Carvacryl acetate,a derivative of carvacrol,reduces nociceptive and inflammatory response in mice

Aims

The present study aimed to investigate the potential anti-inflammatory and anti-nociceptive effects of carvacryl acetate, a derivative of carvacrol, in mice.

Main methods

The anti-inflammatory activity was evaluated using various phlogistic agents that induce paw edema, peritonitis model, myeloperoxidase (MPO) activity, pro and anti-inflammatory cytokine levels. Evaluation of antinociceptive activity was conducted through acetic acid-induced writhing, hot plate test, formalin test, capsaicin and glutamate tests, as well as evaluation of motor performance on rotarod test.

Key findings

Pretreatment of mice with carvacryl acetate (75 mg/kg) significantly reduced carrageenan-induced paw edema (P < 0.05) when compared to vehicle-treated group. Likewise, carvacryl acetate (75 mg/kg) strongly inhibited edema induced by histamine, serotonin, prostaglandin E₂ and compound 48/80. In the peritonitis model, carvacryl acetate significantly decreased total and differential leukocyte counts, and reduced levels of myeloperoxidase and interleukin-1 beta (IL-1β) in the peritoneal exudate. The levels of IL-10, an anti-inflammatory cytokine, were enhanced by carvacryl acetate. Pretreatment with carvacryl acetate also decreased the number of acetic acid-induced writhing, increased the latency time of the animals on the hot plate and decreased paw licking time in the formalin, capsaicin and glutamate tests. The pretreatment with naloxone did not reverse the carvacryl acetate-mediated nociceptive effect.

Significance

In conclusion, the current study demonstrated that carvacryl acetate exhibited anti-inflammatory activity in mice by reducing inflammatory mediators, neutrophil migration and cytokine concentration, and anti-nociceptive activity due to the involvement of capsaicin and glutamate pathways.     

Bioactivity-guided fractionation for analgesic properties and constituents of Vitex negundo L. seeds

This study was undertaken to ascertain the analgesic properties of Vitex negundo L. seeds and to isolate and characterize the active constituents. Among the 80% ethanol extract and some fractions with different polarity, the acetoacetate fraction showed the highest anti-nociceptive activity in acetic acid-induced writhing test in ICR mice. The analgesic bioguided isolation of the acetoacetate fraction yielded two major lignans: 6-hydroxy-4-(4-hydroxy-3-methoxy-phenyl)-3-hydroxymethyl-7-methoxy-3, 4-dihydro-2-naphthaldehyde (1) and vitedoamine A (2). Given orally, compound (1), which was more productive, produced significant inhibitions on chemical nociception induced by intraperitoneal acetic acid and subplantar formalin injections and exhibited notable anti-inflammatory activities in dimethyl benzene-induced ear edema test in a dose-dependent manner. Since co-administration of naloxone fails to antagonize the analgesic activity of compound (1) in the formalin test, we suggest that compound (1) possesses potent analgesic effects which are most likely to be mediated by its anti-inflammatory activity rather than through opioid receptor system and therefore could partially explain the anti-nociceptive effect of V. negundo L. seeds.     

Anti-nociceptive and anti-inflammatory properties of the ethanolic extract of Lagenaria breviflora whole fruit in rat and mice

The present study was conducted to evaluate the anti-nociceptive and anti-inflammatory properties of an ethanol extract of whole fruit of Lagenaria breviflora (LB) in rat and mice. Analgesic activity was measured by hot plate, formalin-induced paw licking, and acetic acid-induced abdominal writhing tests, while anti-inflammatory activity was determined by inhibition of carrageenan-induced paw oedema. Extract-treated animals exhibited significantly (P.     

