Abdominal Constriction Research Articles

Evaluation of antihyperglycemic and antinociceptive activity of Xanthium indicum stem extract in Swiss albino mice

BackgroundXanthium indicum stem is used in folk medicine of Bangladesh to control sugar in diabetic patients and to alleviate pain. The objective of the study was to evaluate antihyperglycemic and antinociceptive activity of methanolic extract of Xanthium indicum stems (XISE) in mice.MethodsAntihyperglycemic activity was measured by oral glucose tolerance tests in glucose-loaded Swiss albino mice. Antinociceptive activity was determined by observed decreases in abdominal constrictions in acetic acid-induced gastric pain model in mice.ResultsThe methanol extract of stems showed dose-dependent and statistically significant antihyperglycemic activity at doses of 50, 100, 200 and 400 mg per kg body weight (p values, respectively, < than 0.01, 0.01, 0.005, and 0.01). Highest reduction in blood glucose level (31.2%) was observed with the highest dose (400 mg) of the extract. A standard antihyperglycemic drug, glibenclamide, reduced blood glucose levels by 46.2%, when administered at a dose of 10 mg per kg body weight. In antinociceptive activity tests, the extract when administered at the afore-mentioned four doses, reduced the number of abdominal constrictions in mice, respectively, by 41.7, 50.0, 54.2, and 61.0%. In comparison, a standard antinociceptive drug, aspirin, when administered at a dose of 200 mg per kg body weight, reduced the number of abdominal constrictions by 37.5%.ConclusionThe experimental results obtained in the present study validate the use of X. indicum stems in folk medicines of Bangladesh to lower blood sugar in diabetic patients and to alleviate pain.

Involvement of spinal cord opioid mechanisms in the acute antinociceptive effect of hyperbaric oxygen in mice

Earlier research has demonstrated that treatment with hyperbaric oxygen (HBO2) can elicit an antinociceptive response in models of acute pain. We have demonstrated that this antinociceptive effect is centrally-mediated and is dependent on opioid receptors. The purpose of the present study was to examine the role of endogenous opioid peptides and opioid receptors specifically in the spinal cord in the acute antinociceptive effect of HBO2 in mice. Male NIH Swiss mice were exposed to HBO2 (100% oxygen at 3.5atm absolute) for 11min and their antinociceptive responsiveness was determined using the glacial acetic acid-induced abdominal constriction test. HBO2-induced antinociception was sensitive to antagonism by intrathecal (i.t.) pretreatment with the κ- and μ-selective opioid antagonists norbinaltorphimine and β-funaltrexamine, respectively, but not the δ-selective antagonist naltrindole. The antinociceptive effect of HBO2 was also significantly attenuated by i.t. pretreatment with a rabbit antiserum against rat dynorphin1–13 but not antisera against β-endorphin or methionine–enkephalin. Based on these experimental findings, the acute antinociceptive effect of HBO2 appears to involve neuronal release of dynorphin and activation of κ- and μ-opioid receptors in the spinal cord.

Inhibitory effect of ethyl acetate extract of Aristolochia yunnanensis on cardiac fibrosis through extracellular signal-regulated kinases 1/2 and transforming growth factor β/small mother against decapentaplegic signaling pathways

Aristolochia yunnanensis, known as Nan Mu Xiang in traditional Chinese medicine, has long been used to treat hypertension and chest pain. In this study, the effect of ethyl acetate extract of Nan Mu Xiang (NMX) on cardiac fibrosis was assessed in vitro by cultured adult rat cardiac fibroblasts with angiotensin II (AngII) stimulation, and in vivo by rats with abdominal aorta constriction (AAC). In cultured adult rat cardiac fibroblasts stimulated by AngII, NMX inhibited cardiac fibroblast proliferation, reduced the expression of fibronectin, α-smooth muscle actin (α-SMA), and transforming growth factor β (TGF-β) in a dose-dependent manner; and suppressed AngII-induced phosphorylation of extracellular signal-regulated kinase (ERK)1/2, C- rapidly accelerated fibrosarcoma (C-Raf), and small mother against decapentaplegic (Smad) 2. Similar results were also observed in AAC rats with intraperitoneal injection of NMX, which not only ameliorated myocardial fibrosis, but also improved cardiac function. The therapeutic effect of NMX on myocardial fibrosis is attributed mainly to the inhibition of ERK and the TGF-β/Smad signaling pathways. NMX may be a promising potential drug candidate for myocardial fibrosis.

