Acetic Acid-induced Writhing Tests Research Articles

Analgesic and anti-inflammatory activities of NPK 500 capsules, a Cassia sieberiana DC. - Based herbal analgesic medicine used to treat dysmenorrhea and peptic ulcer, is mediated through the inhibition of PGE2 and iNOS

Ethnopharmacological relevancePain and inflammation are the most frequent reasons for which people seek medical care. Currently available analgesics against these conditions produce fatal adverse effects. NPK 500 capsules is an alternative herbal analgesic employed to treat dysmenorrhea, peptic ulcer and pain. NPK 500 is produced from Cassia sieberiana. A plant used in traditional medicine to treat pain and inflammation. Aim of the studyThis study reports the analysis, phytochemical characterization and mechanism of analgesic and anti-inflammatory activities of two NPK 500 capsules, called old and new NPK500 capsules (ONPK500 and NNPK500) respectively. Materials and methodsPhysicochemical, organoleptic, GC-MS and LC-MS methods were employed to analyze the NPK 500 capsules. Analgesic activity was evaluated using tail immersion, Randall-Selitto and acetic acid induced writing tests. Anti-inflammatory activity was evaluated using carrageenan-induced rat paw inflammation. Additionally, pro-inflammatory mediators such as prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS), cyclooxygenase 1 and 2 (COX-2 and COX-1) were quantified in the sera of the rats using Enzyme Linked Immunosorbent Assay (ELISA) kits. ResultsThirteen major compounds were characterized in the NNPK 500 capsules via the GC-MS and LC-MS spectroscopies. Kaempferol was the major compound characterized in addition to physcion, β-sitosterol 3-O-β-D-glucopyranoside, betulinic acid and nine others. Physicochemical and organoleptic indices of the capsules were also derived for its authentication and quality control. Furthermore, NNPK 500 0.5–1.5 mg/kg p.o. produce significant (P < 0.5) analgesic activity (160–197%) higher than that of ONPK500 (109.8%) and Morphine (101%) in the tail immersion test. The analgesic activity of NNPK 500 0.5–1.5 mg/kg p.o. (171.0–258.3%) and ONPK 500 (179.5%) were also significant (P < 0.01) and higher than that of Aspirin (103.00%) in the Randall-Selitto test. Both capsules also demonstrated significant (P < 0.5) analgesic and anti-inflammatory activities in the acetic acid-induced writhing and carrageenan-indued paw edema tests respectively. The two NPK500 capsules also, significantly (P < 0.5) inhibited PGE2 and iNOS but not COX-2 and COX-1 in the carrageenan-indued paw edema test. ConclusionThese results show that NNPK 500 and ONPK 500 capsules possessed potent analgesic and anti-inflammatory activities via inhibition of PGE2 and iNOS as a result of their chemical constituents. NPK500 capsules thus, relief acute pain and inflammation without causing gastrointestinal, renal or hepatic injuries, since they did not inhibit COX-1.

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.

Hydroxytakakiamide and Other Constituents from a Marine Sponge-Associated Fungus Aspergillus fischeri MMERU23, and Antinociceptive Activity of Ergosterol Acetate, Acetylaszonalenin and Helvolic Acid.

An unreported prenylated indole derivative hydroxytakakiamide (4) was isolated, together with the previously described ergosterol (1), ergosterol acetate (2), and (3R)-3-(1H-indol-3-ylmethyl)-3, 4-dihydro-1H-1,4-benzodiazepine-2,5-dione (3), from the column fractions of the crude ethyl acetate extract of the culture of a marine sponge-associated fungus, Aspergillus fischeri MMERU 23. The structure of 4 was elucidated by the interpretation of 1D and 2D NMR spectral data and high-resolution mass spectrum. The absolute configuration of the stereogenic carbon in 3 was proposed to be the same as those of the co-occurring congeners on the basis of their biogenetic consideration and was supported by the comparison of its sign of optical rotation with those of its steroisomers. The crude ethyl acetate extract and 2 were evaluated, together with acetylaszonalenin (5) and helvolic acid (6), which were previously isolated from the same extract, for the in vivo antinociceptive activity in the mice model. The crude ethyl acetate extract exhibited antinociceptive activity in the acetic acid-induced writhing and formalin tests, while 2, 5, and 6 displayed the effects in the late phase of the formalin test. On the other hand, neither the crude ethyl acetate extract nor 2, 5, and 6 affected the motor performance of mice in both open-field and rotarod tests. Additionally, docking studies of 2, 5, and 6 were performed with 5-lipoxygenase (5-LOX) and phosphodiesterase (PDE) enzymes, PDE4 and PDE7, which are directly related to pain and inflammatory processes. Molecular docking showed that 6 has low affinity energy to PDE4 and PDE7 targets while retaining high affinity to 5-LOX. On the other hand, while 2 did not display any hydrogen bond interactions in any of its complexes, it achieved overall better energy values than 6 on the three antinociceptive targets. On the other hand, 5 has the best energy profile of all the docked compounds and was able to reproduce the crystallographic interactions of the 5-LOX complex.

