Evaluation of the anticonvulsant activity of 6-(4-chlorophenyoxy)-tetrazolo[5,1-a]phthalazine in various experimental seizure models in mice

This study investigated the anticonvulsant activity of a new phthalazine tetrazole derivative, QUAN-0808 (6-(4-chlorophenoxy)-tetrazolo[5,1-a]phthalazine), in the mouse maximal electroshock (MES) seizure model. The neurotoxicity of QUAN-0808 was investigated using the rotarod neurotoxicity test in mice. QUAN-0808 exhibited higher activity (median effective dose, ED₅₀ = 6.8 mg/ kg) and lower neurotoxicity (median toxic dose, TD₅₀ = 456.4 mg/kg), resulting in a higher protective index (PI = 67.1) compared with carbamazepine (PI = 6.4). In addition, QUAN-0808 exhibited significant oral anticonvulsant activity (ED₅₀ = 24 mg/kg) against MES-induced seizure with low neurotoxicity (TD₅₀ > 4500 mg/kg) in mice, resulting in a PI value of more than 187.5. QUAN-0808 was also tested in chemically induced animal models of seizure (pentylenetetrazole [PTZ], isoniazid [ISO], thiosemicarbazide [THIO] and 3-mercaptopropionic acid [3-MP]) to further investigate the anticonvulsant activity; QUAN-0808 produced significant anticonvulsant activity against seizures induced by ISO, THIO and 3-MP.     

Peripheral antinociception and anti-edematogenic effect of a sulfated polysaccharide from Acanthophora muscoides

BackgroundSulfated polysaccharides from red marine algae have presented a variety of potentially therapeutic biological effects, however, their antinocicpetive and anti-inflammatory properties are not well understood.MethodsMale Swiss mice were pretreated with a sulfated polysaccharidic fraction obtained from the marine alga Acanthophora muscoides (AmII) (1, 3 or 9 mg/kg, iv) 30 min prior to either receiving an injection of 0.8% acetic acid or 1% formalin or prior to a thermal stimulus. AmII (1, 3 or 9 mg/kg, sc) was evaluated on carrageenan-, dextran- bradykinin-, histamine- and serotonin-induced rat paw edema models. AmII (500 jig, sc) was also injected into the paw. Additionally, mice were treated with the total sulfated polysaccharides from A. muscoides (Am-TSP) (20 mg/kg, ip) for 14 days.ResultsAmII reduced the number of acetic acid-induced writhes and licking time in the second phase of the formalin test, but it did not alter the response latency in the hot plate test, suggesting that its antinociceptive action occurs through a peripheral mechanism. AmII did not reduce carrageenan-induced paw edema and MPO activity. However, it reduced dextran-, histamine- and serotonin- induced paw edemas, but not bradykinin-induced edema, suggesting that histamine is the major target of AmII anti-edematogenic activity. AmII inj ected into the paw did not evoke local edema. Furthermore, Am-TSP induced no consistent signs of systemic damage, as revealed by body mass, organs wet weight and by biochemical, hematological and histopathological analyses.ConclusionAmII has important antinociceptive and anti-inflammatory properties and represents an important therapeutic agent warranting future studies.     

Comparison of the effects of crocin,safranal and diclofenac on local inflammation and inflammatory pain responses induced by carrageenan in rats

BackgroundCrocin and safranal are the active substances of saffron and have many biological properties. In the present study, we compared the effects of crocin, safranal and diclofenac on local inflammation and its induced pain in rats.MethodsLocal inflammation was induced by intraplantar (ipl) injection of carrageenan (100 μl, 2%). Paw thickness was measured before and after carrageenan injection. Inflammatory pain responses including cold allodynia, mechanical allodynia and hyperalgesia were assessed using acetone spray and von Frey filament tests, respectively. The number of neutrophils in inflammatory zone was counted 6.5 h after injection of carrageenan.ResultsCarrageenan produced edema, cold allodynia, mechanical allodynia and hyperalgesia and caused neutrophil infiltration in paw tissues. Crocin at doses of 25, 50 and 100 mg/kg, safranal at doses of 0.5, 1 and 2 mg/kg and diclofenac (as a reference drug) at a dose of 10 mg/kg attenuated edema, suppressed inflammatory pain responses and decreased the number of neutrophils.ConclusionThe present study showed anti-inflammatory and antinociceptive activities for crocin, safranal and diclofenac in carrageenan model of local inflammation and inflammatory pain.     

