Effects of Amburoside A and Isokaempferide,Polyphenols from Amburana cearensis,on Rodent Inflammatory Processes and Myeloperoxidase Activity in Human Neutrophils

Abstract: The present study evaluated the anti‐inflammatory activity of amburoside A (a phenol glucoside) and isokaempferide (a flavonol) isolated from the trunk bark of Amburana cearensis, a medicinal plant used in northeast Brazil for the treatment of asthma. Animals (male Wistar rats or Swiss mice) pre‐treated with amburoside A (25 and 50 mg/kg) or isokaempferide (12.5, 25 and 50 mg/kg), orally or intraperitoneally, showed a significant inhibition of the paw oedema induced by carrageenan (1%), prostaglandin E₂ (30 nmol/paw), histamine (200 µg/paw) or serotonin (200 µg/paw). Histological and morphometric evaluations of the rat paw oedema induced by carrageenan showed that amburoside A and isokaempferide also inhibited the accumulation of inflammatory cells. Amburoside A reduced significantly the paw oedema and the increase in vascular permeability induced by dextran, as related to the control group. Similar results were observed with the isokaempferide pre‐treatment. Furthermore, amburoside A or isokaempferide inhibited both leucocyte and neutrophil migrations, in mouse peritoneal cavity, after the carrageenan injection. The polyphenols were not cytotoxic and blocked N‐formyl‐methyl‐leucyl‐phenylalanine‐induced myeloperoxidase release and activity in human neutrophils. In addition, amburoside A and isokaempferide at 50 and 100 µg/ml concentrations reduced significantly the lipopolysaccharide‐mediated increase in tumour necrosis factor‐α (TNF‐α) levels. These results provide, for the first time, evidence to support the anti‐inflammatory activity of amburoside A and isokaempferide that seems to be related to an inhibition of inflammatory mediators, such as TNF‐α, as well as histamine, serotonin and prostaglandin E₂, besides leucocyte infiltration in a dose‐ or concentration‐dependent manner. These anti‐inflammatory effects can be explained, at least in part, by the ability of these compounds to reduce neutrophil degranulation, myeloperoxidase activity, mediators as well as TNF‐α secretion.     

Isopropoxy‐Carvacrol,a Derivative Obtained from Carvacrol,Reduces Acute Inflammation and Nociception in Rodents

Monoterpenes, compounds mainly presented in essential oils, have important pharmacological actions. Isopropoxy‐carvacrol (IPC) is a derivative of the monoterpene carvacrol, and its pharmacological properties have not yet been investigated. The aim of this study was to analyse the acute anti‐inflammatory and antinociceptive properties of IPC. Mice (25–30 g) and rats (150–230 g) were pre‐treated (i.p.) with IPC at the doses of 10, 30 or 100 mg/kg or vehicle (Tween 80, 0.5%), 30 min. before injection of the phlogistic agents. Both the first and the second phases of formalin‐induced nociception were significantly reduced by IPC (100 mg/kg). Injection of carrageenan in mice paw reduced the threshold of stimulus intensity, applied with an analgesymeter, necessary to cause paw withdrawal, which was significantly reduced by 100 mg/kg of IPC. The area under curve (0–4 hr) of rat paw oedema induced by injection of carrageenan was also significantly diminished by the administration of IPC (100 mg/kg). Administration of 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA) markedly increased mice ear oedema and myeloperidase (MPO) activity. Topical co‐administration of IPC (0.3–3 mg/ear) during the induction did not affect TPA‐induced ear oedema, but significantly decreased MPO activity in the ears, when compared with the vehicle. In in vitro experiments, IPC reduced lipoperoxidation induced by different stimuli, showed nitric oxide scavenger activity and did not interfere with murine macrophage viability in concentrations up to 100 μg/mL. These results demonstrate that IPC exerts acute anti‐inflammatory and antinociceptive activities, suggesting that it may represent an alternative in the development of new future therapeutic strategies.     

