY OF METHANOLIC EXTRACT OF BERLERIA PRIONITIS LINN. AERIAL PARTS

Objective: The aim of the present study is to evaluate the aerial parts of a plant of Barleria prionitis Linn., for its antiasthmatic activity with the separation of active moieties.Methods: Adult wistar albino rats were used for the anti-inflammatory study. Histamine-induced bronchospasm was conducted on isolated goat trachea.Results: The dried and powdered aerial parts of Berleria prionitis was extracted with continuous soxhlet extraction with Petroleum ether (40-60 ° C), Chloroform, Ethyl acetate, Acetone, Methanol, and Hydroalcoholic solvents. Preliminary phytochemical screening of all extracts was done. Preliminary animal studies by In vitro isolated goat trachea chain preparation of all extracts were done to find out the potent extract. In this study, the methanolic extract of aerial parts of Berleria prionitis was found to be potent comparative to another extract. The results of carrageenan induced rat paw oedema model indicated the dose-dependant anti-inflammatory activity. As compared to standard drug (Indomethacin), methanolic extract showed similar activity which was found to be statistically significant (P<0.0001). The extent of DPPH radical scavenging was determined by calculated the IC50 value of methanolic extract Berleria prionitis (133.5) compared with the Ascorbic acid (114.7) taken as standard. In the present study, the histamine-induced dose-dependent contraction of goat tracheal chain was significantly inhibited (p<0.001) by methanolic extract of aerial parts of Berleria prionitis (200 μg/ml). Thus the present study revealed that the methanolic extract of Berleria prionitis (MEBP) has significant antihistaminic (H1 receptor antagonist) activity.Conclusion: In view the fact that tribal have well experienced the antiasthmatic effects of the roots of Barleria prionitis Linn. The results of our study, for the first time, show that the methanolic extract of aerial parts of Berleria prionitis Linn. possesses antioxidant, anti-inflammatory, Bronchodilator properties and therefore can be used for the antiasthmatic treatment.

PREPARATION, CHARACTERIZATION, AND EVALUATION OF ANTI-INFLAMMATORY ACTIVITY OF ETORICOXIB LOADED SOLUPLUS® NANOCOMPOSITES

Objective: The objective of this study was to prepare and characterize etoricoxib (ECB) loaded Soluplus® nanocomposites to improve its physicochemical properties. The effect of polymer and surfactant concentration on particle size, in vitro percentage dissolution efficiency and the anti-inflammatory activity of nanocomposites were also investigated.Methods: The nanocomposites were prepared by using a freeze-drying technique. The analytical evidence for the formulation of lyophilized nanocomposites in solid state were generated and confirmed by differential scanning calorimetry (DSC), fourier transformation infrared spectroscopy (FTIR), x-ray powder diffractometry (XPRD) and scanning electron microscopy (SEM). The in vitro drug release profile of nanocomposites was compared with pure ECB powder.Results: The nanocomposites of ECB were contained in a nano range with particle size and zeta potential of 63.5 nm and 46.5 mv, respectively. The solubility and dissolution of the nanocomposites were significantly (p<0.001) improved as compared to ECB alone, evidenced by decreased log P values (1.90±0.002) of the nanocomposites. The characterization studies revealed the formation of amorphous nanocomposites of ECB with existence of physical interactions between drug and polymer. The anti-inflammatory activity of nanocomposites evaluated by carrageenan-induced rat paw edema model demonstrated nonsignificant (p>0.05) increase in anti-inflammatory activity as compared to pure ECB.Conclusion: From the results, it could be concluded that the formation of ECB nanocomposites with Soluplus® could be an effective and alternative approach to modify the physicochemical properties of ECB.

Peels of Citrus Fruits: A Potential Source of Anti-inflammatory and Anti-nociceptive Agents