Potential anti-inflammatory effect of Leea macrophylla Roxb. leaves: A wild edible plant

Leea macrophylla (Leeaceae) is a wild edible plant with ethomedicinal importance as anti-inflammatory agent. However, no systematic studies on its anti-inflammatory activity and mechanisms have been reported. Present study was undertaken to evaluate anti-inflammatory activity of methanol extract of L. macrophylla leaves. Phytochemical investigation revealed presence of sterols, triterpenoids and ascorbic acid in extract. Methanol extract inhibited lipopolysaccharide stimulated production of inflammatory mediators viz. prostaglandin E2, tumor necrotic factor-α, interleukin-6 and interleukin-1β in vitro in mouse peritoneal macrophages. Additionally, the in vivo anti-inflammatory activity of this extract was evaluated by using carrageenan induced paw edema and cotton pellet granuloma assays in experimental rats. Oral administration of extract (100 and 200 mg/kg) exhibited dose dependant inhibition of carrageenan induced inflammation (p < 0.05) and the reduction of the granuloma tissue formation (p < 0.05–0.01). The extract (100 and 200 mg/kg, orally) exhibited significant central and peripheral analgesic activity in hot-plate test (p < 0.01) and acetic acid induced writhing test (p < 0.05–0.01) respectively in experimental mice. Treatment with extract (100 and 200 mg/kg, orally) significantly reduced the yeast provoked elevated body temperature (p < 0.05–0.01) in experimental rats. These results confirmed the traditional anti-inflammatory indication of L. macrophylla leaves.     

Anti-inflammatory properties of rose oxide

Rose-oxide is a fragrance found in roses and rose oil. There are no reports about the pharmacological activity of this molecule. The present study was undertaken to evaluate whether rose-oxide (RO) has anti-inflammatory properties and to investigate possible mechanisms involved with its effects. The anti-inflammatory activity of RO was first suggested by the formalin test in mice, an inflammatory pain model, because intraperitoneal (i.p.) administration of RO (50 and 100 mg/kg) inhibited only the late phase of this test. To further investigate the anti-inflammatory properties of RO, the complete Freund's adjuvant (CFA)- and carrageenan-induced paw inflammation models were used. Pre-treatment with RO (50 and 100 mg/kg) significantly reduced paw edema at 4, 6 and 24 h after the CFA injection. In addition, RO (100 mg/kg) reduced the IL-1β, but not TNF-α, local production induced by CFA. Administration of RO (25–100 mg/kg) decreased the paw edema induced by carrageenan in rats, which was more evident at 3 and 4 h after induction. In addition, neutrophil migration to the hind paw was measured by MPO assay after the carrageenan injection. The MPO activity was significantly inhibited by RO at 25–100 mg/kg, 4 h after stimulus. In another experimental set, administration of RO (25–100 mg/kg) significantly reduced the leukocyte migration in the carrageenan-induced peritonitis model in mice. The results described here are the first report of pharmacological properties of RO and strongly suggest that RO possesses anti-inflammatory activity related to its ability to inhibit the IL-1β production and the leukocyte migration.     

Carvedilol can attenuate histamine-induced paw edema and formaldehyde-induced arthritis in rats without risk of gastric irritation

