Induced Mouse Ear Edema Research Articles

Synthesis and Biological Evaluation of Novel Fusidic Acid Derivatives as Two-in-One Agent with Potent Antibacterial and Anti-Inflammatory Activity.

Fusidic acid (FA), a narrow-spectrum antibiotics, is highly sensitive to various Gram-positive cocci associated with skin infections. It has outstanding antibacterial effects against certain Gram-positive bacteria whilst no cross-resistance with other antibiotics. Two series of FA derivatives were synthesized and their antibacterial activities were tested. A new aromatic side-chain analog, FA-15 exhibited good antibacterial activity with MIC values in the range of 0.781–1.563 µM against three strains of Staphylococcus spp. Furthermore, through the assessment by the kinetic assay, similar characteristics of bacteriostasis by FA and its aromatic derivatives were observed. In addition, anti-inflammatory activities of FA and its aromatic derivatives were evaluated by using a 12-O-tetradecanoylphorbol-13-acetate (TPA) induced mouse ear edema model. The results also indicated that FA and its aromatic derivatives effectively reduced TPA-induced ear edema in a dose-dependent manner. Following, multiform computerized simulation, including homology modeling, molecular docking, molecular dynamic simulation and QSAR was conducted to clarify the mechanism and regularity of activities. Overall, the present work gave vital clues about structural modifications and has profound significance in deeply scouting for bioactive potentials of FA and its derivatives.

Anti-nociceptive, anti-inflammatory and antipyretic activities of the ethanol root bark extract of Salacia lehmbachii in rats and mice

Background: The decoction of the roots of Salacia lehmbachi is used in traditional medicine for the treatment different diseases such as malaria pains diabetes and microbial infections.Methods: Phytochemical screening and oral acute toxicity tests were carried out on the ethanol root extract of the plant. Anti-nocicetive activity using acetic acid induced writhing and tail immersion method in mice, anti-inflammatory activity using carrageenan induced paw oedema in rats and xylene induced ear oedema test in mice and antipyretic activity using Brewer’s yeast and D-amphetamine induced pyrexia in rats were determined at 50 mg/kg, 100 mg/kg and 200 mg/kg doses of the root extract.Results: The ethanol root extract contain alkaloids, saponins, tannins, flavonoids, terpenoids, steroids and cardiac glycosides. The oral acute toxicity tests was found to be greater than 5000 mg/kg. The root extract and the standard drug (Aspirin) significantly (p<0.05 and p<0.01) decreased the number of writhes caused by acetic acid. The extract and morphine significantly (p<0.05 and p<0.01) prolonged reaction time in tail immersion model. The extract produced significant (p<0.05 and p<0.01) dose dependent inhibition of oedema which was comparable to aspirin in carrageenan induced paw oedema model. The root extract also demonstrated significant (p<0.05 and p<0.01) effect in xylene induced mouse ear oedema test compared to dexamethasone. The extract significantly decreased high temperature in both Brewer’s yeast and d-amphetamine induced pyrexia.Conclusions: Findings show that S. lehmbachii may provide a good source of plant compounds with analgesic, anti-inflammatory and antipyretic activities.

Anti-inflammatory, antioxidant and antinociceptive activities of Russelia coccinea (L.) Wettst.

Some species of the Russelia genus have been used different illnesses associated with pain and inflammation. The aim of this work was to characterize the biological activities (anti-inflammatory and analgesic) and antioxidant capacity of methanol and dichloromethane extracts of Russelia coccinea. In this study, topical anti-inflammatory activity was tested in an in vivo model of 12-O-tetradecanoylphorbol acetate (TPA) induced mouse ear edema of organic extracts (doses: 0.03, 0.1 and 0.3 mg/ear). The antinociceptive activity was assessed using the formalin test in mice of organic extracts (doses: 56, 100 and 300 mg/kg). Moreover, the antioxidant capacity of the extracts was determined using 2, 2-diphenyl-1-picrylhydrazyl (DPPH), 2, 2'-azinobis (3-ethylbenzothiaziline-6-sulfonate) (ABTS) and ferric reducing antioxidant power (FRAP) assays. Methanol (RcM) and dichloromethane (RcD) extracts of the R. coccinea aerial parts were found to inhibit ear edema (48.95 and 40.13%, respectively) at a dose of 0.3 mg/ear. Acute treatment with RcM produced a significant antinociceptive effect in the late phase of formalin-induced nociception. Moreover, RcM at doses of 56, 100 and 300 mg/kg showed a significant antinociceptive effect through the early and late phases in the formalin test. RcM and RcD showed weak antioxidant capacities in the ABTS and DPPH assays; however, when their reducing capacity was evaluated by the FRAP assay, RcM showed a reducing activity similar to Camellia sinensis standard at the proven concentration of 1000 μg/ml. According to the experimental findings, the organic extracts of R. coccinea display remarkable antinociceptive and anti-inflammatory activities.