Amelioration of cardiac hypertrophy induced by abdominal aortic banding in ferulic acid treated rats

The objective of the present study was to investigate the beneficial effects of treatment of the abundant phytochemical Ferulic acid (FA), alone or in combination with angiotensin II receptor antagonist telmisartan on pressure overload–induced cardiac hypertrophy in rats. Albino Wistar rats were divided into 6 groups: Sham, abdominal aorta constriction (AAB) and three FA (20mg/kg) treatment groups given as a pretreatment or post-treatment or in combination with telmisartan (Tel; 10mg/kg). The standard drug used was Tel (10mg/kg). The pretreatment was given for 35 days while the other treatments were started from the 29th day of surgery for a period of 7 days orally. After recording the exercise testing and hemodynamic parameters, animals were sacrificed for biochemical and histopathological studies. The AAB group had a significant increase in left ventricular weight (LVW) (p<0.001), elevated blood pressure (p<0.001), a significant increase in reactive oxygen species (ROS) (p<0.001) and serum creatinine kinase-MB (CK-MB) (p<0.001), significantly lowered glutathione concentration and superoxide dismutase (SOD) (p<0.001). Pretreatment with FA alone or post-treatment of FA in combination with telmisartan attenuated the rise in LVW and blood pressure (p<0.001). It eliminated the ROS significantly (p<0.01), reduced CK-MB, raised the glutathione and SOD (p<0.001). These findings confirm the protective role of pretreatment of FA and post-treatment of FA with telmisartan in pressure overload–induced cardiac hypertrophy mediated through its integrated effect of potent antioxidative, anti-hypertensive and anti-inflammatory activity.

Antinociceptive activity of a synthetic oxopyrrolidine-based compound, ASH21374, and determination of its possible mechanisms

This study was carried out to determine the antinociceptive activity of a novel synthetic oxopyrrolidine-based compound, (2R,3R,4S)-ethyl 4-hydroxy-1,2-dimethyl-5-oxopyrrolidine-3-carboxylate (ASH21374), and to elucidate the involvement of the opioid, vanilloid, glutamate, and nitric oxide - cyclic guanosine monophosphate (NO/cGMP) systems in modulating the observed antinociception. ASH21374, in the doses of 2, 10, and 100 mg/kg body mass, was administered orally to mice 60 mins prior to exposure to various antinociceptive assays. From the results obtained, ASH21374 exhibited significant (P < 0.05) antinociceptive activity in the abdominal constriction, hot-plate, and formalin tests that was comparable with 100 mg/kg acetylsalicylic acid or 5 mg/kg morphine, respectively. ASH21374 also attenuated capsaicin- and glutamate-induced paw licking. Pre-treatment with 5 mg/kg naloxone significantly (P < 0.05) inhibited the activity in all assays, while pretreatment with 10 mg/kg β-funaltraxamine, 1 mg/kg naltrindole, or 1 mg/kg nor-binaltorphimine significantly (P < 0.05) reversed the activity in the abdominal constriction test. l-Arginine, N(G)-nitro-l-arginine methyl esters (l-NAME), methylene blue, and their combinations, failed to inhibit the ASH21374 antinociceptive activity. In conclusion, ASH21374 demonstrated antinociceptive activities on the peripheral and central nervous systems, mediated through the activation of opioid receptors, inhibition of the glutamatergic system, and attenuation of vanilloid-mediated nociceptive transmission. Further studies have been planned to determine the pharmacological potential of ASH21374.