Background and aimRheumatoid arthritis treatment aims to control joint damage and any associated complications such as cardiovascular disease. Most anti-inflammatory drugs have a high tendency to cause gastro-intestinal irritation. The present study is designed to investigate the anti-inflammatory effect of carvedilol and to study its effect on gastric mucosa.Experimental approachLornoxicam (1.3 mg/kg) or carvedilol (10 mg/kg) was administrated orally 1 h before histamine injection into animals of a histamine-induced paw edema model and orally daily for 11 days into animals of a formaldehyde-induced arthritis model. Tumor necrosis factor-α and prostaglandin E₂ were measured in animals of the formaldehyde-induced arthritis model. The effect of lornoxicam and carvedilol on gastric mucosa was assessed in normal rats and after induction of cold stress ulcer.ResultsCarvedilol succeeded in reducing hind paw edema in both histamine-induced paw edema and formaldehyde-induced arthritis and in reducing the elevated level of tumor necrosis factor-α and prostaglandin E₂ nearly with near equal efficacy compared with lornoxicam. Carvedilol did not show any ulcerative effect on the gastric mucosa of normal rats, and its use was associated with an improvement of both the gross and histopathological pictures of gastric ulcers in animals of the cold stress ulcer model compared with lornoxicam treated rats.ConclusionThe current findings support the use of carvedilol both in the management of inflammation as well as the prevention of cardiovascular complications in rheumatoid arthritis patients. The use of carvedilol was not associated with any gastro-intestinal tract irritation.     

Gastric anti-ulcerative and anti-inflammatory activity of metyrosine in rats

In this study, the anti-inflammatory and anti-ulcerative effects of metyrosine, a selective tyrosine hydroxylase enzyme inhibitor, were investigated in rats. For ulcer experiments, indomethacin-induced gastric ulcer tests and ethanol-induced gastric ulcer tests were used. For these experiments, rats were fasted for 24 h. Different doses of metyrosine and 25 mg/kg doses of ranitidine were administered to rats, followed by indomethacin at 25 mg/kg for the indomethacin-induced ulcer test, or 50% ethanol for the ethanol-induced test. Results have shown that at all of the doses used (50,100 and 200 mg/kg), metyrosine had significant anti-ulcerative effects in both indomethacin and ethanol-induced ulcer tests. Metyrosine doses of 100 and 200 mg/kg (especially the 200 mg/kg dose) also inhibited carrageenan-induced paw inflammation even more effectively than indomethacin. In addition, to characterize the anti-inflammatory mechanism of metyrosine we investigated its effects on cyclooxygenase (COX) activity in inflammatory tissue (rat paw). The results showed that all doses of metyrosine significantly inhibited high COX-2 activity. The degree of COX-2 inhibition correlated with the increase in anti-inflammatory activity. In conclusion, we found that metyrosine has more anti-inflammatory effects than indomethacin and that these effects can be attributed to the selective inhibition of COX-2 enzymes by metyrosine. We also found that adrenalin levels are reduced upon metyrosine treatment, which may be the cause of the observed gastro-protective effects of this compound.     

Synthesis and pharmacological properties of new GABA uptake inhibitors

Backgroundγ-Aminobutanoic acid (GABA) is the principal inhibitory neurotransmitter in the mammalian central nervous system. The identification and subsequent development of the GABA transport inhibitors which enhance the GABA-ergic transmission has shown the important role that GABA transporters play in the control of numerous functions of the nervous system. Compounds which inhibit GABA uptake are used as antiepileptic drugs (tiagabine - a selective GAT1 inhibitor), they are also being investigated for other indications, including treatment of psychosis, general anxiety, sleep disorders, drug addiction or acute and chronic pain.MethodsIn this paper, the synthesis of 2-substituted-4-(1,3-dioxoisoindolin-2-ylo)-butanamides and 2-substituted-4-amino-butanoic acids derivatives is described. These compounds were tested in vitro for their ability to inhibit GABA uptake. The inhibitory potency towards murine plasma membrane GABA transporters (mGAT1-4) was performed as [³H]GABA uptake assay based on stably transfected HEK cells. Compound 18, which demonstrated the highest affinity for mGAT1-4 (pIC50 ranged from 4.42 for mGAT1 to 5.07 for mGAT3), was additionally investigated in several behavioral tests in mice.ResultsCompound 18 increased the locomotor activity (14–38%) and had anxiolytic-like properties in the four-plate test (ED₅₀ = 9.3 mg/kg). It did not show analgesic activity in acute pain model, namely the hot plate test, however, it was antinociceptive in the acetic acid-induced writhing test (ED₅₀ = 15.3 mg/kg) and in the formalin model of tonic pain. In the latter assay, it diminished nocifensive behavior in both phases and in the first (neurogenic) phase of this test the obtained ED50 value (5.3 mg/kg) was similar to morphine (3.0 mg/kg).ConclusionCompound 18 exhibited significant anxiolytic-like properties and was antinociceptive in some models of pain in mice. Moreover, it did not impair animals' motor coordination in the chimney test. Some of the described pharmacological activities of compound 18 can be partly explained based on its affinity for plasma membrane GABA transporters.     