Antinociceptive and anti-inflammatory activities of sulphated polysaccharides from the red seaweed Gracilaria cornea

Seaweeds have attracted special interest as good sources of sulphated polysaccharides (SP) for use in pharmaceutical industries and biotechnology. In this study, we evaluated the effects of SP from the red seaweed Gracilaria cornea (Gc-TSP) in nociceptive and inflammatory models. In mice, Gc-TSP (3, 9 or 27 mg/kg) significantly reduced nociceptive responses, as measured by the number of writhes, at all tested doses. In a formalin test, Gc-TSP significantly reduced licking time in both phases of the test at a dose of 27 mg/kg. In a hot-plate test, the antinociceptive effect was observed only in animals treated with 27 mg/kg of Gc-TSP, suggesting that the analgesic effect occurs through a central action mechanism at the highest dose. Gc-TSP (3, 9 or 27 mg/kg) caused only a slight reduction in neutrophil migration in the rat peritoneal cavity. However, lower doses of Gc-TSP (3 and 9 mg/kg) significantly inhibited paw oedema induced by carrageenan, especially at 3 hr after treatment. Reduction in oedema was confirmed by myeloperoxidase activity in the affected paw tissue. In addition, treatment (s.c.) of animals with different doses of Gc-TSP inhibited paw oedema induced by dextran within the first hour in all doses tested. After 14 consecutive days of intraperitoneal administration of Gc-TSP (9 mg/kg), we measured the wet weight of the liver, kidney, heart, spleen and thymus and performed biochemical, haematological and histopathological evaluations. No systemic damage was found. These results indicate that Gc-TSP possesses analgesic and anti-inflammatory effects and is a potentially important tool worthy of further study.     

Antinociceptive Properties of the Hydroalcoholic Extract,Fractions and Compounds Obtained from the Aerial Parts of Baccharis illinita DC in Mice

Abstract: The present study assessed the possible antinociceptive action of the hydroalcoholic extract, fractions and pure compounds obtained from the aerial parts of Baccharis illinita DC (Asteraceae) in behavioural models of chemical nociception in mice. The hydroalcoholic extract and fractions (hexane and aqueous but not EtOAc fraction) obtained from B. illinita (30–1000 mg/kg orally) produced a dose‐related inhibition of the acetic acid‐induced nociceptive response. However, the hexane fraction was more potent than the hydroalcoholic extract and the aqueous fraction. The hexane fraction derivatives baurenol, α‐spinasterol and oleanolic acid (0.00001–10 mg/kg intraperitoneally) also caused potent inhibition of acetic acid‐induced pain. The hexane fraction (300–1000 mg/kg orally) produced inhibition of both phases of formalin‐induced pain. Moreover, the hexane fraction (30–600 mg/kg orally) also caused a dose‐dependent inhibition of glutamate‐induced pain. Nevertheless, the hexane fraction only at the dose of 300 mg/kg orally, produced partial inhibition of the paw oedema caused by carrageenan. Furthermore, the hexane fraction (300 mg/kg orally) caused inhibition of the nociceptive response induced by intrathecal injection of N‐methyl‐d ‐aspartic acid, α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid, tumour necrosis factor‐α and interleukin‐1β. In contrast, the hexane fraction did not affect the biting response induced by the metabotropic or ionotropic glutamatergic receptor agonist (±)‐1‐aminocyclopentane‐trans‐1,3‐dicarboxylic acid and kainate, respectively. In addition, the antinociception caused by the hexane fraction (300 mg/kg orally) in the acetic acid test was not affected by intraperitoneal treatment of mice with naloxone (a non‐selective opioid receptor antagonist). The precise mechanism responsible for the antinociceptive effect of the hexane fraction remains unclear, but appears to be partly associated with an inhibition of glutamatergic transmission and an inhibition of pathways dependent on pro‐inflammatory cytokines. Finally, baurenol, α‐spinasterol and oleanolic acid have an important role in the antinociceptive effects of the hexane fraction. Moreover, the antinociceptive action demonstrated in the present study supports the ethnomedical uses of this plant.     