Design, synthesis and biological evaluation of novel benzoxaborole derivatives as potent PDE4 inhibitors for topical treatment of atopic dermatitis.

In this work, a series of structurally novel benzoxaborole derivatives were designed, synthesized and biologically evaluated as PDE4 inhibitors for battling atopic dermatitis (AD). Among them, the majority exhibited superior PDE4B inhibitory activities to that of the lead compound Crisaborole, an approved PDE4 inhibitor. In particular, 72, the most potent PDE4B inhibitor throughout this series, displayed 136-fold improved enzymatic activity (IC50=0.42nM) as compared to Crisaborole (IC50=57.20nM), along with favorable isoform specificity. In the phorbol ester (PMA)-induced mouse ear oedema model, 72 exerted remarkably greater efficacy than Crisaborole at the same dosage (P<0.05). Moreover, the ointment of 72 exerted dramatically enhanced therapeutic potency than the ointment of Crisaborole (P<0.05) in the calcipotriol-induced mouse AD model. In addition to the potent invitro and invivo activity, 72 displayed favorable safety in the repeated oral dose toxicity study and did not exhibit phototoxicity. With the above attractive biological performance, 72 is worthy of further functional investigation as a novel anti-AD therapeutic agent.

Investigation of Modulatory Effect of Pinolenic Acid (PNA) on Inflammatory Responses in Human THP-1 Macrophage-Like Cell and Mouse Models.

Pinolenic acid (PNA) is a rare n-6 polyunsaturated fatty acid (n-6 PUFA) originally identified in pine seeds. Previous studies demonstrated that PNA and its elongation metabolite, Δ7-eicosatrienoic acid (Δ7-ETrA), exerted an anti-inflammatory effect in cultured cells by suppressing prostaglandin E2 (PGE2) production. The objective of this study was to further examine the in vivo anti-inflammatory properties of PNA. Using human THP-1 macrophage, we first confirmed that incorporation of PNA into cellular phospholipids suppressed the production of interleukin-6 (IL-6) (by 46%), tumor necrosis factor-α (TNF-α) (by 18%), and prostaglandin E2 (PGE2) (by 87%), and the expression of type-2 cyclooxygenase (COX-2) (by 27%). Furthermore, we demonstrated that injection of PNA or Δ7-ETrA suppressed 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema, as measured by ear thickness (by 15%) and biopsy weight (by up to 29%). Both PUFA also lowered proportions of infiltrated leukocytes, neutrophils, and macrophages using flow cytometric analysis. Topical application of PNA or Δ7-ETrA on mouse back skin suppressed TPA-induced pro-inflammatory mediator production, including IL-1β, IL-6, TNF-α, and PGE2, as well as the phosphorylation of p38- and JNK-mitogen-activated protein kinase (MAPK), but not that of ERK-MAPK. That no PNA or Δ7-ETrA was detected in the ear disc after the PUFA injection suggests that their anti-inflammatory effect might not be due to fatty acid incorporation, but to modulation of cell signaling. In conclusion, PNA and Δ7-ETrA exerted the in vivo anti-inflammatory effect by suppressing mouse ear edema and dorsal skin inflammation.

마우스 귀 부종 동물모델에서 진피 추출물의 항염증 효능 평가

마우스 귀 부종 동물모델에서 진피 추출물의 항염증 효능 평가

The biological evaluation of fusidic acid and its hydrogenation derivative as antimicrobial and anti-inflammatory agents.