Anti-inflammatory, antinociceptive and antioxidant activities of the endemic Soqotraen Boswellia elongata Balf. f. and Jatropha unicostata Balf. f. in different experimental models

In the present study, the two endemic Soqotraen plants Boswellia elongata and Jatropha unicostata were investigated for their anti-inflammatory, antinociceptive and antioxidant potential. To assess the anti-inflammatory and antinociceptive activities, two concentrations of each extract (200 and 400 mg/kg, p.o.) were tested in carrageenan-induced rat paw edema, cotton pellet granuloma in rats, acetic acid-induced abdominal writhing and hot-plate test model in mice. Moreover, the antioxidant activity was determined in vitro, using scavenging activity of DPPH radical and β-carotene-linoleic acid assays. Both plants produced significant (P < 0.05-0.01) anti-inflammatory and antinociceptive effects; however the results suggest that B. elongata possesses the highest activities. B. elongata and J. unicostata at (400 mg/kg) reduced the paw edema considerably (82% and 53%) and the weight of cotton pellet granuloma (51% and 32%), respectively. Furthermore, they diminished the abdominal constriction induced by acetic acid with a 67% and 41% inhibition respectively, and prolonged significantly the reaction time of animal with relatively extended duration of stimulation. In addition, both plants showed considerable antioxidant activity in both assays. These results clearly confirmed the traditional anti-inflammatory indication of B. elongata and suggest that B. elongata could be a potential source for anti-inflammatory, antinociceptive and antioxidant agents.     

Antinociceptive and anti-inflammatory activities of Viburnum opulus

Water extract of Viburnum opulus L. (Caprifoliaceae) (VO) leaf was investigated for antinociceptive and anti-inflammatory activities in mice and rats. The tail flick test, acetic acid-induced writhing test, and the carrageenan-induced rat paw edema test were used to determine these effects. Our findings show that VO causes dose related inhibition in acetic acid-induced abdominal stretching in mice. VO inhibited abdominal stretching at 100 and 200?mg/kg. VO showed antinociceptive activity, which was quantified by the tail-flick test at doses of 100 and 200?mg/kg. However, VO did not have an anti-inflammatory effect at these doses. The LD₅₀ of VO was determined as 5.447?g/kg.     

Further studies on anti-inflammatory activity of maprotiline in carrageenan-induced paw edema in rat

Antidepressant drugs are commonly used for treatment of different medical disorders besides of psychiatric diseases. Accumulating evidence suggests that antidepressants exhibit anti-inflammatory activity in vivo and in vitro conditions, but the mechanisms of this property are not clear very well. In our earlier work, we demonstrated that i.c.v. and i.p. injection of maprotiline, as an antidepressant, decreased paw edema at the fourth hour after subplantar injection of carrageenan. Therefore, this work was undertaken to investigate anti-inflammatory effects of maprotiline in more details. Our results verified that i.p. (25 and 50 mg/kg) and i.c.v. (100 μg/rat) application of maprotiline significantly reduced paw edema at 1, 2, 3 and 4 h intervals after carrageenan challenge. Pathological examinations and MPO activity also showed that both i.p. and i.c.v. maprotiline considerably inhibited infiltration of PMN leucocytes into the inflamed paws. Additionally, i.p. and i.c.v. maprotiline at all applied doses noticeably declined levels of IL-1β into the site of inflammation, while only i.p. maprotiline at a dose of 50 mg/kg significantly decreased TNF-α levels in the carrageenan-injected paws.These results confirmed anti-edematogenic activity of i.p. and i.c.v. maprotiline in the carrageenan induced paw edema model and showed that these properties of maprotiline might be mediated through inhibition of PMN infiltration and release of IL-1β and TNF-α.     

