Formalin-induced Paw Edema Model Research Articles

Insights about the deleterious impact of a carbamate pesticide on some metabolic immune and antioxidant functions and a focus on the protective ability of a Saharan shrub and its anti-edematous property

Abstract In the Algerian desert, individuals often enjoy a soothing cup of herbal tea made from Ephedra alata Decne before bedtime; this aids in their relaxation. Our previous and earlier investigations demonstrated the richness of the shrub in terms of polyphenols and flavonoids and their effective medicinal properties. In the light of that fact, our interest has been aroused to check for other types of metabolites and for the protective ability of the shrub crude extract (SCE) regarding chemically induced edema and subacute toxicity (following a formalin-induced paw edema model and using a carbamate pesticide “pirimicarb” as a toxic agent, in Wistar male rats, respectively). Evidently, the SCE was used as a preventive agent. Swelling of formalin-injected foot was measured, and the anti-edematous ability was expressed as a percent of paw edema. At the end of induced subacute toxicity procedure, many investigations were carried, namely, checking for biochemical several parameters (hepatic, renal), hematological parameters, oxidative stress status (OSS), and histological examining of liver, spleen, and kidney tissues. The results revealed a remarkable anti-edematous effect. Furthermore, the association of the SCE effect has clearly minimized the OSS, the tissue aberrations, and the disturbance of the other metabolic parameters, along with a reduced immunodepression that was provoked under the effect of pirimicarb. In conclusion, pirimicarb has an important deleterious impact on metabolic and immune functions, and the studied shrub has exhibited an amazing protective potential against chemically induced inflammation and toxicity.

In vivo anti-inflammatory activity of the essential oil of zingiber officinale rhizomes on Wistar rats

Background: Zingiber officinale is a spice consumed in Chad and traditionally used against osteoarthritis, migraine and rheumatic pain, but few pharmacological studies of this plant have been carried out. The aim of this study was to assess the in vivo anti-inflammatory activity of Z. officinale rhizomes essential oil (EO). Methods: A preliminary phytochemical screening was carried out on the EO of Z. officinale rhizomes; the anti-inflammatory activity of the given plant extract was then assessed at the concentrations of 0.20%, 1% and 5% on three experimental models: egg yolk-induced oedema, cotton pellet-induced granuloma and formalin. In addition, the essential oil was tested for its in vitro antioxidant capacity using the 2,2-Diphényl-2-picryl-hydrazyle Free Radical Scavenging Test, acide 2,2'-azino-bis 3éthylbenz- thiazoline-6-sulfonique Radical Test and the Ferric reducing antioxidant power Test. The study was extended to the acute toxicity of the EO of the rhizomes of Z. officinale using the sequential method. Results: Qualitative phytochemical screening of the EO of Z. officinale rhizome revealed the presence of tannins, flavonoids, triterpenes, terpenoids and free quinones. In the egg yolk-induced edema model, the EO of Z .officinale rhizomes significantly inhibited (p < 0.01) oedema by 25.28%, 31.12% and 68.27% at the concentrations of 0.20%, 1% and 5%, respectively, when compared to controls. In the formalin-induced paw edema model, EO of Z. officinale rhizomes inhibited oedema by 24.27%, 30.14% and 43.14% at the concentrations of 0.20%, 1% and 5%, respectively, when compared to the controls. In the cotton pellet-induced granuloma model, EO of Z. officinale rhizomes induced an anti-granulomatous effect of 32.68%, 38.27% and 41.51% at the concentrations of 0.20%, 1% and 5%, respectively, as compared to controls. Additionally, the EO of the rhizomes of Z. officinale also induced in vitro antioxidant and free radical scavenging activity and iron reduction. Definitely, the LD50 of the EO of Z. officinale rhizomes was estimated as more than 2000 mg/kg b.w. Conclusion: The EO of Z. officinale rhizomes exhibited anti-inflammatory activity. This effect can be explained, at least partly to its chemical content and its antioxidant potential.

Ameliorative effects of Atriplex crassifolia (C.A.Mey) on pain and inflammation through modulation of inflammatory biomarkers and GC-MS-based metabolite profiling.

