Acetic Acid-induced Abdominal Writhing Research Articles

Analgesic and Anti-Inflammatory Potential of the New Tetrahydropyran Derivative (2s,6s)-6-ethyl-tetrahydro-2h-pyran-2-yl) Methanol.

The development of analgesic and anti-inflammatory drugs plays a crucial role in modern medicine, aiming to alleviate pain and reduce inflammation in patients. Opioids and nonsteroidal anti-inflammatory drugs are groups of drugs conventionally used to treat pain and inflammation, but a wide range of adverse effects and ineffectiveness in some pathological conditions leads us to search for new drugs with analgesic and anti-inflammatory properties. In this regard, the authors intend to investigate the ((2s,6s)-6-ethyl-tetrahydro-2h-pyran- 2-yl) methanol compound (LS20) on pain and acute inflammation. Male Swiss mice were evaluated using acetic acid-induced abdominal writhing, formalin, and tail-flick as models of nociceptive evaluation and edema paw, air pouch and cell culture as models of inflammatory evaluation besides the rotarod test for assessment of motor impairment. The compound showed an effect on the acetic acid-induced abdominal writhing, formalin and tail-flick tests. Studying the mechanism of action, reversion of the antinociceptive effect of the compound was observed from previous intraperitoneal administration of selective and non-selective opioid antagonists on the tail flick test. In addition, the compound induced an antiedematogenic effect and reduced leukocyte migration and the production of pro-inflammatory cytokines in the air pouch model. LS20 was able to maintain cell viability, in addition to reducing cell production of TNF-α and IL-6. In summary, the LS20 compound presented an antinociceptive effect, demonstrating the participation of the opioid system and an anti-inflammatory effect related to the inhibition of proinflammatory cytokine production. The compound also demonstrated safety at the cellular level.

Heteroaromatic salvinorin A analogue (P-3 l) elicits antinociceptive and anxiolytic-like effects

Previous studies have attributed the prominent analgesic, hallucinogenic, sedative, and anxiolytic properties of Salvia divinorum to Salvinorin A. However, the overall pharmacological profile of this isolate limits its clinical applications. To address these limitations, our study evaluates the C(22)-fused-heteroaromatic analogue of salvinorin A [2-O-salvinorin B benzofuran-2-carboxylate] (P-3l) in mice nociception and anxiety models while assessing possible mechanism of action. In comparison with the control group, orally administered P-3l (1, 3, 10, and 30 mg/kg) attenuates acetic acid-induced abdominal writhing, formalin-induced hind paw licking, the thermal reaction to the hotplate, and/or aversive response in the elevated plus-maze, open field, and light-dark box; and potentiates the effect of morphine and diazepam at sub-effective doses (1.25 and 0.25 mg/kg, respectively) without eliciting significant alterations in relative organ weight, or haematological or biochemical parameters. The in vivo blockade of P-3 l effects by naloxone (non-selective opioid receptor antagonist), naloxonazine (antagonist of specific subtypes mu1 of μ-OR), and nor-binaltorphimine (selective ĸ-OR antagonist) supports initial results from binding assays and the interpretations made possible from computational modeling of the interactions of P-3 l with the opioid receptor subtypes. In addition to the opioidergic mechanism, the blockade of the P-3 l effect by flumazenil suggests benzodiazepine binding site involvement in its biological activities. These results support P-3 l potentially possessing clinical utility and substantiate the need for additional pharmacological characterization.

Anti-inflammatory, antinociceptive, and vasorelaxant effects of a new pyrazole compound 5-(1-(2-fluorophenyl)-1H-pyrazol-4-yl)-1H-tetrazole: role of NO/cGMP pathway and calcium channels.

Molecular modification of compounds remains important strategy towards the discovery of new drugs.In this sense, this study presents a newpyrazole derivative5-(1-(2-fluorophenyl)-1H-pyrazol-4-yl)-1H-tetrazole (LQFM039) and evaluated the anti-inflammatory, analgesic,andvasorelaxanteffects of this compound as well the mechanisms of action involved in the pharmacological effects. For this, mice were orally treated with LQFM039 (17.5, 35, or 70 mg/kg) prior acetic acid-induced abdominal writhing, formalin, tail flick, and carrageenan-induced paw edema protocols. In addition,vascular reactivity protocols were made with aortic rings contraction with phenylephrine and stimulated with graded concentrations of LQFM039. Abdominal writhing and licking time in both neurogenic and inflammatory phases of formalin were reduced with LQFM039 without alteringlatency to nociceptive responsein the tail flick test. Carrageenan-induced paw edema showed that LQFM039 reduces edema and cell migration. In addition, the mechanism of action of LQFM039 involves NO/cGMP pathway and calcium channels, since this new pyrazole derivate elicitedconcentration-dependent relaxation attenuated byNω-nitro-l-arginine methyl esterand1H-[1,2,4] oxadiazolo [4,3-alpha]quinoxalin-1-one, and blockade of CaCl2-induced contraction. Altogether, our finding suggests anti-inflammatory, antinociceptive, and vasorelaxanteffectof this new pyrazole derivative with involvement of NO/cGMP pathway and calcium channels.

