Antibacterial and anti-inflammatory activities of an extract,fractions, and compounds isolated from Gochnatia pulchra aerial parts

This paper reports on the in vitro antibacterial and in vivo anti-inflammatory properties of a hydroethanolic extract of the aerial parts of Gochnatia pulchra (HEGP). It also describes the antibacterial activity of HEGP fractions and of the isolated compounds genkwanin, scutellarin, apigenin, and 3,5-O-dicaffeoylquinic acid, as evaluated by a broth microdilution method. While HEGP and its fractions did not provide promising results, the isolated compounds exhibited pronounced antibacterial activity. The most sensitive microorganism was Streptococcus pyogenes, with minimum inhibitory concentration (MIC) values of 100, 50 and 25 µg/mL for genkwanin and the flavonoids apigenin and scutellarin, respectively. Genkwanin produced an MIC value of 25 µg/mL against Enterococcus faecalis. A paw edema model in rats and a pleurisy inflammation model in mice aided investigation of the anti-inflammatory effects of HEGP. This study also evaluated the ability of HEGP to modulate carrageenan-induced interleukin-1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), and monocyte chemoattractant protein-1 (MCP-1) production. Orally administered HEGP (250 and 500 mg/kg) inhibited carrageenan-induced paw edema. Regarding carrageenan-induced pleurisy, HEGP at 50, 100, and 250 mg/kg diminished leukocyte migration by 71.43%, 69.24%, and 73.34% (P<0.05), respectively. HEGP suppressed IL-1β and MCP-1 production by 55% and 50% at 50 mg/kg (P<0.05) and 60% and 25% at 100 mg/kg (P<0.05), respectively. HEGP abated TNF-α production by macrophages by 6.6%, 33.3%, and 53.3% at 100, 250, and 500 mg/kg (P<0.05), respectively. HEGP probably exerts anti-inflammatory effects by inhibiting production of the pro-inflammatory cytokines TNF-α, IL-1β, and MCP-1.     

The role of central mechanisms in the anti-inflammatory effect of amitriptyline on carrageenan-induced paw edema in rats

OBJECTIVE:

The present study was designed to further investigate the effect of amitriptyline, a classical tricyclic antidepressant, on carrageenan-induced paw edema in rats.

METHODS:

First, amitriptyline was administered intraperitoneally (i.p.) at doses of 20, 40 and 80 mg kg^-1, 30 min before subplantar injection of carrageenan. Second, amitriptyline was given intracerebroventriculary or intrathecally at doses of 25, 50 and 100 µg/rat, 30 min prior to carrageenan challenge. Third, the effect of adrenergic receptor antagonists such as propranolol (10 mg kg^-1, i.p.), prazosin (4 mg kg^-1, i.p.) and yohimbine (10 mg kg^-1, i.p.) and an opioid receptor antagonist (naloxone, 4 mg kg^-1, i.p.) on the anti-inflammatory effect of amitriptyline (40 mg kg^-1, i.p.) was investigated.

RESULTS:

Our data confirm that intraperitoneally administered amitriptyline exhibits a marked anti-inflammatory effect on carrageenan-induced paw edema in rats 4 h postcarrageenan challenge (P < 0.001). Intracerebroventricular (i.c.v.) administration of amitriptyline also reduced the development of paw edema at 4 h postcarrageenan (P < 0.001), but intrathecal (i.t.) application of amitriptyline failed to alter the degree of paw swelling. Furthermore, the applied antagonists did not modify the anti-inflammatory effect of amitriptyline.

CONCLUSION:

These results support the view that amitriptyline has a considerable anti-inflammatory effect on carrageenan-induced paw edema in rats and suggest that at least a part of this property could be mediated through supraspinal sites. Moreover, it seems unlikely that the investigated adrenergic and opioid receptors have a significant role in this effect of amitriptyline.     