Atriplex crassifolia (A. crassifolia) is a locally occurring member of Chenopodiaceae family that has been used in folk medicine for the treatment of joint pain and inflammation. The present study was focused to determine the analgesic and anti-inflammatory potential of the plant. n-hexane (ACNH) and methanol (ACM) extracts of A. crassifolia were evaluated for in vitro anti-inflammatory potential using protein denaturation inhibition assay. In vivo anti-inflammatory potential was determined by oral administration of 250, 500, and 1000mg/kg/day of extracts against carrageenan and formalin-induced paw edema models. Inflammatory mediators such as TNF-α, IL-10, IL-1β, NF-kB, IL-4, and IL-6 were estimated in blood samples of animals subjected to formalin model of inflammation. Analgesic activity was determined using acetic acid-induced writhing and tail flick assay model. Phytochemical profiling was done by GC-mass spectrophotometer. The results of in vitro anti-inflammatory activity revealed that both ACNH and ACM displayed eminent inhibition of protein denaturation in concentration-dependent manner. In acute in vivo carrageenan-induced paw edema model, both extracts reduced inflammation at 5th and 6th hour of study (p < 0.05). A. crassifolia extracts exhibited significant inhibition against formalin-induced inflammation with maximum effect at 1000mg/kg. ACNH and ACM significantly augmented the inflammatory mediators (p < 0.05). Levels of TNF-α, IL-6, IL-1β, and NF-kB were reduced, while those of IL-4 and IL-10 were upregulated. ACNH displayed maximum analgesic effect at 1000mg/kg, while ACM showed potent activity at 500 and 1000mg/kg. The extracts restored the CBC, TLC and CRP toward normal. GC-MS analysis revealed the presence of compounds like n-hexadecanoic acid, Phytol, (9E,11E)-octadecadienoic acid, 2-hydroxy-1-(hydroxymethyl) ethyl ester, 1-hexacosene, vitamin E, campesterol, stigmasterol, gamma sitosterol in both extracts. These compounds have been reported to suppress inflammation by inhibiting inflammatory cytokines. The current study concludes that A. crassifolia possesses significant anti-nociceptive and anti-inflammatory potential owing to the presence of phytochemicals.

In vitro and in vivo anti-inflammatory activity of Cupressus torulosa D.DON needles extract and its chemical characterization

Ethnopharmacological relevanceCupressus torulosa (family Cupressaceae), widely distributed in the north western Himalayan region of India, is a coniferous aromatic tree with various traditional uses of its aerial parts. Its needles have been used for anti-inflammatory, anticonvulsant, antimicrobial, and wound-healing properties. Aim of the studyThe study aimed at investigating the previously unknown anti-inflammatory activity of the hydromethanolic extract of the needles employing in vitro and in vivo assays and scientifically validate traditional claim of their use in treatment of inflammation. Chemical characterization of the extract with the aid of UPLCQTOFMS was also of interest. Materials and methodsC. torulosa needles were first defatted with hexane and sequentially extracted with chloroform and 25% aqueous methanol (AM). Since the presence of phenolics (TPCs, 208.21 ± 0.95 mg GAE/g needles) and flavonoids (TFCs, 84.61 ± 1.21 mg QE/g needles) was observed in the AM extract only, it was chosen for biological and chemical examinations. Acute toxicity of the AM extract on female mice was evaluated following the OECD guideline 423. In vitro anti-inflammatory activity of the AM extract was examined using egg albumin denaturation assay while carrageenan-induced paw edema and formalin-induced paw edema models at doses of 100, 200 and 400 mg/kg po were used to determine the in vivo activity of the AM extract on Wistar rats of either sex. The components of the AM extract were analyzed by UPLC-QTOF-MS method using non-targeted metabolomics approach. ResultsAM extract was found to be non-toxic at 2000 mg/kg b.w. with no signs of abnormal locomotion, seizures and writhing. The extract demonstrated promising in vitro anti-inflammatory activity (IC50 160.01 μg/mL) compared to standard diclofenac sodium (IC50 73.94 μg/mL) in egg albumin denaturation assay. In carrageenan-induced paw edema and formalin-induced paw edema tests the extract showed significant anti- inflammatory activity (57.28% and 51.04% inhibition of paw edema, respectively) at the dose of 400 mg/kg p.o. after 4 h in comparison to the standard diclofenac sodium which displayed 61.39% and 52.90% inhibition, respectively, at the dose of 10 mg/kg p.o. after 4 h in these models. A total of 63 chemical constituents, majority of them being phenolics, were found in the AM extract of the needles. Two compounds namely monotropein (iridoid glycoside), (±)12-HETE (eicosanoid) and fraxin (coumarin glycoside) were reported to have anti-inflammatory effect. ConclusionsFor the first time our study demonstrated that hydro-methanolic extract of C. torulosa needles exhibit anti-inflammatory activity thereby supporting their traditional use in the treatment of inflammatory disorders. UPLCQTOFMS assisted chemical profile of the extract was also unveiled.