Antinociceptive activity of cyclopeptide alkaloids isolated from Ziziphus oxyphylla Edgew (Rhamnaceae)

The current study was designed to evaluate the antinociceptive profile of five cyclopeptide alkaloids isolated from Ziziphus oxyphylla, including Oxyphylline-B 1, Oxyphylline C 2 Oxyphylline-D 3, Nummularin-C 4, and Nummularin-R 5. The effect was studied in acetic acid induced writhing and formalin induced flinching behavior tests, at 2.5 and 5mg/kg i.p. In the post-acetic acid induced writhing test, the compounds significantly ameliorated abdominal constrictions in a dose dependent manner, with compounds 1 and 5 showing 80.98% and 77.87% protection, respectively. When challenged in the formalin induced test, pretreatment of compounds significantly attenuated painful sensation in both phases. Moreover, compounds 1 and 5 were more effective with 45.32% and 75.32% for 1 and 36.77% and 71.10% protection for 5, in the 1st and 2nd phases respectively. The peripheral analgesia was strongly augmented by the central effects of these compounds. The current finding strongly supports the ethnomedicinal use of this valuable medicinal plant in various painful conditions.

Evaluation of the Methanolic Rhizome Extract of Anchomanes difformis for Analgesic and Antipyretic Activities

Objectives: To evaluate rhizomes extract of Anchomanes difformis (extract) for analgesic, antipyretic and local anesthetic activities. Methods: Extract was prepared by cold maceration in 70% methanol. Oral acute toxicity was evaluated and LC50 determined. Extract at 100, 250, 500 and 1000 mg/kg was tested against Sodium pentobarbital (SPB)-induced narcosis, acetic acid (AC)–induced abdominal constrictions, formalin-induced paw-licking (FIPL) and brewer’s yeast-induced pyrexia. Local anesthetic effect tested using twitch response test in guinea pig at 0.33, 0.66 and 1% extract. Results: Mice tolerated extract up to 4000 mg/kg. LC50 was 589.13 ppm. Induction and sleeping times of SPB were significantly (p<0.05) decreased at 500 and 1000 mg/kg and 250, 500 and 1000 mg/kg respectively compared with SPB. Abdominal constriction significantly (p<0.05) decreased at 500 mg/kg compared with negative control. There was significant (p<0.05) decrease in paw licking in both 1st and 2nd phases of FIPL at 250 and 500 mg/kg and 500 and 1000 mg/kg respectively compared with negative control. Rectal temperature significantly (p<0.05) decreased at 1000 mg/kg 1 h post-administration compared with aspirin (100 mg/kg) and at 2 – 4 h compared with negative control. Local anesthetic effect was concentration-dependent. Conclusion: The extract showed promising analgesic, antipyretic and local anesthetic effects.

MicroRNA-26 Was Decreased in Rat Cardiac Hypertrophy Model and May Be a Promising Therapeutic Target

MicroRNA (miR)-26 was found to be downregulated in cardiac diseases. In this study, the critical role of miR-26 in myocardial hypertrophy in both in vivo and in vitro was investigated. Sixteen male Wistar rats that underwent sham or transverse abdominal aortic constriction (TAAC) surgery were divided into control or TAAC group. Cardiomyocytes were isolated from neonatal Sprague-Dawley rats. Our study demonstrated that miR-26a/b was downregulated in both TAAC rat model and cardiomyocytes. The results of luciferase assays also suggested that glycogen synthase kinase 3β (GSK3β) may be a direct target of miR-26. The overexpression of miR-26 attenuated GSK3β expression and inhibited myocardial hypertrophy. The downregulation of miR-26 reversed these effects. Furthermore, silence of GSK3β gene phenocopied the anti-hypertrophy effects of miR-26, whereas overexpression of this protein attenuated the effects of miR-26. Taken together, these data suggest that miR-26 regulates pathological structural changes in the rat heart, which may be associated with suppression of the GSK3β signaling pathway, and implicate the potential application of miR-26 in diagnosis and therapy of cardiac hypertrophy.