Introduction: The present study was contemplated to evaluate the anti-inflammatory and analgesic potentials in peels of some commercially grown Citrus fruits of South India viz, Lime (Citrus aurantifolia), Orange (Citrus reticulata), Sour Orange (Citrus aurantium), Pomello (Citrus grandis) and Citron (Citrus medica). Methods: The peel of the fruits were separated and subjected to cold extraction using 70% alcohol. The extracts obtained were screened for the presence of phytoconstituents by qualitative phytochemical analysis; the anti-inflammatory activity of extracts at 250 and 500mg/Kg body weight concentrations were assessed by in vivo Carrageenan induced rat paw edema model and in vitro HRBC membrane stabilization assay whereas Tail immersion and Hot plate methods have been used to evaluate their analgesic property. Results: The results revealed that, all extracts treated animals have shown significant decrease in paw edema volume at 3rd and 4th hour of treatment and increase in reaction time in tail immersion and hot plate readings at 120 and 150 min and are comparable to the standards. From the results it was evident that Citron peel extract exhibited significant antiinflammatory and analgesic property in all models. Preliminary phytochemical investigation revealed that extracts were bestowed with presence of flavonoids, terpenoids, steroids, glycosides, alkaloids, carotenoids and phenolic compounds which might be responsible for the antinociceptive and anti-inflammatory activities. Conclusion: From the results it was evident that all citrus fruits have prominent activity in terms of parameters assessed in a dose dependent manner and are more effective in the later phase. The study thus documents that Citrus peels are good sources of anti-inflammatory and anti-nociceptive agents.

ANTI-INFLAMMATORY ACTIVITY OF METHANOLIC EXTRACT OF HIBISCUS PLANTIFOLIUS

Objective: The objective of the present study was to carry out anti-inflammatory activity of methanolic extract of Hibiscus plantifolius (MEHP) belonging to the family Malvaceae.Methods: The shade dried stem part of H. plantifolius (1 kg) was powdered and extracted with methanol using soxhletion. The extract was concentrated using rotary evaporator under reduced pressure at 40°C, till free from the solvents and thereby providing crude methanol extract which was subsequently employed for further studies. Anti-inflammatory effect was studied by carrageenan-induced paw edema model in rats at dose level of 50, 150, and 300 mg/kg. Acute oral toxicity study was also studied.Results: The results indicate that MEHP, 300 mg/kg, exhibited significant inhibition (p<0.001) of increase in paw edema at 4th h.Conclusion: The results of the experimental study confirmed that MEHP possesses significant anti-inflammatory activity.

Evaluation of the antioxidant and anti-inflammatory activities of solvent extracts of Tricholepis chaetolepis (Boiss) Rech. f. whole plant

The whole plant, Tricholepis chaetolepis, powder was investigated using proximate and fluorescence analysis along with determining the extractive values. Total phenolics, flavonoids and total protein contents of n-hexane, chloroform and methanolic extracts of the whole plant were also determined. The anti-diabetic activity of all the three extracts of the plant was determined by in vitro alpha-amylase inhibition assay. The anti-oxidant potential was evaluated using Phosophomolybdenum and DPPH methods. The anti-inflammatory potential of all extracts were determined by carrageenan-induced rat paw oedema model. The evaluation of the plant extracts exhibited the anti-diabetic, anti-oxidant, and anti-inflammatory activities in dose dependent fashion. The research concludes that Tricholepis chaetolepis extracts contain phenol, flavonoids, and tannins that show observable anti-oxidant and anti-diabetic potential. It is also concluded that the methanol extract of the plant showed the maximum effect against inflammation induced by carrageenan in rat paw oedema as compared with n-hexane and chloroform extracts.

Therapeutic effects of Smilax glabra and Bolbostemma paniculatum on rheumatoid arthritis using a rat paw edema model.

Smilax glabra Roxb. (Tufuling) and Bolbostemma paniculatum (Maxim.) Franquet (Tubeimu) are used as couplet medicine in traditional Chinese medicine for the treatment of arthritis. This study is conducted to provide evidence on their therapeutic effects on rheumatoid arthritis (RA) and to explore its possible mechanisms of action. The identification and quantification of representative components (Astilbin and Tubeimoside I) in the n-butyl alcohol fraction of this couplet medicine (BFCM) were carried out by HPLC-UV assays. The contents of Astilbin and Tubeimoside I in BFCM were 13.13% (15.434 min) and 3.4% (18.619 min) respectively. For the assessment of anti-RA and anti-inflammatory activities, a carrageenan-induced paw edema model in rats was used. The swelling rates of paws and levels of IL-1β, IL-6 and TNF-α in the swelling tissue were determined. We observed that the BFCM exhibited significant inhibitory activity on carrageenan-induced paw edema model (p<0.01). The down regulated levels of IL-1β, IL-6 and TNF-α (all p<0.05) were reported. The results indicate that BFCM possesses significant anti-RA and anti-inflammatory effects, and it has a potential to be developed as a new therapeutic agent against RA.

Substituted Benzamides from Anti-inflammatory and p38 Kinase Inhibitors to Antitubercular Activity: Design, Synthesis and Screening.

