Carrageenan-induced Paw Swelling Research Articles

Anti-inflammatory Response and Detection of Pharmacologically Active Components in Serum of Rats with Carrageenan-Induced Paw Swelling Treated with Phellodendron chinense

Anti-inflammatory Response and Detection of Pharmacologically Active Components in Serum of Rats with Carrageenan-Induced Paw Swelling Treated with Phellodendron chinense

Ethanol extract of Paridis rhizoma attenuates carrageenan-induced paw swelling in rats by inhibiting the production of inflammatory factors

ContextInflammation has been identified as a key factor contributing to the development of numerous diseases. Several anti-inflammatory drugs have been developed to treat inflammation-related diseases. However, some of such drugs are associated with varying degrees of side effects. Therefore, it is imperative to develop new anti-inflammatory drugs with reducing side effects for the treatment of inflammation-related diseases. Natural anti-inflammatory drugs have emerged as an important area of research in recent years. The study was to determine the anti-inflammatory mechanism of Paridis rhizoma extract (PRE) in rat models of acute inflammation induced by carrageenan and RAW264.7 cells models induced by lipopolysaccharide (LPS).Materials and methodsPRE was investigated using the carrageenan-induced paw oedema model on rats in vivo. Histopathology examined the extent of inflammatory infiltration and tissue damage. The effect of PRE on the levels of specific cytokines was determined using enzyme-linked immunosorbent assay (ELISA). The Cell Counting Kit (CCK)-8 assay evaluated the cytotoxic effects of PRE on Raw264.7 cells. The mRNA expression levels of cytokines were quantified using quantitative real-time reverse transcriptase polymerase chain reaction (RT-PCR). Western blot measured TNF-α, IL6, TLR4, p-P65, p-IKB, HO1, SOD1 and SOD2. Fluorescence measured the cellular levels of reactive oxygen species (ROS).ResultsPRE treatment reduced interstitial edema and structural damage in a dose-dependent manner in vivo. PRE inhibited inflammatory responses in vivo and in vitro, as evidenced by the decreased expression of inflammatory factors, production of ROS, and increased expression of SOD1, SOD2, and HO1. Moreover, PRE inhibited the activity of the nuclear factor kappa B (NF-kB) pathway.ConclusionThe anti-inflammatory activity and potential mechanism of PRE were demonstrated according to the results. PRE reduced LPS-induced inflammation in RAW264.7 cells by inhibiting the NF-KB signaling pathway and ROS production in vitro. PRE alleviated interstitial edema and structural damage in the carrageenan-induced paw edema model on rats in vivo. This study provided an idea for future development of PR-based anti-inflammatory drugs.

Design, synthesis and evaluation of novel pyrrole-hydroxybutenolide hybrids as promising antiplasmodial and anti-inflammatory agents

In the pursuance of novel scaffolds with promising antiplasmodial and anti-inflammatory activity, a series of twenty-one compounds embraced with most promising penta-substituted pyrrole and biodynamic hydroxybutenolide in single skeleton was designed and synthesized. These pyrrole-hydroxybutenolide hybrids were evaluated against Plasmodium falciparum parasite. Four hybrids 5b, 5d, 5t and 5u exhibited good activity with IC50 of 0.60, 0.88, 0.97 and 0.96 μM for chloroquine sensitive (Pf3D7) strain and 3.92, 4.31, 4.21 and 1.67 μM for chloroquine resistant (PfK1) strain, respectively. In vivo efficacy of 5b, 5d, 5t and 5u was studied against the P. yoelii nigeriensis N67 (a chloroquine-resistant) parasite in Swiss mice at a dose of 100 mg/kg/day for 4 days via oral route. 5u was found to show maximum 100% parasite inhibition with considerably increased mean survival time. Simultaneously, the series of compounds was screened for anti-inflammatory potential. In preliminary assays, nine compounds showed more than 85% inhibition in hu-TNFα cytokine levels in LPS stimulated THP-1 monocytes and seven compounds showed more than 40% decrease in fold induction in reporter gene activity analyzed via Luciferase assay. 5p and 5t were found to be most promising amongst the series, thus were taken up for further in vivo studies. Wherein, mice pre-treated with them showed a dose dependent inhibition in carrageenan induced paw swelling. Moreover, the results of in vitro and in vivo pharmacokinetic parameters indicated that the synthesized pyrrole-hydroxybutenolide conjugates abide by the required criteria for the development of orally active drug and thus this scaffold can be used as pharmacologically active framework that should be considered for the development of potential antiplasmodial and anti-inflammatory agents.