Evaluation of anti-inflammatory activity of chloroform extract of Bryonia laciniosa in experimental animal models

The anti-inflammatory effect of the leaves of Bryonia laciniosa was evaluated using carrageenan, dextran, histamine, serotonin induced rat paw oedema and cotton pellet induced granuloma (chronic) models in rats. In mice, carrageenan peritonitis test was performed for the extract by oral administration. The chloroform extract of Bryonia laciniosa (CEBL) exhibited significant anti-inflammatory effect at the dose 50, 100 and 200 mg/kg. Maximum inhibition (52.4%) was noted at the dose of 200 mg/kg after 3 h of drug treatment in carrageenan induced paw oedema, whereas the indomethacin (standard drug) produced 62.1% of inhibition. The extract exhibited significant anti-inflammatory activity in dextran induced paw oedema in a dose dependent manner. The extract also exhibited significant inhibition on the hind paw oedema in rats caused by histamine and serotonin respectively. In the chronic model (cotton pellet induced granuloma) the CEBL (200 mg/kg) and standard drug showed decreased formation of granuloma tissue by 50.1 and 57.3% (p<0.001) respectively. The extract also inhibited peritoneal leukocyte migration in mice. Thus, the present study revealed that the chloroform extract of Bryonia laciniosa exhibited significant anti-inflammatory activity in the tested models.     

Simvastatin and Indomethacin Have Similar Anti‐Inflammatory Activity in a Rat Model of Acute Local Inflammation

Abstract: Statins, such as simvastatin, lower circulating cholesterol levels and are widely prescribed for the treatment of hypercholesterolaemia. Several studies have shown unexpected effects of statins on inflammation. We studied the anti‐inflammatory effect of simvastatin using a standard model of an acute local inflammation, the carrageenan‐induced footpad oedema. Experimental groups (n = 6–8) were given simvastatin in a dose range 5–30 mg/kg, indomethacin 1–8 mg/kg and methylcellulose (control) per os. Footpad volume was measured with a plethysmograph and compared with the pre‐injection volume of the same paw. Swelling (in microlitres) was then calculated, and in drug‐treated animals, per cent inhibition was derived through comparison with the control group. Histopathological examination of the skin biopsies was performed to examine severity of paw skin lesions and to confirm the simvastatin‐induced inhibition of acute inflammation. Both simvastatin and indomethacin administered orally, 1 hr before carrageenan injection, significantly reduced the extent of footpad oedema. Indomethacin dose‐dependently blocked the swelling; the maximal effect was obtained with 8 mg/kg by 48.3% (P < 0.05). Simvastatin produced a comparable anti‐inflammatory activity at a dose of 5 mg/kg (32%), while 10 and 30 mg/kg caused a 47.6% and 51.7% reduction, respectively, with the maximal effect observed at 20 mg/kg by 57.2% (P < 0.05). The comparison of the ED₅₀ of these agents on molar basis showed equipotent anti‐inflammatory activity. Histopathological examination of the footpad skin biopsies revealed that simvastatin, dose‐dependently and comparablly to indomethacin, reduced polymorphonuclear leucocyte infiltration. These data support the hypothesis that simvastatin has an acute anti‐inflammatory activity.     