BackgroundFusidic acid (FA) (WU-FA-00) is the only commercially available antimicrobial from the fusidane family that has a narrow spectrum of activity against Gram-positive bacteria.MethodsHerein, the hydrogenation derivative (WU-FA-01) of FA was prepared and both compounds were examined against a panel of six bacterial strains. In addition, their anti-inflammatory properties were evaluated using a 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema model.ResultsThe results of the antimicrobial assay revealed that both WU-FA-00 and WU-FA-01 displayed a high level of antimicrobial activity against Gram-positive strains. Moreover, killing kinetic studies were performed and the results were in accordance with the minimum inhibitory concentration and minimum bactericidal concentration results. We also demonstrated that the topical application of WU-FA-00 and WU-FA-01 effectively decreased TPA-induced ear edema in a dose-dependent manner. This inhibitory effect was associated with the inhibition of TPA-induced upregulation of proinflammatory cytokines IL-1β, TNF-α, and COX-2. WU-FA-01 significantly suppressed the expression levels of p65, IκB-α, and p-IκB-α in the TPA-induced mouse ear model.ConclusionOverall, our results showed that WU-FA-00 and WU-FA-01 not only had effective antimicrobial activities in vitro, especially to the Gram-positive bacteria, but also possessed strong anti-inflammatory effects in vivo. These results provide a scientific basis for developing FA derivatives as antimicrobial and anti-inflammatory agents.

Antifungal, Anti-Inflammatory and Cytotoxic Effects of &lt;i&gt;Zingiber cassumunar&lt;/i&gt; Gel

This study aimed to investigate the antifungal, anti-inflammatory and cytotoxic effects of Zingiber cassumunar gel. The gel was prepared from essential oil of Zingiber cassumunar rhizome by the Thailand Institute of Scientific and Technological Research. Antifungal activity of the gel was firstly determined by the well diffusion method against Candida albicans ATCC 10238 and candida strain isolated from the patient’s lesion. Then, the Agar overlay technique was used to test the cytotoxicity of Z. cassumunar gel on mouse fibroblasts (ATCC clone 929) according to ISO 7405. For anti-inflammatory effect of the gel, TPA (carrageenan lambda type IV, 12-O-tetradecanoylphorbol-13- acetate)-induced mouse ear edema method was used. The results of well diffusion showed that Z. cassumunar gel was quite a potent antifungal agent against both strains of tested C. albicans with inhibition zones of 12-13 mm. In the cytotoxicity test, the gel exhibited no toxicity to cell culture. In addition, topical administration of Z. cassumunar gel could decrease mouse ear edema induced by TPA. At 30 and 60 min-time points, Z. cassumunar gel showed higher anti-inflammatory activity than triamcinolone which was used as reference anti-inflammatory drug. In conclusion, gel prepared from Z. cassumunar oil showed antifungal activity against both strains of C. albicans. In addition, its anti-inflammatory effect was demonstrated within 30 min by the TPA-induced mouse ear edema model. The gel was non-toxic to cell culture after 24-h incubation. Further studies are needed to clarify the safety and benefit of this gel for clinical use in the treatment of candidal infection and inflammation.

A screening of plants used in Colombian traditional medicine revealed the anti-inflammatory potential of Physalis angulata calyces.

The use of natural products by communities from the Colombian Caribbean region to treat health issues, together with biodiversity and geographical features, constitute a great scenery to develop new therapies based on ethnopharmacological heritage. Here, we investigated the anti-inflammatory potential of 10 commonly used plants in Colombian folk medicine, evaluating their effect on nitric oxide (NO) production by LPS-stimulated RAW 264.7 macrophages. The most active plant was evaluated in vivo using 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced mouse ear edema, along with its effect on the production of pro-inflammatory mediators in vitro. The extract of Physalis angulata L. calyces showed the highest activity. This extract was fractionated and its dichloromethane fraction (DF) was the most active in vitro, inhibiting the production of NO, prostaglandin E2 (PGE2), interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α and monocyte chemotactic protein (MCP)-1 (CCL2). In vivo, DF showed a significant inhibition of ear edema and myeloperoxidase (MPO) activity, with evident reduction of the leukocyte infiltration into tissue. Our results support the ethnopharmacological use of the selected plants in folk medicine. P. angulata dichloromethane fraction represents a promising source of pharmacological compounds with great potential therapeutic use to treat inflammatory illness.