Evaluation Of Writhing And Paw Edema In Swiss Male Mice Of Sesquiterpene Lactones Fraction Obtained From Artemisia annua L.

Introduction: Artemisia annua L. is known for antimalarial properties. The artemisinin production process generates high yields of sesquiterpene lactones fraction (1,72% artemisinin) by-products. In order to enable to access the pharmacological potency of the fraction an antiinflamatory experimental model was evaluated on writhing and paw edema assay induced by carrageenan in Swiss male mice. Methods: In both tests groups of Swiss mice (n = 6) were treated i.p with vehicle (10 ml/kg) and sesquiterpene lactones sample using 100, 300, and 500 mg/kg (i.p.) doses. Writhings were induced by an i.p. injection of 0.8% acetic acid solution (10 ml/kg), 30 min after treatment. After this injection, the numbers of writhings (abdominal constrictions) were cumulatively counted over 15 min, for nociception evaluation. For assessment of edema, 25µL of a 3% solution carrageenan were injected subcutaneously into the plantar region of the left hind paw. Paw measurements (plethysmometer) were taken at 2, 4, 6 and 24hours. Results: Values are expressed as mean ± standard error. Data were analyzed by analysis for variance (ANOVA) and Tukey's test. In the writhing test values obtained were G1 (control) 48 ± 5,2; G2 (500 mg/kg) 9,5 ± 3,23; G3 (300 mg/kg) 31,5 ± 3,5; G4 (100 mg/kg) 48,5 ± 7,58). P < 0,05 G1 vs. G2, G2 vs. G3, G2 vs. G4. Paw edema induced by carrageenan are shown in the graph (Figure 1)

Ursolic acid from Agastache mexicana aerial parts produces antinociceptive activity involving TRPV1 receptors, cGMP and a serotonergic synergism

Agastache mexicana is a plant that has long been used in large demands in Mexican folk medicine to treat anxiety, insomnia and pain, among others affections. Chromatographic technique was used to identify ursolic acid (UA), 130.7mg/g and 20.3mg/g, as an antinociceptive active compound identified in ethyl acetate and methanol extracts of A. mexicana aerial parts, respectively. Temporal course curves of the antinociceptive response demonstrated a dose-dependent and significant activity of UA (1 to 100mg/kg, i.p.) with an ED50=2mg/kg in comparison to the efficacy of diclofenac (1 or 30 to 100mg/kg, i.p.), a non-steroidal anti-inflammatory drug, with an ED50=11.56mg/kg. The antinociceptive response consisted in the reduction of abdominal constrictions induced with 1% acetic acid in mice. Similarly, UA at 2mg/kg produced significant antinociception in the intracolonic administration of 0.3% capsaicin (a TRPV1 agonist) in mice. It has been reported the inhibition produced by UA on the calcium‐flux induced by capsaicin on TRPV1 receptor suggesting the antagonistic activity of this receptor. Finally, an ED50=44mg/kg was calculated in the neurogenic and inflammatory nociception induced in the formalin test in rats. The antinociceptive response of UA in the formalin test was not modified in presence of naloxone, flumazenil or l-arginine. Nevertheless, it was reverted in presence of 1-H-(1,2,4)-oxadiazolo(4,2-a)quinoxalin-1-one (ODQ, an inhibitor of soluble guanylyl cyclase) and increased in presence of N(G)-l-nitro-arginine methyl ester (l-NAME, inhibitor of nitric oxide synthase), theophylline (inhibitor of phosphodiesterase) and WAY100635 (an antagonist of 5-HT1A receptors). Current results provide evidence that the antinociceptive response of A. mexicana depends in part on the presence of UA. Moreover, this triterpene may exerts its antinociceptive effect mediated by the presence of cGMP and an additive synergism with 5HT1A receptors, but also an antagonistic activity towards TRPV1 receptors may be involved.

