Carrageenan-induced Rat Paw Inflammation Research Articles

Analgesic and anti-inflammatory activities of NPK 500 capsules, a Cassia sieberiana DC. - Based herbal analgesic medicine used to treat dysmenorrhea and peptic ulcer, is mediated through the inhibition of PGE2 and iNOS

Ethnopharmacological relevancePain and inflammation are the most frequent reasons for which people seek medical care. Currently available analgesics against these conditions produce fatal adverse effects. NPK 500 capsules is an alternative herbal analgesic employed to treat dysmenorrhea, peptic ulcer and pain. NPK 500 is produced from Cassia sieberiana. A plant used in traditional medicine to treat pain and inflammation. Aim of the studyThis study reports the analysis, phytochemical characterization and mechanism of analgesic and anti-inflammatory activities of two NPK 500 capsules, called old and new NPK500 capsules (ONPK500 and NNPK500) respectively. Materials and methodsPhysicochemical, organoleptic, GC-MS and LC-MS methods were employed to analyze the NPK 500 capsules. Analgesic activity was evaluated using tail immersion, Randall-Selitto and acetic acid induced writing tests. Anti-inflammatory activity was evaluated using carrageenan-induced rat paw inflammation. Additionally, pro-inflammatory mediators such as prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS), cyclooxygenase 1 and 2 (COX-2 and COX-1) were quantified in the sera of the rats using Enzyme Linked Immunosorbent Assay (ELISA) kits. ResultsThirteen major compounds were characterized in the NNPK 500 capsules via the GC-MS and LC-MS spectroscopies. Kaempferol was the major compound characterized in addition to physcion, β-sitosterol 3-O-β-D-glucopyranoside, betulinic acid and nine others. Physicochemical and organoleptic indices of the capsules were also derived for its authentication and quality control. Furthermore, NNPK 500 0.5–1.5 mg/kg p.o. produce significant (P < 0.5) analgesic activity (160–197%) higher than that of ONPK500 (109.8%) and Morphine (101%) in the tail immersion test. The analgesic activity of NNPK 500 0.5–1.5 mg/kg p.o. (171.0–258.3%) and ONPK 500 (179.5%) were also significant (P < 0.01) and higher than that of Aspirin (103.00%) in the Randall-Selitto test. Both capsules also demonstrated significant (P < 0.5) analgesic and anti-inflammatory activities in the acetic acid-induced writhing and carrageenan-indued paw edema tests respectively. The two NPK500 capsules also, significantly (P < 0.5) inhibited PGE2 and iNOS but not COX-2 and COX-1 in the carrageenan-indued paw edema test. ConclusionThese results show that NNPK 500 and ONPK 500 capsules possessed potent analgesic and anti-inflammatory activities via inhibition of PGE2 and iNOS as a result of their chemical constituents. NPK500 capsules thus, relief acute pain and inflammation without causing gastrointestinal, renal or hepatic injuries, since they did not inhibit COX-1.

Fucoidan from Ericaria crinita Alleviates Inflammation in Rat Paw Edema, Downregulates Pro-Inflammatory Cytokine Levels, and Shows Antioxidant Activity.

Fucoidans are sulfated polysaccharides detected mainly in the cell walls of brown seaweeds. Here, we examined the effects of single doses of fucoidan derived from Ericaria crinita (formerly Cystoseira crinita) on carrageenan-induced paw inflammation in rats. The serum levels of TNF-α, IL-1β, IL-6, and IL-10 of rats with LPS-induced systemic inflammation after 14 days of treatment were also evaluated. Subchronic treatment with fucoidan from E. crinita attenuated the inflammation during the late phase of the degraded carrageenan-induced paw edema (3rd to 5th hour after carrageenan injection) with peak activity at the 3rd hour after the application. Both doses of fucoidan from E. crinita (25 and 50 mg/kg bw) significantly decreased the levels of all tested pro-inflammatory cytokines (IL-1β, TNF-α, and IL-6) in the serum of rats with a model of system inflammation but had no effect on the anti-inflammatory cytokine IL-10. The results showed that the repeated application of fucoidan has a more prominent effect on the levels of some pro-inflammatory cytokines in serum in comparison to a single dose of the sulfated polysaccharide. This reveals the potential of E. crinita fucoidan as an anti-inflammatory agent. Furthermore, E. crinita fucoidan exhibited in vitro antioxidant capacity, determined by 2,2-diphenyl-1-picryl-hydrazyl radical scavenging and ferric reducing antioxidant power assays as follows: IC50 = 412 µg/mL and 118.72 μM Trolox equivalent/g, respectively.