Ortho-eugenol exhibits anti-nociceptive and anti-inflammatory activities

Ortho-eugenol is a much used phenylpropanoid whose ability to reduce pain and inflammation has never been studied. Researching ortho-eugenol's antinociceptive and anti-inflammatory activity, and its possible mechanisms of action is therefore of interest. The administration of vehicle, ortho-eugenol (50, 75 and 100 mg/kg i.p.), morphine (6 mg/kg, i.p.) or dexamethasone (2 mg/kg, s.c.) occurred 30 min before the completion of pharmacological tests. Pretreatment with ortho-eugenol did not change motor coordination test results, but reduced the number of writhes and licking times in the writhing test and glutamate test, respectively. The reaction time from thermal stimulus was significantly increased in the hot plate test after administration of ortho-eugenol. Treatment with yohimbine reversed the antinociceptive effect of ortho-eugenol, suggesting involvement of the adrenergic system. In anti-inflammatory tests, ortho-eugenol inhibited acetic acid induced vascular permeability and leukocyte migration, reducing TNF-α and IL-1β by virtue of its suppression of NF-κB and p38 phosphorylated forms in the peritonitis test. From these results, ortho-eugenol antinociceptive effects mediated by the adrenergic system and anti-inflammatory activity through regulation of proinflammatory cytokines and phosphorylation of NF-kB and p38 become evident for the first time.     

Comparative study of the anti-edematogenic effects of anethole and estragole

BackgroundAnethole and estragole are monoterpene position isomers and constituents of essential oils from aromatic plants and were used in this study with the aim of analyzing their anti-inflammatory activity.MethodsThe anti-edematogenic effects of anethole and estragole were evaluated through plethysmometry in Swiss mice.ResultsAnethole inhibited carrageenan-induced edema at doses of 3, 10 and 30 mg/kg from 60 to 240 min after induction. However, the inhibitory effects of estragole were observed only from 60 to 120 min at the two highest doses. Anethole and estragole similarly inhibited edema elicited by substance P, bradykinin, histamine and TNF-α but were different in the inhibition of serotonin-elicited edema. In addition, only estragole inhibited sodium nitroprusside-induced edema.ConclusionsAnethole and estragole showed different profiles in the anti-inflammatory response to substance P, bradykinin, histamine, serotonin and TNF-α. NO is involved only in the inhibition mechanism of estragole.     

Shikimic acid inhibits LPS-induced cellular pro-inflammatory cytokines and attenuates mechanical hyperalgesia in mice

Background and aimsShikimic acid (SA) is present in a wide variety of plants and microorganisms used in traditional and folk medicine and also is an essential starting material for the synthesis of the antiviral drug Oseltamivir (Tamiflu®). Some pharmacological actions observed in SA-enriched products include antioxidant and anti-inflammatory activities. Here, we investigated the anti-inflammatory and antinociceptive actions of isolated SA.MethodsRAW 264.7 macrophage cells were treated with bacterial LPS (1 μg/mL) and the effect of SA on the modulation of cell viability, nitric oxide (NO) production, TNF-α, and IL-1β content and MAPK (ERK1/2 and p38) activation was evaluated. Besides, the anti-hyperalgesic actions of SA on in vivo model of mechanical hyperalgesia induced by carrageenan (CG), dopamine (DA), TNF-α and prostaglandin (PGE₂) were assessed.ResultsIn RAW 264.7 cells, SA suppressed LPS-induced decrease in cell viability and nitrite accumulation to control values and inhibited up-regulation of TNF-α (65%) and IL-1β (39%). These effects may be mediated at least in part by inhibition of LPS-induced ERK 1/2 (22%) and p38 (17%) phosphorylation. In mice, SA at 50, 100, and 200 mg/kg decreased formalin-induced nociceptive behavior (around 50%) and inhibited the inflammatory nociception induced by TNF-α and PGE₂ (50 to 75% each). Moreover, SA (100 and 200 mg/kg) significantly attenuated the mechanical hyperalgesia induced by CG and DA (25 to 40% each).ConclusionsThese results indicate that SA presents anti-inflammatory actions with potential for development of drugs to treat pro-inflammatory and painful conditions.     