Letter from the Editor

This study investigated the antinociceptive and anti‐inflammatory activities of the ethanolic extract (EESAl), fractions and the compound 8‐methoxylapachenol (8ML) obtained from the tubers of Sinningia allagophylla. Male Swiss mice were treated with EESAl (3–300 mg/kg) or vehicle by oral route (p.o.) 1 hr before the injection of formalin 2.5% or carrageenan (Cg) into the hind paw. EESAl (3–30 mg/kg) reduced the inflammatory phase of the nociceptive behaviour induced by formalin (around 65% for all doses). EESAl (3–300 mg/kg, p.o.) also reduced Cg‐induced mechanical hyperalgesia and oedema in a dose‐dependent fashion but did not change the hot‐plate latency or the motor performance of the animals. Oral administration of petroleum ether fraction (PE, 3 mg/kg), but not in the methanolic fraction (30 mg/kg), reduced both Cg‐induced oedema and hyperalgesia. Compound 8ML isolated from PE (1.8 mg/kg, p.o.) abolished Cg‐induced hyperalgesia but also did not change hot‐plate latency or motor performance of the animals. 8ML administration into the paw (0.75–750 pg) dose‐dependently reduced Cg‐induced hyperalgesia. 8ML (750 pg) also blocked the hyperalgesia induced by tumour necrosis factor (TNF‐α), interleukin‐1β (IL‐1β) and prostaglandin E₂ (PGE₂) but failed to change the hyperalgesia induced by cytokine‐induced neutrophil chemoattractant‐1 (CINC‐1) and dopamine (Dopa). These results suggest that EESAl has an important antinociceptive and anti‐inflammatory activity, the former one related, at least in part, to the reduction in the hyperalgesia. Similarly, 8ML reduced Cg‐induced oedema and mechanical hyperalgesia and seems to act in peripheral sites and on the prostaglandin rather than on the sympathetic component of the Cg‐inflammatory hyperalgesia.     

Evaluation of the anti-inflammatory and anti-nociceptive effects of different antidepressants in the rat.

The present study was designed to compare the anti-inflammatory and anti-nociceptive effects of different classes of antidepressant drugs on the carrageenan paw oedema and tail-electric stimulation assays in the rat. Drugs were intraperitoneally administered 30 min prior to carrageenan or nociceptive testing. The non-selective noradrenaline (NA) and serotonin (5-HT) reuptake inhibitors imipramine, amitriptyline and clomipramine displayed anti-inflammatory activity in the carrageenan model of paw inflammation. The maximal degree of oedema inhibitions seen with these agents were 28.8, 41.5 and 46.8% for 5, 10 and 20 mg kg(-1) amitriptyline, 26.2, 38.2 and 51.4% for 3.75, 7.5 and 15 mg kg(-1) imipramine and 51.2 and 54.1% for 16 and 32 mg kg(-1) clomipramine, respectively. The heterocyclic agent trazodone significantly inhibited paw oedema by 46 and 41% at 1 and 2h after dosing at the highest dose (40 mg kg(-1)) examined. Fluoxetine, a selective 5-HT reuptake inhibitor (SSRI) caused dose-related reduction of paw oedema, with 20.7% inhibition at the dose of 10 mg kg(-1). In contrast, sertraline, another SSRI caused dose-dependent enhancement of paw oedema. All antidepressant drugs in the study showed anti-nociceptive properties in the tail-electric stimulation assay with amitriptyline and trazodone being the most effective in this respect. Taken together, data in the present study confirm anti-inflammatory and anti-nociceptive effect for some antidepressant drugs and indicate that SSRIs differently affects inflammation.     

Anti-inflammatory activities of aqueous/ethanol and methanol extracts of <Emphasis Type="Italic">Perna viridis</Emphasis> Linn. in mice

Anti-inflammatory effect of the edible mytilid bivalve Perna viridis was evaluated using formalin, carrageenan and dextran-induced paw oedema in mice. The whole mussel tissue without shell was first extracted with ethyl acetate and then successively with methanol and water:ethanol, 7:3 (aqueous/ethanol). Three doses (100, 500 and 1,000 mg/kg) of the extracts (methanol and aqueous/ethanol) were administered orally prior to the injection of inflammatory agents. The inflammation induced by formalin was inhibited by the administration of both extracts for 7 days and the activity was found to be higher for methanol than aqueous/ethanol extract. A dose-dependent reduction in paw thickness was observed for carrageenan-induced paw oedema on treatment with methanol and aqueous/ethanol extracts which was comparable to the standard drug diclofenac. The effect of extracts on dextran-induced oedema was less than that produced by the other two inflammatory stimulants.     