Anti-Pyretic, Analgesic, and Anti-Inflammatory Activities of Meloxicam and Curcumin Co-Encapsulated PLGA Nanoparticles in Acute Experimental Models.

Herein, we evaluated the in vivo effects of meloxicam and curcumin co-encapsulated PLGA nanoparticles in experimental acute models of pyrexia, nociception, and inflammation. Seven groups (n = 6) were designed for each investigation and pretreated intraperitoneally (i.p.): the control group, meloxicam (4 mg/kg b.w.), curcumin (15 mg/kg b.w.), and equivalent content containing PLGA capped nanoparticles of meloxicam (Mlx-NP) and curcumin (Cur-NP) alone and in combination (Mlx-Cur-NP; at two doses). The results showed that PLGA encapsulation significantly (p ≤ 0.05) improved the in vivo activities of each compound. Furthermore, co-encapsulation of meloxicam and curcumin potentiated the anti-pyretic effect on yeast-induced pyretic rats, anti-nociceptive effect on nociception induced in rats by formalin and heat, and anti-edematogenic activity in xylene-induced ear edema in rats in a dose-dependent manner. In carrageenan-induced paw inflammation in rats, meloxicam and curcumin co-loading (Mlx-Cur-NP) resulted in significant (p ≤ 0.05) inhibition of paw inflammation, reduction in TNF-α and PGE2 levels, downregulation of expressions of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6), as well as a decrease in histopathological changes and TNF-α immunoexpression in paw tissues. Moreover, Mlx-Cur-NP demonstrated noteworthy potentiation in pharmacological effects compared to free compounds and mono-compound-loaded nanoparticles. Thus, the association of meloxicam with curcumin in a biodegradable nanocarrier system could provide a promising anti-pyretic, anti-nociceptive, and anti-inflammatory therapeutic approach for acute conditions.

Vortioxetine as an analgesic in preclinical inflammatory pain models: Mechanism of action.

Vortioxetine is a novel atypical antidepressant with multimodal activity that has recently demonstrated efficacy against neuropathic pain. There is no published data about its analgesic properties in models characterized by peripheral inflammation and consequent pain pathway sensitization, nor data on its mechanism of antinociceptive action. This study aimed to investigate vortioxetine's antinociceptive/antihyperalgesic effects in trigeminal, visceral, and somatic inflammatory pain models, and provide evidence on its mechanism of action in the modulation of trigeminal nociception. Vortioxetine's effects on the nociceptive behavior in orofacial formalin test (OFT) and acetic acid-writhing test in mice and on mechanical hyperalgesia in carrageenan-induced paw inflammation in rats were examined following peroral single administration. The involvement of serotonergic/adrenergic/cholinergic/cannabinoid/adenosine receptors was evaluated in OFT by intraperitoneally treating mice with an appropriate antagonist immediately after vortioxetine application. We used antagonists of 5-HT1B/1D serotonergic (GR 127935), α1 -adrenergic (prazosin), α2 -adrenergic (yohimbine), β1 -adrenergic (metoprolol), muscarinic (atropine), α7 nicotinic (methyllycaconitine), CB1 /CB2 cannabinoid (AM251 and AM630), and adenosine A1 (DPCPX) receptors. Vortioxetine dose-dependently reduced pain behavior in OFT and acetic acid writhing test, as well as inflammatory hyperalgesia in paw pressure test. All examined antagonists except prazosin dose-dependently inhibited vortioxetine's antinociceptive effects. In conclusion, vortioxetine exerted analgesic efficacy in trigeminal, visceral, and somatic inflammatory pain. The effect is at least in part mediated by 5-HT1B/1D serotonergic, α2 /β1 -adrenergic, muscarinic and nicotinic cholinergic, CB1 /CB2 cannabinoid, and adenosine A1 receptors. These findings contribute to better understanding of the analgesic effect of vortioxetine and suggest its potential usefulness for inflammatory pain treatment.