UHPLC-MS and GC-MS phytochemical profiling, amelioration of pain and inflammation with chloroform extract of Funaria hygrometrica Hedw. via modulation of inflammatory biomarkers.

People of Pakistan have undisturbed customs for the employment of medicinal plants for healthcare requisites. Chloroform extract of F. hygrometrica (CE FH) was examined for its ability to reduce inflammation and to produce analgesia. Carrageenan and formalin-induced paw edema model for inflammatory activity, hot-plate and tail-flick methods to assess analgesic activity were executed. Phytochemical analysis was done by UHPLC-MS and GC-mass spectrometer. The results demonstrated that in carrageenan-induced paw edema, maximum reduction in inflammation was observed at 5th hour at the dose 100mg/kg; while at doses 250 and 500mg/kg, maximum response was observed at 5th and 6th hours. Analgesic activity results indicated that maximum analgesia was observed up to 120min at 100mg/kg, while up to 90min in case of 250 and 500mg/kg doses. The formalin-induced rat paw edema showed significant (p < 0.05) anti-inflammatory activity after 5days treatment. After, testing period of 10days, the biochemical parameters such as CBC, CRP, serum enzymes like CAT, SOD, GSH and inflammatory mediators like TNF-α, IL-6, IL-4 and IL-10 were estimated. The administration of formalin resulted in an increase in the level of leucocytes, total WBC, CRP, serum enzymes and in the diameters of paw thickness, while pre-treatment with CE FH at dose levels of 100, 250 and 500mg/kg exhibited a diminution in the levels of SOD, GSH, CAT, total RBC and HB. Acute inflammatory mediators such as TNFα, IL -6 and IL-4 were reduced, and IL-10 was upregulated in the treated group as compared to the control. Many phytoconstituents, i.e., chitobiose, chlorovulone III, γ-tocotrienol, emmotin, cassine, hexacosanedioic acid, neophytadiene, fumaric acid, neophytadiene, hexadecanoic acid, phytol and stigmasterol were detected during UHPLC-MS and GC-MS analysis seems to be responsible for the said activity in correlation with the already reported data about these compounds. The results concluded that CE FH possess noteworthy anti-inflammatory and central analgesic action at different doses (100, 250 and 500mg/kg).

In vivo and In silico Anti Inflammatory Studies of Alstonia scholaris Bark Extract

The present research is focused on screening In vivo anti-inflammatory activity using carrageen and formalin induced paw edema model in rodents and In silico approaches like docking studies (mcule), Ramchandran plot (procheck) and PASS. The extract significantly inhibited inflammation caused by carrageenan and formalin at doses of 200 mg and 400 mg/kg body weight which is compared to the the effect of the standard drugs meloxicam and indomethacin. Docking studies for natural compounds were carried out against PDB ID: 2AZ5, PDB ID: 1IBC, PDB ID: 6COX, and PDB ID: 4NOS in order to assess the ligand-binding affinity of the active principles of the extract. The docking results showed that the phytoconstituents from the extract and standard drugs meloxicam and indomethacin had shown highest glide scores with all the selected proteins which indicate a greater affinity for binding between receptor and ligand. From the PASS results the possible interventions of selected active constituents of Alstonia scholaris were found to be anti- inflammatory intestinal, Prostaglandin-E2 9-reductase inhibitor, TNF expression inhibitor, Cyclooxygenase 1 and 2 inhibitors, NOS2 expression inhibitor, and Interleukin1 and 6 antagonists. From the prediction results of adverse effects the constituents like Stigmasterol, Diospyrolide, D-Friedoolean-14-en-3-one and Lupeol acetate were found to be free from any adverse effects. All the constituents of Alstonia scholaris were found to have interventions either as direct targets or possible targets with Histamine H2 receptor, Arachidonate 5-lipoxygenase, Interleukin-1 receptor-associated kinase 3 TNF-alpha, Cyclooxygenase 1, Prostanoid EP2 receptor, Prostaglandin E synthase, and Serotonin 1e (5-HT1e) receptor. From In vivo and In silico results it is evident that ethanolic bark extract of Alstonia scholaris possessed significant anti-inflammatory activity.