Antinociceptive and anti-inflammatory activities of butein in different nociceptive and inflammatory mice models

BackgroundAround 30% world population affected by acute and chronic pain due to inflammation and accidental injuries. Pain is a uncomfortable sensation and it reduce the patients’ life quality.ObjectiveThe present exploration focuses to explore the beneficial effects of butein on the different chemical and thermal-provoked nociceptive and inflammatory mice models.MethodologyThe nociception was induced to the Swiss mice using different chemical (formalin, acetic acid, glutamate, and capsaicin) and thermal (hot plate and tail immersion) methods. the mice were supplemented with 10, 15, and 20 mg/kg of butein and respective standard drugs like morphine, diclofenac sodium, and dexamethasone. The anti-inflammatory effects of butein was studied using carrageenan-provoked inflammation in mice.ResultsThe present findings clearly demonstrated that the butein was substantially lessened the different thermal and chemical provoked nociception in mice. The carrageenan-triggered paw edema and inflammatory cell infiltrations were appreciably suppressed by the butein treatment. The TNF-α, IL-1β, and IL-6 levels in the carrageenan-induced mice were effectively depleted by the butein.ConclusionAltogether, the present findings evidenced the potent antinociceptive and anti-inflammatory properties of the butein in different nociceptive mice models.     

Anti--Histaminic potentila of fractions from Hedranthera Barteri [(Hook F.) Pichon] root in laboratory rodents

Hedranthera barteri, anti-inflammatory activity, anti-nociceptive activity, anti-histaminic activityL. (HB) is used in the treatment of painful conditions and oedema amongst its folkloric use. The hexane and ethyl acetate fractions of the root of H. barteri were investigated for anti-nociceptive and antiinflammatory properties and probable mechanism of action. Hot plate, tail flick, formalin-induced oedema and acetic acidinduced writhing tests were employed to investigate the anti-nociceptive activity while the anti-inflammatory activity was investigated using carrageenan-induced paw oedema. Anti-histaminic potential of HB root extracts on the rat peritoneal mast cells (RPMCs) was explored through pectrofluorometric method. The root was screened for its phytochemical components. The HB root contains alkaloids,cardenolides and saponins. HXHBR exhibited higher anti-inflammatory potentials (P <0.001). HXHBR dose-dependently (P <0.01) reduced the histamine release from the rat peritoneal mast cells which is comparable with a standard anti-histaminic drug, ketotifen. These results showed that EAHBR and HXHBR possess anti-nociceptive and anti-inflammatory activities, and suggested its mechanism of action through the inhibition of histamine, an inflammatory mediator, usually released during the early phase of allergic responses and chronic phase of inflammatory pain. Flavonoids, alkaloids and/or saponins present in HB root may be responsible for its anti-nociceptive and anti-inflammatory properties.     

Polysaccharide peptides from COV-1 strain of Coriolus versicolor induce hyperalgesia via inflammatory mediator release in the mouse

Polysaccharide peptide (PSP), isolated from Coriolus versicolor COV-1, has been widely used as an adjunct to cancer chemotherapy and as an immuno-stimulator in China. In this study, the anti-nociceptive effects of PSP were investigated in two different pain models in the mouse. In the acetic acid-induced writhing model, initial studies showed that PSP decreased the number of acetic acid-induced writhing by 92.9%, which, by definition, would constitute an analgesic effect. However, further studies showed that PSP itself induced a dose-dependent writhing response. Studies on inflammatory mediator release showed that PSP increased the release of prostaglandin E2, tumor necrosis factor-alpha, interleukin-1beta, and histamine in mouse peritoneal macrophages and mast cells both in vitro and in vivo. The role of inflammatory mediator release in PSP-induced writhing was confirmed when diclofenac and dexamethasone decreased the number of writhing responses by 54% and 58.5%, respectively. Diphenhydramine totally inhibited the PSP-induced writhing. In the hot-plate test, PSP dose-dependently shortened the hind paw withdrawal latency, indicative of a hyperalgesic effect. The hyperalgesic effect was reduced by pretreatment with the anti-inflammatory drugs. In conclusion, the PSP-induced hyperalgesia was related to activation of peritoneal resident cells and an increase in the release of inflammatory mediators.     