Evaluation of Anti-Inflammatory and Antinociceptive Activity of Triphala Recipe

The anti-inflammatory and antinociceptive activities of Triphala recipe were studied in animal models. Triphala recipe (4 mg/ear) significantly exhibited an inhibitory effect on the ear edema formation induced by ethyl phenylpropiolate-induced, but not on the arachidonic acid-induced ear edema in rats. Furthermore, Triphala recipe at the doses of 300, 600 and 1,200 mg/kg significantly reduced carrageenan-induced hind paw edema. Next, the anti-inflammatory action in chronic inflammation was measured using the cotton pellet-induced granuloma formation assay in rats. Triphala recipe (1,200 mg/kg) reduced neither transudative weight nor granuloma formation. It also did not affect on body weight gain and thymus weight indicating that Triphala recipe does not have a steroid-like effect. In antinociceptive study, Triphala recipe (300, 600, 1,200 mg/kg), elicited significant inhibitory effect on both phases, especially in late phase, of the formalin test in mice suggesting that the antinociceptive action of Triphala recipe may be via both peripheral and at least partly centrally acting.     

Studies on the Anti-Inflammatory,Analgesic and Antipyrexic Activities of Betulinic Acid Derived from Tetracera Potatoria

Background

The anti-inflammatory and anti-nociceptive activity of betulinic acid (BA) was investigated in this study. The triterpene was isolated from the ethyl acetate extract of Tetracera potatoria and its structure was verified by IR and NMR spectroscopy. The bioactivity of this compound was assessed using carrageenan-induced paw oedema in rats and carrageenan-induced pulmonary oedema in mice for the anti-inflammatory activity, while acetic acid-induced writhing test in mice and zymosan-induced fever in rats were used for analgesic test.

Materials and Methods

Rats and mice were randomly divided into groups of five animals. For each experiment, betulinic acid at 10, 20 or 40mg/kg b.w was administered intraperitoneally to the first three groups respectively. The fourth group was administered with indomethacin (10mg/kg) or acetylsalicylic acid (150mg/kg), while the fifth group was administered with distilled water (10ml/kg). Data obtained were expressed as mean±S.E.M and significant differences were determined at p<0.05.

Results

BA significantly reduced carrageenan-induced paw oedema by 11.0%, 45.7%, 68.6% or pulmonary oedema by 25.6, 29.2 and 45.13% dose dependently. 40 mg/kg of BA inhibited paw oedema by 68.6% comparably to acetylsalicylic acid (71.4%) or indomethacin (51.33%) respectively. Abdominal writhing was also significantly (p<0.05) reduced to 17.20 writhes by BA (40mg/kg) comparable to Indomethacin (16.3writhes). Fever was inhibited by BA most significantly by 3hours post-injection of zymosan (1.00, 1.45, 0.00°C) and this inhibitory effect was higher than that observed for acetylsalicylic acid (0.30°C).

Conclusion

Betulinic acid derived from Tetracera potatoria exhibited potent anti-inflammatory, analgesic or antipyrexic activity which is comparable to indomethacin or acetylsalicyclic acid.     

Anti-inflammatory activities of Aller-7, a novel polyherbal formulation for allergic rhinitis

Allergic rhinitis is an immunological disorder and an inflammatory response of nasal mucosal membranes. Allergic rhinitis, a state of hypersensitivity, occurs when the body overreacts to a substance such as pollens or dust. A novel, safe polyherbal formulation (Aller-7/NR-A2) has been developed for the treatment of allergic rhinitis using a unique combination of extracts from seven medicinal plants including Phyllanthus emblica, Terminalia chebula, Terminalia bellerica, Albizia lebbeck, Piper nigrum, Zingiber officinale and Piper longum. Since inflammation is an integral mechanistic component of allergy, the present study aimed to determine the anti-inflammatory activity of Aller-7 in various in vivo models. The efficacy of Aller-7 was investigated in compound 48/80-induced paw edema both in Balb/c mice and Swiss Albino mice, carrageenan-induced paw edema in Wistar Albino rats and Freund's adjuvant-induced arthritis in Wistar Albino rats. The trypsin inhibitory activity of Aller-7 was also determined and compared with ovomucoid. At a dose of 250 mg/kg, Aller-7 demonstrated 62.55% inhibition against compound 48/80-induced paw edema in Balb/c mice, while under the same conditions prednisolone at an oral dose of 14 mg/kg exhibited 44.7% inhibition. Aller-7 significantly inhibited compound 48/80-induced paw edema at all three doses of 175, 225 or 275 mg/kg in Swiss Albino mice, while the most potent effect was observed at 225 mg/kg. Aller-7 (120 mg/kg, p.o.) demonstrated 31.3% inhibition against carrageenan-induced acute inflammation in Wistar Albino rats, while ibuprofen (50 mg/kg, p.o.) exerted 68.1% inhibition. Aller-7 also exhibited a dose-dependent (150-350 mg/kg) anti-inflammatory effect against Freund's adjuvant-induced arthritis in Wistar Albino rats and an approximately 63% inhibitory effect was observed at a dose of 350 mg/kg. The trypsin inhibitory activity of Aller-7 was determined, using ovomucoid as a positive control. Ovomucoid and Aller-7 demonstrated IC50 concentrations at 1.5 and 9.0 microg/ml, respectively. These results demonstrate that this novel polyherbal formulation is a potent anti-inflammatory agent that can ameliorate the symptoms of allergic rhinitis.     