Network pharmacological analysis and experimental verification of anti-inflammatory and analgesic effect of Zanthoxyli Pericarpium

To explore the mechanism of anti-inflammatory and analgesic effect of Zanthoxyli Pericarpium based on network pharmacology and inflammatory or pain mouse models. The effective components of Zanthoxyli Pericarpium were screened out by TCMSP database. And their potential corresponding targets were predicted by PharmMapper software. The possible targets relating to inflammation and pain were mainly collected through DrugBank, TTD and DisGeNET databases. The "active ingredient-gene-disease" network diagram was constructed by Cytoscape 3.7.0 software. The network pharmacology results showed 5 potential effective compounds, which were related to 29 targets; 132 targets relating to inflammation and pain were screened out in the DrugBank, TTD and DisGeNET databases. The network analysis results indicated that the phosphatidylinositol 3-kinase catalytic subunit gamma isoform(PIK3 CG) gene may be the key to the anti-inflammatory and analgesic effect of Zanthoxyli Pericarpium. The anti-inflammatory and analgesic effects of essential oil extract and dichloromethane extract of Zanthoxyli Pericarpium were explored through the mouse model of inflammation induced by xylene or carrageenan and the mouse model of pain induced by acetic acid or formalin. The experimental results showed that essential oil extract and dichloromethane extract of Zanthoxyli Pericarpium could reduce xylene-induced ear swelling and carrageenan-induced paw swelling and decrease the number of writhing responses in mice induced by acetic acid and the licking foot time of mice in phase Ⅱ induced by formalin. Western blot results showed that Zanthoxyli Pericarpium extract could inhibit the expressions of PIK3 CG, phosphonated nuclear factor kappaB(p-NF-κB) and phosphonated p38(p-p38 MAPK) protein. The present study showed the anti-inflammatory and analgesic effect of Zanthoxyli Pericarpium through multiple components and targets, so as to provide a pharmacodynamic basis for the study of Zanthoxyli Pericarpium and its mechanism.

DC591017, a phosphodiesterase-4 (PDE4) inhibitor with robust anti-inflammation through regulating PKA-CREB signaling

Phosphodiesterase-4 (PDE4) functions as a critical intracellular enzyme in immune cells and keratinocytes through the hydrolysis of cAMP. Inhibition of PDE4 has been considered as an effective therapeutic strategy in multiple inflammatory diseases. This study was intended to assess the anti-inflammatory effects of the PDE4 inhibitor, DC591017, both in vitro and in vivo. Murine RAW264.7 cells, BMDMs, BMDCs, and human NHEKs were incubated with DC591017 and then inflammatory mediators, intracellular cAMP and cAMP-mediated signaling pathways were analyzed. Carrageenan-induced acute inflammation in murine air pouches and rat paws, as well as imiquimod (IMQ)-induced psoriasis-like skin lesions were conducted to explore the therapeutic effects and underlying mechanisms of DC591017. We demonstrated herein that DC591017 suppressed the inflammatory responses of macrophages and DCs through promoting cAMP-dependent PKA-CREB signaling. Addition of forskolin functioned synergistically with DC591017, which could be blocked following H89 intervention or knockdown of PKA expression by siRNA transfection. In vivo, DC591017 treatment alleviated the leukocytes infiltration and secretion of inflammatory cytokines in murine air pouches and significantly attenuated carrageenan-induced paw swelling in rats. Moreover, we also illustrated that topical application of DC591017 ointment ameliorated IMQ-caused experimental psoriatic skin lesions, as evidenced by decreasing epidermal thickening and inflammatory infiltrations to inflamed skins. Consistently, DC591017 decreased expression of PDE4 isoforms and subsequently regulated PKA-CREB and NF-κB signaling. In brief, our study brought out a patent PDE4 inhibitor with robust anti-inflammation and provided the credible evidence in the treatment of patients with psoriasis.