The study of antiexudative action of S-alkylated 1,3,4-oxadiazole-3-thionе derivatives

Несмотря на значительную популярность и эффективность нестероидных противовоспалительных препаратов (НПВП), а также их широкое использование в клинической практике, данная группа лекарственных средств характеризуется также большим количеством побочных эффектов, поэтому получение новых безопасных и эффективных НПВП является одним из приоритетных заданий для современной фармацевтической и медицинской химии. Цель работы – изучение противовоспалительной активности S-алкилированных производных 1,3,4-оксадиазол-2-тиола с фрагментом диклофенака в молекулах. Материалы и методы. Исследование антиэкссудативной активности соединений проводили на модели каррагенинового отека лап крыс, количественно эффект оценивали по показателям угнетения воспалительной реакции. Результаты. При проведении исследований идентифицировали ряд высокоактивных S-алкилированных производных 1,3,4-оксадиазол-2-тиола с антиэкссудативной активностью в пределах 42,4–44,6%, что соразмерно с эффектом эталонных лекарственных средств диклофенака натрия и кеторолака. Выводы. Полученные результаты свидетельствуют о выраженной антиэксудативной активности в ряду S-замещенных производных 1,3,4-оксадиазол-2-тиола, актуализируя вопросы изучения данного класса гетероциклических соединений.

Maprotiline inhibits COX2 and iNOS gene expression in lipopolysaccharide-stimulated U937 macrophages and carrageenan-induced paw edema in rats.

Maprotiline, a tetracyclic antidepressant, is used for the management of mental disorders and various types of chronic pain. In our previous work, we found the inhibitory effect of maprotiline on inflammatory mediator’s expression like tumor necrosis factor α (TNF-α and interleukin 1β (IL-1β. As part of that study, we sought to evaluate the effect of maprotiline on the expression of some inflammatory mediators such as cyclooxygenases 2 (COX2) and inducible nitric oxide synthase (iNOS). For this reason we used an in vitro model system of lipopolysaccharide (LPS)-stimulated human U937 macrophages and also an in vivo model of carrageenan-induced paw edema in rats. We measured the expression of these genes by quantitative RT-real time PCR. The expression of COX2 and iNOS significantly decreased by maprotiline in U937 macrophages and carrageenan-induced paw inflammation in rats. Our finding also confirmed that intraperitoneal (i.p.) injection of maprotiline inhibited carrageenan-induced paw edema. Moreover, maprotiline significantly decreased the migration of polymorphonuclear (PMN) leukocytes to the site of inflammation. The results of the present study provide further evidence for the anti-inflammatory effect of maprotiline. This effect appears to be mediated by down regulation of inflammatory genes. Further studies are needed to evaluate the complex cellular and molecular mechanisms of maprotiline.

Anti-inflammatory activity of Tetragronula species from Indonesia.

Anti-inflammatory drugs inhibit inflammation, particularly those classified as nonsteroidal anti-inflammatory drugs (NSAIDs). Several studies have reported that propolis has both anti-ulcerogenic and anti-inflammatory effects. In this study, we investigated the bioactive compound and in vivo anti-inflammatory properties of both smooth and rough propolis from Tetragronula sp. To further identify anti-inflammatory markers in propolis, LC-MS/MS was used, and results were analyzed by Mass Lynx 4.1. Rough and smooth propolis of Tetragonula sp. were microcapsulated with maltodextrin and arabic gum. Propolis microcapsules at dose 25–200 mg/kg were applied for carrageenan-induced rat’s paw-inflammation model. Data were analyzed by one-way ANOVA and Kruskal–Wallis statistical tests. LC-MS/MS experiments identified seven anti-inflammatory compounds, including [6]-dehydrogingerdione, alpha-tocopherol succinate, adhyperforin, 6-epiangustifolin, deoxypodophyllotoxin, kurarinone, and xanthoxyletin. Our results indicated that smooth propolis at 50 mg/kg inhibited inflammation to the greatest extent, followed by rough propolis at a dose of 25 mg/kg. SPM and RPM with the dose of 25 mg/kg had inflammatory inhibition value of 62.24% and 58.12%, respectively, which is comparable with the value 70.26% of sodium diclofenac with the dose of 135 mg/kg. This study suggests that propolis has the potential candidate to develop as a non-steroid anti-inflammatory drug.