Smad‐interacting protein 1 affects acute and tonic, but not chronic pain

Smad-interacting protein 1 (also named Zeb2 and Zfhx1b) is a transcription factor that plays an important role in neuronal development and, when mutated, causes Mowat-Wilson syndrome (MWS). A corresponding mouse model carrying a heterozygous Zeb2 deletion was comprehensively analysed in the German Mouse Clinic. The most prominent phenotype was the reduced pain sensitivity. In this study, we investigated the role of Zeb2 in inflammatory and neuropathic pain. For this, we tested mutant Zeb2 animals in different models of inflammatory pain like abdominal constriction, formalin and carrageenan test. Furthermore, we studied the pain reactivity of the mice after peripheral nerve ligation. To examine the nociceptive transmission of primary sensory dorsal root ganglia (DRG) neurons, we determined the neuronal activity in the spinal dorsal horn after the formalin test using staining of c-Fos. Next, we characterized the neuronal cell population in the DRGs and in the sciatic nerve to study the effect of the Zeb2 mutation on peripheral nerve morphology. The present data show that Zeb2 is involved in the development of primary sensory DRG neurons, especially of C- and Aδ fibres. These alterations contribute to a hypoalgesic phenotype in inflammatory but not in neuropathic pain in these Zeb2(+/-) mice. Our data suggest that the under-reaction to pain observed in MWS patients results from a reduced responsivity to nociceptive stimulation rather than an inability to communicate discomfort.

Cardiac Insulin-Resistance and Decreased Mitochondrial Energy Production Precede the Development of Systolic Heart Failure After Pressure-Overload Hypertrophy

Cardiac hypertrophy is accompanied by significant alterations in energy metabolism. Whether these changes in energy metabolism precede and contribute to the development of heart failure in the hypertrophied heart is not clear. Mice were subjected to cardiac hypertrophy secondary to pressure-overload as a result of an abdominal aortic constriction (AAC). The rates of energy substrate metabolism were assessed in isolated working hearts obtained 1, 2, and 3 weeks after AAC. Mice subjected to AAC demonstrated a progressive development of cardiac hypertrophy. In vivo assessment of cardiac function (via echocardiography) demonstrated diastolic dysfunction by 2 weeks (20% increase in E/E'), and systolic dysfunction by 3 weeks (16% decrease in % ejection fraction). Marked cardiac insulin-resistance by 2 weeks post-AAC was evidenced by a significant decrease in insulin-stimulated rates of glycolysis and glucose oxidation, and plasma membrane translocation of glucose transporter 4. Overall ATP production rates were decreased at 2 and 3 weeks post-AAC (by 37% and 47%, respectively) because of a reduction in mitochondrial oxidation of glucose, lactate, and fatty acids that was not accompanied by an increase in myocardial glycolysis rates. Reduced mitochondrial complex V activity was evident at 3 weeks post-AAC, concomitant with a reduction in the ratio of phosphocreatine to ATP. The development of cardiac insulin-resistance and decreased mitochondrial oxidative metabolism are early metabolic changes in the development of cardiac hypertrophy, which create an energy deficit that may contribute to the progression from hypertrophy to heart failure.

Rosuvastatin prevents pressure overload-induced myocardial hypertrophy via inactivation of the Akt, ERK1/2 and GATA4 signaling pathways in rats