Evaluation of Antinociceptive Activity of Ficus Religiosa Root Extract in Swiss Albino Mice

Background 
 Ficus religiosa, commonly known as peepal, is widely distributed in Indian subcontinent. It has been used as an antiepileptic, aphrodisiac, analgesic, anti-inflammatory and laxative in traditional medicine.
 Objective To explore the analgesic effect of aqueous root extract of Ficus religiosa using thermal and chemical models of pain in swiss albino mice.
 Method The aqueous aerial root extract of Ficus religiosa was prepared using soxhlet apparatus. The anti-nociceptive effect of the extract at doses of 50 and 100 mg/kg was evaluated using peripheral (acetic acid-induced abdominal writhing), spinal (tail flick) and supra-spinal (hot plate) behavioral models of pain. All data were presented as Mean ± SEM. Statistical differences between Ficus religiosa (50 and 100 mg/kg) and standard control groups were evaluated using Mann-Whitney U test.
 Result There was significant dose dependent increase in the mean reaction time compared to the vehicle control in hot plate and tail- flick test. In acetic acid induced writhing test, mice treated with Ficus religiosa (50 and 100 mg/kg) exhibited significant dose-dependent decrease in the mean number of writhes (57.45% and 79.20% respectively) compared to the vehicle control. The activity of Ficus religiosa extract at doses of 50 and 100 mg/kg was equipotent to Standard control (Morphine and Indomethacin) used in different test models.
 Conclusion The extract of Ficus religiosa possesses both central and peripheral analgesic activity thus validating the traditional use of this plant in the management of pain.

Antinociceptive and anti-inflammatory properties of aqueous extract obtained from Serjania marginata Casar leaves

Ethnopharmacological relevanceSerjania marginata Casar (Sapindaceae Family) Leaves are popularly used against abdominal pain.Antiulcer properties of S. marginata were scientifically described, however rare studies showed the antinociceptive effects of this plant. Aim of studyIn this study, we investigated the antinociceptive and anti-inflammatory effects of aqueous extract obtained from Serjania marginata leaves (AESM) in nociception/inflammation models. Material and methodsAESM was analyzed in FIA-ESI-IT-MS and Mass spectrometer LTQ XL. AESM oral administration (p.o.) (30, 100 and 300 mg/kg), dexamethasone subcutaneous injection (1 mg/kg, s.c.) and morphine (5 mg/kg, s.c.) were tested against the acetic acid-induced nociception, carrageenan-induced acute inflammatory paw edema/hyperalgesia, formalin-induced nociception and carrageenan-induced pleurisy in Swiss mice. ResultsFlavonoids rutin was detected in the phytochemical analysis of this extract. Oral treatment of AESM 300 mg/kg significantly reduced the number of acetic acid-induced abdominal writhing. AESM (100 and 300 mg/kg) significantly inhibited formalin-induced nociception, mechanical hyperalgesia and paw edema in carrageenan-model. Furthermore, AESM significantly inhibited leukocyte migration and protein exudation in the carrageenan-induced pleurisy test. ConclusionThis study confirms the antinociceptive, and anti-inflammatory activity of AESM, which may explain, in part, the popular use of this plant as a natural antinociceptive agent. This pharmacological action can be caused by flavonoids such as rutin and other compounds present in AESM.