Beneficial Pharmacological Effects of Levosimendan on Antioxidant Status of Acute Inflammation Induced in Paw of Rat: Involvement in Inflammatory Mediators

Levosimendan (LEVO) is a new calcium sensitizer with positive inotropic and vasodilating properties that represents a new pharmacological class of inotropic drugs that stimulate elevated cardiac output. The purpose of this study was to examine anti‐inflammatory effect and antioxidant activity of LEVO in a carrageenan (CAR)‐induced inflammatory paw oedema rat model. The CAR‐induced rat groups received LEVO 1, 2 and 3 mg/kg by intraperitonally and indomethacin (IND) 25 mg/kg by oral gavage. LEVO inhibited CAR‐induced paw oedema and suppressed the production of TNF‐α, IL‐1 and IL‐6 at doses of 2 and 3 mg/kg. In contrast to CAR‐injected paws, 2 and 3 mg/kg doses of LEVO and IND increased superoxide dismutase (SOD) activity and also both doses of LEVO, and IND decreased the 8‐isoprostaglandin F2α (8‐ISO) level. A 2 mg/kg dose of LEVO produced 39%, 46%, 61% and 64.7% anti‐inflammatory effects (p < 0.0001) for the 1st, 2nd, 3rd and 4th hours, respectively. Other results of our current study have shown that SOD and glutathione for CAR‐injected groups were lower, and 8‐ISO level was higher than those for the healthy rat group. LEVO may be provided as a pharmacological agent in the prevention or treatment of diseases in which acute or chronic inflammation occurs based on a pathogenic factor.     

The kinin antagonist hoe 140 reduces acute paw oedema in rats caused by carrageenan, bradykinin and kaolin

The present study aimed to evaluate the effect of Hoe 140, a BK receptor B₂ antagonist, on acute oedema induced by carrageenan, BK and kaolin in male Wistar Kyoto rats. Hoe 140 (0.2 mg/kg and 20 mg/kg) given ip caused significant (p<0.05 and p<0.01) inhibition of carrageenan and BK-induced paw oedema. This suggests that BK is the prime inflammatory mediator of carrageenan oedema, and that it is also a specific blocker of oedema caused by BK. Furthermore, Hoe 140 was found to be less effective in reducing kaolin-induced oedema in rats. This might reflect that BK is not a prime inflammatory mediator of kaolin-induced oedema. The possible significance of these findings is discussed.     

Antinociceptive and anti-inflammatory activities of nicotinamide and its isomers in different experimental models

Although there is evidence for the anti-inflammatory activity of nicotinamide, there is no evaluation of its effects in models of nociceptive and inflammatory pain. In addition, there is no information about the potential anti-inflammatory and antinociceptive activities of the nicotinamide isomers, picolinamide and isonicotinamide. Per os (p.o.) administration of nicotinamide (1000 mg/kg, −1 h) inhibited the first and second phases of the nociceptive response induced by formalin in mice. In the model of nociceptive pain, exposure of mice to a hot-plate (50 °C), nicotinamide (1000 mg/kg, −1 h) also presented antinociceptive activity. Nicotinamide (500 mg/kg, −1 and 3 h) also inhibited the mechanical allodynia induced by carrageenan in rats, a model of inflammatory pain. In addition to inhibiting the nociceptive response, nicotinamide (500 or 1000 mg/kg, −1 and 3 h) inhibited the paw edema induced by carrageenan in mice and rats. P.o. administration of picolinamide (125 mg/kg, −1 h) and isonicotinamide (500 or 1000 mg/kg, −1 h) inhibited the second phase of the nociceptive response induced by formalin in mice. The paw edema induced by carrageenan in mice was also inhibited by isonicotinamide (500 or 1000 mg/kg, −1 h) and picolinamide (125 mg/kg, −1 h and 3 h). The results represent the first demonstration of the activity of nicotinamide and its isomers in models of nociceptive and inflammatory pain and provide support to their anti-inflammatory activity. The demonstration of new activities for nicotinamide is important as it may contribute to expand its use in the treatment of other pathological conditions.     