Experimental and pharmacoinformatic approaches unveil the neuropharmacological and analgesic potential of chloroform fraction of Roktoshirinchi (Achyranthes ferruginea Roxb.)

Ethnopharmacological relevanceAchyranthes ferruginea (A. ferruginea) Roxb. is a common plant used in traditional medicine in Asia and Africa. It has a variety of local names, including “Gulmanci” in Nigeria, “Dangar” in Pakistan, “Thola” in Ethiopia, and “Roktoshirinchi” in Bangladesh. It is edible and has several ethnomedical uses for a wide range of illnesses, including hysteria, dropsy, constipation, piles, boils, asthma, and shigellosis. However, the neuropharmacological and analgesic potential of A. ferruginea remains uninvestigated. Aim of the studyTo assess the neuropharmacological and analgesic potential of A. ferruginea through a multifaceted approach encompassing both experimental and computational models. Materials and methodsMethanol was used to extract the leaves of A. ferruginea. It was then fractionated with low to high polar solvents (n-hexane, chloroform, ethyl acetate, and water) to get different fractions, including chloroform fraction (CLF). The study selected CLF at different doses and conducted advanced chemical element and proximate analyses, as well as phytochemical profiling using GC-MS. Toxicological studies were done at 300 μg per rat per day for 14 days. Cholinesterase inhibitory potential was checked using an in-vitro colorimetric assay. Acetic acid-induced writhing (AAWT) and formalin-induced licking tests (FILT) were used to assess anti-nociceptive effects. The forced swim test (FST), tail suspension test (TST), elevated plus maze (EPM), hole board test (HBT), and light and dark box test (LDB) were among the behavioral tests used to assess depression and anxiolytic activity. Network pharmacology-based analysis was performed on selected compounds using the search tool for interacting chemicals-5 (STITCH 5), Swiss target prediction tool, and search tool for the retrieval of interacting genes and proteins (STRING) database to link their role with genes involved in neurological disorders through gene ontology and reactome analysis. ResultsQualitative chemical element analysis revealed the presence of 15 elements, including Na, K, Ca, Mg, P, and Zn. The moisture content, ash value, and organic matter were found to be 11.12, 11.03, and 88.97%, respectively. GC-MS data revealed that the CLF possesses 25 phytoconstituents. Toxicological studies suggested the CLF has no effects on normal growth, hematological and biochemical parameters, or cellular organs after 14 days at 300 μg per rat. The CLF markedly reduced the activity of both acetylcholinesterase and butyrylcholinesterase (IC50: 56.22 and 13.22 μg/mL, respectively). Promising dose-dependent analgesic activity (p < 0.05) was observed in chemically-induced pain models. The TST and FST showed a dose-dependent substantial reduction in immobility time due to the CLF. Treatment with CLF notably increased the number of open arm entries and time spent in the EPM test at doses of 200 and 400 mg/kg b.w. The CLF showed significant anxiolytic activity at 200 mg/kg b.w. in the HBT test, whereas a similar activity was observed at 400 mg/kg b.w. in the EPM test. A notable increase in the amount of time spent in the light compartment was observed in the LDB test by mice treated with CLF, suggesting an anxiolytic effect. A network pharmacology study demonstrated the relationship between the phytochemicals and a number of targets, such as PPARA, PPARG, CHRM1, and HTR2, which are connected to the shown bioactivities. ConclusionsThis study demonstrated the safety of A. ferruginea and its efficacy in attenuating cholinesterase inhibitory activity, central and peripheral pain, anxiety, and depression, warranting further exploration of its therapeutic potential.