β-caryophyllene and docosahexaenoic acid, isolated or associated, have potential antinociceptive and anti-inflammatory effects in vitro and in vivo

Inflammation is a complex biological response involving the immune, autonomic, vascular, and somatosensory systems that occurs through the synthesis of inflammatory mediators and pain induction by the activation of nociceptors. Staphylococcus aureus, the main cause of bacteremia, is one of the most common and potent causes of inflammation in public health, with worse clinical outcomes in hospitals. Antioxidant substances have been evaluated as alternative therapeutic analgesics, antioxidants, anti-inflammatory agents, antitumor agents, and bactericides. Among these, we highlight the essential oils of aromatic plants, such as β-caryophyllene (BCP), and polyunsaturated fatty acids, such as docosahexaenoic acid (DHA). The objective of this study was to evaluate the biological activities of BCP–DHA association in in vitro and in vivo experimental models of antinociception and inflammation. To determine the anti-inflammatory effects, monocytes isolated from the peripheral blood of adult male volunteers were infected with methicillin-resistant S. aureus and incubated with treatment for cytokine dosage and gene expression analysis. Antinociceptive effects were observed in the three models when comparing the control (saline) and the BCP-DHA treatment groups. For this purpose, the antinociceptive effects were evaluated in animal models using the following tests: acetic acid-induced abdominal writhing, paw edema induced by formalin intraplantar injection, and von Frey hypernociception. There was a significant reduction in the GM-CSF, TNFα, IL-1, IL-6, and IL-12 levels and an increase in IL-10 levels in the BCP-DHA treatment groups, in addition to negative regulation of the expression of the genes involved in the intracellular inflammatory signaling cascade (IL-2, IL-6, IRF7, NLRP3, and TYK2) in all groups receiving treatment, regardless of the presence of infection. Statistically significant results (p < 0.05) were obtained in the acetic acid-induced abdominal writhing test, evaluation of paw edema, evaluation of paw flinching and licking in the formalin intraplantar injection model, and the von Frey hypernociception test. Therefore, BCP and DHA, either administered individually or combined, demonstrate potent anti-inflammatory and antinociceptive effects.

Anti-inflammatory, antinociceptive effects and involvement of opioid receptors in the antinociceptive activity of Eugenia uniflora leaves obtained with water, ethanol, and propylene glycol mixture

Ethnopharmacological relevanceEugenia uniflora (Myrtaceae) is a species native to Brazil and has a traditional use in the treatment of inflammation. Aim of the studyTo evaluate the anti-inflammatory and antinociceptive effects, and the involvement of opioid receptors in the antinociceptive activity of extract and fractions from Eugenia uniflora leaves. Materials and methodsTLC and HPLC were used to characterize the spray-dried extract (SDE) and fractions. In the in vivo assays, Swiss (Mus musculus) mice were used. Carrageenan-induced hind-paw edema and carrageenan-induced peritonitis models were used to determine the anti-inflammatory effect of the extract (50, 100, or 200 mg/kg). Acetic acid-induced writhing, tail-flick, and formalin tests were used to determine the antinociceptive effect of the extract (50, 100, or 200 mg/kg). The aqueous (AqF) and ethyl acetate (EAF) fractions (6.25, 12.5, and 25 mg/kg) were then combined with naloxone to evaluate the involvement of opioid receptors in the antinociceptive activity. ResultsIn this work, the TLC and HPLC analysis evidenced the enrichment of EAF, which higher concentration of gallic acid (5.29 ± 0.0004 %w/w), and ellagic acid (1.28 ± 0.0002 %w/w) and mainly myricitrin (8.64 ± 0.0002 %w/w). The extract decreased the number of total leukocytes and neutrophils in the peritoneal cavity (p < 0.05), at doses of 100 and 200 mg/kg and showed significant inhibition in the increase of paw edema volume (p < 0.05). The treatment per oral route (doses of 50, 100, and 200 mg/kg) significantly reduced the nociceptive response in acetic acid-induced abdominal writhing (p < 0.05). The effect of the extract on the tail-flick test showed a significant increase in latency time of animals treated at doses of 200 and 100 mg/kg (p < 0.05). The extract and ethyl acetate fraction reduced the nociceptive effect in both phases of formalin at all tested doses. The naloxone reversed the antinociceptive effect of EAF, suggesting that opioid receptors are involved in mediating the antinociceptive activity of EAF of E. uniflora in the formalin test. ConclusionThe current study demonstrates the anti-inflammatory and analgesic activities of water: ethanol: propylene glycol spray-dried extract from E. uniflora leaves using in vivo pharmacological models in mice. Our findings suggest that spray-dried extract and ethyl acetate fraction exhibit peripheral and central antinociceptive activity with the involvement of opioid receptors that may be related to the presence of flavonoids, mainly myricitrin.