Anti-inflammatory, analgesic and antipyretic activity of aqueous extract of fresh leaves of Coccinia indica

This study was aimed to evaluate both post- and pre-treatment anti-inflammatory activities of the aqueous extract of fresh leaves of Coccinia indica in rats using the carrageenan-induced paw oedema method at various dose levels. Analgesic and antipyretic properties were evaluated using tail flick model and yeast-induced hyperpyrexia, respectively. Ceiling effect of the extract was observed at 50 mg/kg in pre-treatment carrageenan test. In post-treatment studies, a dose-dependent anti-inflammatory effect was observed in the dose range of 25–300 mg/kg. The effect was equivalent to diclofenac (20 mg/kg) at 50 mg/kg but it was significantly pronounced at higher doses. Effectiveness of extract in the early phase of inflammation suggests the inhibition of histamine and serotonin release. The extract produced marked analgesic activity comparable to morphine at 300 mg/kg, which suggests the involvement of central mechanisms. A significant reduction in hyperpyrexia in rats was also produced by all doses of extract with maximum effect at 300 mg/kg comparable to paracetamol. In conclusion, this study has established the anti-inflammatory activity, analgesic and antipyretic activity of C. indica and, thus, justifies the ethnic uses of the plant.     

Modulation of inflammatory paw oedema by cysteamine in the rat.

Cysteamine, a potent somatostatin depletor, was used in the present study to investigate the role of endogenous somatostatin in acute peripheral inflammation. The acute inflammation was induced by intraplantar injection of carrageenan (1%), histamine (5 micromol), or formalin (2.5%) in the rat hind paw. The induced inflammation and the formation of oedema were determined by measurement of the paw thickness. Given subcutaneously (s.c.) 1 h before carrageenan, cysteamine caused significant, dose-dependent and long-lasting inhibition of rat paw oedema induced by carrageenan. At doses of 12.5, 25, 50 or 100 mg kg (-1), cysteamine significantly inhibited the carrageenan-induced paw oedema at 4 h by 52.3, 40, 40.7 or 26.3%. Cysteamine given at 300 mg kg (-1), a dose well known to deplete tissue somatostatin, reduced oedema by only 16.2% vs control values. Significant inhibition of the carrageenan-induced rat paw oedema was still evident 24 h post-injection at cysteamine doses of 12.5, 25, 50 or 100 mg kg (-1). Given s.c. at 300 mg kg (-1), 4 h prior to carrageenan, cysteamine decreased rat paw oedema at 4 h by 14.9%. Cysteamine (300 mg kg (-1)), 4 h beforehand, had little modulatory effect on the oedema induced by formalin (2.5%) but reduced that caused by intraplantar histamine (5 micromol). The anti-oedematogenic effect of indomethacin, but not that of the selective COX-2 inhibitor celecoxib, was less marked in rats pre-treated with cysteamine at 300 mg kg (-1). Cysteamine (0.3 microg- 0.3 mg paw (-1)) co-administered with carrageenan was devoid of anti-inflammatory effect and even promoted inflammation at low concentrations. Cysteamine given locally alone induced slight paw oedema. These data indicate that systemic cysteamine possesses potent and long-lasting anti-inflammatory effects and modulates the anti-inflammatory effect of cyclooxygenase inhibitors in a model of peripheral inflammation in the rat. The effect of cysteamine is likely to be mediated via central action.     

Acute and chronic anti-inflammatory properties of the stem bark aqueous and methanol extracts of Sclerocarya birrea (Anacardiaceae)

Sclerocarya birrea is used in folk medicine for the treatment of inflammatory disorders. The effect of the stem bark aqueous and methanol extracts of S. birrea (150 or 300 mg/kg) was evaluated on carrageenan-, histamine- or serotonin-induced paw oedema in rats. The methanol extract of S. birrea (300 mg/kg) being the most active, exhibited a maximum inhibition of 75.45 and 55.31% on carrageenan- and histamine-induced inflammation, respectively. When administered at 300 mg/kg, the methanol extract of S. birrea also exhibited 80.68% inhibition on the 10th day and 54.43% inhibition on the 21st day in formalin- or complete Freund’s adjuvant (CFA)-induced paw oedema in rats. GSH level was significantly increased (75.14%), while MAD level was significantly decreased (31.22%) in the liver of CFA rats treated with S. birrea (300 mg/kg). The results suggest that the anti-inflammatory activity of the aqueous and methanol extracts of S. birrea is due to the inhibition of histamine and prostaglandin pathways and to its antioxidant activity.     