Participation of the NO/cGMP/K+ATP pathway in the antinociception induced by Walker tumor bearing in rats

Implantation of Walker 256 tumor decreases acute systemic inflammation in rats. Inflammatory hyperalgesia is one of the most important events of acute inflammation. The L-arginine/NO/cGMP/K⁺ATP pathway has been proposed as the mechanism of peripheral antinociception mediated by several drugs and physical exercise. The objective of this study was to investigate a possible involvement of the NO/cGMP/K⁺ATP pathway in antinociception induced in Walker 256 tumor-bearing male Wistar rats (180-220 g). The groups consisted of 5-6 animals. Mechanical inflammatory hypernociception was evaluated using an electronic version of the von Frey test. Walker tumor (4th and 7th day post-implantation) reduced prostaglandin E₂- (PGE₂, 400 ng/paw; 50 µL; intraplantar injection) and carrageenan-induced hypernociception (500 µg/paw; 100 µL; intraplantar injection). Walker tumor-induced analgesia was reversed (99.3% for carrageenan and 77.2% for PGE₂) by a selective inhibitor of nitric oxide synthase (L-NAME; 90 mg/kg, ip) and L-arginine (200 mg/kg, ip), which prevented (80% for carrageenan and 65% for PGE₂) the effect of L-NAME. Treatment with the soluble guanylyl cyclase inhibitor ODQ (100% for carrageenan and 95% for PGE₂; 8 µg/paw) and the ATP-sensitive K⁺ channel (KATP) blocker glibenclamide (87.5% for carrageenan and 100% for PGE₂; 160 µg/paw) reversed the antinociceptive effect of tumor bearing in a statistically significant manner (P < 0.05). The present study confirmed an intrinsic peripheral antinociceptive effect of Walker tumor bearing in rats. This antinociceptive effect seemed to be mediated by activation of the NO/cGMP pathway followed by the opening of KATP channels.     

Toxicity,analgesic and anti-inflammatory activities of tectorigenin

Abstract

Objective: Belamcanda chinensis has been used in oriental medicine for the treatment of inflammatory diseases. Tectorigenin is a main compound in B. chinensis and possess inhibitory activity against inflammatory responses. Thus, the current study aimed at evaluating toxicity as well as analgesic and anti-inflammatory effects of tectorigenin in animal models.

Methods: Tectorigenin was employed to evaluate acute and subacute toxicity. Acetic acid-induced writhing in mice was used for analgesic test. The anti-inflammatory activity was tested in carrageenan-induced paw edema.

Results: LD₅₀ of tectorigenin was 1.78?g/kg p.o. in mice and no toxic symptoms were observed at doses up to 300?mg/kg in a subacute toxicity test during 28-day treatment. Tectorigenin at doses of 50 and 100?mg/kg had an analgesic effect on acetic acid-induced acute visceral pain in mice. In inflammatory rat model, tectorigenin at 60?mg/kg significantly reduced carrageenan-induced edema.

Conclusion: We demonstrated that tectorigenin is a safe and promising analgesic and anti-inflammatory agent.     