Twenty one amide compounds possessing phenoxy/benzyloxy/pyridinyl groups have been synthesized by benzoylation of respective amines in presence of base with moderate to encouraging yields. Upon confirmation of structure, compounds were subjected for p38 kinase inhibitory, anti-inflammatory, antimicrobial and antitubercular activities. Anti-inflammatory activity was determined using carrageenan induced rat paw edema model while p38 kinase inhibitory activity was studied using ELISA method and serial dilution method was employed to determine MICs. Two compounds 4g and 4n showed over 30% p38 kinase inhibitory activity at 10 µM and best anti-inflammatory activity was found for compounds 4g, 4i, 4n and 4o which exhibited to reduce paw edema over 70%. Compound 4b was observed to be the most potent against gram +ve organisms with MIC value of 1.6 µG/mL and compound 4u displayed potent antibacterial activity against gram negative organisms. Most encouraging antitubercular activity was noticed for compounds 4u, 4r and 4k with 6.25, 12.5 and 12.5 µG/mL Further, in order to know the binding site interactions, a docking simulations of compounds was performed. These preliminary results will certainly show fruitful directions to improve the activities of compounds.

1,2,4-Triazole-based benzothiazole/benzoxazole derivatives: Design, synthesis, p38α MAP kinase inhibition, anti-inflammatory activity and molecular docking studies

Novel N-(benzothiazol/oxazol-2-yl)-2-[(5-(phenoxymethyl)-4-aryl-4H-1,2,4-triazol-3-yl)thio] acetamide derivatives (5a-n) were synthesized and investigated for in vitro anti-inflammatory activity and p38α MAP kinase inhibition. Compounds showing good in vitro activities (5a, 5b, 5d, 5e, 5i, 5k and 5l) were studied for their in vivo anti-inflammatory activity using carrageenan induced rat paw edema model. Compound 5b emerged as the most active compound with an edema inhibition of 84.43%. It also showed improved GI safety profile with lower ulcer severity index and lipid peroxidation potential. Also, p38α MAP kinase assay of 5b showed superior inhibitory potency (IC50:0.031 ± 0.14 µM) than the standard SB 203580 (IC50:0.043 ± 0.14 µM). To predict their binding mode compounds were also docked against p38α MAP kinase enzyme. Compound 5b and SB 203580 showed hinge region interaction with MET 109.

Synthesis, Characterization of Ethyl 5-(substituted)-1H-pyrazole- 3-carboxylate Derivative as Potent Anti-inflammatory Agents.

Recently, pyrazole derivatives have shown significant antiinflammatory activity. Non-steroidal anti-inflammatory drugs have some side effects, mainly gastric irritation and gastric ulceration during the treatment of inflammation. So the current study deals with the synthesis and pharmacological evaluation of a series of novel pyrazole derivatives as anti-inflammatory agents. A series of novel ethyl 5-(substituted)-1H-pyrazole-3-carboxylate (2a-j) were synthesized and evaluated for anti-inflammatory activity using carrageenan-induced inflammation in rat paw edema model. In the first step, diethyl oxalate react with acetophenone derivatives in presense of sodium ethoxide to form substituted ethyl-2,4-dioxo-4- phenyl butanoate derivatives as intermediate (1a-j). Further the suspension was prepared from dioxo-esters with hydrazine hydrate in glacial acetic acid yielded novel ethyl 5- (substituted)-1H-pyrazole-3-carboxylate (2a-j) derivatives. The structure of the final analogues (2a-j) has been confirmed on the basis of elemental analysis, IR, 1 H NMR and mass spectra. All the values of elemental analysis, FTIR, 1H NMR, and mass spectra were found to be prominent. The anti-inflammatory activity test revealed that Ethyl 5-(3,4- dimethoxyphenyl)-1H-pyrazole-3-carboxylate (2f) and ethyl 5-(2,3-dimethoxyphenyl)-1Hpyrazole- 3-carboxylate (2e) exhibited significant anti-inflammatory activity as compared to control group. The results of the current study indicate that the substitution at pyrazole scaffold could improve anti-inflammatory activity.