Anti-inflammatory Activity of Sclerotium stipitatum Berk. et. Curr. an Ethnomedicinal Fungus, in Chronic and Acute Animal Models of Inflammation

Sclerotium stipitatum Berk. et. Curr., locally known as ‘nilamanga’ is a rare macro fungus, traditionally used to treat numerous diseases like arthritis, earache, jaundice etc. The present study aims to evaluate the anti-inflammatory activity of ethanol extract of S. stipitatum and identify the bioactive compounds present in them. Phytochemical screening of extracts obtained using different solvents like petroleum ether, chloroform, ethanol and water were done. The best extract was chosen for the acute carrageenan-induced and chronic formalin-induced anti-inflammatory studies. Diclofenac was used as the standard drug. Ethanol extract showed significant inhibition of inflammation induced by carrageenan and formalin-induced paw edema models compared to the control. GC-MS analysis shows certain bioactive compounds. The significant inhibitory effect on paw edema proves that S. stipitatum possesses remarkable anti-inflammatory activity, and isolation and identification of bioactive compounds can be used for new drug formulations.

Anti-inflammatory and analgesic actions of bufotenine through inhibiting lipid metabolism pathway

Inflammation is a primary defense and immune response. However, under pathological conditions, the inflammation processes always become uncontrolled and lead to chronic diseases. Bufotenine, as a natural component from toad venom, showed great potential for development as a novel anti-inflammation and analgesia agent. This study aimed to investigate the therapeutic effects of bufotenine against inflammation and pain on animal models with a focus on lipid metabolism. In pharmacological studies, bufotenine significantly inhibited the swelling rates on formalin-induced paw edema model, and increased paw withdrawal mechanical thresholds (PWMTs) in von Frey test and thermal pain thresholds (TPTs) in hot-plate test. High-sensitivity lipidomics analysis revealed the effects might be related to the down-regulation of inflammatory mediators from cyclooxygenase (COX), lipoxygenase (LOX), cytochrome P450 (CYP450), linoleic acid (LA), docosahexaenoic acid (DHA) and other pathways. The activities might result from the binding of bufotenine and its receptors, including sigma-1 receptor and 5-Hydroxytryptamine receptor 3A, thus regulating lipid metabolism pathway. The research provided a systemic evidence for the actions and mechanism of bufotenine. It suggested that the natural compound might be a potential candidate for reducing inflammatory pain disorders.

Phytol anti-inflammatory activity: Pre-clinical assessment and possible mechanism of action elucidation

Phytol (PHY) is an acyclic natural diterpene alcohol and a chlorophyll constituent that exhibits several pharmacological effects, such as anticancer, antioxidant, and antimicrobial. Here, we aimed to assess the PHY anti-inflammatory effect in vitro and in vivo, and to deepen knowledge on the possible mechanism of action. For this purpose, egg albumin (in vitro) test was performed by using acetyl salicylic acid (ASA) as a standard nonsteroidal anti-inflammatory drugs (NSAID). For in vivo test, male Wistar albino rats were treated (intraperitoneally) with 100 mg/kg of PHY and/or standard NSAIDs ASA (100 mg/kg) and diclofenac sodium (Diclo-Na, 10 mg/kg) to evaluate the combined effect of PHY in formalin-induced paw edema model. Furthermore, an in silico (CADD) study was accomplished to assess the effect of PHY against cyclooxygenase (COX)-1 and 2 enzymes, nuclear factor kappa B (NF-κB), and interleukin-1β (IL-1β). Results revealed that PHY exhibits dose-dependent anti-inflammatory effect using the egg albumin method. PHY (100 mg/kg) co-treated with ASA and/or Diclo-Na reduced paw edema better than PHY alone or NSAIDs individual groups. Computational study showed that PHY efficiently interacts with COX-1 and 2, NF-κB, and IL-1β. In conclusion, PHY exhibits anti-inflammatory activity, possibly via COX-1 and 2, NF-κB, and IL-1β dependent pathways.

