Plate Test In Mice Research Articles

Isolation, purification, and characterization of lectins from medicinal plant Combretum glutinosum seeds endowed with analgesic and antiulcer properties

In the pursuit of safer and more effective treatments, there is a growing interest in plant-derived compounds, particularly lectins, because of their diverse pharmacological properties. This study focused on isolating, purifying, and characterizing lectin from Combretum glutinosum seeds (CGSLs) to assess its potential as an analgesic and antiulcer agent. CGSL extraction involved defatting and buffer extraction, followed by purification using ammonium sulfate fractionation and fetuin-agarose affinity column chromatography. The isolectins (iso-CGSLs), each consisting of 60 kDa and 57 kDa heterodimeric subunits, displayed glycoprotein properties with a 40 % neutral sugar content. They exhibited peak activity at 55 °C and remained stable for up to the fifth day at room temperature. The activity exhibited a pH dependence, peaking between 7.5 and 10.5, and all seemingly operated independently of metal ions. CGSL, at optimal doses ranging from 6 to 12 mg/kg, had significant analgesic effects on acetic acid-induced writhing and hot plate tests in mice. Evaluation using 0.7 % acetic acid resulted in notable pain reduction across all doses (P < 0.05). The analgesic effect of lectin was partially reversed by naloxone (a morphine antagonist), indicating partial involvement of the opioid receptor system. Furthermore, CGSL exhibited antiulcer effects in ethanol-induced gastric ulcer models in rats, highlighting its therapeutic potential as a natural alternative for analgesic and antiulcer treatments.

In vivo Anti-Inflammatory and Antinociceptive Activity Evaluation of Brassica Rapa Ssp. Chinensis Ethanolic Extract with In Vitro Thrombolytic and Anthelmintic Activity Test

Objective: Brassica rapa ssp. chinensis is a well-known vegetable plant (Family: Brassicaceae) often grown as a type of Chinese cabbage. The present study was designed to explore the thrombolytic, anthelmintic, anti-inflammatory, and antinociceptive activities of ethanolic extract of the Brassica rapa ssp. chinensis leaves. Methods: The in vitro thrombolytic activity of the leaf extract was evaluated by clot analysis using Streptokinase as a standard drug. The in vitro anthelmintic activity was assessed by applying four different concentrations of the plant extract (10 mg/ml, 20 mg/ml, 40 mg/ml, and 60mg/ml) and recording the time of paralysis and death of worms. Two different doses (100mg/kg and 250mg/kg b.w.) were administered to evaluate the anti-inflammatory activity of the carrageenan-induced paw edema model. The antinociceptive activity was evaluated by hot plate test in mice by two different doses (200mg/kg and 400 mg/kg b.w.). Results: The ethanolic leave extract had thrombolytic action, which broke up blood clots that had already formed. The ethanolic leaf extract showed both paralysis and faster worm death at those concentrations in the anthelmintic test. The extract showed significant anti-inflammatory action in pedal edema compared to the control group. The results show that the highest level of anti-inflammatory action against carrageenan-induced hind paw edema may be achieved with an ethanolic extract of Brassica rapa ssp. chinensis (250 mg/kg, p.o.). The proportion of maximum possible effect in the hot plate test was 82.49 percent in the antinociceptive evaluation. Conclusion: The pharmacological test of leaf extract endorsed the clinical uses of Brassica rapa ssp. chinensis in treating thrombosis, intestinal worms, and inflammation. Thus, this plant could be subjected to extensive bioactive compounds to discover novel therapeutic agents. Keywords: Brassica rapa ssp. chinensis, ethanolic extract, thrombolytic activity, anthelmintic activity, anti-inflammatory activity, antinociceptive activity

Evaluation of the biological activity of different 4-aminoquinolines for the development of new drugs against painful and inflammatory disorders