Analgesic and Anti-Inflammatory Properties of Gelsolin in Acetic Acid Induced Writhing,Tail Immersion and Carrageenan Induced Paw Edema in Mice

Plasma gelsolin levels significantly decline in several disease conditions, since gelsolin gets scavenged when it depolymerizes and caps filamentous actin released in the circulation following tissue injury. It is well established that our body require/implement inflammatory and analgesic responses to protect against cell damage and injury to the tissue. This study was envisaged to examine analgesic and anti-inflammatory activity of exogenous gelsolin (8 mg/mouse) in mice models of pain and acute inflammation. Administration of gelsolin in acetic acid-induced writhing and tail immersion tests not only demonstrated a significant reduction in the number of acetic acid-induced writhing effects, but also exhibited an analgesic activity in tail immersion test in mice as compared to placebo treated mice. Additionally, anti-inflammatory function of gelsolin (8 mg/mouse) compared with anti-inflammatory drug diclofenac sodium (10 mg/kg)] was confirmed in the carrageenan injection induced paw edema where latter was measured by vernier caliper and fluorescent tomography imaging. Interestingly, results showed that plasma gelsolin was capable of reducing severity of inflammation in mice comparable to diclofenac sodium. Analysis of cytokines and histo-pathological examinations of tissue revealed administration of gelsolin and diclofenac sodium significantly reduced production of pro-inflammatory cytokines, TNF-α and IL-6. Additionally, carrageenan groups pretreated with diclofenac sodium or gelsolin showed a marked decrease in edema and infiltration of inflammatory cells in paw tissue. Our study provides evidence that administration of gelsolin can effectively reduce the pain and inflammation in mice model.     

Elucidation of possible mechanism of analgesic action of Valeriana wallichii DC chemotype (patchouli alcohol) in experimental animal models

Valeriana wallichii (Family Valerianaceae), popularly named as Indian valerian, exists as three chemotypes. Aim of the study was to evaluate the effect of V. wallichii chemotype (patchouli alcohol) extract (DCME) and essential oil (VPAEO) on experimental models of nociception and to elucidate its possible mechanism of action. Analgesic effect was evaluated using acetic acid induced writhing and tail flick model. DCME and VPAEO (40 and 80 mg/kg, p.o.) significantly inhibited the number of writhings as compared to vehicle treated group. None of the doses of DCME and VPAEO exhibited any effect in tail flick model suggesting only peripheral analgesic activity. When studied for mechanism of action in acetic acid induced writhing, subeffective dose of essential oil significantly potentiated the effect of aspirin while no potentiation was seen in case of extract. These data suggest that essential oil VPAEO exerted peripheral analgesic via inhibition of prostaglandin synthesis.     

Antinociceptive properties of acetylenic thiophene and furan derivatives: evidence for the mechanism of action

The aim of the present study was to evaluate the antinociceptive potential of the acetylenic thiophene and furan derivatives: 3-(furan-2-il) prop-2-yn-1-ol 1, 1-(thiofen-2-il) pent-1yn-3-ol 2 and 4-(thiofen-2-il)-2-metilbut-3-yn-2-ol 3 on three different pain models in mice. The pain models evaluated were the acetic acid-induced writhing, capsaicin-induced pain and the tail immersion test. The possible mechanisms involved in the antinociceptive effect of these compounds were also investigated. Thus, the acetylenic thiophene and furan derivatives presented antinociceptive effect in the pain tests caused by chemical agents. Statistical analysis showed that compounds 1 and 3 increased the latency for tail withdrawal in the tail immersion test (phasic pain). Besides, the role of the opioidergic, muscarinic cholinergic and dopaminergic systems in the acetic acid-induced writhing was examined. The antinociceptive effect of compounds 2 and 3 was prevented by pretreatment with naloxone (1 mg/kg, s.c), but not by atropine (5 mg/kg, s.c) or metoclopramide (1 mg/kg, s.c). Neither naloxone nor metoclopramide prevented the antinociceptive effect caused by compound 1, while the pretreatment with atropine antagonized the antinociceptive action of this compound. The compounds 1-3 used in this study did not reveal any motor impairment to mice in the open field. The results suggest that compounds 2 and 3 induced antinociception in the abdominal writhing test and that their effects are mediated by opiodergic receptors, while the antinociceptive effect of compound 1 may involve muscarinic cholinergic receptors.     