Analgesic and anti-inflammatory effects and molecular mechanisms of Kadsura heteroclita stems, an anti-arthritic Chinese Tujia ethnomedicinal herb

Ethnopharmacological relevanceRheumatoid arthritis (RA) is a chronic autoimmune disease characterized by failure of spontaneous resolution of inflammation. The stem of Kadsura heteroclite (KHS) is a well-known anti-arthritic Tujia ethnomedicinal plant, which named Xuetong in folk, has long been used for the prevention and treatment of rheumatic and arthritic diseases. Aim of the studyThe analgesic and anti-inflammatory effects and the potential mechanisms behind such effects of KHS would be investigated by using different animal models. Materials and methodsThe abdominal writhing episodes of mice induced by intraperitoneal injection of acetic acid and the tail-flick response induced by radiant heat stimulation were used to evaluate the analgesic effect of KHS. The number of abdominal writhing episodes of mice and the latency of tail-flick in rats were measured and recorded. In acute inflammatory models, the ear edema of mice was induced by applying xylene on the ear surface, while the paw edema of male and female rats was induced by subcutaneous injection of carrageenan into the right hind paws of animals. The carrageenan-induced paw swelling in rats were selected as an anti-acute inflammatory mechanism of KHS. Serum levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor (TNF-α) were measured by ELISA, and protein expression of cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) were detected by Western blot. ResultsThe maximal tolerated single dose of KHS was determined to be 26 g/kg in both sexes of mice. Pharmacological studies showed that KHS at the dose of 200 mg/kg significantly prolonged the reaction time of rats to radiant heat stimulation and suppressed abdominal writhing episodes of mice induced by intraperitoneal injection of acetic acid. KHS at the dose of 200, 400, and 800 mg/kg, showed dose-dependent inhibition of xylene-induced ear swelling in mice. KHS at the dose of 100, 200, 400, and 800 mg/kg demonstrated dose- and time-dependent suppression of paw edema induced by subcutaneous injection of carrageenan in both all rats. Mechanistic studies revealed that the anti-inflammatory effect of KHS was associated with inhibition of the production of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α and effectively decreased the expression of COX and iNOS proteins in the carrageenan-injected rat serum, paw tissues and inflammatory exudates. The positive reference drug, rotundine at a dosage of 100 mg/kg and indomethacin at a dosage of 10 mg/kg were used in both mice and rat models. ConclusionThese results suggested that KHS has significant effects on analgesia and anti-inflammation with decreasing the pro-inflammation cytokines of IL-1β, IL-6, and TNF-α and inhibiting the proteins expression of COX-2 and iNOS.

INVESTIGATION OF ANTI-INFLAMMATORY AND ANTINOCICEPTIVE EFFECTS OF AQUEOUS EXTRACTS OF ARTEMISIA AFRA IN WISTAR RATS

Objective: The objective of the study was to evaluate the anti-inflammatory and antinociceptive effects of Artemisia afra.Methods: Animals were randomly divided into five groups of six animals each and administered with normal saline (2 ml/kg), indomethacin (10 mg/ kg), and A. afra at doses of 100, 200, and 400 mg/kg, respectively. For the anti-inflammatory activity, carrageenan-induced paw edema was used while the hot plate and acetic acid induced-writhing tests were used to assess the antinociceptive activity.Results: Pretreatment with A. afra at a dose of 100 mg/kg did not show any significant biological effects (p>0.05) for any of the three tests, when compared against saline-treated control group. At a dose of 200 mg/kg, A. afra demonstrated significant effects (p<0.01), during the 5th h reducing carrageenan-induced paw edema by 12%. The highest dose (400 mg/kg) of A. afra demonstrated more potent effects by decreasing the carrageenan-induced paw swelling (p<0.001–0.05) during the 3rd, 4th, and 5th h, by up to 38% when compared against saline-treated control group. Both the 200 and 400 mg/kg, A. afra doses achieved a significant increase (p<0.05) in reaction time in the hot plate test. In the acetic acid-induced writhing test, pretreatment with A. afra (400 mg/kg) significantly reduced pain by 39% (p<0.01) by comparison with the saline control.Conclusion: Experimental data demonstrated that aqueous extract of A. afra possesses anti-inflammatory and antinociceptive properties in experimental acute inflammation and pain. These findings support the usage of A. afra in managing inflammation and pain in traditional practice.