The potential biological properties of four 4-aminoquinoline derivatives (1–4) have been previously demonstrated. However, the evaluation of important aspects of their toxicity, anti-inflammatory, and antinociceptive activities has not been described. Here, we report other pharmacological properties of 1–4 using classic in vivo models of pain and inflammation. Preliminary toxicity tests revealed the narrow therapeutic window of the compounds, and the doses for biological tests were chosen after median lethal dose (LD50) determination. Then, the formalin-induced nociception test was used for screening. The antinociceptive and anti-inflammatory potentials were observed only in the inflammatory phase among 1–3 at the highest administered dose (50 mg/kg, p.o.). This response pattern was confirmed for all compounds in the acute inflammation model of zymosan-induced peritonitis. The intriguing lack of activity in the first phase of the formalin test led us to explore other pathways through other methods. The derivatives exhibited antinociceptive activity in peripheral and central components of pain in different patterns among models. In the acetic acid-induced writhing test, oral pretreatment with 1 and 2 significantly reduced painful behavior. Glutamate-mediated nociceptive induction was attenuated by 1 and 3. Under thermal stimulation, all compounds produced antinociception in the hot plate test in mice, confirming a centrally mediated action. Moreover, 1–3 at antinociceptive and anti-inflammatory doses did not affect the motor performance in mice in the rotarod test, thus validating the data. This work is the first report of these activities for 1–3. Because they are chloroquine analogs, these compounds represent ideal prototypes of antinociceptive and anti-inflammatory drugs that are able to induce peripheral and central effects on pain and inflammation pathways. Further studies are needed for pharmacodynamic characterizations.

The study of the spectrum of pharmacological activity of the new original NT-3 mimetic dipeptide GTS-302

BACKGROUND: The association of the pathogenesis of neurodegenerative diseases, depression, anxiety, and cognitive disorders with the deficit of neurotrophin-3 determines the prospect of creating drugs with a similar mechanism of action. Since the use of full-size neurotrophin-3 is limited by unsatisfactory pharmacokinetic properties, it is relevant to create low-molecular-weight mimetics of neurotrophin-3 that are active when administered systemically. A dimeric dipeptide mimetic of the 4th loop of neurotrophin-3, hexamethylenediamide bis(N--oxibutyryl-L-glutamyl-L-asparagine) GTS-302, which activates TrkC and TrkB receptors, has been developed at the V.V. Zakusov Research Institute of Pharmacology.&#x0D; AIM: The aim of this study was to investigate the spectrum of pharmacological activity of GTS-302.&#x0D; MATERIALS AND МETHODS: The pharmacological effects of GTS-302 were investigated following its intraperitoneal administration. The antidepressant-like activity of GTS-302 was studied in the forced swim test in mice after acute and 7-day administration. The anxiolytic and cognitive activity of the dipeptide were studied in the elevated plus maze test in mice and the novel object recognition test in rats after acute administration, respectively. The effect of GTS-302 on pain sensitivity was studied in the hot plate test in mice after acute administration.&#x0D; RESULTS: It was found that GTS-302 exhibits antidepressant-like activity after acute administration at doses of 0.5, 1.0, 5.0 and 10 mg/kg. After 7-day administration, the antidepressant-like activity of GTS-302 was more pronounced in terms of effect size and statistical significance. The dipeptide GTS-302 at doses of 1.0, 5.0 and 10.0 mg/kg showed anxiolytic and cognitive activity and did not affect pain sensitivity.&#x0D; CONCLUSIONS: The pharmacological spectrum of the low-molecular-weight mimetic of neurotrophin-3, dipeptide GTS-302, revealed upon systemic administration includes a number of neuropsychotropic effects characteristic of the full-sized neurotrophin. This allows us to consider GTS-302 as a potential neuropsychotropic drug.

Antinociceptive and anti-inflammatory activity of DW-1021, the ionic complex of pelubiprofen and tramadol, in rodents

Although drugs such as acetaminophen, opioids, and nonsteroidal anti-inflammatory drugs (NSAIDs), are commonly used for pain management, the side effects of these drugs such as hepatotoxicity, nephrotoxicity, nausea, and vomiting, can not be neglected. Therefore, combinations of analgesics with different mechanisms raise the possibility of developing novel analgesics. Therefore, the aim of the present study was to evaluate whether DW-1021, the ionic complex of pelubiprofen (NSAID) and tramadol (opioid), has synergic antinociceptive and anti-inflammatory effects in nociceptive as well as inflammation-induced nociceptive models compared to pelubiprofen- or tramadol-only administration. Strong synergistic antinociceptive efficacy of DW-1021 was observed in the mouse writhing test and von Frey paw withdrawal threshold test in the carrageenan-induced rats. The hot plate test in mice and the Randall-Selitto mechanical paw pressure test in carrageenan-induced rats revealed that DW-1021 had a preferable effect on relieving pain to pelubiprofen, but not as much as tramadol. In the carrageenan-induced rats, DW-1021 had a more potent effect on reducing paw inflammation (paw volume, width, and thickness) via the suppression of PGE2 production than tramadol, but less than that of pelubiprofen. Taken together, our results suggest that the administration of DW-1021, a combination of pelubiprofen and tramadol, exerted a potent effect and can be used as a potential therapeutic agent for relieving pain and inflammation.