Comparison of the anti-inflammatory effects of Sinapis alba and Brassica juncea in mouse models of inflammation

BackgroundSinapis Semen is derived from the dried mature seeds of Sinapis alba L. or Brassica juncea (L.) Czern. et Coss. Traditionally, the seeds from S. alba are called “White Sinapis Semen” while those from B. juncea are called “Yellow Sinapis Semen”. PurposeThe present study aimed to compare the chemical composition and the anti-inflammatory effects of 50% aqueous ethanol extracts of the White Sinapis Semen (EWSS) and Yellow Sinapis Semen (EYSS) using both acute (12-O-tetradecanoylphorbol-acetate (TPA)- and arachidonic acid (AA)-induced mouse ear edema) and chronic (multiple applications of croton oil (CO)) inflammatory models. MethodsThe anti-inflammatory effects of EWSS and EYSS were determined by measuring the ear thickness and myeloperoxidase (MPO) activity. The anti-inflammatory mechanism was explored by measuring the protein and mRNA levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6 in the ear of the TPA-treated mice. ResultsThe results showed that both EWSS and EYSS significantly decreased the ear thickness in both the TPA- and AA-induced acute models, as well as in the CO-induced chronic model. In addition, EWSS and EYSS could markedly inhibit the MPO activity in the ears of TPA-, AA- or CO-treated mice. Moreover, EWSS and EYSS also remarkably inhibited the protein and mRNA levels of TNF-α and IL-6 in the ears of TPA-treated mice. Comparatively, EWSS exerted more potent anti-inflammatory effect than that of EYSS. ConclusionOur results revealed that both EWSS and EYSS are effective anti-inflammatory agents against acute and chronic inflammatory processes, and EWSS possess more potent anti-inflammatory effect than EYSS. The anti-inflammatory effect of the two herbs may be mediated, at least in part, by suppressing the mRNA expression of a panel of inflammatory mediators including TNF-α, IL-6 and IL-1β.

Effect of Pterospermum acerifolium Willd on Inflammation and ProInflammatory Cytokines

In our present study, the effect of alcoholic fraction of Pterospermum acerifolium seeds on inflammation and inflammatory cytokines was evaluated in-vitro by using human peripheral blood mononuclear cells (PBMCs) and in vivo by croton oil induced mouse ear edema (acute study) and Carrageen induced rat paw edema. The extract exhibited significant inhibition of the production of tumor necrotic factor- and interleukin-6 by PBMCs stimulated lipropolysaccirides (LPS) in a dose dependent manner. The extract, at the selected dose of 150 and 300mg/kg body weight per oral exhibited significant dose dependent anti-inflammatory response with 27.77% and 47.17% inhibition of inflammation in croton oil induced mouse ear edema and Carrageen induced rat paw edema respectively.

Anti-Inflammatory Activity and Cheminformatics Analysis of New Poten t 2-Substituted 1-Methyl-5-Nitroindazolinones.

After the identification of the anti-inflammatory properties of VA5-13l (2-benzyl-1- methyl-5-nitroindazolinone) in previous investigations, some of its analogous compounds were designed, synthesized and evaluated in two anti-inflammatory methods: LPS-enhanced leukocyte migration assay in zebrafish; and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema. The products evaluated (3, 6, 8, 9 and 10) showed the lower values of relative leukocyte migration at 30 &#181;M (0.14, 0.07, 0.10, 0.13 and 0.07, respectively), while in ear edema and myeloperoxidase activity methods, all the compounds reduced inflammation, only 4 and 16 yielded unsatisfactory results. The relationship linking structure and activity (SAR analysis) was determinate by using SARANEA software. The importance of the 5-Nitro group of the indazole ring for the activity was evident, and showed modest reduction when benzyl (Bn) is changed by alkyl group. A substituted Bn moiety at N2 (R) is the best substituent (5-10); nevertheless, if methylene group of Bn is deleted, the activity is affected. Also, introduction of halogen atoms mainly at positions 3 or 4 of the benzyl moiety (6 and 10) leads in general to strong activities. In fact, compounds 7 and 8 (R = 4-FBn or 4-ClBn, respectively) exhibit satisfactory results in in vivo tests and appear promising. The production of IL-6 at all doses assayed was significantly reduced, except with 16. Nonetheless, the production of TNF-α was significantly inhibited only by this chemical (16) at concentration of 50 μM. On the other hand, compound 2 was the one that mostly inhibited the expression of COX-2 and iNOS. From these results, it can be concluded that the inhibition in the release of cytokines can be one of the mechanisms of action responsible for the anti-inflammatory effect for 2-benzyl derivates while other 2-alkyl derivatives can inhibit production of NO. Therefore, nitroindazolinone chemical prototype could be an interesting structural group with anti-inflammatory purposes in the therapeutic.