Ginsenoside metabolite compound K exerts anti-inflammatory and analgesic effects via downregulating COX2

The present study aimed to evaluate the anti-inflammatory and analgesic activities of the ginsenoside metabolite compound K (CK) and its mechanisms. Mice model of xylene-induced ear swelling and rat model of carrageenan-induced paw swelling were used to evaluate the effect of CK on acute inflammation. The analgesic effect of CK was evaluated on heat-, acetic acid-, and carrageenan-induced hyperalgesia. The levels of prostaglandin E2 (PGE2), cyclooxygenase-1 (COX-1), and COX-2 in carrageenan-induced rat paw swelling and gastric mucosa were detected by enzyme-linked immunosorbent assay (ELISA). COX-1 and COX-2 expressions in carrageenan-induced rat paw swelling and gastric mucosa were detected by western blotting. In vitro effect of CK (10-9, 10-8, 10-7, 10-6, 10-5 M) on COX-1 and COX-2 activities was evaluated by measuring the production of 6-keto-PGF1α and PGE2 in rat peritoneal macrophages. CK at doses of 7, 14, 28, 56, 112, and 224mg/kg alleviated xylene-induced ear oedema, whereas CK at 40, 80, and 160mg/kg alleviated carrageenan-induced paw oedema. CK at 224mg/kg showed an analgesic effect against acetic acid-induced pain. CK at 40, 80, and 160mg/kg significantly increased rat inflammatory pain threshold, but had no effect on heat-induced pain threshold. CK at 10, 20, 40, 80, and 160mg/kg reduced PGE2 level in the paw tissue, but showed no effect on that in the gastric mucosa. CK at 20, 40, 80, and 160mg/kg decreased COX-2 expression in the paw tissue and gastric mucosa, but exhibited no effect on COX-1 expression or on COX-1 and COX-2 activities. CK exerted anti-inflammatory and analgesic effects, possibly by reducing the catalytic synthesis of PGE2 via downregulation of COX-2 expression.

Time-dependent changes in paw carrageenan-induced inflammation above and below the level of low thoracic spinal cord injury in rats.

This was an animal study. Local inflammation is attenuated below high thoracic SCI, where innervation of major lymphoid organs is involved. However, whether inflammatory responses are affected after low thoracic SCI, remains undetermined. The aim of this study was to characterize the influence of low thoracic SCI on carrageenan-induced paw swelling in intact and paralyzed limbs, at acute and subacute stages. University and hospital-based research center, Mexico City, Mexico. Rats received a severe contusive SCI at T9 spinal level or sham injury. Then, 1 and 15 days after lesion, carrageenan or vehicle was subcutaneously injected in forelimb and hindlimb paws. Paw swelling was measured over a 6-h period using a plethysmometer. Swelling increased progressively reaching the maximum 6 h post-carrageenan injection. Swelling increase in sham-injured rats was approximately 130% and 70% compared with baseline values of forelimbs and hindlimbs, respectively. Paws injected with saline exhibited no measurable swelling. Carrageenan-induced paw swelling 1-day post-SCI was suppressed in both intact and paralyzed limbs. Fifteen days post-injury, the swelling response to carrageenan was completely reestablished in forelimbs, whereas in hindlimbs it remained significantly attenuated compared with sham-injured rats. SCI at low spinal level affects the induced swelling response in a different way depending on both, the neurological status of challenged regions and the stage of injury. These findings suggest that neurological compromise of the main immunological organs is not a prerequisite for the local swelling response to be affected after injury.