Release-Active Dilutions of Diclofenac Enhance Anti-inflammatory Effect of Diclofenac in Carrageenan-Induced Rat Paw Edema Model

The study was aimed to investigate the effect of technologically treated diclofenac (release-active dilutions of diclofenac (RAD of diclofenac)) on anti-inflammatory activity of diclofenac in carrageenan-induced rat paw edema model. Ninety male Wistar albino rats (6–8 weeks) divided into nine groups (n?=?10) were used. Anti-inflammatory activity was assessed at 1, 2, 3, 4, and 6 h after subplantar injection of carrageenan (0.1 ml of a 1 % solution in normal saline). Diclofenac alone was studied at 5 and 20 mg/kg, RAD of diclofenac alone at 7.5 ml/kg and their combination at 5 and 7.5 ml/kg, respectively. Diclofenac reduced (p?<?0.05 at least) paw edema at all time points. RAD of diclofenac enhanced (p?<?0.05) anti-inflammatory effect of diclofenac (5 mg/kg) at 2, 4, and 6 h on concurrent and at 2 and 4 h on sequential administration. Moreover at 2 h, anti-inflammatory effect of combination treatment reached values comparable to those of diclofenac (20 mg/kg). In conclusion, RAD of diclofenac enhanced anti-inflammatory effect of diclofenac.     

A meta-analysis on the efficacy and tolerability of natalizumab in relapsing multiple sclerosis

Introduction

Natalizumab is a new humanized monoclonal antibody used in multiple sclerosis (MS). The aim of this meta-analysis was to evaluate the efficacy and tolerability of this drug in relapsing MS. PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials were searched for studies that investigated the efficacy and/or tolerability of natalizumab in MS. Data were collected from 1966 to 2008 (up to October).

Material and methods

The search terms were: “multiple sclerosis” or “MS” and “natalizumab”. “Mean change in Expanded Disability Status Scale (EDSS)”, “number of patients with at least one relapse”, and “number of patients with at least one new gadolinium (Gd)-enhancing lesion” were the key outcomes of interest for assessment of efficacy. “Any adverse events”, “serious adverse events”, “death”, and “withdrawal because of adverse events” were the key outcomes for tolerability. Among existing trials, four randomized placebo controlled clinical trials met our criteria and were included.

Results

Pooled relative risk for at least one relapse in four trials including all doses was 0.7, with a non-significant RR (95% CI: 0.42–1.17, p = 0. 17). Summary RR for at least one relapse in two trials in which doses of 3 mg/kg or 6 mg/kg or 300 mg every 4 weeks were administered gave a value of 0.5 asa significant RR (95% CI: 0.42–0.61, p < 0.0001). The summary RR for at least one new Gd-enhancing lesion was 0.22, a non-significant RR (95% CI: 0.05–1.01, p = 0.051). Three deaths were reported in the natalizumab group. Comparing adverse events between natalizumab and placebo yielded a non-significant RR of 0.99 (95% CI: 0.96–1.01, p = 0.34) for any adverse events (n = 3), and a significant RR of 0.39 (95% CI: 0.29–0.52, p < 0.0001) for serious adverse events (n = 2). The summary RR for withdrawal due to adverse events by natalizumab vs. placebo therapy between two trials was 1.43, a non-significant RR (95% CI: 0.68–3.02, p = 0.35).

Conclusions

It seems that using 3 or 6 mg/kg every 4 weeks is the best method of administration of natalizumab for preventing relapse and occurrence of new Gd-enhancing lesions. The current data on the efficacy and safety of natalizumab are insufficient to reach a convincing conclusion and thus further clinical trials are still needed.     

Physio-pharmacological Investigations About the Anti-inflammatory and Antinociceptive Efficacy of (+)-Limonene Epoxide

D-limonene epoxidation generates (+)-limonene epoxide, an understudied compound in the pharmacologically point of view. Herein, we investigated the anti-inflammatory and antinociceptive potentialities of (+)-limonene epoxide and suggested a mechanism of action. The anti-inflammatory potential was analyzed using agents to induce paw edema, permeability, and myeloperoxidase (MPO) activity. Pro-inflammatory cytokines and cell migration of peritoneal cells were also assessed. Antinociceptive effects were evaluated by writhing test induced by acetic acid, formalin, and hot plate assays and contribution of opioid pathways. Pretreated animals with (+)-limonene epoxide showed reduced carrageenan-induced paw edema in all doses (25, 50, and 75 mg/kg) (P?<?0.05). At 75 mg/kg, it suppressed edema provoked by compound 48/80, histamine, prostaglandin E₂, and serotonin and reduced permeability determined by Evans blue and MPO activity. It also reduced leukocytes, neutrophils, and IL-1β levels in the peritoneal cavity in comparison with carrageenan group (P?<?0.05). (+)-Limonene epoxide diminished abdominal contortions induced by acetic acid (78.9%) and paw licking times in both 1 (41.8%) and 2 (51.5%) phases and a pretreatment with naloxone (3 mg/kg) reverted the antinociceptive action in morphine- and (+)-limonene epoxide-treated groups (P?<?0.05). Additionally, it enlarged response times to the thermal stimulus after 60 and 90 min. In conclusion, (+)-limonene epoxide inhibited release/activity of inflammatory mediators, vascular permeability, migration of neutrophils and displayed systemic and peripheral analgesic-dependent effects of the opioid system.     