IN VITRO ANTIOXIDANT AND IN VIVO ANTI-INFLAMMATORY ACTIVITY OF THE AERIAL PART OF BLUMEA ERIANTHA DC

Objective: Objective of the present study was to carry out in vivo anti-inflammatory and in vitro antioxidant activity of methanol extract of aerial part of the Blumea eriantha DC belonging to family Asteraceae.Methods: The shade dried aerial part of B. eriantha (0.5 kg) was powdered and extracted with methanol (1.5 x 3L) at room temperature (24h x 3). After filtration combined all the three extracts and were concentrated on rotary evaporator under reduced pressure at 40 °C, thereby providing crude methanol extract which was subsequently employed for further studies. Anti-inflammatory effect was studied by carrageenan-induced paw edema model in rats at dose level 100, 200, and 400 mg/kg. Acute oral toxicity study and in vitro antioxidant potential of the extract was also studied. The in vitro antioxidant activity of methanol extract of aerial part of Blumea eriantha DC was evaluated against 1,1-diphenyl-2-picrylhydrazyl (DPPH), hydrogen peroxide (H2O2) and hydroxyl (OH) radicalscavenging and reducing power assays.Results: The results indicate that methanol extract of Blumea eriantha (BEME, 400 mg/kg) exhibited significant inhibition (p&lt;0.001) of increase in paw edema at 5th h. IC50 value of BEME showed significant antioxidant activity. The extract exhibits promising free radical scavenging effect of DPPH, H2O2, OH and reducing power in a dose-dependent manner up to 100µg/ml concentration while the reference standard Ascorbic acid demonstrated more scavenging potential than the methanol extract of Blumea eriantha The methanol extract was found to be safe at the dose of 2000 mg/kg.Conclusion: The results of the experimental study confirmed that methanol extract of Blumea eriantha DC possesses significant anti-inflammatory and antioxidant activity.

Synthesis and biological properties of aryl methyl sulfones

A novel group of aryl methyl sulfones based on nonsteroidal anti-inflammatory compounds exhibiting a methyl sulfone instead of the acetic or propionic acid group was designed, synthesized and evaluated in vitro for inhibition against the human cyclooxygenase of COX-1 and COX-2 isoenzymes and in vivo for anti-inflammatory activity using the carrageenan induced rat paw edema model in rats. Also, in vitro chemosensitivity and in vivo analgesic and intestinal side effects were determined for defining the therapeutic and safety profile. Molecular modeling assisted the design of compounds and the interpretation of the experimental results. Biological assay results showed that methyl sulfone compounds 2 and 7 were the most potent COX inhibitors of this series and best than the corresponding carboxylic acids (methyl sulfone 2: IC50 COX-1 = 0.04 and COX-2 = 0.10 μM, and naproxen: IC50 COX-1 = 11.3 and COX-2 = 3.36 μM). Interestingly, the inhibitory activity of compound 2 represents a significant improvement compared to that of the parent carboxylic compound, naproxen. Further support to the results were gained by the docking studies which suggested the ability of compound 2 and 7 to bind into COX enzyme with low binding free energies.The improvement of the activity of some sulfones compared to the carboxylic analogues would be performed through a change of the binding mode or mechanism compared to the standard binding mode displayed by ibuprofen, as disclosed by molecular modeling studies. So, this study paves the way for further attention in investigating the participation of these new compounds in the pain inhibitory mechanisms. The most promising compounds 2 and 7 possess a therapeutical profile that enables their chemical scaffolds to be utilized for development of new NSAIDs.

Synthesis, evaluation and docking studies of some 4-thiazolone derivatives as effective lipoxygenase inhibitors

Some promising 4-thiazolone derivatives as lipoxygenase inhibitors were designed, synthesized, characterized and evaluated for anti-inflammatory activity and respective ulcerogenic liabilities. Compounds (1b, 1e, 3b, and 3e) exhibited considerable in vivo anti-inflammatory activity (57.61, 79.35, 75.00, and 79.35%) against carrageenan-induced rat paw edema model, whereas compounds (1e, 3b, and 3e) were found active against the arachidonic acid-induced paw edema model (55.38, 55.38, and 58.46%). The most potent compound (3e) exhibited lesser ulcerogenic liability compared to the standard diclofenac and zileuton. Further, the promising compounds (1e and 3e) were evaluated for in vitro lipoxygenase (LOX; IC50 = 12.98 µM and IC50 = 12.67 µM) and cyclooxygenase (COX) inhibition assay (COX-1; IC50 > 50 µM and, COX-2; IC50 > 50 µM). The enzyme kinetics of compound 3e was evaluated against LOX enzyme and supported by in silico molecular docking and molecular dynamics simulations studies. Overall, the results substantiated that 5-benzylidene-2-phenyl-4-thiazolones are promising pharmacophore for anti-inflammatory activity.