Anti-inflammatory and analgesic effects of 6α,7β–dihydroxy-vouacapan-17β-oic acid isolated from <Emphasis Type="Italic">Pterodon emarginatus</Emphasis> Vog. fruits

6α,7β-dihydroxy-vouacapan-17β-oic (tricyclic furanoid diterpene; DHVO) acid was isolated from the hexane extract of Pterodon emarginatus fruits and evaluated for anti-inflammatory and analgesic effects using an assay that induces paw oedema with carrageenan, dextran and prostaglandin E₂ (PGE₂) in rats and the writhing and formalin tests in mice. Oral administration of 50 mg/kg DHVO significantly inhibited carrageenan-induced oedema formation by 24% (p < 0.05). This treatment did not inhibit dextran-induced oedema but was effective when the inflammatory effect was triggered by PGE₂, inhibiting oedema formation by 39% (p < 0.05). In the writhing test, doses of 50, 200 and 400 mg/kg resulted in a dose-dependent effect with a correlation coefficient (r) of 0.983 (F = 29.04, ANOVA). Doses of 50 and 100 mg/kg inhibited both the neurogenic and inflammatory phases (p < 0.05) in the formalin test but were not effective for increasing the lag time in the hot plate test. Together, these results suggest that DHVO has both anti-inflammatory and peripheral analgesic effects.     

Is Fleming's lysozyme an analgesic agent? An experimental reappraisal of clinical data

Hen egg white lysozyme (Fleming's lysozyme) was tested for antinociceptive activity in rats against foot hyperalgesia provoked by a subplantar injection of a number of irritants: arachidonic acid, brewer's yeast, carrageenan, kaolin, mepartricin and rabbit anti-rat serum (Randall-Selitto method). The compound was active when given p.o., i.m. or i.v. (100-200-400 mg/kg) as well as when injected locally in the foot pad concurrently with the irritant (1-2-4 mg/rat). Lysozyme decreased the sensitivity of the inflamed paw to the nociceptive stimulation, left unmodified the sensitivity of the normal paw and did not reduce the oedema of the inflamed paw. It differed in its activity from steroidal and non-steroidal anti-inflammatory drugs and from central analgesics that were used as standard reference drugs. Its activity was not shared by hen egg white and ovalbumin. Contrary to dextran, lysozyme i.p. did not induce anaphylactoid reactions. Lysozyme did not provoke tolerance and did not interfere with the antinociceptive activity of morphine. The results are in agreement with clinical data published years ago. Lysozyme was claimed to be an active agent against herpes zoster and cancer pain.     

Studies on the anti-inflammatory and anti-nociceptive effects of melatonin in the rat.