High Anti-Inflammatory Activity and Low Toxicity of Thalidomide Analogs

Thalidomide is an immunomodulatoryagent with anti-inflammatory activity, however it may also cause serious side effects. New compounds derived from thalidomide effective in modulating inflammatory responses and having an improved safety profile is being investigated. In this study, two thalidomide analogs, GI-16 and SC-15, were evaluated using the carrageenan-induced paw swelling and the lipopolysaccharide (LPS)-induced lung inflammation in mice. Acute and sub-chronic toxicity of the compounds were investigated in blood and serum samples of Wistar rats by measurements of hematological and biochemical parameters. Histopathological analyses were conducted to assess inflammatory cell infiltration in heart, liver and kidneys. Our results show that treatment with GI-16 and SC-15 reduced the carrageenan-induced paw edema over a 24 hour period. GI-16 and SC-15 treatments inhibited LPS-induced TNF-α and IL-6 in lung homogenates. In contrast, thalidomide and SC-15 enhanced IL-10 (p<0.05). Histopathological analysis showed reduction in LPS–induced lung inflammation after treatment with GI-16 and SC-15. Wistar rats treated with the compounds did not develop any clinical signs of acute or sub-chronic toxicity. No mortality occurred in both control and treated animals and body weight gain over time was similar in all groups. In addition, no significant alterations were detected in enzyme activity of aspartate aminotransferase, alanine aminotransferase or alkaline phosphatase, and no significant alterations were found in glucose, urea, creatinine, total cholesterol or triglyceride levels. GI-16 and SC-15 treatments did not modify hemoglobin, red and white blood cell count, and sections of liver, kidneys and heart tissues showed no pathological alterations under light microscopy. In conclusion, the remarkable in vivo anti-inflammatory activity and low toxicity of SC-15 and GI-16 makes them promising drug candidates to treat inflammatory conditions.

Analgesic and Anti-inflammatory Activity of Teucrium chamaedrys Leaves Aqueous Extract in Male Rats

Results The extract of T. chamaedrys (50–200 mg/kg) and acetylsalicylic acid (100 mg/kg) produced a significant (P< 0.01) inhibition of the second phase response in the formalin pain model, while only the high dose (200 mg/kg) of the extract showed an analgesic effect in the first phase. The extract also inhibited acetic acid-induced abdominal writhes in a dose-dependent manner. The tail flick latency was dose dependently enhanced by the extract but this was significantly (P< 0.05) lower than that produced by morphine (10 mg/kg). The extract (25–250 mg/kg) administered 1 hr before carrageenan-induced paw swelling produced a dose dependent inhibition of the oedema. No effect was observed with the dextran-induced oedema model. Results of the phytochemical screening show the presence of alkaloids, flavonoids and triterpenoids in the extract. Conclusion The data obtained also suggest that the anti-inflammatory and analgesic effects of the extract may be mediated via both peripheral and central mechanisms. The role of alkaloids, flavonoids and triterpenoids will evaluate in future studies.

Analgesic, antipyretic and anti-inflammatory properties of &lt;i&gt;Mezoneuron benthamianum&lt;/i&gt; baill(Caesalpiniaceae)

The analgesic, antipyretic and anti-inflammatory effects of the aqueous extract of Mezoneuron benthamianum (MB) were evaluated in mice, rats and rabbits using the mouse writhing, tail flick, hot plate and formalin-induced pain tests; 2-4-Dinitrophenol (DNP), D-Amphetamine and E-coli Lipopolysaccharide-induced pyrexia and carrageenan, egg albumin and xylene-induced oedema. The extract (400-1600 mg/kg) and acetylsalicylic acid (100 mg/ kg) produced a significant (P < 0.05) inhibition of the second phase response in the formalin pain model, while only the highest dose (1600 mg/kg) of the extract showed a comparable antinociceptive effect in the first phase. The extract also showed a dose-dependent inhibition of acetic acid induced abdominal writhing. The tail flick latency and the hot plate pain threshold were dose dependently enhanced by the extract but these were significantly lower than that produced by morphine (2 mg/kg). The 2,4-DNP and D-Amphetamine (10 and 5 mg/kg, i.p.respectively) increased the rectal temperatures of rats within 30 minutes of their administration. The extract at doses of 400,800 and 1600 mg/kg produced significant lowering of the elevated body temperature in rats. The extract (800 mg/ kg) administered orally to rabbits passaged with E. coil lipopolysacharride was able to relieve the pyrogen induced fever. The antipyretic effect produced by the extract was comparable to a standard antipyretic drug, aspirin. The extract (400-1600 mg/kg) administered 1h after carrageenan-induced paw swelling did not inhibit the oedema. No inhibitions were observed with the egg albumin and xylene induced oedema models. Phytochemical analysis revealed the presence of flavonoids, tannins, cardiac glycosides, anthraquinones, and saponins. Administration of the extract up to 2 g/kg (orally) did not produce any toxic effect in the acute toxicity studies in mice. The LD50 of the extract when administered intraperitoneally was 1021.31 mg/kg. The data obtained show that MB extract possesses analgesic and antipyretic activities but lacks an anti-inflammatory property.