Evaluation of Analgesic, Anti-inflammatory and Antipyretic activities of the Methanol Extract of Crinum jagus Bulb in Rats

This study evaluated the analgesic, anti-inflammatory and antipyretic activities of the methanol extract of Crinum jagus bulb. The preliminary phytochemical analysis and acute toxicity studies were carried out following standard procedures. Assessment of analgesic activity in mice was performed using acetic acid-induced writhing and formalin-induced pain tests. Anti-inflammatory and antipyretic activities were performed in rats using egg albumin-induced pedal oedema and Brewer’s yeast-induced pyrexia models respectively. The results of the qualitative phytochemical analysis revealed that the bulb contained alkaloids, flavonoids, steroids, saponins, phenols and terpenoids. The extract was non-toxic; the oral LD was greater than 5000 mgkg-1 at 24 h. The 50 maximal analgesic effect of the extract against acetic acid-induced pain was 47.2% at 400 mgkg-1 compared to 82.2% with aspirin (50 mgkg-1). The extract exerted no significant (p&gt;0.05) analgesic effect different from the control in the first phase (5 min) of formalin-induced pain test. However, there was dose dependent inhibition of pain sensitivity which peaked 85% at 400 mg/kg compared to 94% with piroxicam (500 mgkg-1) in the second phase (15-30 min) of the test indicating a peripherally mediated effect. The lowest test dose (100 mgkg-1) of extract had a comparable oedema inhibition (20%) to aspirin (50 mg/kg). C. jagus bulb extract produced a maximal antipyretic potency (79.5%) at 100 mgkg-1 compared to 83% with paracetamol (50 mgkg-1). Crinum jagus bulb could be a source of potent compounds against pain, inflammation and fever.

HPLC profiling and anti-inflammatory potential of Citrus macroptera leaves along with in silico analysis

BackgroundCitrus macroptera (Family-Rutaceae), is a scarce medicinal plant that has much therapeutic importance and is also reported to possess various medicinal components. Regarding the uses and the compounds, selected pharmacological tests on its leaves were conducted along with HPLC and in silico analysis. MethodsHPLC analysis of polyphenolic compounds was conducted using sixteen standards. In both qualitative and quantitative ways, antioxidant tests were conducted. The total contents of different antioxidant components were also measured. Free radicals from 2,2-diphenyl-1-picryl hydrazyl (DPPH), hydrogen peroxide, and superoxide radicals were scavenged along with FeCl3 reduction. To measure analgesic effects, acetic acid-induced writhing and tail immersion tests were experimented. Formalin-induced paw edema and Brewer's yeast-induced pyrexia methods were followed to evaluate anti-inflammatory and antipyretic potentialities, respectively. Finally, molecular docking and absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis of reported compounds were carried out. ResultsC. macroptera leaves showed the presence of eight polyphenols from HPLC analysis. The measured contents of phenols, tannins, flavonoids, and antioxidant capacities were noteworthy. The extract scavenged the obtained free radicals from the oxidants and also showed good FeCl3-reducing capabilities. In the case of pharmacological assays, it showed a considerable analgesic effect by reducing writhing impulse and elongating tail withdrawal time. Over the period of time, this extract significantly lessened the paw edema and elevated body temperature which revealed good anti-inflammatory and antipyretic outcomes, respectively. With the findings and from in silico analysis, we suppose six molecules to be treated as new leads. ConclusionOur experiment expressed that C. macroptera leaves are abundant with antioxidants and it also revealed nice anti-inflammatory potentialities.

Anti-inflammatory and antinociceptive activities of Daniellia oliveri (Fabaceace) stem bark extract.