Central administration of perfluorooctanoic acid inhibits cutaneous inflammation

Objective: To elucidate the site of action of perfluorooctanoic acid (PFOA) in the carrageenan model of peripheral inflammation.Subjects: Male Sprague-Dawley rats.Treatment: We first compared the anti-edema effects of systemic PFOA (50–150 mg/kg) with prototypical nonsteroidal (acetylsalicylic acid, ASA, 50–200 mg/kg) and steroidal (dexamethasone, 0.5–5.0 mg/kg) drugs after the intraplantar injection of carrageenan (1%). We then compared the anti-edema effects of systemic PFOA with local intraplantar (10 mg/kg), and intracerebroventricular (i.c.v., 0.1–50 μg) routes of administration.Results: Systemic PFOA was at least as or more efficacious than ASA or dexamethasone in reducing carrageenan-induced edema. RU-486 did not change the anti-edema effect of PFOA, ruling out a contribution of endogenous release of glucorticoids. I. c. v. PFOA, but not perfluorooctanes, dramatically reduced multiple signs of inflammation at doses well below the systemically-effective dose. We conclude that the anti-edema effect of high systemic doses of PFOA (≥100 mg/kg, i. p.) is mediated in part by actions in the brain.Received 30 August 2004; returned for revision 29 October 2004; accepted by G. Geisslinger 8 February 2005     

The hydrogen sulfide donor,Lawesson's reagent,prevents alendronate-induced gastric damage in rats

Our objective was to investigate the protective effect of Lawesson''s reagent, an H₂S donor, against alendronate (ALD)-induced gastric damage in rats. Rats were pretreated with saline or Lawesson''s reagent (3, 9, or 27 µmol/kg, po) once daily for 4 days. After 30 min, gastric damage was induced by ALD (30 mg/kg) administration by gavage. On the last day of treatment, the animals were killed 4 h after ALD administration. Gastric lesions were measured using a computer planimetry program, and gastric corpus pieces were assayed for malondialdehyde (MDA), glutathione (GSH), proinflammatory cytokines [tumor necrosis factor (TNF)-α and interleukin (IL)-1β], and myeloperoxidase (MPO). Other groups were pretreated with glibenclamide (5 mg/kg, ip) or with glibenclamide (5 mg/kg, ip)+diazoxide (3 mg/kg, ip). After 1 h, 27 µmol/kg Lawesson''s reagent was administered. After 30 min, 30 mg/kg ALD was administered. ALD caused gastric damage (63.35±9.8 mm²); increased levels of TNF-α, IL-1β, and MDA (2311±302.3 pg/mL, 901.9±106.2 pg/mL, 121.1±4.3 nmol/g, respectively); increased MPO activity (26.1±3.8 U/mg); and reduced GSH levels (180.3±21.9 µg/g). ALD also increased cystathionine-γ-lyase immunoreactivity in the gastric mucosa. Pretreatment with Lawesson''s reagent (27 µmol/kg) attenuated ALD-mediated gastric damage (15.77±5.3 mm²); reduced TNF-α, IL-1β, and MDA formation (1502±150.2 pg/mL, 632.3±43.4 pg/mL, 78.4±7.6 nmol/g, respectively); lowered MPO activity (11.7±2.8 U/mg); and increased the level of GSH in the gastric tissue (397.9±40.2 µg/g). Glibenclamide alone reversed the gastric protective effect of Lawesson''s reagent. However, glibenclamide plus diazoxide did not alter the effects of Lawesson''s reagent. Our results suggest that Lawesson''s reagent plays a protective role against ALD-induced gastric damage through mechanisms that depend at least in part on activation of ATP-sensitive potassium (K_ATP) channels.     