Analgesic, Antipyretic and Anti-Inflammatory Properties of Mezoneuron Benthamianum Baill (Caesalpiniaceae)

The analgesic, antipyretic and anti-inflammatory effects of the aqueous extract of Mezoneuron benthamianum (MB) were evaluated in mice, rats and rabbits using the mouse writhing, tail flick, hot plate and formalin-induced pain tests; 2-4-Dinitrophenol (DNP), D-Amphetamine and E-coli Lipopolysaccharide-induced pyrexia and carrageenan, egg albumin and xylene-induced oedema. The extract (400-1600 mg/kg) and acetylsalicylic acid (100 mg/ kg) produced a significant (P < 0.05) inhibition of the second phase response in the formalin pain model, while only the highest dose (1600 mg/kg) of the extract showed a comparable antinociceptive effect in the first phase. The extract also showed a dose-dependent inhibition of acetic acid induced abdominal writhing. The tail flick latency and the hot plate pain threshold were dose dependently enhanced by the extract but these were significantly lower than that produced by morphine (2 mg/kg). The 2,4-DNP and D-Amphetamine (10 and 5 mg/kg, i.p.respectively) increased the rectal temperatures of rats within 30 minutes of their administration. The extract at doses of 400,800 and 1600 mg/kg produced significant lowering of the elevated body temperature in rats. The extract (800 mg/ kg) administered orally to rabbits passaged with E. coil lipopolysacharride was able to relieve the pyrogen induced fever. The antipyretic effect produced by the extract was comparable to a standard antipyretic drug, aspirin. The extract (400-1600 mg/kg) administered 1h after carrageenan-induced paw swelling did not inhibit the oedema. No inhibitions were observed with the egg albumin and xylene induced oedema models. Phytochemical analysis revealed the presence of flavonoids, tannins, cardiac glycosides, anthraquinones, and saponins. Administration of the extract up to 2 g/kg (orally) did not produce any toxic effect in the acute toxicity studies in mice. The LD50 of the extract when administered intraperitoneally was 1021.31 mg/kg. The data obtained show that MB extract possesses analgesic and antipyretic activities but lacks an anti-inflammatory property.

The contribution of peripheral 5-hydroxytryptamine2A receptor to carrageenan-evoked hyperalgesia, inflammation and spinal Fos protein expression in the rat

The present study was conducted to test the hypothesis that the peripheral 5-hydroxytryptamine (5-HT)2A receptor is involved in inflammatory hyperalgesia and production of noxious stimulus-induced neuronal activity at the level of the spinal cord dorsal horn. Intraplantar (i.pl.) injection of carrageenan dramatically reduced paw withdrawal latency to noxious heat (47 °C) and caused paw swelling. Pretreatment with ketanserin, a selective antagonist of 5-HT2A receptor, in the hindpaw produced dose-dependent inhibition of the hyperalgesia (0.5, 3 and 5 μg; i.pl.) with full relief at 5 μg. The drug also moderately reduced carrageenan-induced paw swelling in a dose-dependent manner. Carrageenan induced conspicuous expression of c- fos-like immunoreactivity (FLI) in the spinal dorsal horn of segments L4-5. Ketanserin (5 μg) markedly reduced carrageenan-induced FLI in all laminae of the dorsal horn. However, blockade of peripheral 5-HT1A receptors by ( N-2-[4-(2-methoxyphenyl-1-piperazinyl] ethyl]- N-2-pyridinylcyclohexanecarboxamide at maximally effective doses (30 and 100 μg; i.pl.) did not alter carrageenan-induced hyperalgesia, edema or expression of FLI. The present study provided evidence at cellular level that the peripheral 5-HT2A receptor is preferentially involved in the development of thermal hyperalgesia in the carrageenan model of inflammation.