Salicytamide: a New Anti-inflammatory Designed Drug Candidate.

Salicytamide is a new drug developed through molecular modelling and rational drug design by the molecular association of paracetamol and salicylic acid. This study was conducted to assess the acute oral toxicity, antinociceptive, and antioedematogenic properties of salicytamide. Acute toxicity was based on the OECD 423 guidelines. Antinociceptive properties were investigated using the writhing, hot plate and formalin tests in Swiss mice. Antioedematogenic properties were evaluated using the carrageenan-induced paw oedema model and croton oil-induced dermatitis in Wistar rats. Salicytamide did not promote behavioural changes or animal deaths during acute oral toxicity evaluation. Furthermore, salicytamide exhibited peripheral antinociceptive activity as evidenced by the reduction in writhing behaviour (ED50 = 4.95mg/kg) and licking time in the formalin test's inflammatory phase. Also, salicytamide elicited central antinociceptive activity on both hot plate test and formalin test's neurogenic phase. Additionally, salicytamide was effective in reducing carrageenan or croton oil-induced oedema formation. Overall, we have shown that salicytamide, proposed here as a new NSAID candidate, did not induce oral acute toxicity and elicited both peripheral antinociceptive effects (about 10-25 times more potent than its precursors in the writhing test) and antioedematogenic properties. Salicytamide also presented central antinociceptive activity, which seems to be mediated through opioid-independent mechanisms. These findings reveal salicytamide as a promising antinociceptive/antioedematogenic drug candidate.

MG17, A Novel Triazole Derivative Abrogated Neuroinflammation and Related Neurodegenerative Symptoms in Rodents.

The objective of present study is to explore multiple effects of the compound MG17 and relate them to achieve better therapeutic potential against neuroinflammation related disorders. We examined whether our compound is acting through regulating neuroinflammatory mediators. We have done some preliminary behavioral studies to shortlist the derivatives using rodent models of peripheral nerve injury in our earlier publication and now we extended our screening studies to explore the test compounds efficacy on other related peripheral neurological disorders such as Streptozotocin- induced diabetic peripheral neuropathy (DPN) and methyl mercury (MeHg) induced neurodegeneration in rats. Pro-inflammatory cytokines interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were quantified with RT-qPCR studies and histopathology studies were performed taking tissue samples from MeHg induced neurodegeneration rats. The effect of MG17 was assessed on local and acute inflammation through carrageenan-induced rat paw edema model. We observed the reduction in nociceptive responses in DPN rats. Pain threshold was reduced greater than 50% in various pain assessment modules. Upregulated pro-inflammatory cytokines which are thought to have a prominent role in neuroinflammation was controlled near to normal level quantified by RT-PCR studies. However, MG17 was able to regulate IL-6 and TNF-α but not IL-1β. Our results clearly suggest the beneficial potential of compound MG17 through inhibition of pro-inflammatory cytokines upregulation. MG17 could be an intriguing therapeutic approach in diabetesrelated neuro-pathophysiological conditions.

Chemical Profile and Anti-inflammatory Activity of Total Flavonoids from Glycyrrhiza Uralensis Fisch.

Glycyrrhiza uralensis Fisch. (G. uralensis) is one of the most widely used herbal medicines. This study was designed to enrich total flavonoids (TFF) from G. uralensis. The chemical profile of TFF was identified by HPLC and colorimetric assay. The TFF mainly contained liquiritin apioside, liquiritin, isoliquiritin apioside, liquiritigenin and isoliquiritigenin without glycyrrhizic acid. To study the anti-inflammatory activity of TFF, the DMB-induced ear vasodilatation assay and carrageenan-induced rat paw edema model have been utilized. Treatment with TFF showed significant anti-inflammatory activities in the two models. The two in-vivo edema assays demonstrated that the TFF possesses significant dose-dependent anti-inflammatory activity, similar to that of indomethacin at a dose of 500 mg/kg. In rat paws with carrageenan, treatment with TFF (500 and 250 mg/kg) markedly inhibited the expression of IL-1β and iNOS. TFF at all doses noticeably decreased levels of NO and MDA at the site of inflammation, while only i.g. TFF at a dose of 500 mg/kg significantly decreased TNF-α levels in the carrageenan-injected paws. In addition, an increase in SOD activity was induced by TFF at all doses. These results revealed that TFF exhibited significant anti-inflammatory activity in acute inflammatory models.