The involvement of the HO-1 pathway in the anti-inflammatory action of a sulfated polysaccharide isolated from the red seaweed Gracilaria birdiae

Objectives

The aim of this study was to investigate the involvement of the hemoxigenase-1 (HO-1) pathway in the anti-inflammatory action of a sulfated polysaccharide from the red seaweed Gracilaria birdiae (SP-Gb).

Methods

SP-Gb (5, 10 and 20?mg/kg) was administered to Wistar rats in a peritonitis model using carrageenan or a paw edema model using carrageenan or dextran. To analyze the involvement of HO-1 in the anti-inflammatory activity of SP-Gb, the animals were pretreated subcutaneously with a specific HO-1 inhibitor (ZnPP IX). To evaluate the systemic effects, SP-Gb (10?mg/kg) was administered to mice intraperitoneally before waiting for 48?h or for 14?days.

Results

SP-Gb (10?mg/kg) caused an anti-inflammatory effect that was evidenced by a decrease in leukocytes in the peritoneal cavity. SP-Gb also reduced the paw edema induced by carrageenan and inhibited the paw edema induced by dextran in the first half-hour. After being inhibited by ZnPP IX, the anti-inflammatory effect of SP-Gb on carrageenan-induced rat paw edema was not observed. SP-Gb did not cause mortality or significant changes in the biochemical, hematological and histopathological parameters.

Conclusion

SP-Gb may be used as a tool for further investigations into the inflammatory processes associated with the hemoxigenase-1 pathway.     

Anti-inflammatory and antipyretic effects of boldine

Boldine, and antioxidant alkaloid isolated fromPeumus boldus, exhibits a dose-dependent anti-inflammatory activity in the carrageenan-induced guinea pig paw edema test with an oral ED₅₀ of 34 mg/kg. Boldine also reduces bacterial pyrogen-induced hyperthermia in rabbits to an extent which varied between 51% and 98% at a dose of 60 mg/kg p.o.In vitro studies carried out in rat aortal rings revealed that boldine is an effective inhibitor of prostaglandin biosynthesis, promoting 53% inhibition at 75 M. The latterin vitro effect may be mechanistically linked to the anti-inflammatory and antipyretic effects of boldine exertedin vivo.     

Cyane-carvone,a Synthetic Derivative of Carvone,Inhibits Inflammatory Response by Reducing Cytokine Production and Oxidative Stress and Shows Antinociceptive Effect in Mice

Cyane-carvone (CC) was studied to elucidate its anti-inflammatory, antinociceptive, and antioxidant effects in Mus musculus. Anti-inflammatory (bradykinin, histamine, prostaglandin E₂, serotonin, and carrageenan) and antinociceptive (acetic acid and formalin) models were utilized. Myeloperoxidase activity, interleukin (IL)-1β, tumor necrosis factor alpha (TNF-α), and glutathione (GSH) levels were evaluated. Analysis of variance followed by Student-Newman-Keuls’ test was done. Results were compared with control groups (significantly when p?<?0.05). In bradykinin, histamine, prostaglandin E₂, and serotonin tests, 75 mg/kg CC decreased significantly paw edema (t?=?30, 60, 90, and/or 120 min). In carrageenan test, 50 and 75 mg/kg CC (t?=?3 h and t?=?4 h) and 25 mg/kg CC (t?=?4 h) decreased significantly paw edema. CC (75 mg/kg) inhibited significantly mieloperoxidase activity and decreased IL-1β and TNF-α, and all doses increased GSH levels. CC (75 mg/kg) decreased significantly the number of contortions of animals and time of licking (phase 2). CC showed anti-inflammatory, antinociceptive, and antioxidant effects in mice.     