Daniellia oliveri (Rolfe) Hutch. & Dalziel (Fabaceae) is used for the treatment of inflammatory diseases and pains (chest pain, toothache and lumbago) and rheumatism. The study investigates the anti-inflammatory and antinociceptive properties of D. oliveri and possible mechanism of antiinflammatory action. Acute toxicity of the extract was evaluated in mice using the limit test. The anti-inflammatory activity was assessed in xylene-induced paw oedema and carrageenan-induced air-pouch models at doses of 50, 100 and 200mg/kg, p.o. Volume of exudate, total protein, leukocyte counts, myeloperoxidase (MPO) and concentration of cytokines (TNF-α and IL-6) were measured in the exudate of rats in the carrageenan-induced air-pouch model. Other parameters include lipid peroxidation (LPO), nitric oxide (NO) and antioxidant indices (SOD, CAT and GSH). Histopathology of the air pouch tissue was also carried out. The antinociceptive effect was assessed using acetic acid-induced writhing, tail flick and formalin tests. Locomotor activity was done in the open field test. The extract was analysed with HPLC-DAD-UV technique. The extract showed significant anti-inflammatory effect (73.68 and 75.79%, inhibition) in xylene-induced ear oedema test at the dose of 100 and 200mg/kg, respectively. In carrageenan air pouch model, the extract significantly reduced exudate volume, protein concentration, the migration of leukocytes and MPO production in the exudate. The concentrations of cytokines TNF-α (12.25±1.80pg/mL) and IL-6 (21.12pg/mL) in the exudate at the dose of 200mg/kg were reduced compared to carrageenan alone group (48.15±4.50pg/mL; 82.62pg/mL) respectively. The extract showed significant increase in the activities of CAT and SOD and GSH concentration. The histopathological assessment of the pouch lining revealed reduction of immuno-inflammatory cell influx. Nociception was significantly inhibited by the extract in acetic acid-induced writhing model and the second phase of formalin test indicating a peripheral mechanism of action. The open field test showed that D. oliveri did not alter locomotor activity. The acute toxicity study did not cause mortality or signs of toxicity at 2000mg/kg, p.o. We identified and quantified caffeic acid, p-coumaric acid, ferulic acid, rutin, apigenin-7-glucoside, quercetin and kaempferol in the extract. The results of our study showed that the stem bark extract of D. oliveri possesses anti-inflammatory and antinociceptive activities thereby supporting its traditional use in the treatment of some inflammatory and painful disorders.

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.

Analgesic and Anti-Inflammatory Activities of 80% Methanol Extract and Solvent Fractions of Ehretia cymosa Thonn (Boraginaceae) Leaves in Rodents.

Ethnobotanical studies in various districts of Ethiopia reported that Ehretia cymosa (E. cymosa) is used for the management of headache, abdominal pain, arthritis and rheumatism. However, there is no scientific investigation done so far to confirm these traditional claims. Thus, the aim of this study was to assess the analgesic and anti-inflammatory effects of the 80% methanol extract and fractions of E. cymosa leaves. The dried and pulverized leaves of E. cymosa were soaked with 80% methanol to obtain a crude extract. Fractionation was done using chloroform, ethyl acetate and water by a soxhlet apparatus. The analgesic effects of the crude extract and solvent fractions were assessed using acetic acid-induced writhing and hot plate tests whereas anti-inflammatory activities were investigated using carrageenan-induced paw edema and cotton-pellet-induced granuloma models. In all the tested doses, the 80% methanol extract and solvent fractions revealed substantial (p < 0.001) analgesic activities in acetic acid induced writhing test. In the hot plate method, all the tested doses of E. cymosa crude extract and the solvent fractions produced significant analgesic activities (p < 0.05). In the carrageenan-induced acute inflammation model, all tested doses of the crude extract and solvent fractions resulted in a significant decline in paw edema. The 80% methanol extract and solvent fractions of E. cymosa at all the tested doses significantly reduced inflammatory exudates and granuloma mass formations (p < 0.001). From the results of this investigation, it can be stated that 80% methanol extract, aqueous, ethyl acetate and chloroform fractions of E. cymosa exhibited considerable analgesic and anti-inflammatory activities, supporting the plant's traditional use as a remedy for a variety of painful and inflammatory conditions.