Analgesic activity of methanol extract of Eupatorium adenophorum Spreng. leaves

The methanol extract of the leaves of E. adenophorum (100, 200 and 300 mg/kg, po) showed significant analgesic activity, as compared to standard drugs diclofenac sodium and pentazocine, employing acetic acid-induced writhing test, tail immersion test and tail flick test models.     

Inhibition of <Emphasis Type="SmallCaps">d</Emphasis>-Amino-Acid Oxidase Activity Induces Pain Relief in Mice

(1). We investigated the effects of inhibiting d-amino-acid oxidase (DAO) activity on nociceptive responses through the use of mutant ddY/DAO⁻ mice, which lack DAO activity, and through the application of a selective inhibitor of DAO, sodium benzoate, in the tail flick test, hot-plate test, formalin test, and acetic acid-induced writhing test. (2). Compared with normal ddY/DAO⁺ mice, ddY/DAO⁻ mice showed significantly prolonged tail withdrawal latency in the tail flick test and licking/jumping latency in the hot-plate test, as well as significantly reduced duration of licking/biting in the late phase of the formalin test and the number of abdominal writhing in the acetic acid-induced writhing test. (3). In addition, we investigated the effects of sodium benzoate in Kunming mice having normal DAO activity. (4). Intravenous administration of sodium benzoate (400 mg/kg) significantly inhibited pain responses of the late phase of the formalin test and abdominal writhing responses in the acetic acid-induced writhing test, with no effects on the early phase flinch responses in the formalin test, nociceptive responses in the tail flick test, or hot-plate test. (5). These results suggest that DAO acts as a pro-nociceptive factor in pain, particularly chronic pain, transmission and modulation, and may be a target for pain treatment.     

Antinociceptive activity of methanolic extract of leaves of Achyranthes aspera Linn. (Amaranthaceae) in animal models of nociception

Antinociceptive activity of methanolic extract of leaves of A. aspera was studied by peripheral/non-narcotic model of nociception like acetic acid induced writhing syndrome test and central/narcotic models like hot plate and tail flick tests. The methanolic extract of the plant, administered orally (@ 300, 600 and 900 mg/kg, body weight) and the standard drug (piroxicam; 10 mg/kg body weight, po) produced significant analgesic activity in acetic acid induced writhing syndrome as compared to the vehicle treated control group. In the hot plate analgesic test, in A. aspera at the above doses and the standard drug treated group (morphine sulphate @ 1.5 mg/kg, ip), the duration of reaction time (sec) increased dose dependently and significantly compared to the control group. In the tail flick test, the plant extract produced dose dependant increase in reaction time which was significantly higher in the test and standard group compared to the control group. The plant possesses significant antinociceptive property as evidenced in all the animal models of nociception. It might possibly exert its effect through diverse mechanism that may involve both central and peripheral pathways. The preliminary phytochemical investigation revealed the presence of steroids, alkaloids and triterpene in the methanolic extract of leaves of A. aspera which may be responsible for its antinociceptive activity.     