Pressure overload‑induced myocardial hypertrophy is associated with a poor prognosis in humans and contributes to the development of cardiac arrhythmias, diastolic dysfunction and ultimate congestive heart failure. 3‑Hydroxy‑3‑methylglutaryl‑CoA (HMG‑CoA) reductase inhibitors, also known as statins, have been previously shown to induce regression of myocardial hypertrophy in aortic banding models. However, there is limited knowledge regarding the underlying molecular mechanisms. Therefore, we hypothesized that the myocardial hypertrophy‑related signaling pathways protein kinase B (Akt), extracellular signal‑regulated kinases 1 or 2 (ERK1/2) and GATA binding protein 4 (GATA4) activation pathways constitute targets of rosuvastatin (RSV). Therefore, the above‑mentioned activation pathways were hypothesized to be involved in the regression of pressure overload‑induced myocardial hypertrophy treated by RSV. Twenty‑eight Wistar rats were randomly allocated into 4 groups: the sham operation‑vehicle (SH‑V), abdominal aortic constriction‑vehicle (AAC‑V), abdominal aortic constriction‑RSV 10 mg/kg/day (AAC‑LO) and the abdominal aortic constriction‑RSV 20 mg/kg/day (AAC‑HI) group. Following the establishment of the abdominal aorta constriction model, we investigated the effect of RSV, a new hydrophilic statin, on abdominal aortic constriction‑induced myocardial hypertrophy as well as the underlying intercellular signaling pathways after 5 days and 4 weeks of drug intervention. Moreover, echocardiographic features and the left ventricular weight to final body weight ratio (LVW/BW) were determined. Cross‑sectional areas (CSAs) of cardiomyocytes were assessed by hematoxylin and eosin (H&E) staining. Atrial natriuretic factor (ANF), β‑myosin heavy chain (β‑MHC) and peroxisome proliferator‑activated receptor α (PPARα) messenger RNA (mRNA) expression was assessed using RT‑PCR. The phosphorylation of Akt, ERK1/2 and GATA4 were also examined using western blot analysis. Our results showed that RSV significantly attenuates pressure overload‑induced myocardial hypertrophy by preventing myocardial hypertrophy‑related activation of Akt, ERK1/2 and GATA4 signaling pathways.

Phytochemical investigations and bioactivity evaluation of liverworts as a function of anti-inflammatory and antinociceptive properties in animal models

Context: Liverworts (Marchantiophyta) are the second largest group of bryophytes exhibiting promising pharmacological and biological activities. They have been used as remedies for cuts, fractures, burns, bruises, open wounds, inflammation and pneumonia.Objective: In the present study, eight liverwort species [Corsinia coriandrina (Spreng.) Lindb. (Corsiniaceae), Mannia androgyna (L.) A. Evans (Aytoniaceae), Plagiochasma rupestre (J.R. Forst et G. Forst) Steph. (Aytoniaceae), Porella cordaeana (Huebener) Moore (Porellaceae), Porella platyphylla (L.) Pfeiff. (Porellaceae), Reboulia hemisphaerica (L.) Raddi (Aytoniaceae), Riccia fluitans L. (Ricciaceae), and Targionia hypophylla L. (Targioniaceae)] have been investigated for their phytochemical composition and pharmacological effects as a function of anti-inflammatory and antinociceptive potentials, in connection with the major volatile components of the extracts.Material and methods: The chemical compositions of these species and major constituents were identified using GC/MS. In addition, carrageenan-induced paw edema and p-benzoquinone-induced abdominal constriction models were used for the activity assessments.Results: Sesquiterpenes were detected as common constituents of all liverworts. The in vivo experimental models revealed that P. cordeana, P. rupestre and R. haemispherica show significant inhibitory effect on carrageenan-induced paw edema with the inhibition values of 25.4, 27.2 and 29.4%, respectively. Porella cordaeana, P. platyphylla, P. rupestre and R. haemispherica exhibit promising suppressing effect on p-benzoquinone-induced abdominal constriction animal models with the values of 27.6, 31.5, 44.6, and 41.1%, respectively.Discussion: It is suggested that the sesquiterpenes are partly responsible for mentioned activities of the liverworts.Conclusion: The present study confirms the claimed anti-inflammatory activity of liverworts in a scientific platform.