The present study aimed to evaluate the anti-inflammatory and anti-nociceptive effects of melatonin in the rat. Acute inflammation was induced by sub-plantar injection of carrageenan (1%) in the rat hind paw. The rats received vehicle or drug 30 min before carrageenan administration and were evaluated for paw oedema at 1, 2, 3, and 4 h post-carrageenan. The induced inflammation and the formation of oedema were determined by measurement of the paw thickness. Nociception was tested by determining vocalization following electrical stimulation of the tail. Given intraperitoneally (i.p.) 30 min before carrageenan, melatonin caused significant and a dose-dependent reduction of hind paw swelling induced by carrageenan. At doses of 0.5 and 1 mg kg(-1), melatonin inhibited the carrageenan-induced oedema by 20.5 and 29.6% versus control values at 4 h post-carrageenan, respectively. Melatonin (0.5 and 1 mg kg(-1), i.p.) 30 min beforehand displayed anti-nociceptive effect in the electric stimulation of the rat tail test, increasing nociceptive thresholds to electrically-induced pain at 4 h post-treatment by 29.6 and 39.5%, respectively. Melatonin given simultaneously with the non-selective COX-1 and COX-2 inhibitor indomethacin (5 mg kg(-1), i.p.) 30 min prior to carrageenan, enhanced the anti-inflammatory effect of the latter in the carrageenan-induced paw oedema model by 23%. Melatonin (0.5 mg kg(-1), i.p.) increased the anti-nociceptive effect of indomethacin (5 mg kg(-1), i.p.). Meanwhile, the anti-inflammatory and anti-nociceptive effect of the highly selective COX-2 inhibitor rofecoxib (2.25 mg kg(-1), i.p.) was only slightly increased by melatonin administration at 0.5 mg kg(-1). Melatonin enhanced the anti-inflammatory effect of cysteamine (300 mg kg(-1), s.c.) in the carrageenan-induced paw oedema. Melatonin (20 and 40 microg per paw) given prior to carrageenan into the rat hind paw was devoid of anti-inflammatory effect. These results indicate that melatonin possesses anti-inflammatory and anti-nociceptive properties in the rat and enhance those of indomethacin. This effect is likely to be centrally mediated.     

Anti-inflammatory and antinociceptive properties of blueberry extract (Vaccinium corymbosum)

Blueberries are among the edible fruits that are recognized best for their potential health benefits. The crude extract from Vaccinium corymbosum was assessed in anti-inflammatory and antinociceptive models. The crude hydroalcoholic extract was administered orally at doses of 100, 200 or 300 mg kg (-1) for all the assays. In the carrageenan test, the crude extract reduced rat paw oedema by 9.8, 28.5 and 65.9%, respectively. For the histamine assay, the reductions of oedema were 70.1, 71.7 and 81.9%, respectively. In the myeloperoxidase (MPO) assay, 300 mg kg (-1) crude extract produced a significant inhibition of the MPO activity, at 6 h and 24 h after injection of carrageenan, by 42.8 and 46.2%, respectively. With the granulomatous tissue assay dexamethasone displayed significant activity, whereas the blueberry extract was inactive. For the abdominal constriction test, inhibitions of 49.0, 54.5, 53.5%, respectively, were observed for the crude extract, and 61.4% for indometacin. In the formalin test, the crude extract (200 and 300 mg kg (-1)) and indometacin inhibited only the second phase by 36.2, 35.3 and 45.8%, respectively. Considering that the crude extract of blueberry displayed antinociceptive and anti-inflammatory activity, its consumption may be helpful for the treatment of inflammatory disorders.     

On the ability of prostaglandin E1, and arachidonic acid to modulate experimentally induced oedema in the rat paw.

1 Prostaglandins E1 and E2 but not prostaglandin F2alpha, arachidonic acid or linolenic acid, produced slight oedema when injected into the rat hindpaw. 2 Prostaglandin E1 potentiated hindpaw oedema produced by carrageenan, kaolin, bradykinin and trypsin but not that produced by 5-hydroxytryptamine (5-HT), histamine, dextran B or compound 48/80. Carrageenan- and bradykinin-induced paw oedemas were also potentiated by prostaglandin E2. Arachidonic acid potentiated responses to carrageenan and kaolin but not responses to bradykinin, trypsin, 5-HT, histamine, dextran B or compound 48/80. Linolenic acid did not potentiate hindpaw oedema induced by carrageenan. 3 Potentiation of carrageenan-induced oedema by prostaglandin E1 was not diminished by pretreatment with indomethacin, hydrocortisone or cyproheptadine. However, arachidonic acid potentiation of carrageenan oedema was reduced by pretreatment with non-steroidal anti-inflammatory drugs but not by anti-inflammatory steroids or by paracetamol. 4 The enhancement of the response to carrageenan and kaolin by prostaglandins E1, E2 and arachidonic acid is discussed in terms of kinin mediation.