Pharmacological insights into Merremia vitifolia (Burm.f.) Hallier f. leaf for its antioxidant,thrombolytic, anti-arthritic and anti-nociceptive potential

Merremia vitifolia (Burm.f.) Hallier f., an ethnomedicinally important plant, used in the tribal areas to treat various ailments including fever, headache, eye inflammation, rheumatism, dysentery, jaundice and urinary diseases. The present study explored the biological efficacy of the aqueous fraction of M. vitifolia leaves (AFMV) through in vitro and in vivo experimental models. The thrombolytic and anti-arthritic effects of AFMV were evaluated by using the clot lysis technique and inhibition of protein denaturation technique, respectively. The anti-nociceptive activity of AFMV was investigated in Swiss Albino mice by acetic acid-induced writhing test and formalin-induced paw licking test. The antioxidant activities of AFMV, including 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical and total reducing power, were also tested. The qualitative phytochemical assays exhibited AFMV contains secondary metabolites such as alkaloid, carbohydrate, flavonoid, tannin, triterpenoids and phenols. In addition, AFMV showed strong antioxidant effects with the highest scavenging activity (IC₅₀ 146.61 µg/mL) and reducing power was increased with a dose-dependent manner. AFMV also revealed notable clot lysis effect and substantial anti-arthritic activity at higher doses (500 µg/mL) as compared with the control. The results demonstrated a promising reduction of the number of writhing and duration of paw licking in acetic acid-induced writhing test and formalin-induced paw licking test in a dose-dependent manner, respectively. In conclusion, AFMV provides the scientific basis of its folkloric usage, suggesting it as the vital source of dietary supplement.     

Analgesic,anti-inflammatory and anti-ulcer properties of Thai Perilla frutescence fruit oil in animals

Perilla frutescens fruit oil (PFO) is rich in α-linolenic acid (ALA) and exhibits biological activities. We aimed to investigate analgesic, anti-inflammatory and anti-ulcer activities of PFO and PFO-supplemented soybean milk (PFO-SM) in animal models. Analgesic activity was assessed in acetic acid-induced writhing in mice, while anti-inflammatory activity was performed in ethyl phenylpropiolate (EPP)-induced ear edema and carrageenan-induced hind paw edema in rats. Anti-ulcer effects were conducted in water immersion stress, HCl/ethanol and indomethacin-induced gastric ulcer in rats. Distinctly, PFO, containing 6.96 mg ALA and 2.61 mg LA equivalence/g, did not induce acute toxicity (LD₅₀ > 10 mL/kg) in mice. PFO (2.5 and 5 mL/kg) and PFO-SM (0.05 mL PFO equivalence/kg) inhibited incidences of writhing (16.8, 18.0 and 32.3%, respectively) in acetic acid-induced mice. In addition, topical applications of PFO (0.1 and 1 mL/ear) significantly inhibited EPP-induced ear edema (59.3 and 65.7%, respectively) in rats, while PFO-SM slightly inhibited ear edema (25.9%). However, PFO and PFO-SM did not inhibit carrageenan-induced hind paw edema in rats. Indeed, PFO (2.5 and 5 mL/kg) significantly inhibited gastric ulcers in rats that induced by water immersion stress (92.4 and 96.6%, respectively), HCl/ethanol (74.8 and 73.3%, respectively) and indomethacin (68.8 and 88.9%, respectively), while PFO-SM did not. PFO displayed potent analgesic, anti-inflammatory and anti-ulcer properties, while PFO-SM exerted only analgesic properties. Thus, Thai PFO and its functional drink offer potential benefits in treatment of analgesic, inflammatory diseases and gastric ulcer.     

Antinociceptive activity of petroleum ether fraction from the MeOH extracts of Paederia scandens in mice