Synthesis and Biological Evaluation of Hydroxypropyl Ester of Mefenamic Acid as a Promising Prodrug

Background: The free carboxylic acid group in the mefenamic acid (MFA) structure plays a potential role in developing various neuromuscular side effects after MFA administration. In this study, the hydroxypropyl promoiety was added to the carboxylic acid group of MFA in an attempt to reduce the neuromuscular side effects of MFA and improve its therapeutic effects. Methods: Hydroxypropylester of MFA (HPEMA) was synthesized and subjected to various in vivo investigations compared to MFA. The neuromuscular toxicity was conducted following high doses administration in mice and was evaluated at various measuring parameters, such as the percentage of catalepsy, clonic-tonic seizure, and death. In addition, the anti-inflammatory and anti-nociceptive effects of HPEMA were evaluated in the carrageenan-induced paw edema test and acetic acid-induced writhing test, respectively. Results: The findings of this study reveal that the percentage of catalepsy, clonic-tonic seizure, and death is significantly lower in mice treated with HPEMA than in those treated with equimolar doses of MFA. In addition, treatment with HPEMA caused a comparable anti-inflammatory activity in the carrageenaninduced paw edema test and a significantly higher anti-nociceptive effect in the acetic acid-induced writhing test than the MFA treatment. Conclusion: This study’s findings suggest that HPEMA is a promising prodrug for MFA.

Evaluation of in vitro antioxidant, anti-bacterial, cytotoxic and in vivo analgesic and neuro-pharmacological investigation of alysicarpus vaginalis available in Bangladesh

Purpose: The objectives of this research were to investigate the effects of Alysicarpus vaginalis L. (Alyce clover) leaf extracts prepared with ethyl acetate and methanol on in vitro activities like antioxidant, antimicrobial and cytotoxic, as well as on some in vivo activities like analgesic and neuropharmacological properties in an animal model. Study Design: Phytochemical screening was used as the primary method of evaluation for both the ethyl acetate (EAEAV) and methanolic extract (MEAV) of Alysicarpus vaginalis (L.). Because of the pharmacological interest in the plant&#39;s constituent components, it was decided to investigate its potential on in vitro activities, such as antioxidant, cytotoxic and antibacterial. Whether or if the observed effects on its in vivo analgesic and neuropharmacological properties in animal models are statistically significant. Place and Duration of Study: This investigation was performed in Laboratory of Phytochemistry and Pharmacology, Department of Pharmacy and Laboratory of Microbiology, Stamford University Bangladesh, Dhaka between June 2022 to October 2022. Methodology: Both EAEAV and MEAV was subjected for phytochemical screening using various test reagent and was also researched for its potential antioxidant, antibacterial, cytotoxic, analgesic, and neuropharmacological effects. The DPPH Free Radical Scavenging Assay, the Disk Diffusion Method and the Brine Shrimp Lethality Bioassay were all used to determine cytotoxic, antimicrobial and antioxidant activity, using different concentrations respectively. Swiss albino mice were subjected to acetic acid-induced writhing and hot plate tests to determine analgesic efficacy. cGMP pathway induced mechanism test was used to confirm the actual analgesic activity. Open field and hole cross tests were used to evaluate locomotor activity as part of the neuropharmacological experiment. Results: Different phytochemical constituent were detected in the experimental result of EAEAV and MEAV&#39;s phytochemical screening. MEAV showed highest antioxidant activity with an IC50 value of 34.70 μg/mL where EAEAV showed IC50 value of 12.49 μg/mL and MEAV also showed higher antibacterial activity compared to EAEAV. EAEAV and MEAV showed most notable lethality with LC50 value of 3.89 μg/mL and 8.71 μg/mL compared to the conventional vincristine sulphate&#39;s LC50 value in the brine shrimp lethality bioassay. As opposed to this, EAEAV reduced peripheral nociception in the acetic acid-induced writhing nociceptive paradigm, with percent inhibitions of 42.48% and 47.00% where MEAV reduced 40.63% and 51.77% at the aforementioned dosages as opposed to conventional Diclofenac sodium. cGMP pathway mechanism confirmed the % inhibition of pain using both EAEAV which boosted the pain reduction into 59.62% and 71.12%. Additionally, a considerable analgesic effect was seen in the hot plate test. The extract, when compared to the usual Diazepam, was also shown to reduce motor coordination in the Open Field and Hole Cross Tests. Conclusion: These results confirmed the conventional medicine claims of the Alysicarpus vaginalis (L.) plant&#39;s therapeutic virtues and suggest potential mechanisms of action.