Flavonoid-Rich Fraction from Croton blanchetianus (Euphorbiaceae) Leaves Exerts Peripheral and Central Analgesic Effects by Acting via the Opioid and Cholinergic Systems.

The ethanolic extract from Croton blanchetianus leaves has been shown to have antinociceptive activity in mice. Here, we investigated the antinociceptive activity of an ethyl acetate fraction (EAF) from this extract in mice and the possible pathways involved in the analgesic effect. Adverse effects on behavior and motor coordination were also evaluated. The EAF was characterized by liquid chromatography coupled with mass spectrometry and evaluated (12.5, 25, and 50 mg/kg per os) in the acetic acid-induced abdominal writhing, formalin, hot plate, and tail immersion assays. Naloxone, atropine, glibenclamide, prazosin, or yohimbine was pre-administered to mice to investigate the involved pathways in the formalin test. The open-field, rotarod, and elevated plus-maze tests were used to assess behavior and locomotion. The main components of the EAF were quercetin-3-O-(2-rhamnosyl) rutinoside, hyperoside, quercetin rutinoside pentoside, and quercetin hexoside deoxyhexoside. EAF showed antinociceptive effects in all models and was effective against both neurogenic and inflammatory pain. The reversion of the effects in the formalin test by naloxone and atropine revealed that the EAF acted via the opioid and cholinergic systems. In the open-field test, the behavior of the animals treated with the EAF was like that of control, except at the highest dose, when hypnosis, eyelid ptosis, decreased walking, hygiene, and rearing behaviors were observed. No muscle relaxant effect was observed, but an anxiogenic effect was observed at all doses. This study provides new scientific evidence on the pharmacological properties of C. blanchetianus leaves and their potential for the development of phytomedicines with analgesic properties.

Curcumin and n-acetylcysteine cocrystal produced with supercritical solvent: characterization, solubility, and preclinical evaluation of antinociceptive and anti-inflammatory activities.

Curcumin presents a promising anti-inflammatory potential, but its low water-solubility and bioavailability hinder its application. In this sense, cocrystallization represents a tool for improving physicochemical properties, solubility, permeability, and bioavailability of new drug candidates. Thus, the aim of this work was to produce curcumin cocrystals (with n-acetylcysteine as coformer, which possesses anti-inflammatory and antioxidant activities), by the anti-solvent gas technique using supercritical carbon dioxide, and to test its antinociceptive and anti-inflammatory potential. The cocrystal was characterized by differential scanning calorimetry, powder X-ray diffraction and scanning electron microscopy. The cocrystal solubility and antichemotaxic activity were also assessed in vitro. Antinociceptive and anti-inflammatory activities were carried out in vivo using the acetic acid-induced abdominal writhing and carrageenan-induced paw oedema assays in mice. The results demonstrated the formation of a new crystalline structure, thereby confirming the successful formation of the cocrystal. The higher solubility of the cocrystal compared to pure curcumin was verified in acidic and neutral pH, and the cocrystal inhibited the chemotaxis of neutrophils in vitro. In vivo assays showed that cocrystal presents increased antinociceptive and anti-inflammatory potency when compared to pure curcumin, which could be related to an improvement in its bioavailability.

Analgesic-like activity of perillyl acetate: In vivo and in silico studies

Objective: To evaluate the antinociceptive activity of perillyl acetate in mice and in silico simulations.Methods: The vehicle, perillyl acetate (100, 150 and/or 200 mg/ kg, i.p.), diazepam (2 mg/kg, i.p.) or morphine (6 mg/kg, i.p.) was administered to mice, respectively. Rotarod test, acetic acid-induced abdominal writhing, formalin-induced nociception, hot plate test, and tail-flick test were performed. Opioid receptors-involvement in perillyl acetate antinociceptive effect was also investigated.Results: Perillyl acetate did not affect the motor coordination of mice. However, it reduced the number of acetic acid-induced abdominal twitches and licking times in the formalin test. There was an increase of latency time in the tail-flick test of 30 and 60 minutes. Pretreatment with naloxone reversed the antinociceptive effect of perillyl acetate (200 mg/kg). In silico analysis demonstrated that perillyl acetate could bind to μ-opioid receptors.Conclusions: Perillyl acetate has antinociceptive effect at the spinal level in animal nociception models, without affecting the locomotor integrity and possibly through μ-opioid receptors. In silico studies have suggested that perillyl acetate can act as a μ-opioid receptor agonist.

Evaluation of the systemic and spinal antinociceptive effect of a new hybrid NSAID tetrahydropyran derivative.