The petroleum ether fraction of MeOH extract from Paederia scandens was evaluated on anti-nociceptive activity in mice using chemical and thermal models of nociception. Given orally, the petroleum ether fraction (PEF) at doses of 20, 40 and 80 mg/kg produced significant inhibitions on chemical nociception induced by intraperitoneal acetic acid and subplantar formalin or capsaicin injections and on thermal nociception in the tail-flick test and in the hot plate test. More significant inhibition of nociception was observed at dose of 80 mg/kg of the petroleum ether fraction. In the pentobarbital sodium-induced sleeping time test and the open-field test, the petroleum ether fraction neither significantly enhanced the pentobarbital sodium-induced sleeping time nor impaired the motor performance, indicating that the observed anti-nociception was unlikely due to sedation or motor abnormality. Moreover, the petroleum ether fraction-induced anti-nociception in both capsaicin and formalin tests was insensitive to naloxone, but was significantly antagonized by glibenclamide. These results suggested that the petroleum ether fraction produced anti-nociception possibly related to glibenclamide-sensitive K⁺-ATP channels, which merited further studies regarding the precise site and mechanism of action. The major constituents of the petroleum ether fraction (PEF) determined by GC/MS analysis, are linoleic acid, the sterols and vitamin E. Therefore it can be suggested that they exert synergetic effects and are together responsible for the antinociceptive activity of the PEF-fraction.     

Molecular docking and analgesic studies of Erythrina variegata?s derived phytochemicals with COX enzymes

Secondary metabolites from plants are a good source for the NSAID drug development. We studied the analgesic activity of ethanolic extract of Erythrina variegata L. (Fabaceae) followed by molecular docking analysis. The analgesic activity of Erythrina variegata L. is evaluated by various methods viz., acetic acid-induced writhing test, hot plate and tail immersion test. Subsequently, molecular docking analysis has been performed to identify compounds having activity against COX-1 and COX-2 enzymes by using GOLD docking fitness. The result of preliminary phytochemical screening revealed that the extract contains alkaloids and flavonoids. In analgesic activity tests, the extract at the doses of 50, 100 and 200 mg/kg body weight (b.w.) produced a increase in pain threshold in a dose dependent manner. In acetic acid induced writhing test, the inhibitory effect was similar to the reference drug diclofenac sodium. The extract showed 18.89% writhing inhibitory effect at the dose 200 mg/kg b.w., whereas diclofenac sodium showed 79.42% inhibition of writhing at a dose of 10 mg/kg b.w. The results of tail immersion and hot plate test also showed potential analgesic activity of the extract which is also comparable to the standard drug morphine (5 mg/kg b.w.). Docking studies shows that phaseollin of Erythrina variegata L. has the best fitness score against the COX-1 which is 56.64 and 59.63 for COX- 2 enzyme. Phaseollin of Erythrina variegata L. detected with significant fitness score and hydrogen bonding against COX-1 and COX-2 is reported for further validation.     

In-vivo antinociceptive,anti-inflammatory and antipyretic activity of pistagremic acid isolated from Pistacia integerrima

The current study was designed to explore the antinociceptive, antiinflammatory and antipyretic activity of pistagremic acid (PA), isolated from Pistacia integerima bark in various animal paradigms. The results illustrated significant inhibition of noxious stimulation in acetic acid induced writhing test with maximum effect of 68% at 10 mg/kg i.p. In tail immersion test, pretreatment with PA demonstrated marked activity during various assessment times in a dose dependent manner. The maximum pain inhibition was 59.46% at 10 mg/kg i.p. after 90 min of PA treatment. However, the injection of naloxone did not antagonize this induced effect. PA significantly ameliorated post carrageenan induced edema dose dependently during various stages of inflammation. The effect was most dominant (60.02%) after 3^rd h of drug administration when examined for 5 h. Similarly, it provoked dose dependent antipyretic effect in febrile mice with maximum of 60.04% activity at 10 mg/kg i.p. after 3rd hour of PA post treatment. Furthermore, molecular docking was carried out to understand the binding mode of PA. From the docking study it was observed that PA fits well in the active site of COX-2 enzyme due to hydrogen and hydrophobic moiety interactions to the important active site of molecule.In conclusion, PA possesses strong peripheral and central antinociceptive activity independent of opioidergic effect which was augmented by its anti-inflammatory and antipyretic activities.     