Evaluation of Analgesics and Anti-Inflammatory Activity of the Root Extract of Impatiens rothii (Balsaminaceae) in Rodents.

The roots of Impatiens rothii has been used as a traditional remedy for painful conditions, rheumatism, isthmus and crural aches. However, the analgesic and anti-inflammatory properties of this plant have yet to be scientifically confirmed. The purpose of this study was to explore possible analgesic and anti-inflammatory activities 80% methanolic root extract of Impatiens rothii. To obtain the crude extract, the roots of Impatiens rothii that had been dried and ground up were macerated in 80% methanol. The analgesic activity was determined using acetic acid-induced writhing and hot plate tests in mice, whereas the anti-inflammatory activity was analyzed using carrageenan-induced paw edema model in rats. The extract was orally administered at a dose of 100, 200 and 400 mg/kg. All tested doses of Impatiens rothii extract showed significant analgesic activity (p<0.05) at observations of 30 to 120 minutes compared to the negative control in the hot plate test. In acetic acid-induced writhing test all tested doses of the 80% methanol extract of Impatiens rothii significantly (p < 0.001) reduced the number of writhing. In comparison to the control group, all tested doses displayed a significant decrease in paw edema, which appeared 2-5 hours after induction (p<0.05). From the results of this study, it can be stated that 80% methanolic extract of Impatiens rothii possessed substantial analgesic and anti-inflammatory activities, hence providing scientific basis for the use of this plant in the treatment of pain and inflammatory diseases.

Synthesis and Characterization of an Analgesic Potential Conotoxin Lv32.1

In our work of screening analgesic peptides from the conotoxin libraries of diverse Conus species, we decoded a peptide sequence from Conus lividus and named it Lv32.1 (LvXXXIIA). The folding conditions of linear Lv32.1 on buffer, oxidizing agent, concentration of GSH/GSSG and reaction time were optimized for a maximum yield of (34.94 ± 0.96)%, providing an efficient solution for the synthesis of Lv32.1. Its disulfide connectivity was identified to be 1-3, 2-6, 4-5, which was first reported for the conotoxins with cysteine framework XXXII and different from the common connectivities established for conotoxins with six cysteines. The analgesic effect of Lv32.1 was determined by a hot plate test in mice. An evident increase in the pain threshold with time illustrated that Lv32.1 exhibited analgesic potency. The effects on Nav1.8 channel and α9α10 nAChR were detected, but weak inhibition was observed. In this work, we highlight the efficient synthesis, novel disulfide linkage and analgesic potential of Lv32.1, which laid a positive foundation for further development of conotoxin Lv32.1 as an analgesic candidate.

Potential pharmacological properties of methanol leaves extract of Culcasia Angolensis (Araceae): antinociceptive, antiinflammatory and antipyretic activities in laboratory animals

BackgroundPain, inflammation and fever are serious conditions that are associated with various disease conditions. In modern medicine, non-steroidal anti-inflammatory drugs (NSAIDs), opioids together with corticosteroids have been considered to manage algesia and inflammation-related conditions. However, these conventional drugs are not affordable, not readily available, particularly to people living in rural areas in developing nations. Besides, they are associated with undesirable pharmacological actions. Generally, medicinal plants have been employed to manage various ailments. In Northern-Nigeria, the leaves of Culcasia angolensis (Araceae) are used traditionally to manage pain, fever and inflammation. However, scientific data validating its folkloric claim in treating pain and inflammatory-related abnormalities are not available. Hence, the current study aims to validate the antinociceptive, anti-inflammatory and antipyretic potentials of the methanol leaf extract of Culcasia angolensis (MECA). Phytochemical and acute toxicity effects of the MECA were conducted as per standard experimental procedures. The analgesic potential of the MECA was determined using abdominal writhing elicited by acetic acid and hot plate tests in mice. The actions of the MECA on acute inflammation were conducted using formalin-induced hind paw oedema and carrageenan-induced paw oedema. The Brewer's yeast-induced pyrexia was employed to check its antipyretic effect.ResultsThe MECA inhibited abdominal writhes produced by acetic acid administration (p < 0.05) and elevated the pain threshold in the hot plate test. The MECA also reduced the formalin-induced paw oedema. Besides, it produced an effective (p < 0.05) and dose-dependent action against oedema produced by carrageenan and reduced the rectal temperature against the pyrexia caused by Brewer's yeast administration.ConclusionsThe outcome of the study suggests that the MECA could possess pharmacologically active constituents with antinociceptive, anti-inflammatory and antipyretic properties. Therefore, the results justified its ethnomedicinal use to manage pain and inflammatory-associated conditions.