Phytochemical Screening and Anti-Inflammatory Effect of Marrubium vulgare L. Methanol Extract on Carrageenan-Induced Paw Inflammation in Rats

Background: The upward desire in using traditional medicine as a remedy for treatment of different diseases has led the scientists to be thoughtful on plants as alternative sources of conventional drugs. Methods: Herein, anti-inflammatory effects of Marrubium vulgare methanolic extract was evaluated in carrageenan- induced paw edema in rats through examining paw thickness, histological studies and myeloperoxidase activity (MPO). The antioxidant activity of M. vulgare extract and its phenolic and flavonoids content were evaluated by folin-Ciocalteau, and aluminum chloride colorimetric assay, separately. Results: The results showed that M. vulgare alleviated paw inflammation as indexed by reduction paw thickness (p<0.001) as well as MPO activity (p<0.001), which was associated with a marked decrease in tissue edema. Moreover, the extract RC50 value for DPPH and nitric oxide antioxidant activity was 177 µg/mL and 370.5 µg/ml, besides, the total phenolic and flavonoids were as 625 mg gallic acid equivalent and 1.62 g quercetin equivalent per 100 g of dried plant material. Conclusion: In the main, the observed anti-inflammatory and antioxidant properties of M. vulgare could be attributed to the high amounts of phenolic and flavonoid content identified in the extract.

ДІЯ ХОНДРОЇТИН СУЛЬФАТУ НА РІВЕНЬ ЦИТОКІНІВ ТА АКТИВНИХ ФОРМ КИСНЮ У СИРОВАТЦІ КРОВІ ЗА УМОВ КАРАГІНАН-ІНДУКОВАНОГО ЗАПАЛЕННЯ

Increase of concentration of pro-inflammatory cytokines (IL-1β, TNF-α) is fixed in blood serum at carrageenan-induced rat paw inflammation, as well as increase of the content of reactive oxygen species (superoxide radical, hydrogen peroxide). At introduction of the preparation on the basis of chondroitin sulfate the level of pro-inflammatory cytokines and reactive oxygen species in blood serum decreases, while the concentration of IL10 increases in 1,7 times concerning the group of animals with сarrageenan-induced inflammation.

ДІЯ ХОНДРОЇТИН СУЛЬФАТУ НА ГЛУТАТІОНОВУ СИСТЕМУ В СИРОВАТЦІ КРОВІ ПРИ КАРРАГІНАН-ІНДУКОВАНОМУ ГОСТРОМУ ЗАПАЛЕННІ

Increase of content of oxidized glutathione (GSSG) is fixed in blood serum at carrageenan-induced rat paw inflammation, as well as increase of the glutathione transferase activity. Upon the same experimental conditions, the level of reduced glutathione (GSH) and activity of glutathione peroxidase and glutathione reductase were decreased. All above mentioned indices was closer to control values in animals treated simultaneously with сarrageenan and drug on the basis of chondroitin sulfate.

Local and Systemic Profiles of Inflammatory Cytokines in Carrageenan-induced Paw Inflammation in Rats

ABSTRACTObjective: Carrageenan (CA)-induced edema has been described as highly reproducible model of acute inflammation. However, little is known about the cytokines attributed to the CA-induced inflammation. In this study, we aimed to investigate the local and systemic expression profiles of various inflammatory cytokines following the subplantar injection of CA in rats.Methodology: Acute inflammation was induced in male Wistar rats by subplantar injection of CA. Serum and paw tissue were examined for the level of 19 specific inflammatory cytokines using antibody array. Further, the CA-elicited level of key inflammatory cytokines, cytokine-induced neutrophil chemoattractant (CINC)-2, CINC-3, interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, were quantified by enzyme-linked immunosorbent assay (ELISA).Results: Edema was peaked 3 h postinjection of CA in hind paw. Among 19 specific cytokines profiled using antibody array, CA significantly (p < 0.05) elicited the levels of CINC-2, CINC-3, IL-1β, IL-6, β-NGF, TNF-α, and VEGF in paw tissue and that of CINC-2 and CINC-3 in serum. Consistently, levels of CINC-2, CINC-3, IL-1β, IL-6, and TNF-α in tissue and CINC-2 and CINC-3 in serum were upregulated in CA-treated rats when compared to control, quantified by ELISA.Conclusions: This study corroborates the distinct pattern of inflammatory cytokines involved during CA-induced acute inflammation. Furthermore, data provide new evidence on elevated expression of rat CXC chemokines: CINC-2 and CINC-3 at the site of inflammation as well as their significant reflection in the circulation, thereby suggesting their frontline role in CA-induced acute inflammation.