Antiedematogenic Effect of ?-Phellandrene in Animal Models

α-phellandrene antiedematogenic effect (α-Phel) was evaluated in carrageenan, histamine, prostaglandin and substance P induced paw edema and croton oil, TPA and arachidonic acid induced ear edemain mice. Experimental protocols were approved by Ethical Committee for Animal Experimentation (CEEA/UFPI, Protocol Nº 010/2011). α-Phel (100 and 200 mg.kg-1, p.o.) reduced carrageenan and prostaglandina (40.97 % and 61.41 %, respectively) induced paw edema, in doses 50, 100 e 200 mg.kg-1, p.o. reduced histamina induced paw edema formation (31.27 %; 45.14 % e 47.29 %, respectively); on substance P induced paw edema the inhibition occurred when the animal were treated with 200 mg.kg-1 of α-Phel, p.o. (44.05 %).When administered topically, α-Phel (0.2 e 0.4 mg/ear) reduced croton oil (57.34 % e 62.42 %, respectively), TPA (48.29 % e 62.10 %, respectively)and arachidonic acid(0.4 mg/ear) induced ear edema (29.55 %).α-Phelpresents antiedematogenic activity in acute inflammation models. Keywords: Monoterpene, α-Phellandrene, anti-inflammatory activity, edema.

Anti-inflammatory Effects of Novel Polysaccharide Sacran Extracted from Cyanobacterium Aphanothece sacrum in Various Inflammatory Animal Models.

The goal of this study was to investigate the topical anti-inflammatory effects of the megamolecular polysaccharide sacran extracted from cyanobacterium Aphanothece sacrum using various inflammatory animal models. Sacran showed potent anti-inflammatory effects with optimum effective concentrations at 0.01 and 0.05% (w/v). Sacran markedly inhibited paw swelling and neutrophil infiltration in carrageenan-induced rat paw edema. Additionally, 6,7-dimethoxy-1-methyl-2(1H)-quinoxalinone-3-propionyl-carboxylic acid (DMEQ)-labeled sacran had the ability to penetrate carrageenan-induced rat paw skin rather than normal skin. Also, sacran significantly suppressed kaolin-induced and dextran-induced rat paw edema throughout the duration of the study. Furthermore, sacran significantly suppressed 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema and mRNA expression levels of cyclooxygenase (COX)-2 as well as pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6. Safety of sacran solution was verified by negligible cytotoxicity in HaCaT cells. These results suggest that sacran may be useful as a therapeutic agent against inflammatory skin diseases with no life-threatening adverse effects.

Scientific Assessment Of The Anti-Inflammatory And Wound Healing Potential Of Campanula Lyrata Subsp. Lyrata, A Turkish Folk Remedy

The aim of the present study is to evaluate the anti-inflammatory and wound healing activities of the extracts prepared from the aerial parts of Campanula lyrata Lam. subsp. lyrata (Campanulaceae) by using in vivo methods in order to confirm the traditional utilization. n-Hexane, diethyl ether, ethyl acetate (EtOAc), methanol (MeOH) and aqueous extracts were separately prepared from the air-dried and powdered plant materials. Carrageenan-, and serotonin- induced hind paw edema, 12-Otetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema and acetic acid-induced increase in capillary permeability models were employed in mice for the anti-inflammatory activity assessment. Wound-healing activity was investigated by using incision and excision wound models along with hydroxyproline determination and histopathological analyses. MeOH extract displayed significant antiinflammatory effect in the carrageenan- and serotonin- induced hind paw edema model and in acetic acidinduced increase in capillary permeability model with the values of 25.3, 27.8 and 31.8%, respectively. MeOH extract was also found to have significant wound healing potential in the incision and excision wound models with the values of 26.9 and 39.6%, respectively. MeOH extract ointment treated group tissues also showed enhaced hydroxyproline content. The present study confirms the anti-inflammatory