The hydroethanolic root extract of Psydrax subcordata (DC.) Bridson exhibits antinociceptive and anti-inflammatory effects in animal models

Psydrax subcordata (DC.) Bridson (Rubiaceae) is traditionally used to treat pain and inflammatory conditions in Ghana. There is, however, little scientific evidence to support its use in Ghanaian Traditional Medicine. This study, therefore, evaluated the antinociceptive and anti-inflammatory effects of hydroethanolic root extract of Psydrax subcordata (PSRE) using rodent models. Acute toxicity of PSRE was assessed in the Irwin's test. The antinociceptive effect was evaluated in the acetic acid-induced writhing and formalin-induced nociception tests. Xylene-induced ear oedema test and cotton pellet-induced granuloma models were used to assess the ameliorative effects of PSRE in acute and subacute inflammation. Effect of PSRE on tissue integrity in xylene-induced inflammation was also evaluated by histological examination. Oral treatment of PSRE up to the dose of 5000 mg kg−1 did not produce any lethal effect in mice. Oral PSRE (30–300 mg kg−1) significantly (at least P < 0.01) attenuated nociception in both acetic acid-induced writhing and formalin-induced nociception tests. In the xylene-induced ear oedema test, PSRE decreased acute inflammation dose-dependently. The extract also attenuated transudate and exudate formation in the cotton pellet-induced granuloma test. The findings show that hydroethanolic root extract of Psydrax subcordata possesses antinociceptive and anti-inflammatory properties in rodents. The study provides pharmacological support for the traditional use of the plant in the management of pain and inflammatory conditions.

Efficacy of 2-Hydroxyflavanone in Rodent Models of Pain and Inflammation: Involvement of Opioidergic and GABAergic Anti-Nociceptive Mechanisms

The current work examined the pharmacological potential of a selected flavanone derivative 2-hydroxyflavanone as a promising remedy for the treatment and management of pain. The selected flavanone derivative (2-HF) was evaluated for its analgesic and anti-inflammatory potentials following standard pharmacological protocols including hot plate, acetic acid-induced writhing and tail immersion tests. Naloxone and pentylenetetrazol were used to evaluate the potential implication of GABAergic and opioidergic mechanisms. The anti-inflammatory potential of 2-HF was confirmed using carrageenan-, serotonin- and histamine-induced paw edema models as well as a xylene-induced ear edema model. Furthermore, the anti-neuropathic potential of 2-HF was tested using a cisplatin-induced neuropathic pain model. Our sample, at the tested concentrations of 15, 30 and 45 mg kg−1, showed considerable analgesic, anti-inflammatory effects, as well as efficacy against neuropathic pain. Naloxone and pentylenetetrazol at 1 and 15 mg kg−1 antagonized the anti-nociceptive activities of 2-hydroxyflavanone indicating the involvement of opioidergic and GABAergic mechanisms. In the static allodynia model, combination of gabapentin 75 mg kg−1 with 2-HF at 15, 30, 45 mg kg−1 doses exhibited considerable efficacy. In cold allodynia, 2-hydroxyflavanone, at doses of 15, 30 and 45 mg kg−1 and in combination with gabapentin (75 mg kg−1), demonstrated prominent anti-allodynic effects. The paw withdrawal latency was considerably increased in gabapentin + cisplatin treated groups. Moreover, cisplatin + 2-hydroxyflavanone 15, 30, 45 mg kg−1 showed increases in paw withdrawal latency. Likewise, considerable efficacy was observed for 2-hydroxyflavanone in thermal hyperalgesia and dynamic allodynia models. Our findings suggest that 2-hydroxyflavanone is a potential remedy for pain syndrome, possibly mediated through opioidergic and GABAergic mechanisms.