Anti-nociceptive and anti-inflammatory effects of the hydroethanolic extract of a polyherbal preparation (Cov-Pla 2) in laboratory animals

Symptoms of Coronavirus Disease-2019 include pulmonary hyper-inflammation; managing local and systemic inflammatory responses may be key in treatment. This study evaluated the anti-inflammatory, analgesic and antipyretic effects of a mixture (Cov-Pla 2) containing five medicinal plants in laboratory animals. The antinociceptive activity of Cov-Pla 2 was evaluated using acetic acid-induced writhing, Brewer’s Yeast Pyrexia test in rats and hot plate tests in mice. The egg albumin-induced rat paw oedema test was employed to evaluate the extract’s anti-inflammatory activity. The extract produced a dose-dependent (125-500 mg/kg, p.o.) inhibition of pain response elicited by acetic acid, compared to normal saline and increased reaction latency in the hot plate test. The antiinflammatory test showed a significant (P&lt;0.05) reduction in paw size diameter at 125 mg/kg from 2 hours, compared to control. In the antipyretic test, the extract produced a significant (P&lt;0.05) time-dependent decrease in rectal temperature at 125 mg/kg after 2 and 3 hours and at 250 and 500 mg/kg after 3 hours, compared to normal saline. The extract did not produce mortality up to 5000 mg/kg per oral. The results indicated that the extract possesses antinociceptive and anti-inflammatory properties, which support its recommendation for trials in the treatment of symptoms associated with COVID-19.&#x0D; Keywords: COVID-19; Inflammation; Nociception; Polyherbal; SARS-CoV-2

Studying of analgesic and anti-inflammatory activity of 2,4-dioxobutanoic acid hydrazine derivatives

Objective. To study the analgesic and anti-inflammatory activity of water-soluble hydrazine derivatives of 2,4-dioxobutanoic acids, as well as to determine the relationship between the structure of substances and their biological effects.&#x0D; Materials and methods. The laboratory synthesis methods were applied to obtain 2-hydrazine derivatives of 2,4-dioxobutanoic acids. The compounds were tested for biological activity using a hot plate test in mice and an acute inflammatory reaction caused by carrageenan-induced paw edema in rats.&#x0D; Results. The analgesic activity of four compounds is comparable to that of nimesulide. One of the substances obtained is found to exhibit higher anti-inflammatory activity than nimesulide during the 1st and 3rd hours of the experiment. Two compounds with a combination of high analgesic and anti-inflammatory activity were identified. The effect of certain radicals in the structure of the substances on the activities studied was discovered.&#x0D; Conclusions. The revealed relationship between the structure of original compounds and their biological activities can be used in the further synthesis and search for new domestic pharmaceutical substances with investigated effects.

Synthesis and Evaluation of a Series of New Bulleyaconitine A Derivatives as Analgesics.

As a nonaddictive analgesic widely used in clinics, the LD50 of bulleyaconitine A is just only 0.92 mg/kg, which exhibits obvious toxicity. Therefore, 31 new non-natural C19-diterpenoid alkaloids (2a–w, 2′a–e, 3, 4a, and 4b) were designed and synthesized from bulleyaconitine A to develop nonaddictive analgesics with low toxicity. The chemical structures were characterized by 1H NMR, 13C NMR, and high-resolution mass spectrometry (HRMS) spectra. The analgesic activities were evaluated by a hot plate test in mice. At the dosage of 10 mg/kg, six compounds (2d, 2j, 2k, 2m, 2t, 2w) exhibited good analgesic activities (increased pain threshold >100%) with a long duration. Among them, 2w showed the best analgesic activity and the longest duration. Its pain threshold reached 166.35% in 15 min, peaked at 30 min (182.35%), and remained 82.59% even at 60 min.

Aqueous extract of dry powder blend of seeds and leaves of Picralima nitida (Stapf) T. & H. Durand reduce pain and inflammation in animal models.