Fatty acid composition and preclinical resarches on Anthemis wiedemanniana Fisch. & Mey.: Discovery of a new anti-inflammatory agent.

Background:Anthemis species have been used for the treatment of gastrointestinal disorders, hemorrhoid, stomachache and inflammatory diseases in Turkish folk medicine. Anthemis wiedemanniana Fisch. And Mey. is an endemic plant used as painkiller, antispasmodic, sedative and for the treatment of urinary inflammations.Objective:The objective of the present study is to evaluate the anti-inflamatory activity of the extracts of A. wiedemanniana by using in vivo methods.Materials and Methods:Carrageenan-, PGE2- and serotonin-induced hind paw edema, 12-O-tetradecanoyl-13-acetate (TPA)-induced mouse ear edema and acetic acid-induced increase in capillary permeability models were used for the anti-inflammatory activity assessment. Moreover, the fatty acid composition of A. wiedemanniana was investigated by gas chromatography (GC).Results:n-Hexane, diethyl ether and total sesquiterpene lactone extracts exhibited significant inhibition in carrageenan-induced hind paw edema and acetic acid-induced increase in capillary permeability model. n-Hexane and total sesquiterperne lactone extracts showed anti-inflammatory activity in PGE2- and serotonin-induced hind paw edema model. However none of the extracts displayed significant activity in TPA-induced ear edema model in mice. C4:0 (Buthyric acid), C20:0 (Arachidic acid) and C16:1 (Palmitoleik acid) were found to be the major fatty acids in these species. Saturated fatty acids (SFA) were found in higher amounts than monounsaturated fatty acids and polyunsaturated fatty acids. SFAs were determined as 63.17%, UFAs as 20.89% and PuFAs as 15.95%.Conclusion:This study confirms the traditional usage of A. wiedemanniana for inflammatory diseases.

Anti-inflammatory R-prostaglandins from Caribbean Colombian soft coral Plexaura homomalla

This study aims to evaluate the effect of prostaglandins isolated from soft coral Plexaura homomalla, collected in Colombian Caribbean Sea, on in vivo and in vitro inflammation models. Extracts from P. homomalla were fractionated and sequentially chromatographed to obtain the prostaglandins: (15R)-PGA2 (1), (15R)-PGA2 -Me (2), (15R)-O-Ac-PGA2 (3), (15R)-O-Ac-PGA2 -Me (4) and (15R)-PGE2 (5) in addition to three semi-synthetic prostaglandins obtained by transformations of the natural products. The anti-inflammatory properties of natural and semi-synthetic compounds were determined in vivo using 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear oedema model and in vitro leucocyte degranulation, myeloperoxidase (MPO) and elastase enzymatic activities from human polymorphonuclear cells (PMNs). The cell viability was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. In the in vivo assay, (15R)-PGE2 (1) and (15R)-O-Ac-PGA2 (3) showed anti-inflammatory activity, as well as in vitro inhibition of elastase release from PMNs. In the PMNs degranulation assay, (15R)-PGE2 (5), was the most active compound in the inhibition of MPO release. Finally, all the tested prostaglandins showed moderate inhibition for elastase enzyme activity, whereas none of the prostaglandins exhibit significative inhibition on MPO activity. (15R)-PGE2 (1) and (15R)-O-Ac-PGA2 (3) present significant inhibition on three important events related to the topical inflammatory response induced by TPA: the oedema formation, the PMNs degranulation, events that modulate MPO and elastase levels at inflammation site, and the inhibition of the enzyme activity.