Anti-inflammatory activity of bartogenic acid containing fraction of fruits of Barringtonia racemosa Roxb. in acute and chronic animal models of inflammation

The fruits of Barringtonia racemosa are traditionally used in Indian medicine for the treatment of pain and inflammatory conditions. In this study, a fraction of ethyl acetate extract of fruits of B. racemosa (BREAF) was investigated for anti-inflammatory activity in experimental models of acute and chronic inflammation. Activity against acute inflammation was evaluated in inflammogens induced rat paw edema models. Whereas, effect in chronic inflammation was evaluated in cotton pellet granuloma and oxazolone induced delayed type hypersensitivity (DTH) model in mice. The BREAF exhibited dose dependent anti-inflammatory activity in both acute and chronic models at oral doses of 5, 10 and 20 mg/kg. BREAF inhibited both phases of carrageenan induced rat paw inflammation. The reduction in paw inflammation by BREAF was also evident in histamine and serotonin induced inflammation in rats. Effect of BREAF on DTH indicates inhibition of immune mediated inflammation. The reduction in cotton pellet granuloma by BREAF treatment shows inhibition of proliferative changes associated with chronic inflammation. Analysis of BREAF after chromatographic separations showed presence of bartogenic acid as a major constituent. Hence, it is proposed that anti-inflammatory effects of BREAF can be partially attributed to its bartogenic acid content. The minute doses at which this fraction shows anti-inflammatory effects emphasizes the need for further investigations on its efficacy in the immuno-inflammatory conditions.

Evaluation of the Anti-Inflammatory, Antioxidant and Immunomodulatory Effects of the Organic Extract of the Red Sea Marine Sponge Xestospongia testudinaria against Carrageenan Induced Rat Paw Inflammation.

Marine sponges are found to be a rich source of bioactive compounds which show a wide range of biological activities including antiviral, antibacterial, and anti-inflammatory activities. This study aimed to investigate the possible anti-inflammatory, antioxidant and immunomodulator effects of the methanolic extract of the Red Sea marine sponge Xestospongia testudinaria. The chemical composition of the Xestospongia testudinaria methanolic extract was determined using Gas chromatography-mass spectroscopy (GC-MS) analysis. DPPH (2, 2-diphenyl-1-picryl-hydrazyl) was measured to assess the antioxidant activity of the sponge extract. Carrageenan-induced rat hind paw edema was adopted in this study. Six groups of rats were used: group1: Control, group 2: Carrageenan, group 3: indomethacin (10 mg/kg), group 4–6: Xestospongia testudinaria methanolic extract (25, 50, and 100 mg/kg). Evaluation of the anti-inflammatory activity was performed by both calculating the percentage increase in paw weight and hisopathologically. Assessment of the antioxidant and immunomodulatory activity was performed. GC-MS analysis revealed that there were 41 different compounds present in the methanolic extract. Sponge extract exhibited antioxidant activity against DPPH free radicals. Xestospongia testudinaria methanolic extract (100 mg/kg) significantly decreased % increase in paw weight measured at 1, 2, 3 and 4 h after carrageenan injection. Histopathologically, the extract caused a marked decrease in the capillary congestion and inflammatory cells infiltrate. The extract decreased paw malondialdehyde (MDA) and nitric oxide (NO) and increased the reduced glutathione (GSH), glutathione peroxidase (GPx), and catalase (CAT) activity. It also decreased the inflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin-1 β(IL-1β) and IL-6. The results of this study demonstrated the anti-inflammatory, antioxidant, and immunomodulatory effects of the methanolic extract of the Red Sea sponge Xestospongia testudinaria (100 mg/kg).