Potentiation of diclofenac-induced anti-inflammatory response by aminoguanidine in carrageenan-induced acute inflammation in rats: The role of nitric oxide

Objective: To investigate whether aminoguanidine (AG) treatment enhances the anti-inflammatory effect of diclofenac in an acute inflammation model in rats.Material and methods: In 48 rats carrageenan-induced paw edema was used as an acute inflammation model. Inflammatory activity was assessed at 1.5, 3 and 6 h after sub-planter injection of carrageenan (0.1 ml of a 1% solution in 0.85% saline). The anti-inflammatory effect of diclofenac (25 mg/kg, i.p.) was studied in comparison to that of the selective inducible nitric oxide synthase (iNOS) inhibitor, AG, and of nitric oxide donor, sodium nitroprusside (SNP).Results: AG, failed to inhibit inflammation during the first 3 h following carrageenan administration, but caused a slight, although statistically insignificant inhibition at 6 h. Diclofenac significantly reduced the carrageenan-induced edema in rat paw at all the time points studied. Administration of diclofenac after AG pretreatment caused significant (P < 0.001) reduction in edema that was double that of diclofenac alone 6 h after carrageenan injection. Administration of SNP as a single dose after AG pretreatment prevented any potentiation of anti-inflammatory response that was observed in the case of AG combined with diclofenac treatment.Conclusion: These results show that AG markedly potentiates the anti-inflammatory activity of diclofenac at 6 h and this potentiation effect is nitric oxide-dependent.Received 28 October 2002; returned for revision 1 April 2003; accepted by I. Ahnfelt-Rønne 5 May 2003     

Role of endotoxin-like contaminants in the apparent anti-inflammatory activity of bovine superoxide dismutase

Bovine CuZn superoxide dismutase (SOD: 1, 3 and 10 mg/kg) dose-dependently reduced carrageenan-induced paw edema in rats when administered intravenously 30 min before irritant injection. However, heat-treated SOD (10 mg/kg) was as effective as native SOD (10 mg/kg) although the enzymic activity was reduced to 9.7%. Examination of the contaminants of the native SOD revealed a fairly large amount of endotoxin-like activity, 47 ng asEscherichia coli endotoxin per mg, and 59.6% of this activity remained after heat treatment. Bovine CuZn SOD (1, 3 and 10 mg/kg), which contained negligible endotoxin-like materials and 1.5 times more enzyme units, had no effect on edema under the same conditions. Furthermore,Escherichia coli endotoxin (10, 100 and 1000 ng/kg) reduced edema dose-dependently. These results suggest that contamination by endotoxin-like materials is responsible for the anti-inflammatory action of the SOD preparation we observed. Hence, the anti-inflammatory action of contaminating endotoxin-like materials may lead to misinterpretation as a protective effect of SOD unless stringent precautions are taken against endotoxin-like contaminants in the SOD under examination.accepted by M. Katori     

Antinociceptive,Anti-Inflammatory and Antipyretic Activities of the Leaf Methanol Extract of Ruta Graveolens L. (Rutaceae) in Mice and Rats

Background

Ruta graveolens has been used to treat toothache, earache, rheumatism and fever with little scientific evidence corroborating these uses.

Materials and Methods

The leaf methanol extract of Ruta graveolens was evaluated for antinociceptive activity using the acetic acid writhing and hot-plate tests in mice, also anti-inflammatory and antipyretic activities using the carrageenan-induced oedema and E. coli-induced pyrexia tests in rats, respectively.

Results

R. graveolens (100 mg/kg, i.p.), significantly reduced the number of acetic acid-induced writhes by 54 %. R. graveolens (400 mg/kg, i.p.), significantly delayed the reaction time in mice to thermal stimulation 15, 30, 45, and 60 min after treatment. Combined treatment of the lowest and sub-effective doses of the leaf methanol extract (25 mg/kg, i.p.), and indomethacin (10 mg/kg, i.p.) significantly reduced the number of acetic acid-induced writhes in mice. The leaf methanol extract of R. graveolens (50 – 400 mg/kg, i.p.), significantly reduced carrageenan-induced oedema over the 4 h period of testing. Combined treatment of the lowest doses of R. graveolens (25 mg/kg, i.p.) and indomethacin (2 mg/kg, i.p.) produced a significant reduction in carrageenan-induced oedema over the 4 h period of testing. R. graveolens (100 -400 mg/kg, i.p.) significantly reduced E. coli-induced pyrexia over the 5 h period of testing. Given together, the lowest dose of R. graveolens (25 mg/kg, i.p.) and pentoxifylline (10 mg/kg, i.p.) produced a significant reduction in pyrexia induced by E. coli (50 µg/kg, i.m.) over the 5 h period of measurement. The LD₅₀ value obtained for R. graveolens was greater than 4000mg/kg (p.o), suggesting that the plant species may be safe in or nontoxic to mice.