In vivo anti-inflammatory properties of aerial parts of Nasturtium officinale

Context: Nasturtium officinale R. Br. (watercress) has long been used in Iranian folk medicine to treat hypertension, hyperglycemia, and renal colic. Moreover, anticancer, antioxidant, and hepatoprotective properties of N. officinale have been reported.Objective: In this study, anti-inflammatory activity of the hydro-alcoholic extract from aerial parts of N. officinale was investigated.Materials and methods: Oral administration of the hydro-alcoholic extract of N. officinale (250, 500 and 750 mg kg−1) was investigated on two well-characterized animal models of inflammation, including carrageenan- or formalin-induced paw edema in rats. Then, the topical anti-inflammatory effect of N. officinale (2 and 5 mg/ear) was studied on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema. Finally, biopsy of the paw or ear was performed for pathological evaluation.Results: Acute toxicity tests of N. officinale in rats established an oral LD50 of >5 g kg−1. The extract of watercress (250, 500 and 750 mg kg−1) significantly inhibited carrageenan-induced paw edema 1, 2, 3 and 4 h after carrageenan challenge (p < 0.001). The extract (500 mg kg−1) also showed considerable activity against formalin-evoked paw edema over a period of 24 h (p < 0.001). Furthermore, topical application of N. officinale (5 mg/ear) reduced TPA-induced ear edema (p < 0.05). Histopathologically, the extract decreased swelling and the tissue damage induced by carrageenan or TPA.Discussion and conclusion: Our findings indicate potent anti-inflammatory activity of N. officinale in systemic and topical application and propose its potential as an anti-inflammatory agent for treatment of inflammatory conditions.

Mechanisms by Which Licochalcone E Exhibits Potent Anti-Inflammatory Properties: Studies with Phorbol Ester-Treated Mouse Skin and Lipopolysaccharide-Stimulated Murine Macrophages

In this study we found that licochalcone E (LicE), a recently isolated retrochalcone from Glycyrrhiza inflata, exhibits potent anti-inflammatory effects in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema and lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophage models. Topical application of LicE (0.5–2 mg) effectively inhibited TPA-induced (1) ear edema formation; (2) phosphorylation of stress-activated protein kinase/c-Jun-N-terminal kinase (SAPK/JNK), c-Jun, and extracellular signal regulated kinase 1/2; and (3) expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 proteins in mouse skin. The treatment of RAW 264.7 cells with LicE (2.5–7.5 μmol/L) induced a profound reduction in LPS-induced (1) release of NO and prostaglandin E2; (2) mRNA expression and secretion of interleukin (IL)-6, IL-1β and tumor necrosis factor-α; (3) promoter activity of iNOS and COX-2 and expression of their corresponding mRNAs and proteins; (4) activation of AKT, p38 mitogen activated protein kinase (MAPK), SAPK/JNK and c-Jun; (5) phosphorylation of inhibitor of κB (IκB) kinase-αβ and IκBα, degradation of IκBα, translocation of p65 (RelA) to the nucleus and transcriptional activity of nuclear factor (NF)-κB; and (6) transcriptional activity of activator protein (AP)-1. These results indicate that the LicE inhibition of NF-κB and AP-1 transcriptional activity through the inhibition of AKT and MAPK activation contributes to decreases in the expression of pro-inflammatory cytokines and the inducible enzymes iNOS and COX-2.

Synthesis and Anti-inflammatory Activity of Novel Furochromenes

A series of variously substituted furochromenes, hemiacetals 2, acetals 3, and rearranged compounds 4, were synthesized from variously substituted 4-hydroxycoumarins and evaluated in several in vitro assays, inhibition of mast cell degranulation induced by the activation of Fce receptor type I or calcium ionophore and leukotriene B4 (LTB4) inhibition. The most active derivatives, 3p and 4p (8-iso-propyl substitution in coumarin ring) and 3r (5-methyl-8-chloro substitution), showed significant inhibition of mast cell degranulation (Fctriggered) and LTB4, and exhibited significant local anti-inflammatory activity in PMA induced ear edema in CD1 mice, with potency equal (compounds 3p and 4p) or better (compound 3r) in comparison with zileuton, a reference drug used. It might be a promising direction for developing novel drugs as potential agents for the treatment of allergies and other inflammatory diseases.(doi: 10.5562/cca2240)