Antinociceptive, anti-inflammatory and smooth muscle relaxant activities of the pyrrolo[3,4-d]pyridazinone derivatives: Possible mechanisms of action

The aim of this study was to evaluate the analgesic as well as anti-inflammatory activities of the new pyrrolo[3,4-d]pyridazinone derivatives. Moreover, the present study attempted to assess some of the mechanisms involved in the pharmacological activity of these compounds.In the previous studies it was shown that these compounds were highly active in the phenylbenzoquinone-induced ‘writhing syndrome’ test and had much lower activity in the hot plate, which indicates that mainly peripheral mechanisms of analgesia are involved in their effects.In these extended studies the analgesic activity of two tested compounds (4c, 4f) was confirmed in some animal models of pain. The studied compounds showed a significant and dose-related antinociceptive effect in the models of pain induced by formalin, capsaicin and glutamic acid. Both compounds decreased the edema formation and one of them (4c) attenuated mechanical hyperalgesia in carrageenan-induced paw inflammation in rats. Furthermore, both compounds inhibited cell migration, plasma exudation and nociceptive reaction in zymosan A-induced mouse peritonitis.In the subsequent studies, including experiments on isolated organs (ileum, trachea, aorta), radioligand assays and biochemical tests, it was demonstrated that analgesic and anti-inflammatory effects of the investigated structures are largely due to their competitive antagonism for histamine H1 receptor. The influence on the level of cAMP in inflammatory cells (shown in RAW 264.7 macrophages) and subsequent inhibition of cytokine (TNFα, IL-1β) release can also be one of the important mechanisms of their action. Moreover some additional mechanisms may also be involved in the eventual analgesic effect of tested pyrrolo[3,4-d]pyridazinone derivatives.

Systemic changes following carrageenan-induced paw inflammation in rats.

Carrageenan-induced paw edema has been described as a local and acute inflammatory process. In fact, little is known about the time course and systemic changes following a carrageenan injection. In this study, we examine the systemic changes that follow carrageenan injection in the paw. Acute inflammation was produced by subplantar injection of carrageenan in a hind paw of Sprague-Dawley rats. Saline was used in control rats. Paw volume was measured with a plethysmometer. The hot plate latency test was used to quantify antinociception. C-reactive protein (CRP) levels were measured with a sandwich enzyme immunoassay. Fibrinogen concentration was measured using the gravimetric method. Lung morphometric analysis was performed using an image processing package. Lungs and paws were also examined for tissue factor (TF) and proinflammatory cytokines expression by immunohistochemistry. We found diverse systemic changes including increased levels of acute phase proteins, such as CRP and fibrinogen, and a lung inflammatory process characterized by lung edema, fibrin deposition, and leukocyte infiltration. An elevated expression of TF, IL-6, IL-1β, and TNFα, was observed in paw and lung tissue sections by immunohistochemical methods. This study provides new evidence that a local carrageenan injection induces a systemic response.

Analgesic and anti-inflammatory activities of Piper nigrum L.

ObjectiveTo evaluate and compare the analgesic and anti-inflammatory activity of pure compound, piperine along with hexane and ethanol extracts of Piper nigrum L. fruit in mice and rats. MethodsThe analgesic activity was determined by tail immersion method, analgesy-meter, hot plate and acetic acid induced writhing test. While the anti-inflammatory activity was evaluated by carrageenan-induced paw inflammation in rats. ResultsPiperine at a dose of 5 mg/kg and ethanol extract at a dose of 15 mg/kg after 120 min and hexane extract at a dose of 10 mg/kg after 60 min exhibited significant (P<0.05) analgesic activity by tail immersion method, in comparison to ethanol extract at a dose of 10 mg/kg using analgesy-meter in rats. However, with hotplate method, piperine produced significant (P<0.05) analgesic activity at lower doses (5 and 10 mg/kg) after 120 min. A similar analgesic activity was noted with hexane extract at 15 mg/kg. However, in writhing test, ethanol extract significantly (P<0.05) stopped the number of writhes at a dose of 15 mg/kg, while piperine at a dose of 10 mg/kg completely terminated the writhes in mice. In the evaluation of anti-inflammatory effect using plethysmometer, piperine at doses of 10 and 15 mg/kg started producing anti-inflammatory effect after 30 min, which lasted till 60 min, whereas hexane and ethanol extracts also produced a similar activity at a slightly low dose (10 mg/kg) but lasted for 120 min. ConclusionsIt is concluded from the present study that Piper nigrum L possesses potent analgesic and anti-inflammatory activities.