Pain is responsible for inducing physical and mental stress, interfering negatively in patients' quality of life. Classic analgesic drugs, such as opioids and non-steroidal anti-inflammatory drugs, are known for their wide range of adverse effects, making it important to develop new drugs. Thus, this study aimed to analyse the action of the hybrid compound cis- (±) -acetate of 4-chloro-6- (naphthalene-1-yl) -tetrahydro-2h-pyran -2-yl) methyl2- (2- [2,6-dichlorophenylamine] phenyl (LS19) under acute nociceptive conditions, and deepened the understanding of the responsible mechanisms. Male Swiss mice were evaluated in the acetic acid-induced abdominal writhing, formalin, tail flick, capsaicin- and glutamate-induced nociception, thermal stimulation in animals injected with capsaicin and rotarod tests besides the acute and subchronic toxicological evaluation. The compound showed effect on the acetic acid-induced abdominal writhing, formalin (both phases), tail flick, thermal stimulation in animals injected with capsaicin and capsaicin-induced nociception tests. In the study of the mechanism of action was observed reversion of the antihyperalgesic effect of the compound from the previous intraperitoneal and intrathecal administration of naloxone, nor-binaltorphimine, naltrindole, methylnaltrexone, 7-nitroindazole, L-NAME, ODQ, glibenclamide on the tail flick test. In the thermal stimulation in animals injected with capsaicin, the compound showed antinociceptive effect by oral and intraplantar routes, besides to reducing the levels of TNF-α, IL-1β and PGE2 in the paws previously administered with capsaicin. There were no signs of acute and subchronic intoxication with the compound. In summary, the compound LS19 presented spinal and local antihyperalgesic effect, demonstrating participation of the opioid/NO/cGMP/K+ ATP pathway and TRPV1 receptors and it demonstrated safety in its use in mice.

Bioguided Isolation of Alkaloids and Pharmacological Effects of the Total Alkaloid Fraction from Aspidosperma pyrifolium Mart. (Apocynaceae).

Aspidosperma pyrifolium is used in traditional medicine to treat inflammatory disorders. The aim of the study was to perform phytochemical characterization and evaluate the anti-inflammatory, anti-nociceptive and acute toxicity effects of the total alkaloid fraction (TAF-Ap) from stem barks. Two monoterpenic indole alkaloids were isolated by high performance liquid chromatography coupled with mass spectrometry (HPLC-MS) and the structural elucidation was performed using 1D and 2D NMR analysis. As for toxicity, no animals died at 50 mg kg−1 and this concentration presented mild sedation and forced breathing within the first 24 h. The lethal dose capable of killing 50% of the animals (LD50) was estimated to be 160 mg kg−1. In the pharmacological tests, the models used were 1% carrageenan-induced paw edema and peritonitis, 1% formalin-induced nociception and 1% acetic acid-induced abdominal writhing in Swiss mice. The study made it possible to isolate 15-methoxyaspidospermine and 15-methoxypyrifolidine, corroborating the results of pharmacological assays, which showed anti-inflammatory and analgesic potential, especially at 30 mg kg−1 (p < 0.001). Thus, the species was shown to be a promising source of active substances, with special attention paid to its toxicological potential.

LASSBio-596: a New Pre-clinical Candidate for Rheumatoid Arthritis?

Pain and inflammatory disorders are significant health problems because of prevalence and associated disabilities. In this context, LASSBio-596 is a hybrid compound able to modulate TNF-α and phosphodiesterases 4 and 5, exhibiting an anti-inflammatory effect in the pulmonary inflammatory model. Aiming at a better description of the activities of LASSBio-596, we initially conducted nociception tests (acetic acid-induced abdominal writhing, glutamate, and formalin-induced nociception and hot plate test) and later inflammatory tests (acute, peritonitis; and chronic, arthritis) that directed us to this last one. In the abdominal writhing test, there was a dose-dependent inhibition, whose response occurred at the maximum dose (50mg/kg, p.o.), used in the subsequent tests. LASSBio-596 also inhibited nociception induced by chemical (glutamate by 31.9%; and formalin, in both phases, 1st phase: 25.7%; 2nd phase: 23.9%) and thermal agents (hotplate, by increased latency for pain at two different times). These effects were independent of the motor function, legitimated in rotarod. As there was a response in the inflammatory component of nociception, we performed the peritonitis test, in which migration was inhibited by LASSBio-596 by 39.9%. As the inflammatory process is present in autoimmune diseases, we also performed the arthritis test. LASSBio-596 reduced paw edema from the 15th day to the 21st day of treatment (no liver changes and with fewer paw injuries). In addition, LASSBio-596 decreased serum levels of TNF-α by 67.1%. These data demonstrated the antinociceptive effect of LASSBio-596 and reinforces its anti-inflammatory property (i.e., RA), amplifying the therapeutic potential of this molecule.