PHYTOCHEMICAL PROFILING, FREE-RADICAL SCAVENGING AND ANTI-INFLAMMATORY ACTIVITIES OF MELIOSMA SIMPLICIFOLIA (L.)

Objective: In the current research, to determine the stem extract of Meliosma simplicifolia (L.) for total phenol, tannin, total flavonoid, antioxidant activity, anti-inflammatory and identify the phytoconstituents utilizing GC-MS and FT-IR.&#x0D; Methods: The ability of the plant extract to act as hydrogen/electrons donor or scavenger of radicals was determined by in vitro antioxidant assays using 2,2-diphenyl-2-picryl-hydrazyl free radical (DPPH) scavenging, reducing power assay, superoxide radical (O2•) scavenging activity. The anti-inflammatory activity was evaluated using carrageenan and formalin-induced paw edema models using Wistar albino rats. The GC-MS and FT-IR analysis of the methanolic stem extract of M. simplicifolia was revealed the presence of phytochemicals.&#x0D; Results: Quantitative studies of estimated phenol, flavonoid and tannin, as for the methanol extract of stem showed the highest content of phenolic compounds (39.83±3.62GAE mg/100). Antioxidant activities were concluded the estimation M. simplicifolia stem for as followed the studies. In stem the methanol extract showed the highest DPPH scavenging activity (124.3µg/ml). The anti-inflammatory activity has shown in high doses of methanolic extract 250 mg/kg of significant value (p&lt;0.05) inhibition of paw edema, on 6th hour, respectively. The FT-IR analysis has confirmed their characteristic peak values and functional groups.&#x0D; Conclusion: M. simplicifolia has an effective of anti-inflammatory activity and constitutes a potential source for the development of new treatments.

Chrysophyllum albidum fruit peel attenuates nociceptive pain and inflammatory response in rodents by inhibition of pro-inflammatory cytokines and COX-2 expression through suppression of NF-κB activation

Chrysophyllum abidum fruit is a seasonal fruit commonly eaten as snacks with abundant health promoting phytochemicals in the fruit peels. The fruit peels have been reported to be rich in anti-inflammatory eleagnine, myricetin rhamnoside, quercetin, linoleic acid and oleic acid. We hypothesized that the anti-inflammatory effect of the peel extract involve suppression of pro-inflammatory cytokines, cyclooxygenase-2 and nuclear factor-kappa B (NF-κB). Hence, this study was designed to assess the anti-nociceptive and anti-inflammatory effects of fruit peel extract of Chrysophyllum albidum in animal models of nociception and inflammation. The anti-nociceptive activity of CAPEE (100 and 400 mg/kg) was evaluated in acetic acid-induced writhing and formalin-induced paw licking in mice. Formalin-induced paw edema and carrageenan-induced air pouch models of inflammation were used to evaluate the anti-inflammatory activity. CAPEE (100 and 400 mg/kg) significantly reduced abdominal writhing and paw licking in acetic acid and formalin tests in mice, respectively. CAPEE demonstrated significant inhibition of paw edema at 24 h (41.0% and 55.7%) and 72 h (52.3% and 86.6%) after formalin injection. CAPEE suppressed inflammatory responses in carrageenan-induced air pouch by reducing exudates, inflammatory cells infiltration, nitrites and myeloperoxidase activity. There was significant inhibition of tumor necrosis factor-alpha, interleukin-6 levels and reduced immunopositive expression of COX-2 and NF-κB. In conclusion, CAPEE has anti-nociceptive and anti-inflammatory potentials via mechanisms associated with inhibition of pro-inflammatory cytokines and cyclooxygenase-2 (COX-2) expression through suppression of nuclear factor kappa B (NF-κB) activation, and has potential as a functional food ingredient.

Tannic acid exhibits anti-inflammatory effects on formalin-induced paw edema model of inflammation in rats.