Analgesic and anti-inflammatory activity of Crinum glaucum aqueous extract

The anti-inflammatory and analgesic effects of the aqueous extract of Crinum glaucum were evaluated in mice and rats using the carrageenan- and dextran-induced paw oedema, acetic acid-induced writhing, cold water tail flick and formalin pain tests. The extract (100–400 mg/kg) and acetylsalicylic acid (100 mg/kg) produced a significant ( P<0.05) inhibition of the second phase response in the formalin pain model, while only the high dose (400 mg/kg) of the extract showed an antinociceptive effect in the first phase. The extract also showed a dose-dependent inhibition of acetic acid-induced abdominal writhes. The tail flick latency was dose dependently enhanced by the extract but this was significantly ( P<0.05) lower than that produced by morphine (2 mg/kg). The extract (125–500 mg/kg) administered 1 h before or after carrageenan-induced paw swelling produced a dose dependent inhibition of the oedema. No effect was observed with the dextran-induced oedema model. The data obtained suggest that the anti-inflammatory and analgesic effects of the extract may be mediated via both peripheral and central mechanisms.

Effect of neurotropin on cerebral edema, calcium and other elements in mice subarachnoidally injected with carrageenan

Neurotropin, an inhibitor of the kallikrein-kinin system, was therapeutically i.p. administered to mice with brain inflammation induced by subarachnoidal injection of carrageenan. Brain water content was determined by the wet/dry weight ratio. The concentrations of cerebral Ca, K, Mn, Fe, Cu, Zn, Se, Rb, and Sr were measured by particle-induced X-ray emission. It was found that neurotropin dose dependently reduced brain water content. The mean concentration of cerebral calcium was significantly lower in the neurotropin-treated group than that in the non-treated group, suggesting less cell damage. Since it has been reported that dexamethasone and some prostaglandin inhibitors have no effect on brain swelling in this model and that, in contrast to these drugs, neurotropin has only a weak inhibiting activity on carrageenan-induced paw swelling, it is hypothesized that the kallikrein-kinin system is differently implicated in cerebral and peripheral inflammation.

Ethnopharmacologic investigation of ginger ( Zingiber officinale)

An ethanolic extract of the rhizomes of Zingiber officinale was investigated for anti-inflammatory, analgesic, antipyretic, antimicrobial and hypoglycaemic activities. In rats, the extract reduced carrageenan-induced paw swelling and yeast-induced fever but was ineffective in suppressing the writhing induced by intraperitoneal acetic acid. The extract produced blood glucose lowering in rabbits. The growth of both Gram-positive and Gramnegative bacteria was significantly inhibited. A dose-dependent inhibition of prostaglandin release effect was observed using rat peritoneal leucocytes.

Direct evidence for the anti-inflammatory effect of human interferon-alpha in CFLP mice. Brief report.

In CFLP mice, intravenously administered partially purified interferon-alpha (IFN-alpha 2 X 10(6) mu/mg protein), prepared from human leukocytes, reduced carrageenan-induced paw swelling and produced slight irritation when injected into the footpad. Anti-human IFN-alpha serum abolished the anti-inflammatory effect but did not influence local phlogogenic activity. Highly purified human IFN-alpha (1.2 X 10(8) mu/mg protein) was also found to be anti-inflammatory after intravenous administration, and devoid of irritative effect at the injection site. These results suggest that human IFN-alpha possesses a direct inhibitory effect on acute inflammation in mice, and the irritation appearing at the site of its application might be due to some impurities being present in the partially purified preparations.