Blend of seeds and leaves of Picralima nitida herein referred to as West African Durand powder (WDP) was investigated for antinociceptive and anti-inflammatory properties. Acute toxic effect of the aqueous extract was evaluated in mice of both sexes. Antinociceptive effect of WDP (100-400mg/kg) was evaluated in models of acetic acid-induced writhing and thermal nociception on hot plate in mice. Carrageenan-induced paw oedema and air pouch rat models were used to evaluate the anti-inflammatory activity of the extract. WDP (2,000mg/kg) showed no toxic effect in mice. WDP at 100, 200 and 400mg/kg inhibited abdominal writhings by 59.9, 66.0 and 79.0%, respectively. There was a significant increase in reaction time on the hot plate tests in mice treated with WDP (400mg/kg). The paw oedema was reduced by WDP (100, 200 and 400mg/kg) 5h post-carrageeenan. Exudate volume was significantly reduced to 39.8 and 44.8% by 200 and 400mg/kg WDP, respectively. WDP reduced Leucocytes counts (23.3 and 57.1%, respectively) and neutrophil counts (28.1 and 60.0%, as well as reduced nitrites, malondialdehyde levels and increased glutathione concentrations in the air pouch. These results suggest that aqueous extract of blend of seeds and leaves of P. nitida possesses antinociceptive and anti-inflammatory properties.

Anti-nociceptive, anti-inflammatory and possible mechanism of anti-nociceptive action of methanol leaf extract of Nymphaea lotus Linn (Nymphaeceae)

The leaf of Nymphaea lotus has been used traditionally for the management of pain and inflammatory diseases. The methanol leaf extract of Nymphaea lotus (NLE) was evaluated for possible anti-nociceptive and anti-inflammatory activities in rats and mice (at the doses of 250, 500 and 1,000 mg/kg) to investigate the existence of scientific basis for the folkloric use of the plant. The standard drugs used were piroxicam (10 mg/kg) and morphine (10 mg/kg). The possible pharmacological mechanism involved in the anti-nociceptive activity was also investigated. The acute toxicity was determined in mice and rats using method of Lorke. The anti-nociceptive activity was evaluated using acetic acid-induced writhing and hot plate tests in mice, while the anti-inflammatory activity was evaluated using carrageenan-induced hind paw edema model in rats. The oral median lethal dose of NLE was found to be greater than 5,000 mg/kg in rats and mice. NLE demonstrated significant and dose-dependent protection against acetic acid induced writhes and increased the reaction time of mice in hot plate test. Pretreatment of the animals with naloxone (2 mg/kg) significantly (p < 0.05) attenuated the anti-nociception elicited by both NLE and morphine. NLE at the doses of 250 and 1,000 mg/kg significantly (p < 0.05) decreased rat paw edema at the 2nd hour in the carrageenan-induced paw edema test. The result of the study revealed that Nymphaea lotus possesses anti-nociceptive activities which may be mediated via the opioidergic system as well as mild anti-inflammatory activities thus providing scientific basis for the use of the plant in the management of pain and inflammatory diseases.

Anti-nociceptive and anti-inflammatory effects of the ethanol extract of Arenga pinnata (Wurmb) Merr. fruit