The aim of the study was to determine the relationship between anti-inflammatory effects of the natural polyphenolic compound tannic acid (CAS number: 1401-55-4) and myeloperoxidase (MPO) enzyme activity in paw edema model. Thirty-five female rats were divided into five groups. The paws of rats were injected subcutaneously in the plantar surface with formalin except for the control group. Indomethacin and tannic acid were intraperitoneally administered 1 h after formalin injection. The paws volume was measured by using vernier caliper. MPO enzyme activity was determined using 4-aminoantipyrine-phenol solution as the substrate for MPO-mediated oxidation by H2O2. About 17% and 13% edema inhibition has detected in the indomethacin-applied group, at the measurements run every other hour right after the treatment. An inhibition of 16% was found at the group treated with 25 mg/kg tannic acid. However, in the group treated with 50 mg/kg tannic acid, 15% and 7% of the edema inhibition was observed. Serum and paw tissue MPO activities were decreased in treated groups with indomethacin and tannic acid according to formalin control group. Our study results suggest that tannic acid may contribute to the treatment of inflammation by decreasing MPO enzyme activity, but the molecular mechanism is still not clear.

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.

Antinociceptive and Anti-inflammatory Activities of Marine Sponges Aplysina Caissara, Haliclona sp. and Dragmacidon Reticulatum

ABSTRACT Marine sponges are a rich source of bioactive natural products with multiple pharmacological properties. In this study, the anti-inflammatory and antinociceptive effects of extracts obtained from Aplysina caissara, Haliclona sp. and Dragmacidon reticulatum were evaluated by using the writhing test and formalin-induced mouse paw edema model in mice. All extracts were administered via oral pathway in the doses of 60 and 90 mg/kg. In the writhing test the pre-treatment with all sponges resulted in significant inhibition of the acetic acid-induced response, suggesting an antinociceptive effect. The formalin test showed that the extracts from A. caissara, Haliclona sp. and D. reticulatum, in the tested doses, did not affect the first formalin phase, however, they were effective in the late phase. To assess the potential anti-inflammatory activity of the extracts, the test of formalin-induced paw edema was used. The oral administration of A. caissara, Haliclona sp. and D. reticulatum extracts significantly reduced the formalin-induced paw edema in mice. In conclusion, our data show that marine sponges can be an important source of anti-inflammatory and antinocicpetive products that can be promising therapeutical leads. Furthermore, pharmacological and chemical studies have been developed not only to characterize the mechanism(s) that is/are responsible for the antinociceptive and anti-inflammatory action but also to identify the active principles of sponges.

Design, synthesis and evaluation of some pyrazolo[3,4-d]pyrimidine derivatives bearing thiazolidinone moiety as anti-inflammatory agents

Two new series of pyrazolo[3,4-d]pyrimidine bearing thiazolidinone moiety were designed and synthesized. The newly synthesized compounds were evaluated for their in vitro (COX-1 and COX-2) inhibitory assay. Compounds that showed promising COX-2 selectivity were further subjected to in vivo anti-inflammatory screening applying formalin induced paw edema (acute model) and cotton-pellet induced granuloma (chronic model) assays using celecoxib and diclofenac sodium as reference drugs. The histopathological and ulcerogenic potential were also determined. In vivo anti-inflammatory data showed that compounds 2, 6, 7d displayed anti-inflammatory activity higher than both references in the formalin induced paw edema model. On the other hand, compounds 2, 3d, 3e, 7b and 7d displayed anti-inflammatory activity greater than or nearly equivalent to diclofenac sodium in the cotton pellet-induced granuloma assay. Moreover, most of the tested compounds revealed good gastrointestinal safety profile. Collectively, compounds 2 and 7d were considered as promising candidates in managing both acute and chronic inflammation with safe gastrointestinal margin.

Design, synthesis and evaluation of some pyrazolo[3,4-d]pyrimidines as anti-inflammatory agents

New pyrazolo[3,4-d]pyrimidines substituted with various functionalities or attached to a substituted pyrazole ring through different linkages were synthesized. The synthesized compounds were evaluated for their anti-inflammatory activity using in vitro COX-1/COX-2 inhibition assay and in vivo formalin induced paw edema and cotton pellet-induced granuloma assays. Results revealed that compounds 17b and 18 possessed COX-1/COX-2 selectivity indices higher than diclofenac sodium and celecoxib. However, compounds 16a,b exhibited selectivity indices higher than diclofenac sodium and nearly equivalent to celecoxib, whereas, 9b displayed selectivity index comparable to diclofenac sodium. In vivo anti-inflammatory data showed that compounds 9b, 16a, 18 displayed anti-inflammatory activity higher than both references in the formalin induced paw edema model. On the other hand, the pyrazolyl derivatives 9b, 16b and 17b displayed anti-inflammatory activity about 2–2.5-fold that of diclofenac sodium and nearly 8–10.5-fold that of celecoxib in the cotton pellet-induced granuloma assay. The ulcerogenic effect of the active compounds was also investigated and results revealed that compounds 16a, 17a,b and 18 showed good gastrointestinal safety profile. Based on this, compounds 16a and 18 were considered as safe and effective leads in managing acute inflammation, while, 17b was prominent in controlling chronic inflammation.