Activation of AQP4, p66Shc and endoplasmic reticulum stress is involved in inflammation by carrageenan and is suppressed by argirein, a derivative of rhein

We investigated the effect of argirein on acute inflammation edema and examined that aquaporin 4 (AQP4), p66Shc and activating transcription factor (ATF-6) might be involved in carrageenan-induced rat paw inflammation and be reversed by argirein, rhein and indometacin, but not L-arginine. Inflammation was produced by carrageenan injected into rat paw and treated orally with argirein (100 mg/kg), rhein (100 mg/kg), L-arginine (100 mg/kg) or indometacin (5 mg/kg). Inflammatory oedema and biomarkers were examined. Swelling was reduced by argirein, rhein and indometacin; argirein was more effective than rhein at 1 h following medication. Activation of AQP4, p66Shc, ATF-6, NADPH oxidase subunits p22phox, gp91phox and matrix metalloproteinase 2 (P < 0.01) was significant and was suppressed by arginine, rhein and indometacin but not by l-arginine. Activated AQP4, endoplasmic reticulum stress and p66Shc were actively implicated in the inflammation and these were suppressed by argirein, and its activity is favorable due to synergism in combination with L-arginine.

Effect of centrally administered prostaglandin D2 and some prostaglandin synthesis inhibitors on carrageenan-induced paw oedema in rats

The putative modulatory role of central prostaglandins (PGs) on peripheral inflammation has been explored by investigating the effects of intracerebroventricularly (i.c.v.) administered PGD2, the major rodent brain PG, hydrocortisone, a phospholipase A2 inhibitor, and the cyclo-oxygenase inhibitors, paracetamol and mefenamic acid, on carrageenan-induced paw inflammation in rats. PGD2 produced a dose-related inflammation-augmenting effect, whereas hydrocortisone and the PG synthesis inhibitors, paracetamol and mefenamic acid, induced attenuation of the peripheral oedema. These findings confirm an earlier report from this laboratory which had indicated that central PGs may modulate peripheral inflammation and that conventional anti-inflammatory agents exert at least part of their effect by inhibiting central PG synthesis.

Proniosome based drug delivery system of piroxicam

Piroxicam is a widely used potent non-steroidal anti-inflammatory drug, with due potential for dermal delivery. Permeation of piroxicam from proniosome based reservoir type transdermal gel formulation across excised rat abdominal skin was investigated using Keshery Chein diffusion cell. There was considerable improvement in flux over the control gel formulation. The lipid vesicles were evaluated for entrapment efficiency and vesicle size of niosomes formed. It was observed that Span 60 based formulations produced vesicles of smallest size and higher entrapment efficiency while those of Span 80 produced vesicles of least entrapment efficiency. Incorporation of lecithin further enhanced entrapment efficiency. Proniosomes were prepared by conventional technique and employing maltodextrin and sorbitol as base. The morphology of the proniosomes was studied by scanning electron microscopy. Maximum flux achieved was 35.61 μg/cm2/h, an enhancement of 7.39 times was achieved for transdermal system based on proniosomal gel as compared to control gel. Anti-inflammatory studies revealed that proniosome based transdermal drug delivery system of piroxicam were promising carriers for delivery of piroxicam. There was significant reduction in carrageenan induced rat paw inflammation compared to control. Key words: Piroxicam, niosomes, permeation enhancement, dermal delivery.

Antioxidant and antiinflammatory activity of new water-soluble sulfur-containing phenolic compounds

We synthesized a series of structurally related water-soluble alkyl phenols - sodium 4-hydroxyphenyl propyl sulfonates and thiosulfonates with different number of tert-butyl groups at the ortho-position. In experimental systems of transient metal-induced ethyl oleate and low-density lipoprotein oxidation the antioxidant activity of the compounds increased when the tert-butyl group number at the ortho-position increased and when the sulfonate group was replaced with thiosulfonate. Compounds containing thiosulfonate group in para-propyl substituent also more effectively inhibited reactive oxygen metabolites generated in xanthine-xanthine oxidase system and during morpholinosydnonimine decomposition compared to sulfonate-containing analogs. Phenols with one tert-butyl group at the ortho-position have been shown to exhibit the highest antiinflammatory activity in the model of carrageenan-induced rat paw inflammation, as well as with regard to the expression of the glutathione S-transferase P1-1 gene in HepG2 human hepatoma cell line. Thus, it can be reasonably speculated that the antiinflammatory activity of sulfur-containing phenolic antioxidants in vivo is mediated by their effect on redox-sensitive transcription factors.