Arenga pinnata (Wurmb) Merr. is a medicinal and edible plant belonging to family Palmae. The fruits of this plant were used in traditional folk medicine due to its analgesia and anti-inflammatory activities. This study aimed to investigate the analgesic and anti-inflammatory properties and the mechanism of the ethanol extract of A. pinnata (Wurmb) Merr. fruit (EAF) on different experimental models. High-performance liquid chromatography (HPLC) was used to determine the chromatographic profile and to analyze the composition of EAF. In the acute toxicity test, all mice were orally administered EAF at a maximum dosage of 26g/kg and were then monitored for 14 days. The potential analgesic activity of EAF was evaluated by using animal pain models, namely the acetic acid-induced writhing test and the hot plate test in mice. The underlying mechanisms of analgesia were determined by pretreating with naloxone, capsaicin and cinnamaldehyde to evaluate the involvement of the opioid system and transient receptor potential channels (TRP channels). The anti-inflammatory activity of EAF was evaluated by using the following inflammatory animal models: xylene-induced ear edema in mice and Complete Freund's adjuvant (CFA)-induced paw swelling in rats. EAF was orally administered at the doses of 1.625, 3.25 and 6.5g/kg in mice and 1.125, 2.25 and 4.5g/kg in rats. The underlying mechanism of the anti-inflammatory activity was determined by enzyme-linked immunosorbent assay (ELISA) kits and real time-PCR used to measure the expression levels of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), prostaglandin E2 (PGE2) and cyclooxygenase-2 (COX-2). Western blot analysis was used to determine the expression levels of proteins related to the nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPK) signaling pathways in paw tissues. Five compounds, namely (5-(hydroxymethyl) furan-2-yl) methanediol,4'-hydroxy-N-(4-hydroxy-3-methoxybenzoyl)-3',5'-dimethoxybenzamide, (+)-lyonirenisol-3a-O-β-D-glucopyranoside, (-)-lyonirenisol-3a-O-β-glucopyranoside and liquiritin, were firstly identified from A. pinnata (Wurmb) Merr. fruit by HPLC-UV analysis. In the acute toxicity test, no treatment-related toxicological signs or mortality was observed in mice administered doses up to 26g/kg. Bodyweight was not obviously different among the treatment groups and the vehicle group. EAF significantly inhibited the pain response induced by acetic acid and increased the latency time in the hot plate test in mice. The anti-nociception effect of EAF in the formalin test was not alleviated by pretreatment with naloxone. However, the nociception induced by injection with capsaicin and cinnamaldehyde was significantly reduced by EAF. Compared with vehicle treatment, EAF significantly inhibited the formation of xylene-induced ear edema and CFA adjuvant-induced paw swelling. EAF markedly inhibited the production of IL-1β, TNF-α, PGE2 and IL-6 induced by CFA in paw tissues. Furthermore, the phosphorylation of IKKα, IKKβ, IκBα, p38, ERK1/2, and JNK and the nuclear translation of NF-κB p65 induced by CFA in paw tissues were significantly inhibited by EAF treatment compared with vehicle treatment. For the first time, this study provides pharmacological evidence for the analgesic and anti-inflammatory activities of EAF and the underlying mechanism, suggesting that EAF might be a potential candidate for reducing pain and inflammatory disorders.

Effect of Ethyl Cellulose Content on Release Profile and Pharmacodynamics of Fenoprofen Microparticles

Abstract: Introduction: Fenoprofen calcium (FC) is a non-steroidal anti-inflammatory drug and due to its short half-life, high absorption, extensive metabolism and adverse effect, sustained release formulation of FC is desired. Objective: this study was to develop sustained release microcapsules of FC to obtain better drug delivery. Material and methods: Different formulae of FC microcapsules were prepared by o/w emulsion solvent evaporation method using Ethyl cellulose (EC) in three different ratios. The processed microcapsules were evaluated In-vitro for production yield, entrapment efficiency, micromeritic properties and thermal characteristics and In-vivo for its pharmacodynamics. Results: In-vitro release studies of formulae H1 and H3 showed regression coefficient (r) value in the Higuchi diffusion model of 0.967 and 0.946 respectively, suggesting diffusion mechanism release from these forms. While marketed capsules and H2 microcapsules showed regression coefficient value in the zero-order model (0.985 and 0.985 respectively), suggesting non-linear release. In-vivo, the carrageenan-induced hind paw edema was induced in rats; the area under the inhibition of inflammation percentage–time curve (AUC0-24) showed that formula H3 possesses the highest therapeutic efficiency comparing with marketed capsules followed by formula H1 and finally H2. Moreover, in hot plate test in mice, there were highly significant increases in the mean reaction time in groups H2 and H3 over the marketed capsule at 12h interval (p<0.001). Conclusion: FC loaded EC microcapsule H3 produced a sustained and effective drug release over a prolonged timeframe that led to greater therapeutic efficacy. Key words: Ethylcellulose, Microencapsulation, Fenoprofen calcium, Sustained release, Pharmacodynamics, Microparticles.

The Systemic Administration of the Chemokine CCL1 Evokes Thermal Analgesia in Mice Through the Activation of the Endocannabinoid System.