Conclusion

The data obtained indicate that R. graveolens has antinociceptive, anti-inflammatory and antipyretic activities, justifying the use of the plant species by traditional medicine practitioners in the management and treatment of pain, inflammation and fever.     

Evidence for the involvement of peripheral β-adrenoceptors in delayed liquid gastric emptying induced by dipyrone, 4-aminoantipyrine,and antipyrine in rats

Dipyrone (Dp), 4-aminoantipyrine (AA), and antipyrine (At) delay liquid gastric emptying (GE) in rats. We evaluated adrenergic participation in this phenomenon in a study in male Wistar rats (250-300 g) pretreated subcutaneously with guanethidine (GUA), 100 mg·kg⁻¹·day⁻¹, or vehicle (V) for 2 days before experimental treatments. Other groups of animals were pretreated intravenously (iv) 15 min before treatment with V, prazosin (PRA; 1 mg/kg), yohimbine (YOH; 3 mg/kg), or propranolol (PRO; 4 mg/kg), or with intracerebroventricular (icv) administration of 25 µg PRO or V. The groups were treated iv with saline or with 240 µmol/kg Dp, AA, or At. GE was determined 10 min later by measuring the percentage of gastric retention (%GR) of saline labeled with phenol red 10 min after gavage. %GR (mean±SE, n=8) indicated that GUA abolished the effect of Dp (GUA vs V=31.7±1.6 vs 47.1±2.3%) and of At (33.2±2.3 vs 54.7±3.6%) on GE and significantly reduced the effect of AA (48.1±3.2 vs 67.2±3.1%). PRA and YOH did not modify the effect of the drugs. %GR (mean±SE, n=8) indicated that iv, but not icv, PRO abolished the effect of Dp (PRO vs V=29.1±1.7 vs 46.9±2.7%) and At (30.5±1.7 vs 49±3.2%) and significantly reduced the effect of AA (48.4±2.6 vs 59.5±3.1%). These data suggest activation of peripheral β-adrenoceptors in the delayed GE induced by phenylpyrazolone derivatives.     

Anti-Inflammatory and Antioxidant Effects of an Ethanolic Extract of the Aerial Parts of Hilleria Latifolia (Lam.) H. Walt. (Phytolaccaceae)

Various parts of the perennial herb Hilleria latifolia (Lam.) H. Walt. (Family: Phytolaccaceae) are used in Ghanaian traditional medicine for the treatment of several inflammatory-related disorders. The present study examined the anti-inflammatory effect of an ethanolic extract of the aerial parts of Hilleria latifolia (HLE) in acute and chronic inflammation models. Since free radicals and reactive oxygen species are implicated in inflammatory diseases, the antioxidant potential of HLE was also investigated in in vitro experimental models. HLE (10–300 mg kg⁻¹, p.o.), either preemptively or curatively, significantly inhibited carrageenan-induced foot oedema in 7-day old chicks. Similarly, the NSAID diclofenac (10–100 mg kg⁻¹, i.p.) and the steroidal anti-inflammatory agent dexamethasone (0.3–3 mg kg⁻¹, i.p.) dose-dependently reduced the oedema in both pre-emptive and curative treatments. In the Freund''s adjuvant induced-arthritis model in rats, HLE as well as the positive controls, dexamethasone and methotrexate, showed significant anti-arthritic properties when applied to established adjuvant arthritis. HLE (10–300 mg kg⁻¹, p.o.) significantly reduced oedema in the ipsilateral paw of rats but failed to prevent systemic arthritic spread. The DMARD methotrexate (0.1–1 mg kg⁻¹, i.p.) and dexamethasone (0.3–3 mg kg⁻¹, i.p.) reduced significantly the total polyarthritic oedema as well as the spread of the arthritis from the ipsilateral to the contralateral paws of the treated animals. The extract (0.03–1.00 mg ml⁻¹) exhibited Fe³⁺ reducing activity, scavenged DPPH and prevented lipid peroxidation. These findings suggest that the extract exerts in vivo anti-inflammatory activity after oral administration and also has antioxidant properties which may contribute to its activity.