Network Pharmacology and ­Experimental Analyses of the Mechanism of Analgesic and Glucose Intolerance Through Glucocorticoid Signaling in C57 Mice Treated with Water Extract of Prunella vulgaris L. Spica

The aim of this study was to confirm the anti-inflammatory effect and explore the adverse effects and underlying mechanisms of Prunella vulgaris L., which has been extensively used for hundreds of years in East Asia. Network pharmacology studies predicted that glucocorticoids (GCs), GC-targeting molecules, and brain-derived neurotrophic factor (BDNF) were intensively involved in the anti-inflammation and glucose intolerance. To attest the effects and underlying mechanisms, C57 male mice were randomly divided into 5 groups, control (C), dexamethasone (Dex), water extract of P. vulgaris (PE 35 or 70 mg), and PE (70 mg) + mifepristone (PEM). After a 3-week treatment, acetic acid-induced writhing and hot plate tests confirmed the peripheral and central analgesic effects, respectively. Plasma GCs and BDNF were significantly increased. Coincidently, plasma pro-inflammatory cytokines, including IL1β, IL6, and IL10, were decreased by PE treatment, which were blocked by the application of mifepristone ( P &lt; 0.5). Western blots confirmed GC receptor (GR) translocation, and decreased cyclooxygenase 2 in the lumber spine by PE treatment. Food intake was impeded after a 4-week PE treatment, but the ratio of bodyweight gain to food intake was increased in a time-dependent manner. An intraperitoneal glucose tolerance test disclosed that PE treatment impaired glucose disposal in mice. Quantitative polymerase chain reaction (PCR) showed that hepatic GC-responsive genes such as GC-induced leucine zipper protein and glucose-6-phosphatase catalytic subunit 1 were up-regulated, and hypothalamic neuropeptide Y and agouti-related protein expressions were decreased by PE treatment. Hypothalamic BDNF was up-regulated, whereas hepatic BDNF was down-regulated. The regulation of these genes by PE was reversed by mifepristone administration. In conclusion, PE treatment plays analgesic and glucose regulation roles simultaneously through GC-induced signaling pathways, and P. vulgaris may provide a natural ligand of GR for the treatment of inflammation with glucose dysregulation.

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.

New Hybrid Molecules Based on Sulfur-Containing Nicotinonitriles: Synthesis, Analgesic Activity in Acetic Acid-Induced Writhing Test, and Molecular Docking Studies

New Hybrid Molecules Based on Sulfur-Containing Nicotinonitriles: Synthesis, Analgesic Activity in Acetic Acid-Induced Writhing Test, and Molecular Docking Studies

Phytochemical screening and analgesic effect, in mice, of the methanolic leaf extract of Manniophyton fulvum Mull.-Arg. (Euphorbiaceae)

Medicinal plants continue to attract attention as an alternative form of therapy. Phytochemical screening, analgesic properties and probable mechanism/s of action of the methanol leaf extract of Manniophyton fulvum were carried out following claimed folkloric usefulness in this regard. Standard methods were used to screen for classes of phytochemicals. Acetic acid-induced writhing and hot plate tests in albino mice were used to evaluate the peripheral and central analgesic effects using acetylsalicylic acid and morphine respectively as positive controls, while 50% DMSO served as negative control. Elucidation of the possible mechanism/s of action of the extract was carried using phenoxybenzamine, naloxen, ondansetron, atropine and haloperidol. Alkaloids, saponins, carbohydrates, terpenoids, steroids tannins, and flavonoids were detected in the extract. At 100 mg/kg dose, significant (P&lt;0.01) reduction in pain stimuli, compared to the negative control group in both models was observed. Higher doses of extract (200 and 400 mg/kg) did not produce any significant effect. Observed results suggest that the leaf extract of M. fulvum may have an analgesic effect that is centrally and peripherally mediated at a lower dose compared to the high dose. The findings provide possible scientific basis for the ethnomedicinal use of the plant in several pain conditions.

Phytochemical Screening and Antinociceptive Activity of the Hydroalcoholic Extract of Potentilla reptans L.

