Mouse Ear Edema Assay Research Articles

Anti-inflammatory and antitumor activities of the chloroform extract and anti-inflammatory effect of the three diterpenes isolated from Salvia ballotiflora Benth

BackgroundDrugs used for the treatment of diseases associated with chronic inflammation, such as cancer and rheumatoid arthritis have the potential to cause undesirable side-effects, which might result in patients ending treatment prematurely. However, plants are a viable option for the treatment of inflammatory diseases. In this study, we assessed the in vivo and in vitro anti-inflammatory activity, and the antitumor effects of the chloroform extract of Salvia ballotiflora (ECL). The pro-apoptotic effects of ECL in CT26 cells were also determined.MethodsThe chloroform extract of Salvia ballotiflora (ECL) was standardized using 19-deoxyicetexone (DEOX) as a phytochemical marker. The anti-inflammatory activity of ECL was determined on acute and chronic inflammatory models using the TPA-induced mouse ear edema assay. The antitumor activity of ECL was evaluated by the subcutaneous inoculation of CT26 cells on the back of Balb/c mice. In vitro CT26 cell death induced by ECL was determined by Annexin V/propidium iodide staining assay using flow cytometry. ECL and the diterpenes isolated from the chloroform extract included 19-deoxyicetexone (DEOX), icetexone (ICT), and 7,20-dihydroanastomosine (DAM), which were tested in LPS-stimulated J774A.1 macrophages to quantify pro-inflammatory cytokine levels. The in vitro anti-arthritic activity of ECL was determined using the bovine serum protein (BSP) denaturation assay.ResultsECL exerted anti-inflammatory activities in acute (84% of inhibition, 2 mg/ear) and chronic models (62.71%, at 100 mg/kg). ECL showed antitumor activity at 200 mg/kg and 300 mg/kg, reducing tumor volume by 30 and 40%, respectively. ECL (9.5 μg/mL) induced in vitro apoptosis in CT26 cells by 29.1% (48 h of treatment) and 93.9% (72 h of treatment). ECL (10 μg/ml) decreased levels of NO (53.7%), pro-inflammatory cytokines IL-6 (44.9%), IL-1β (71.9%), and TNF-α (40.1%), but increased the production of the anti-inflammatory cytokine IL-10 (44%). The diterpenes DEOX, ICT, and DAM decreased levels of NO (38.34, 47.63, 67.15%), IL-6 (57.84, 60.45, 44.26%), and TNF-α (38.90, 31.30, 32.83%), respectively. ECL showed in vitro antiarthritic activity (IC50 = 482.65 μg/mL).ConclusionsECL exhibited anti-inflammatory and anti-tumor activities. Furthermore, the diterpenes DEOX, DAM, and ICT showed anti-inflammatory activity by reducing levels of NO, TNF-α, and IL-6.

6-Deoxy- and 11-Hydroxytolypodiols: Meroterpenoids from the Cyanobacterium HT-58-2.

Chemical investigation of cyanobacterial strain HT-58-2, which most closely aligns with the genus Brasilomena, has led to the isolation of two compounds related to tolypodiol. The structures and absolute configuration of 6-deoxytolypodiol (1) and 11-hydroxytolypodiol (2) were elucidated by spectroscopic and spectrometric analysis. While tolypodiol previously showed anti-inflammatory activity in a mouse ear edema assay, only 2 reduced in vitro thromboxane B2 and superoxide anion (O2-) generation from Escherichia coli lipopolysaccharide-activated rat neonatal microglia to any appreciable degree.

Synthetic Studies on the Natural Product Myrsinoic Acid F Reveal Biologically Active Analogues.

The synthesis of the structure, 1, assigned to the anti-inflammatory natural product myrsinoic acid F is reported together with a means for preparing its Z-isomer 21. While neither of these compounds corresponds to the natural product, both of them are anti-inflammatory agents (as determined using a mouse ear edema assay) with congener 1 being notably more potent than the widely prescribed NSAID indometacin.

Anti-diabetic activity in type 2 diabetic mice and α-glucosidase inhibitory, antioxidant and anti-inflammatory potential of chemically profiled pear peel and pulp extracts (Pyrus spp.)

Total phenolic acids, total flavonoids, total triterpenes contents, and eleven monomeric compounds, derived from eight different pears' peel and pulp, were qualitatively and quantitively profiled utilizing HPLC and HPLC-MS. All the chemical components found in the peel were approximately 2 to 18 folds concentrated than those in the pulp. Their antioxidant (reducing power and 2, 2-diphenyl-1-picrylhydrazyl/DPPH assay) and anti-inflammatory (xylene-induced mouse ear edema assay) activities were comparatively evaluated. Correlation analysis and principal component analysis were utilized to seek bioactive components in antioxidant and anti-inflammatory activities. Subsequently, Yaguang pear (Pyrus ussuriensis Maxim, with high polyphenols content) was selected to investigate in vitro and in vivo anti-diabetic potential (α-glucosidase inhibition assay and hypoglycemic assay in streptozocin-induced type 2 diabetic mice). Eleven monomeric compounds were seriatim examined for α-glucosidase inhibitory activity to fish out anti-diabetic components. For the first time, this study delineated pear peel's anti-diabetic prospect of treatment for type 2 diabetes.