Apart from its involvement in immune functions, the chemokine CCL1 can participate in the modulation of nociceptive processing. Previous studies have demonstrated the hypernociceptive effect produced by CCL1 in the spinal cord, but its possible action on peripheral nociception has not yet been characterized. We describe here that the subcutaneous administration of CCL1 (1-10µg/kg) produces dose-dependent and long-lasting increases in thermal withdrawal latencies measured by the unilateral hot plate test in mice. The antinociceptive nature of this effect is further supported by the reduction of spinal neurons expressing Fos protein in response to a noxious thermal stimulus observed after the administration of 10µg/kg of CCL1. CCL1-induced antinociception was inhibited after systemic, but not spinal administration of the selective antagonist R243 (0.1-1mg/kg), demonstrating the participation of peripheral CCR8 receptors. The absence of this analgesic effect in mice treated with a dose of cyclophosphamide that produces a drastic depletion of leukocytes suggests its dependency on white blood cells. Furthermore, whereas the antinociceptive effect of CCL1 was unaffected after the treatment with either the antagonist of opioid receptors naloxone or the cannabinoid type 1 receptor blocker AM251, it was dose-dependently inhibited after the administration of the CB2 receptor antagonist SR144528 (0.1-1mg/kg). The detection by ELISA of an increased presence of the endocannabinoid 2-arachidonoylglycerol after the administration of an analgesic dose of CCL1 supports the notion that CCL1 can evoke thermal analgesia through the release of this endocannabinoid from circulating leukocytes.

Antinociceptive and anti-arthritic effects of aqueous whole plant extract of Trianthema portulacastrum in rodents: Possible mechanisms of action

Ethnopharmacological relevanceTrianthema portulacastrum L. (Aizoaceae) is used in traditional African Medicine for the treatment of various illnesses including dropsy, inflammation and rheumatism. Aim of the studyThis study was designed to investigate the anti-nociceptive and anti-arthritic properties of the aqueous whole plant extract of Trianthema portulacastrum (AETP), possible mechanisms of action and characterize some of the active constituents. Materials and methodsAntinociceptive activity was evaluated using the acetic acid-induced writhing and hot plate tests in mice. The carrageenan test was used to induce a transient inflammation while arthritis was induced with complete Freund’s adjuvant (CFA) in rats. On completion of CFA-induced arthritis macroscopic observations, the rats were euthanized to isolate the spleen, liver and limbs for estimation of oxidative stress and histological analysis. ResultsAETP (10, 50, or 250 mg/kg; p.o.) produced significant (p < 0.05) and dose-dependent inhibition (41.10, 50.40, and 67.10%, respectively) of writhing response elicited by acetic acid. Also, increased pain threshold of supraspinally mediated nociceptive behaviour, with peak maximum possible effect (MPE) obtained at 250 mg/kg (22.98%; 30 min post-treatment). However, the pre-treatment of mice with Nitro-L-arginine (L-NNA) or naloxone reversed AETP-induced antinociception. In another experiment, AETP produced time course inhibition of carrageenan-induced paw oedema with peak effect (50.60%) at 250 mg/kg as well as significant reduction in CFA-induced arthritis by 58.56%, on day 27 and arthritic index (26.84%). Similarly, AETP attenuated CFA-induced MDA generation and deficit in antioxidant enzyme activities. Histological analysis of rat joints revealed a reduction in the synovial hyperplasia and mononuclear infiltration induced by CFA in AETP treated groups. ConclusionFindings from this study showed that T. portulacastrum possesses anti-nociceptive action through nitrergic and opioidergic signalling as well as anti-arthritic effect through enhancement of antioxidant defense system and inhibition of release or actions of inflammatory mediators.

Antinociceptive and anti-inflammatory properties of Tetracera alnifolia Willd. (Dilleniaceae) hydroethanolic leaf extract.

Background Tetracera alnifolia Willd. (Dilleniaceae) is used in traditional African Medicine for the treatment of headache, abdominal pain, and rheumatism. Hence, this study sought to investigate the antinociceptive and anti-inflammatory effects of the hydroethanolic leaf extract of T. alnifolia (HeTA) in rodents. Methods Antinociceptive activity was evaluated using the acetic acid-induced writhing, formalin-/capsaicin-induced paw licking and hot plate tests in mice. The contribution of opioidergic, l-arginine-nitric oxide, and ATP-sensitive potassium channel pathways in HeTA-induced antinociception was also evaluated. The anti-inflammatory effect was assessed using the carrageenan-induced paw edema, xylene ear edema, cotton pellet granuloma, and complete Freund's adjuvant (CFA)-induced arthritis in rats. Results HeTA (100, 200, and 400 mg/kg, p.o.) produced significant (p<0.05) decrease in mean number of acetic acid-induced writhing, time spent licking paw in formalin, and capsaicin tests as well as time course increase in nociceptive reaction latency in hot plate test. HeTA-induced antinociception was prevented by pretreatment of mice with naloxone (non-selective opioid receptor antagonist), l-arginine (nitric oxide precursor), or glibenclamide (ATP-sensitive potassium channel blocker). HeTA (100 mg/kg, p.o.) produced a significant anti-inflammatory effect against carrageenan-induced rat paw edema (1-5 h), xylene-induced ear edema, cotton pellet-induced granuloma formation, and CFA-induced arthritis in rats. The effects of HeTA in various models were similar to the effect of the standard reference drugs. Conclusions Findings from this study showed that HeTA possesses antinociceptive effect possibly mediated through peripheral opioid receptors with activation of l-arginine-nitric oxide and ATP-sensitive potassium channel pathway as well as anti-inflammatory activity.