The validation of Calophyllum brasiliense (“guanandi”) uses in Brazilian traditional medicine as analgesic by in vivo antinociceptive evaluation and its chemical analysis

Calophyllum brasiliense is used as anti-inflammatory and analgesic in Brazilian traditional medicine. Thus, the main purpose of this study is to evaluate the antinociceptive effect of the chloroform fraction of C. brasiliense (CFCB) roots and to investigate its main mechanism of action. The antinociceptive effect of CFCB was evaluated in mice using acetic acid-induced writhing, formalin-induced paw licking, and hot-plate tests and capsaicin- and glutamate-induced nociception. Brasiliensic acid and 1,2-dimethoxyxanthone were isolated and evaluated in writhing test. The amount of 1,2-dimethoxyxanthone was determined in the fraction by UPLC-DAD. CFCB inhibited abdominal constrictions induced by acetic acid up to 97%, with an ID₅₀ of 9.4 mg/kg (i.p.) and 131.8 mg/kg (p.o.). In the formalin test, CFCB impaired paw licking with an ID₅₀ of 26.3 mg/kg for the first phase and 27.5 mg/kg for the second phase (i.p.). The painful response evoked by capsaicin and glutamate was significantly reduced (ID₅₀ 26.7 and 47.9 mg/kg, i.p.). The latency time was increased up to 76% at 60 mg/kg (i.p.) in the hot-plate test. 1,2-Dimethoxyxanthone was almost three times more potent (ID₅₀ 27.6 μmol/kg, i.p.) than brasiliensic acid (72.0 μmol/kg) in acetic acid-induced writhing test. The amount of the xanthone was estimated as 92.5 mg/g in the extract. CFCB inhibited the nociceptive response associated to several agents. TRPV1 channels play an important role in the mechanism of action of the fraction. In addition, 1,2-dimethoxyxanthone largely contributes to the antinociceptive effect of CFCB.

     

Analgesic,anti-inflammatory and anti-platelet activities of the methanolic extract of <Emphasis Type="Italic">Acacia modesta</Emphasis> leaves

The current study was aimed to evaluate Acacia modesta for analgesic, anti-inflammatory, and anti-platelet activities. The analgesic and anti-inflammatory effects were assessed in rodents using acetic acid and formalin-induced nociception, hot plate and carrageenan-induced rat paw oedema tests. The intraperitoneal (i.p.) administration of the methanolic extract (50 and 100 mg/kg) produced significant inhibition (P < 0.01) of the acetic acid-induced writhing in mice and suppressed formalin-induced licking response of animals in both phases of the test. In the hot plate assay the plant extract (100 mg/kg) increased pain threshold of mice. Naloxone (5 mg/kg i.p.) partially reversed the analgesic effect of the extract in formalin and hot plate tests. A. modesta (100 and 200 mg/kg i.p.) exhibited sedative effect in barbiturate-induced hypnosis test similar to that produced by diazepam (10 mg/kg i.p.). The plant extract (50–200 mg/kg i.p.) produced marked anti-inflammatory effect in carrageenan-induced rat paw oedema assay comparable to diclofenac and produced a dose-dependent (0.5–2.5 mg/mL) inhibitory effect against arachidonic acid induced platelet aggregation. These data suggest that A. modesta possesses peripheral analgesic and anti-inflammatory properties, with analgesic effects partially associated with the opioid system.     

Antinociceptive effect of d-Lys2, Dab4 N-(ureidoethyl)amide,a new cyclic 1-4 dermorphin/deltorphin analog