Background: Potentilla species have traditionally been used as anti-inflammatory and analgesic agents in Iran and other countries.&#x0D; Objectives: This study aimed to investigate the antinociceptive effect of Potentilla reptans L., which has a wide distribution in the north of Iran.&#x0D; Methods: The biological activities of the hydroalcoholic extract of P. reptans aerial parts have been investigated using the acetic acid-induced writhing, hot plate, and rotarod tests in the male mice. In addition, the phytochemical profile of the extract has been evaluated.&#x0D; Results: The phytochemical investigation detected secondary metabolites such as flavonoids, saponins, triterpenoids, and tannins in the extract. Moreover, the Mean±SD total phenolic and tannin contents of the extract were 251±2.08 and 111.5±1.3 mg gallic acid equivalents per gram of dried extract, respectively. Also, the Mean±SD total flavonoid content was 29.42±3.31 mg quercetin equivalents per gram of dried extract. Oral administration of the extract (100, 300, and 500 mg/kg) dose-dependently reduced the number of writhing responses induced by acetic acid and increased the reaction time in the hot-plate test. The antinociceptive effect of the extract, similar to morphine, was significantly antagonized by naloxone (4 mg/kg; IP) in the writhing test. In the rotarod test, none of the extract doses used in the experiment caused a loss of locomotor activity.&#x0D; Conclusion: In this study, the hydroalcoholic extract of P. reptans showed a practical antinociceptive effect in hot plate and writhing tests. It seems that opioid receptors mediate the observed effect.

Antinociceptive activities and mechanism of action of Cepharanthine

Cepharanthine is an alkaloid that isolated from Stephania cepharantha Hayata, however，its analgesic properties are unclear and the molecular targets that mediating Cepharanthine-induced analgesia are not explored yet. In the current study, mice pain models including hot plate, acetic acid-induced writhing and formalin tests were conducted to evaluate the antinociceptive actions of Cepharanthine. [3H]-ligand competitive binding assay was applied to determine the binding affinity and selectivity of Cepharanthine at κ, μ and δ opioid receptors. Cepharanthine-induced constipation was investigated using the small intestinal transit test. The results showed that intraperitoneal injection of Cepharanthine produced potent antinociception with an ED50 value of 24.5 mg/kg in the acetic acid-induced writhing test. In the formalin test, Cepharanthine produced moderate antinociception with the maximum analgesic activity of 42.6 ± 11.3% in phase I and 60.1 ± 7.7% in phase Ⅱ, respectively. Cepharanthine had no effects in the hot plate test. In vitro radioligand binding assay, Cepharanthine exhibited a high affinity for μ opioid receptors with a Ki value of 80 nM, without binding to κ and δ opioid receptors. Correspondingly, Cepharanthine-mediated antinociceptive effects were antagonized by pretreatment with opioid receptor antagonist naloxone. Cepharanthine also decreased the small intestine propulsion rates in the small intestinal transit test. Together, this study firstly demonstrates that Cepharanthine produces potent antinociception in acetic acid-induced visceral pain and moderate antinociception in formalin-induced inflammatory pain, and its mechanism of action may be through activation of μ opioid receptors.

CNS Depressant and Analgesic Activities of Thysanolaena maxima Roxb. Available in Bangladesh

In Bangladesh, numerous tribal people of Chittagong Hill Tracts have been using different parts of Thysanolaena maxima Roxb. for many years. The present study was designed to investigate CNS depressant and analgesic activities of methanol extract of the aerial parts of the plant in mice models. CNS depressant activity of the crude extract (200 and 400 mg/kg) was evaluated using open field, hole cross and thiopental-induced sleeping time tests using diazepam as the standard. Analgesic activity was determined using acetic acid-induced writhing and hot plate tests using diclofenac sodium as the standard. The extract showed dose dependent suppression of locomotion in open field and hole cross tests and exerted sedative action in thiopental induced sleeping time. In the open field and the hole-cross tests, maximum CNS depressant activity was observed at 90 min after administration of extract and the standard drug. The extract significantly induced the onset of sleep and prolonged the sleeping time in thiopental induced sleeping test compared to the control group. The extract produced significant (p &lt; 0.05) analgesic activity by inhibiting writhing by 41.89% and 60.81%, at doses of 200 and 400 mg/kg body weight, respectively, which was comparable to the inhibition of diclofenac sodium (73.64%). Additionally, in hot plate test, the extract exhibited a significant (p &lt; 0.05) increase in pain threshold in a dose dependent manner. The findings of the study are encouraging and demands further investigation of other bioactivities with isolation of pure compounds. Dhaka Univ. J. Pharm. Sci. 20(2): 227-233, 2021 (December)