Semisynthesis of fuscoside B analogues and eunicosides, and analysis of anti-inflammatory activity

A small library of semisynthetic analogues of fuscol and eunicol have been prepared and evaluated for in vivo topical anti-inflammatory activity using the mouse-ear edema assay. The first glycosylation of fuscol and eunicol has been achieved using a modified Koenigs–Knorr glycosylation to synthesize new fuscosides and eunicosides, a novel structural class of diterpene glycosides. The availability of adequate glycosylation methods for this synthesis was limited owing to the instability of the glycosyl acceptors. Glycosyl donor protecting group type had a pronounced effect on overall glycosylation yields of a model glycosyl acceptor. This synthesis provided access to the unnatural β-glycosides allowing for an evaluation of the effect of differing anomeric stereochemistry on anti-inflammatory activity. The PEGylated derivatives of fuscol and eunicol were also synthesized by a convenient acid-promoted solvolysis of the natural product aglycones. This work highlights the importance of the glycan portion of fuscoside B, notably the stereochemical configuration of the glycosidic linkage, in the observed anti-inflammatory activity.

Synthesis, biological evaluation and molecular docking studies of stellatin derivatives as cyclooxygenase (COX-1, COX-2) inhibitors and anti-inflammatory agents

Stellatin (4), isolated from Dysophylla stellata is a cyclooxygenase (COX) inhibitor. The present study reports the synthesis and biological evaluation of new stellatin derivatives for COX-1, COX-2 inhibitory and anti-inflammatory activities. Eight derivatives showed more pronounced COX-2 inhibition than stellatin and, 17 and 21 exhibited the highest COX-2 inhibition. They also exhibited the significant anti-inflammatory activity in TPA-induced mouse ear edema assay and their anti-inflammatory effects were more than that of stellatin and indomethacin at 0.5mg/ear. The derivatives were further evaluated for antioxidant activity wherein 16 and 17 showed potent free radical scavenging activity against DPPH and ABTS radicals. Molecular docking study revealed the binding orientations of stellatin and its derivatives into the active sites of COX-1 and COX-2 and thereby helps to design the potent inhibitors.

Anti-inflammatory effect of Ajuga bracteosa Wall Ex Benth. mediated through cyclooxygenase (COX) inhibition

Ajuga bracteosa Wall Ex Benth. (Labiateae) is described in Ayurveda for the treatment of rheumatism, gout, palsy and amenorrhea. The aim of present investigation is to study anti-inflammatory activity of Ajuga bracteosa, to understand possible mechanism of action and to identify the constituents responsible for its activity. The anti-inflammatory activity of 70% ethanolic extract was evaluated in TPA-induced mouse ear edema assay and in vitro cyclooxygenase (COX)-1 and COX-2 inhibitory activity was determined using EIA kits employing appropriate reference standards. Aajugarin I, lupulin A, withaferin A, reptoside and 6-deoxyharpagide were isolated from the 70% ethanolic extract by silica gel column chromatography. The 70% ethanol extract of whole plants of Ajuga bracteosa showed a significant (p<0.05) and dose-dependent anti-inflammatory activity in an acute inflammation model at the dose of 0.5 and 1.0 mg/ear. The extract also exhibited a strong in vitro COX-1 and COX-2 inhibitory activity at 25 and 50 μg/mL concentration. Among the isolated compounds 6-deoxyharpagide exhibited highest COX-2 inhibition while rest of the compounds exhibited weak to moderate COX-1 and COX-2 inhibition at 30 μM concentration. The results suggest that the 70% ethanol extract of Ajuga bracteosa possesses promising anti-inflammatory activity, which is possibly mediated through inhibition of COX-1 and COX-2 enzymes. The isolated constituents could be responsible in part for its anti-inflammatory and COX inhibitory activity. The study supports traditional use of Ajuga bracteosa for inflammatory diseases.

Synthesis and Biological Evaluation of 12-Aminoacylphorboids

Spurred by the paradoxical anti-inflammatory activity of some aminoacylphorbol derivatives, the naturally occurring and epimeric N,N-dimethylvalinoyl-4alpha-4-deoxyphorbol derivatives 3b and 3d have been prepared from 4alpha-4-deoxyphorbol (3e), a byproduct of the isolation of phorbol from Croton oil and a phorboid polyol so far largely overlooked in terms of biological activity. The configuration of the side chain stereocenter was confirmed for both natural products, and to investigate the side chain structure-activity relationships within this class of compounds, their corresponding N,N-dimethylglycinate (3g) and nor (3h) and di-nor derivatives (3i, 3j) were also prepared. By using a PKC-sensitive model of HIV-1 latency (activation of HIV- gene expression in Jurkat-LAT-GFP cells), it was found that both 3b and 3d can activate PKC-dependent responses, while a series of experiments with isoform-specific PKC inhibitors showed that these compounds target PKCalpha and -delta. Both N,N-dimethylation and the presence of side chain alpha-substitution were critical for activity. Selective PKC binding, rather than COX inhibition, might explain the paradoxical anti-inflammatory activity of extracts containing aminoacylphorboids in the mouse ear edema assay.