Acute toxicity, antinociceptive, and anti-inflammatory activities of the orally administered crotamine in mice.

Crotamine is a polypeptide toxin isolated from rattlesnake venom. Although several studies have been developed identifying many biological effects of isolated crotamine, none of them evaluated its acute toxicity, antinociceptive, and anti-inflammatory activities through oral administration. All in vivo experiments from this study were performed in mice. The up-and-down procedure and hippocratic screening were carried out to evaluate possible pharmacological and toxic effects. Antinociceptive and anti-inflammatory activities of this toxin were evaluated using acetic acid-induced abdominal writhing, formalin-induced pain assays, croton oil-induced ear edema, and carrageenan-induced pleurisy. Crotamine did not cause lethality or signs of intoxication up to the maximum dose tested (10.88mg/kg). The number of contortions was reduced significantly by 34, 57, and 74% at the oral doses of 0.08, 0.16, and 0.32mg/kg, respectively. At the dose of 0.16mg/kg, crotamine decreases pain time-reactivity at neurogenic phase by 45% and at inflammatory phase by 60%. Also, crotamine elicited antiedematogenic activity through the attenuation of the croton oil-induced ear edema by 77%. In the carrageenan-induced pleurisy, the leukocyte, neutrophil, and mononuclear cell migration to the lesion site were reduced by 52%, 46%, and 59%, respectively. Altogether, crotamine demonstrated in vivo antinociceptive and anti-inflammatory effect through acute oral administration, generating an anti-migratory mechanism of action at non-toxic doses.

EVALUATION OF THE ANALGESIC ACTIVITY OF AQUEOUS AND ALCOHOLIC EXTRACT OF FLOWERS OF PLUMERIA ALBA LINN IN EXPERIMENTAL ANIMALS

Objective: Plumeria alba (Apocynaceae), commonly known as “Frangipani” is an important medicinal plant, widely distributed throughout Southern India. In the traditional medicinal system, different parts of this plant have been mentioned to be useful in a wide variety of diseases. In this study, analgesic activity of aqueous and alcoholic extract of flowers of P. alba Linn was evaluated by hot-plate and acetic acid-induced writhing methods to substantiate and expand its clinical applications.&#x0D; Methods: The flowers of P. alba were collected from the local area in and around Coimbatore (India). The flowers were dried, powdered, and were extracted using soxhlet apparatus for 12 h using water and 95% of ethanol as a solvent. The test extracts were administered orally at a dose of 100 &amp; 200 mg/kg while diclofenac sodium (10 mg/kg) served as standard.&#x0D; Results: The ethanolic flower extract of 200 mg/kg had significant analgesic activity in acetic acid-induced abdominal writhing response (***p&lt;0.001) when compared to control and standard drug diclofenac. It also exhibited significant analgesic activity (***p&lt;0.001) by increasing the pain reaction time of the rats in comparison to control and standard in hot plate method.&#x0D; Conclusion: The results suggest that ethanolic flower extracts of P. alba possess potent analgesic properties, which support its use in traditional medicine and suggesting that the plant should be further investigated for its pharmacological active natural products.

Essential oil of Myrciaria tenella (DC.) O. Berg: effects of distillation time on its chemical composition and evaluation of its anti-inflammatory and antinociceptive effects

ABSTRACT The objective of the present study was to characterize the essential oil of Myrciaria tenella (MTEO) leaves, to determine the effects of distillation time (1 to 5 h), and to evaluate its action on acute pain and inflammation both in vivo and in vitro. MTEO was obtained by hydrodistillation for 4 h and 36 compounds were detected, mainly consisting of hydrocarbon terpenes such as β-pinene (21.46%), α-pinene (19.43%), E-caryophyllene (10.89%) and aromadendrene (9.17%). A high yield of α-pinene/β-pinene-rich MTEO was obtained after only 2 h of extraction. For in vivo biological assays, MTEO was administered to male Swiss mice, showing an action against hypernociception (acetic acid-induced abdominal writhing, formalin and Von Frey models) and inhibiting carrageenan-induced paw edema. Production of IL-6, TNF-α, IL-1β, PGE2 was reduced and production of IL-10 was increased, with no change in motor performance. MTEO also reduced cell production of NO and cytokines, in addition to inhibiting COX activity.