Design, Synthesis and Anti-inflammatory Activity of Derivatives 10-R-3-Aryl-6,7-dihydro-2H-[1,2,4] triazino[2,3-c]quinazolin-2-ones of Spiro-fused Cyclic Frameworks.

Present work is devoted to the purposeful search of novel promising anti-inflammatory agents among the insufficiently known 3'-R-10'-R1-spiro[hetaryl-3(4),6'-[1,2,4]triazino[2,3-c]quinazolin]-2'(7'H)-ones. The virtual combinatorial library of previously unknown spiro-condensed derivatives of [1,2,4]triazino[2,3-c]quinazolines was formed and promising COX-2 inhibitors were identified by molecular docking method. Potential anti-inflammatory agents were synthesized by [5+1]-cyclocondensation of substituted 3-(2-aminophenyl)-6-R-1,2,4-triazin-5(2H)-ones with heterocyclic ketones. The structures of synthsized compounds were verified by complex of physicochemical methods and spectral characteristics features were discussed. Obtained compounds were studied for anti-inflammatory activity using formalin induced paw edema model and highly active compounds were identified. Conducted SAR-analysis showed that combination of triazino[2,3-c] quinazoline moiety with spiro-condensed fragments is a reasonable approach for creating novel anti-inflammatory agents.

Search for Anti-Inflammatory Agents in the Tetrahydropyrido[2,1-B ][1,3,5]-Thiadiazine Series

Tetrahydropyrido[2,1-b ][1,3,5]thiadiazine derivatives were investigated for anti-inflammatory activity as compared with that of diclofenac sodium using the formalin-induced paw edema model in albino rats. Compounds with anti-inflammatory activity 1.5 – 3.5 times more potent than that of diclofenac sodium were discovered.

Поиск средств с противовоспалительной активностью среди производных тетрагидропиридо[2,1-&lt;i&gt;b&lt;/i&gt;][1,3,5]тиадиазина

Проведены исследования противовоспалительной активности производных тетрагидропиридо[2,1-b][1,3,5]тиадиазина на модели «формалинового отека» конечностей белых беспородных крыс в сравнении с диклофенаком натрия. Обнаружены соединения с выраженной противовоспалительной активностью, превышающей в 1,5 – 3,5 раза активность диклофенака натрия.

Antioxidant, anti-inflammatory and antinociceptive activities of methanolic extract of Justicia secunda Vahl leaf

Background of studyPlants used for traditional medicine contain a wide range of substances which can be used to treat various infectious diseases. AimThe study evaluated the in vitro antioxidant, antinociceptive, and anti-inflammatory activities of the methanolic extract of Justicia secunda Vahl leaf. MethodsThe acute toxicity was performed with up and down method and the highest dose used was 2g/kg. The anti-inflammatory activity was evaluated using the carrageenan and formalin-induced paw edema models, and antinociceptive activity was evaluated using acetic acid-induced writhing reflex and tail flick test models while the antioxidant activity was evaluated using 2,2-diphenyl-2-picryl hydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) photometric assay. ResultsThe extract was well tolerated as no signs of toxicity or death were noticed during the period of observation. The extract produced a concentration dependent increase in antioxidant activities in both DPPH and FRAP models. The extract produced its optimum activity at 400μg/ml in both DPPH (54.07%) assay and FRAP (1.58μM) assay. The extract produced significant (P<0.05) dose-dependent increase in both anti-inflammatory and antinociceptive activities. The antinociceptive and anti-inflammatory activities of the extract (0.4g/kg) were comparable with the reference drugs (aspirin and pentazocine) used in the study. ConclusionThis study suggests that J. secunda possesses anti-inflammatory, antinociceptive and antioxidant activities and also provide the pharmacological basis for its uses in traditional medicine for these purposes.