Oxepinamides A-C and fumiquinazolines H--I: bioactive metabolites from a marine isolate of a fungus of the genus Acremonium.

Three new oxepin-containing natural products (1-3) and two new fumiquinazoline metabolites (4-5) have been isolated from organic extracts of the culture broth and mycelia of an Acremonium sp., a fungus obtained from the surface of the Caribbean tunicate Ecteinascidia turbinata. The structures of the five compounds were determined through extensive analysis of 1D- and 2D-NMR data, and mass spectrometry. Compound 1 exhibited good anti-inflammatory activity in a topical RTX-induced mouse ear edema assay. Compounds 4 and 5 exhibited weak antifungal activity toward Candida albicans in a broth microdilution assay.

Dicarboxylic acid inhibitors of phospholipase A 2

Ten diacids were synthesized via a simple regio- and stereoselective aldol reaction. All of these compounds were good to excellent inhibitors of 14 kDa human platelet PLA 2, and many of these derivatives displayed activity in a phorbol-ester induced mouse ear edema assay. One of the new compounds reported here was selected for further development as a potential antipsoriasis agent.

Tolypodiol, an antiinflammatory diterpenoid from the cyanobacterium Tolypothrix nodosa.

A new diterpenoid, tolypodiol (1), has been isolated from the terrestrial cyanobacterium Tolypothrix nodosa (HT-58-2) and identified by NMR and mass spectral analysis. The monoacetate derivative 2 was prepared. Tolypodiol (1) and its monoacetate derivative 2 show potent antiinflammatory activity in the mouse ear edema assay.

Halogenated cannabinoid synthesis

A convenient synthesis of several tricyclic and bicyclic fluoro- and iodo analogs of cannabinoids has been reported. A new, mild methodology for the synthesis of vinyl fluorides from vinylstannanes has also been demonstrated. These C9 halo-functionalized cannabinoid analogs, along with (−) and (+)-Δ 9-THC carboxylic acids, were screened for anti-inflammatory activity in the mouse ear edema assay. It was interesting to find that both enantiomers of Δ 9-THC carboxylic acid were moderately active as anti-inflammatories. The bicyclic vinyl iodide ( 18C) also showed appreciable anti-inflammatory activity.

Antiinflammatory activity of naturally occurring flavone and flavonol glycosides

Our previous report demonstrated that certain flavonoid aglycones such as apigenin (flavone), quercetin, morin (flavonols), and biochanin A (isoflavone) showedin vivo antiinflammatory activityvia topical and oral routes of administration. As a continual study, the various flavonoid glycosides have been evaluated in mouse ear edema assay using archidonic acid or crotonoil as a inflammagen. Flavonoids were orally administered (2 mg/mouse) and ear edema inhibition was measured. Significant antiinflammatory activities were found especially in flavone and flavonol glycosides (15–19% inhibition) although the flavonoid derivatives tested showed less antiinflammatory activity than hydrocortisone or indomethacin. Chalcone and flavanone derivatives were not significantly active. And in general, flavonol glycosides of kaempferol-type were found to have a higher oral antiinflammatory activity than that of flavonol glycosides of quercetin-type in mice.

The Anti-Inflammatory Effects of Phenolic Dental Medicaments as Determined by Mouse Ear Edema Assay

The anti-inflammatory effects of phenolic dental medicaments were evaluated by mouse ear edema assay. p-Chlorophenol (PCP) inhibited edema when applied topically in dosages of 0.2 and 0.5 mg per site at 1 5 min before or 1.0 and 2.0 mg per site at 60 min after the application of croton oil. The inhibitory effects were also noted with eugenol, guaiacol, o-cresol, phenol and orally administered indomethacin (10 mg/kg). The involvement of the effects on prostaglandin biosynthesis in the anti-inflammatory effects of these compounds is discussed.

The anti-inflammatory effects of phenolic dental medicaments as determined by mouse ear edema assay.

The anti-inflammatory effects of phenolic dental medicaments were evaluated by mouse ear edema assay. p-Chlorophenol (PCP) inhibited edema when applied topically in dosages of 0.2 and 0.5 mg per site at 15 min before or 1.0 and 2.0 mg per site at 60 min after the application of croton oil. The inhibitory effects were also noted with eugenol, guaiacol, o-cresol, phenol and orally administered indomethacin (10 mg/kg). The involvement of the effects on prostaglandin biosynthesis in the anti-inflammatory effects of these compounds is discussed.