Anti-inflammatory and analgesic effects of methanol extract of red cultivar Allium cepa bulbs in rats and mice.

Several cultivars of Allium cepa L. have been studied for anti-inflammatory and analgesic activities but there is inadequate information on such biological activities of the concentrated extracts of the Nigerian grown red cultivar A.cepa bulb. The anti-inflammatory models used in this study were Carrageenan-induced paw oedema and formalin-induced paw lick in rats, while acetic acid-induced abdominal writhing, hot plate reaction, hot water tail flick tests in mice were the analgesic models. At 30min post-induction (pi), the inhibition of paw oedema (62.50%) by 200mg/kg of methanol extract of red cultivar A.cepa bulb (MERCACB) was significantly (p<0.001) higher than that of indomethacin (15.63%) at 10mg/kg. The paw oedema inhibition at 60min pi by MERCACB (76.92%) was significantly higher than that of indomethacin (41.03%). At the early phase of formalin paw-lick test, the pain reaction time (PRT) of rat treated with MERCACB (400mg/kg) was significantly lower than that of indomethacin and the control groups. The hotplate test revealed that PRT of mice treated with 800mg/kg of MERCACB were significantly (p<0.01) longer in comparism to indomethacin and control groups. The PRT of mice subjected to thermal pain due to hot water and treated with 800mg/kg of MERCACB was significantly (p<0.05) longer than that of the control group. These findings indicate that MERCACB possesses potent anti-inflammatory and analgesic properties which confirm the traditional use of the plant for the treatment of inflammatory diseases and may be useful as a future therapeutic agent.

Antinociceptive and anti-inflammatory activities of Copaifera pubiflora Benth oleoresin and its major metabolite ent-hardwickiic acid

Ethnopharmacological relevanceCopaifera species folkloric names are “copaíbas, copaibeiras, copaívas or oil stick”, which are widely used in Brazilian folk medicine. Among all ethnopharmacological applications described for Copaifera spp oleoresins, their anti-inflammatory effect stands out. However, the knowledge of anti-inflammatory and antinociceptive properties of Copaifera pubiflora Benth is scarce. Aim of the studyTo investigate the cytotoxic, anti-inflammatory, and antinociceptive activities of C. pubiflora oleoresin (CPO), and its major compound ent-hardwickiic acid (HA). Material and methodsThe phosphatase assay was used to evaluate the cytotoxicity of CPO and HA in three different cell lines. CPO and HA doses of 1, 3, and 10 mg/kg were employed in the biological assays. The assessment of motor activity was performed using open-field and rotarod tests. Anti-inflammatory activity of CPO and HA was assessed through luciferase assay, measurement of INF-γ, IL-1β, IL-6, IL-10, and TNF-α in a multi-spot system with the immortalized cell line THP-1, zymosan-induced arthritis, and carrageenan-induced paw edema. Acetic acid-induced abdominal writhing and formalin tests were undertaken to evaluate the antinociceptive potential of CPO and HA. In addition, the evaluation using carrageenan was performed to investigate the effect of CPO in pain intensity to a mechanical stimulus (mechanical hyperalgesia), using the von Frey filaments. A tail-flick test was used to evaluate possible central CPO and HA actions. ResultsIn the cytotoxicity evaluation, CPO and HA were not cytotoxic to the cell lines tested. CPO and HA (10 mg/kg) did not affect animals' locomotor capacity in both open-field and rotarod tests. In the luciferase assay, CPO and HA significantly reduced luciferase activity (p < 0.05). This reduction indicates a decrease in NF-κB activity. HA and CPO decreased INF-γ, IL-1β, IL-6, IL-10, and TNF-α at 24 and 72 h in the multi-spot system. In zymosan-induced arthritis, CPO and HA decreased the number of neutrophils in the joint of arthritic mice and the number of total leukocytes (p < 0.05). In experimental arthritis HA significantly decreased joint swelling (p < 0.05). CPO and HA also increased the mechanical threshold during experimental arthritis. HA and CPO significantly inhibited the carrageenan-induced paw edema, being the doses of 10 mg/kg the most effective, registering maximum inhibitions of 58 ± 8% and 76 ± 6% respectively, p < 0.05. CPO and HA reduced the nociceptive behavior in both phases of formalin at all tested doses. The highest doses tested displayed inhibitions of 87 ± 1% and 72 ± 4%, respectively, p < 0.001, in the first phase, and 87 ± 1% and 81 ± 2%, respectively, p < 0.001, in the second phase. Oral treatment of CPO and HA (1, 3, 10 mg/kg) significantly reduced the nociceptive response in acetic acid-induced abdominal writhings, and the 10 mg/kg dose was the most effective with maximum inhibitions of 86 ± 2% and 82 ± 1%, respectively, p < 0.001. Both HA and CPO significantly decreased the intensity of mechanical inflammatory hyper-nociception on carrageenan-induced hyperalgesia at all tested doses, and 10 mg/kg was the most effective dose with maximum inhibitions of 73 ± 5% and 74 ± 7%, respectively, p < 0.05.CPO increased the tail-flick latencies in mice, and concomitant administration of naloxone partially reduced its effect. ConclusionsCPO and HA may inhibit the production of inflammatory cytokines by suppressing the NF-κB signaling pathway, resulting in anti-inflammatory and antinociceptive activities.