In vivo analgesic and anti-inflammatory activities of Rosmarinus officinalis aqueous extracts, rosmarinic acid and its acetyl ester derivative

Context: Despite several pharmacological applications of Rosmarinus officinalis L. (Lamiaceae), studies on its analgesic and anti-inflammatory properties have been scarce.Objective: The aim of this work was to use in vivo models to evaluate the analgesic and anti-inflammatory activities of the aqueous extracts obtained from leaves (AEL) and stems (AES) of Rosmarinus officinalis, as well as its isolated compound – rosmarinic acid (RA). We also prepared and assessed the acetyl ester derivative of RA.Materials and methods: The analgesic activity was evaluated using abdominal constriction and formalin tests. For the evaluation of the anti-inflammatory effects, carrageenin-induced paw edema in rats were used. The extracts were used at doses of 100, 200 and 400 mg kg−1 compounds were tested at 10, 20 and 40 mg kg−1.Results: Orally administered AEL, AES and RA were not significantly active at any of the doses tested during the abdominal constriction test; the acetyl ester derivative of RA displayed significant analgesic activity. In the carrageenin-induced paw edema assay, the acetyl derivative of RA at all the tested doses produced significant anti-inflammatory effects and reduced the number of paw licks in the second phase of the formalin test.Discussion and conclusion: The results suggest that the analgesic effects of the acetyl derivative of RA operate via a peripheral-mediated mechanism. The acetyl ester derivative of RA is potentially applicable as a new lead compound for the management of pain and inflammation.

Analgesic activity of ethyl acetate fraction of Leucas hyssopifolia Benth

Leucas hyssopifolia Benth. (Lamiaceae) is an annual herb found throughout the India as a weed in cultivated fields, wastelands and roadsides. The aim of the present study was to investigate the presence of phytochemicals and to screen pharmacological activity of Leucas hyssopifolia. The ethyl acetate fraction of the L. hyssopifolia roots was prepared and varying doses (25, 50 & 75 mg/kg, i.p.) of ethyl acetate fraction were given 30 minutes prior to the induction of abdominal constrictions and determination of the mean reaction time in hot plate maintained at 55.0 ± 0.50°C. The ethyl acetate fraction exhibited significant and dose dependent antinociceptive property against acetic acid induced abdominal constrictions in mice. The percentage reduction in numbers of writhes observed with ethyl acetate fraction was 56.9, 75.3 and 80.0%, respectively with 25, 50 and 75 mg/kg doses (p<0.05). In the hot plate, all the doses of ethyl acetate fraction produced a time dependent increase in mean reaction time and a significant effect was observed after 30 min of administration (p<0.05).

Evaluation of mechanisms involved in the antinociception of the ethanol extract from the inner bark of Caesalpinia pyramidalis in mice

Ethnopharmacological relevanceCaesalpinia pyramidalis Tul. (Fabaceae) is an endemic tree of the Northeast region of Brazil, mainly in the Caatinga region. More commonly, inner bark or flowers are traditionally used to treat many painful and inflammatory processes. A common use of this plant is made by macerating a handful of its stem bark in a liter of wine or sugarcane brandy. It is drunk against stomachache, dysenteries, and diarrheas. Materials and methodsThe ethanol extract of Caesalpinia pyramidalis inner bark was used in mice via oral route, at the doses of 10, 30, and 100mg/kg, in behavioral models of nociception and investigates some of the mechanisms underlying this effect. ResultsThe ethanol extract (30 and 100mg/kg, P<0.001), given orally, produced dose dependent inhibition of acetic acid-induced visceral pain. The ethanol extract also caused significant and dose-dependent inhibition of capsaicin-(100mg/kg, P<0.001) and glutamate-(10, 30, and 100mg/kg, P<0.01) induced pain. The antinociception caused by the ethanol extract (30mg/kg) in the abdominal constriction test was significantly attenuated (P<0.001) by intraperitoneal treatment of mice with l-arginine (600mg/kg). ConclusionsCollectively, the present results suggest that the ethanol extract of Caesalpinia pyramidalis produced dose-related antinociception in several models of pain through mechanisms that involved both glutamatergic system and/or the l-arginine–nitric oxide pathway, supporting the folkloric usage of the plant to treat various painful processes.