BackgroundA preliminary evaluation of antinociceptive activity of a new cyclic dermorphin/deltorphin tetrapeptide analog restricted via a urea bridge and containing C-terminal ureidoethylamid {[H-Tyr-d-Lys(&¹)-Phe-Dab(&²)-CH₂CH₂NHCONH₂][&¹CO&²]} (cUP-1) revealed a significant and long-lasting increase of pain threshold to thermal stimulation after systemic application. The current studies were aimed at further evaluation of cUP-1 activity in animal models of somatic and visceral pain. The influence of cUP-1 on motor functions was also investigated.MethodsThe influence of cUP-1 (0.5–2 mg kg⁻¹, iv) on nociceptive threshold to mechanical pressure and analgesic efficacy in formalin and acetic acid-induced writhing tests were estimated. The antinociceptive effect of cUP-1 was compared to that of morphine (MF). The influence of cUP-1 (1, 4 and 8 mg kg⁻¹, iv) on locomotor activity, motor coordination and muscle strength was estimated using open field and rota-rod tests and a grip strength measurement.ResultsAdministration of cUP-1 in doses of 1 and 2 mg kg⁻¹ elicited a significant increase of nociceptive threshold to mechanical pressure. MF applied in the same doses induced an antinociceptive effect only at the higher dose (2 mg kg⁻¹). There were no marked differences between the effect of cUP-1 and MF at each dose, at relative time points. In the writhing test and both phases of the formalin test, cUP-1 showed a significant, dose-dependent antinociceptive effect which did not markedly differ from that of MF. cUP-1 did not significantly affect motor functions of mice.ConclusionsSystemic application of cUP-1 elicited a dose-dependent antinociceptive effect. The analgesic efficacy of cUP-1 on mechanical nociception, visceral and formalin-induced pain was comparable to that of MF. cUP-1 did not impair motor functions of mice.     

Influence of zinc hydroaspartate on the anti-inflammatory and gastric activity of ketoprofen in rats

BackgroundThe study's aim was to evaluate the anti-inflammatory effect and influence on gastric mucosa after the combined administration of ketoprofen and zinc hydroaspartate (ZHA, 60 mg/kg).MethodsAntiedematous activity was determined according to Winter et al., analgesic activity according to the Randall and Selitto test, the influence on gastric mucosa in accordance to Komatsu.ResultsSingle and subchronic administration of ZHA and single ketoprofenpo caused a significant reduction of the rat hind paw edema in comparison to the control groups. ZHA alone administrated ip four times was active after the 1^st, 2^nd and 3^rd h from the carrageenan injection.ConclusionsZHA enhanced the anti-inflammatory effect of ketoprofen.     

Isolates of Alpinia officinarum Hance as COX-2 inhibitors: Evidence from anti-inflammatory,antioxidant and molecular docking studies

BackgroundInflammation triggered by oxidative stress can cause various ailments, such as cancer, rheumatoid arthritis, asthma, diabetes etc. In the last few years, there has been a renewed interest in studying the antioxidant and anti-inflammatory action of plant constituents such as flavonoids and diarylheptanoids.AimTo evaluate the antioxidant, anti-inflammatory activity and the total phenolic content of isolated compounds from Alpinia officinarum rhizomes. Furthermore, molecular docking was performed to study the binding mode of these compounds into the active site of cyclooxygenase-2 (COX-2).MethodsA. officinarum rhizomes were extracted by maceration, using methanol. This extract was further fractionated by partitioning with hexane, chloroform and ethyl acetate and these fractions on further purification resulted in isolation of five pure compounds. Characterization was carried out by using ¹H NMR, ¹³C NMR and MS. They were further evaluated for antioxidant and anti-inflammatory activity using carrageenan-induced paw edema model in rats. Molecular docking study was performed using Glide module integrated in Schrodinger molecular modeling software.ResultsThe compounds were identified as 1,7-diphenylhept-4-en-3-one (1), 5-hydroxy-1,7-diphenyl-3-heptanone (2), 3,5,7-trihydroxyflavone (Galangin, 3), 3,5,7-trihydroxy-4′-methoxyflavone (Kaempferide, 4) and 5-hydroxy-7-(4″-hydroxy-3″-methoxyphenyl)-1-phenyl-3-heptanone (5). The compound-3 and compound-5 (10 mg/kg) showed significant (p < 0.001) antioxidant and anti-inflammatory potential. Moreover, total phenolic content was detected as 72.96 mg and 51.18 mg gallic acid equivalent respectively. All the five isolates were found to be good binders with COX-2 (average docking score − 9.03).ConclusionsGalangin and 5-hydroxy-7-(4″-hydroxy-3″-methoxyphenyl)-1-phenyl-3-heptanone exhibited anti-inflammatory and in-vitro antioxidant activity which may be due to presence of phenolic content in it. The molecular docking study revealed that these compounds have affinity towards COX-2 active site which can further be explored as selective COX-2 inhibitors. The results obtained in this work justify the use of A. officinarum in the treatment of inflammatory disorders like rheumatoid arthritis and inflammatory bowel diseases.