Effect of Leaf Methanol Extract of Boswellia Dalzielii on the Experimental Inflammatory and Nociceptive Models in Albino Mice

Inflammation is a physiological protective response by the organism to remove the injurious stimuli, microbial infections, and trauma. The prolong treatment for inflammation and pain with NSAID’s has been shown greater unwanted effects, so there is a rising scope for traditional medicines. Boswellia dalzielii leaves are used traditionally as folk remedies for the treatment of health problems caused by inflammation. The present study was an attempt to investigate the qualitative phytochemical constituents and the activity of methanol extract of Boswellia dalzielii leaves (MEBD) on the experimental inflammatory and nociceptive models in mice. Qualitative phytochemical constituents of the MEBD were performed using standard protocol. Anti-inflammatory activity was evaluated by studying carrageenan and egg-albumin induced paw oedema and xylene induced ear oedema animal models. Acetic acid-induced abdominal writhing, tail immersion and hot plate tests had been performed to evaluate the anti-nociceptive effect. This MEBD revealed the absence of alkaloids and saponins. The all doses (100, 200 and 400 mg) of the MEBD significantly (p < 0.001) inhibited the acute inflammatory process compared to the negative control. Highest percentage inhibition was 90.69±0.42% in carrageenan paw oedema test 100 mg/kg, 94.01±8.72 (Egg-albumin paw oedema test, 100 mg/kg) at 6 hrs, 57.43±0.03% (xylene test, 400 mg/kg). In anti-nociceptive experiments, MEBD of all doses were significantly reduced (p < 0.001) acetic acid-induced writhing (82.24±3.03%, 400 mg/kg). In addition, MEBD significantly increased the latency time (p < 0.001) in the tail flick (12.15±0.01, 400 mg/kg) at 90 min and in the hot plate test (13.37±0.10, 200 mg/kg) at 60 min compared to the control group. In conclusion, the study revealed that Boswellia dalzielii leaves, widely used in traditional medicine in North Cameroon, and affectively has antinociceptive and anti-inflammatory powers.

An Overview of Phytochemical and Biological Activities: Ficus deltoidea Jack and Other Ficus spp.

ABSTRACTFicus deltoidea Jack (Moraceae) is a well-known medicinal plant used in customary medication among the Malay people to reduce and mend sicknesses such as ulcers, psoriasis, cytotoxicity, cardioprotective, inflammation, jaundice, vitiligo, hemorrhage, diabetes, convulsion, hepatitis, dysentery injuries, wounds, and stiffness. Ficus deltoidea contains a wide variety of bioactive compounds from different phytochemical groups such as alkaloids, phenols, flavonoids, saponins, sterols, terpenes, carbohydrates, and proteins. The genus Ficus has several hundreds of species, which shows excellent therapeutic effects and a wide variety of helpful properties for human welfare. Searching information was collected by using electronic databases including Web of Science, Science Direct, Springer, SciFinder, PubMed, Scopus, Medline, Embase, and Google Scholar. This review is, therefore, an effort to give a detailed survey of the literature on its pharmacognosy, phytochemistry, phytochemical, and pharmacological properties of Ficus and its important species. This summary could be beneficial for future research aiming to exploit the therapeutic potential of Ficus and its useful medicinal species.