Antinociceptive Activity of Stephanolepis hispidus Skin Aqueous Extract Depends Partly on Opioid System Activation

Stephanolepis hispidus is one of the most common filefish species in Brazil. Its skin is traditionally used as a complementary treatment for inflammatory disorders. However, there are very few studies on chemical and pharmacological properties using the skin of this fish. This study was undertaken in order to investigate the effect of aqueous crude extract of S. hispidus skin (SAE) in different nociception models. Here, we report that intraperitoneal administration of SAE inhibited the abdominal constrictions induced by acetic acid in mice. In addition to the effect seen in the abdominal constriction model, SAE was also able to inhibit the hyperalgesia induced by carrageenan and prostaglandin E2 (PGE2) in mice. This potent antinociceptive effect was observed in the hot plate model too, but not in tail-flick test. Naloxone, an opioid receptor antagonist, was able to block the antinociceptive effect of SAE in the abdominal constriction and hot plate models. In addition, SAE did not present cytotoxic or genotoxic effect in human peripheral blood cells. Our results suggest that aqueous crude extract from S. hispidus skin has antinociceptive activity in close relationship with the partial activation of opioid receptors in the nervous system. Moreover, aqueous crude extract from S. hispidus skin does not present toxicity and is therefore endowed with the potential for pharmacological control of pain.

Oxysophocarpine induces anti-nociception and increases the expression of GABAAα1 receptors in mice

Oxysophocarpine (OSC) is an alkaloid extracted from Siphocampylus verticillatus. The aim of this study was to investigate the anti-nociceptive effects of OSC through systemic and intracerebroventricular administration in mice. Moreover, to evaluate its effectiveness and mechanism of action, this study investigated whether OSC altered the expression of γ-aminobutyric acid type A α1 (GABAAα1) receptors in the central nervous system. Thermal and chemical behavioral models of nociception were used to assess the anti‑nociceptive action of OSC. The warm water tail-flick test, the hot‑plate test, acetic acid-induced abdominal constriction and formalin‑induced pain were used in mice. OSC was administered intraperitoneally (i.p.) or intracerebroventricularly (i.c.v.). Results showed that OSC (80 mg/kg, i.p.) significantly increased the tail withdrawal threshold with a peak effect of 25.46% maximal possible effect (MPE) at 60 min (P﹤0.01). Additionally, OSC (80 mg/kg) increased the positive staining of GABAAα1 receptors in cells. In conclusion, OSC administration is suggested to have anti-nociceptive effects on the central and peripheral nervous systems. The involvement of GABAA receptors in the anti-nociceptive activity of OSC is currently being investigated.

The Acute Antinociceptive Effect of Hyperbaric Oxygen (HBO2) Is Not Accompanied by an Increase in Markers of Oxidative Stress

Exposure to 3.5 ATA HBO2 causes antinociception in mice (Ohgami et al., NeuroReport 20:1325, 2010). However, breathing O2 at an elevated pressure can potentially cause oxygen toxicity. The aim of this study was to identify the determinants of HBO2 antinociception and the toxicity profile of HBO2. Male NIH Swiss mice were assessed for acute antinociceptive responsiveness under room air or 100% O2 at 1.0 or 3.5 ATA, using the acetic acid‐induced abdominal constriction test. Only the combination of 100% O2 and 3.5 ATA caused significant antinociception. The antinociceptive effect of 100% O2 was pressure‐dependent up to 3.5 ATA. Oxygen toxicity was assessed by analyzing the levels of two oxidative stress markers, MDA (malondialdehyde) and protein carbonyl, in brain, spinal cord and lung after HBO2 exposure. The results showed no significant increase of either marker in the tested tissues, indicating an absence of significant oxidative stress caused by an 11‐min HBO2 treatment. In fact, even a 60‐min HBO2 treatment failed to produce any significant changes. It is concluded that HBO2 at 3.5 ATA is able to produce significant antinociception without causing oxygen toxicity in mice. (This research was supported by NIH Grant AT‐007222 and the Allen I. White Distinguished Professorship at Washington State University.)