杜香不同提取部位的镇痛抗炎作用研究

采用小鼠醋酸扭体法和角叉菜胶致小鼠足掌肿胀模型筛选杜香三种提取部位镇痛抗炎作用.结果显示,甲醇提取物(10.0、1.0 mg/kg)和水提物(10.0 mg/kg)能显著抑制醋酸引起的小鼠扭体反应和角叉菜胶引起的小鼠足趾水肿.水提物(10.0 mg/kg)在致炎后2～4 h内效果接近吲哚美辛.高效液相色谱结果提示甲醇提取物的镇痛抗炎效果可能通过其所含黄酮类化合物实现.     

Analgesic activity of new synthetic thiazolidine-4-ones derivatives

Ten new synthetic thiazolidine-4-ones derivatives (5 chlorothiazolidine-4-ones, 3 methoxythiazolidine-4-ones and 2 hydoxythiazolidine-4-ones) having different substituents at R1, R2 and R3 were evaluated for their analgesic activity using different animal models and their structure activity relationship was also elucidated. Chlorothiazolidine-4-ones and methoxythiazolidine-4-ones exhibited analgesic activity in tail flick test, tail immersion test and acetic acid writhing test. C-III (chloride substituents at R1 and R2) produced higher latencies than any other compounds in tail flick test and C-I (no substituents at R1 and R2) was not effective in acetic acid writhing test. Hydroxythiazolidine-4-ones did not show analgesic activity in any of the animal models used. In conclusion, the character of substituents at R3 of thiazolidine moiety position may have an effect on the analgesic activity of thiazolidine-4-ones and either chloride or methoxy substitution may be necessary to produce analgesic activity. Two chloride substituents in a compound may increase the central analgesic activity of the compound.     

Antinociceptive,anti-inflammatory and antipyretic effects of 1.5-diphenyl-1H-Pyrazole-3-carbohydrazide,a new heterocyclic pyrazole derivative

Aims

Heterocyclic pyrazole derivative has been described for the treatment of pain and inflammatory diseases. This study evaluated the in vivo, antinociceptive, anti-inflammatory and antipyretic effects of 1.5-diphenyl-1H-Pyrazole-3-carbohydrazide (1.5-DHP) and the in vivo or in vitro mechanism of action.

Main methods

Acetic acid-induced writhing, hot-plate and formalin-induced nociception tests were used to evaluate the antinociceptive effect, while the rota-rod test was used to assess the motor activity. Croton oil-induced ear edema and carrageenan-induced peritonitis tests were used to investigate the anti-inflammatory effect of 1.5-DHP. The antipyretic effect was assessed using the LPS-induced fever model. The mechanism of action was evaluated by PGE₂ and TNF-α measurement and cyclooxygenase inhibition assay.

Key findings

Oral administration (p.o.) of 1.5-DHP (1, 3, 10 mg/kg) caused a dose-related inhibition of the acetic acid-induced writhing, however the highest dose was not effective on the hot-plate and rota-rod. In the formalin-induced nociception, 1.5-DHP (10 mg/kg, p.o.) inhibited only the late phase of nociception. This same dose of 1.5-DHP also reduced the croton oil-induced ear edema. 1.5-DHP (3, 10, 30 mg/kg, p.o.) produced a dose-related reduction of leukocyte migration on the carrageenan-induced peritonitis. 1.5-DHP (60 mg/kg, p.o.) reduced the fever and the increase of PGE₂ concentration in the cerebrospinal fluid induced by LPS. 1.5-DHP inhibited both COXs in vitro. Finally, 1.5-DHP (10 mg/kg, p.o.) reduced the TNF-α concentration in peritoneal exudates after carrageenan injection.

Significance

These results indicate that 1.5-DHP produces anti-inflammatory, antinociceptive and antipyretic effects by PGE₂ synthesis reduction through COX-1/COX-2 inhibition and by TNF-α synthesis/release inhibition.