Assessment of pharmacological activity and bioavailability of the new derivative 1,3,4-thiadiazole

Introduction: Acexazolamide is a new derivative of 1,3,4-thiadiazole and acexamic acid.&#x0D; Materials and methods: In animal experiments, acute toxicity, pharmacological activity and bioavailability of acexazolamide were evaluated. Anti-inflammatory activity was assessed on the model of formalin edema of paw and cotton pellet granuloma in rats. Assessment of analgesic activity was carried out in a hot plate test in mice, chemical pain stimulation of the peritoneum and inflammatory hyperalgesia in rats. The antipyretic activity of acexazolamide was evaluated in a model of yeast-induced hyperthermia in rats. The anti-burn activity of acexazolamide was evaluated in a thermal skin burn model in rats. Bioavailability of acexazolamide with intragastric administration was determined in rabbits. The content of acetaxazolamide in blood plasma was determined by HPLC-MS/MS method.&#x0D; Results and discussion: DL50 of acexazolamide after intragastric administration to mice was 860.99 (95% CIs, 462.2 to 1259.8) mg/kg. The anti-inflammatory activity of acexazolamide (21.5 mg/kg) with formalin-induced paw edema and fetal granuloma in rats was higher than that of ketoprofen (23.0 mg/kg). ED50 value for analgesic activity with acetic acid induced cortex was 24.99 (95% CIs: 15.31–34.68) mg/kg. With thermal stimulation of the paw in mice, the ED50 value was 25.56 (95% CIs: 15.13 to 35.98) mg/kg. ED50 value for antipyretic activity was 31.85 (95% CIs: 19.22–44.47) mg/kg. Acexazolamide (21.5 mg/kg) had a stimulating effect on the regeneration of damaged tissues in case of thermal skin burns. Bioavailability of acexazolamide (1 mg/kg) with intragastric administration was 37%.&#x0D; Conclusion: Acexazolamide has the properties of a non-steroidal anti-inflammatory agent.

Analgesic and anti-inflammatory studies on crude ethanol extract of &lt;i&gt;Cadaba farinosa&lt;/i&gt; Forssk leaf in mice and rats

The plant Cadaba farinosa Forssk. is used in the treatment of pains, dysentery, rheumatism, cough, and fever. Phytoconstituents include alkaloids, anthraquinones, cardiac glycosides, flavonoids, saponins and tannins. The intraperitoneal LD 50 of the crude ethanol leaf extract (CEE) was found to be 2154.1 mg/kg body weight in mice. The analgesic activity was investigated using acetic acid-induced writhing and hot plate tests in mice while Antiinflammation potential was investigated using carrageenan-induced hind paw oedema in rats. The extract at all the doses tested and piroxicam produced significant decrease in number of writhes at p ≤ 0.05 for extract and piroxicam compared to normal saline group. There was a significant increase (p≤ 0.01) in the pain-reaction time for thermally induced pain at 30 min of both 300 mg/kg CEE and 20 mg/kg pentazocine (standard drug). At 60 min, the significant increase (p≤ 0.05) was at 75 mg/kg CEE and 20 mg/kg pentazocine when compared to the control. The highest significant increase in mean pain reaction time for 75, 150 mg/kg CEE and pentazocine was observed at 90 min compared to the normal saline group. There was no significant difference in the mean pain latency time for thermally-induced pain between CEE and pentazocine for doses tested at 30, 60 and 120 min except for pentazocine with significant increase of p≤ 0.05 compared to the control group. There was generally a significant reduction (p ≤ 0.01) in mean paw diameter for both the extract and piroxicam treated groups compared to control group throughout the study. Keywords: Analgesic activity, Cadaba farinosa , acetic acid, carrageenan, pain, writhes, hot plate, paw oedema