Reference Drug Diclofenac Sodium Research Articles

SYNTHESIS AND ANALGESIC ACTIVITY OF METHYL-1-ANTIPYRYL-4-AROYL-2,3-DIOXO-2,3,5,10-TETRAHYDROBENZO[B]PYRROLO[2,3-E][1,4]DIAZEPINE-10A(1H) –CARBOXYLATES

In order to obtain new biologically active compounds, methyl-1-antipyryl-4-aroyl-2,3-dioxo-2,3,5,10-tetrahydrobenzo[b]pyrrolo[2,3-e][1,4]diazepine was synthesized-10a(1H)-carboxylates by reacting 1-antipyryl-4-aroyl-5-methoxycarbonyl-1H-pyrrole-2,3-diones with o-phenylenediamine. The structures of the obtained compounds were confirmed by 1H NMR, IR spectroscopy, X-ray diffraction and elemental analysis. The presence of several electrophilic centers in the structure of antipyryl-substituted 1H-pyrrole-2,3-diones gives them a high reactivity with respect to binucleophilic reagents. Apparently, the described interaction is carried out by the initial nucleophilic attack of one aminogroup of o-phenylenediamine on the C5 carbon atom of the pyrrole-2,3-dione ring, followed by the attack of another aminogroup on the carbonyl carbon atom of the aroyl fragment, closing the diazepine ring. The described reaction is a convenient preparative method for the synthesis of previously undescribed methyl-1-antipyryl-4-aroyl-2,3-dioxo-2,3,5,10-tetrahydrobenzo[b]pyrrolo[2,3-e][1,4]diazepine-10a(1H)-carboxylates, which are of interest as pharmacological substances. The described interaction proceeds quickly and with high yields. The obtained compounds were screened for analgesic activity, as a result of which a more pronounced effect was found in some products compared to the reference drug (diclofenac sodium). A preliminary assessment of acute toxicity was carried out, according to which the derivatives of 2,3,5,10-tetrahydrobenzo[b]pyrrolo[2,3-e][1,4]diazepine proved to be safe for further studies. The survival rate of animals in all groups is 100% after 24 h and 100% after 14 days. Screening of analgesic activity was performed by the hot plate method. Registration of time was carried out from the moment of placement on a hot surface until the appearance of a behavioral response to nociceptive stimulation 60 and 120 min after the administration of substances. For citation: Lyadov V.A., Makrushin D.E., Denislamova E.S., Maslivets A.N., Triandafilova G.A., Solodnikov S.I. Synthesis and analgesic activity of methyl-1-antipyryl-4-aroyl-2,3-dioxo-2,3,5,10-tetrahydrobenzo[b]pyrrolo[2,3-e][1,4]diazepine-10a(1H) –carboxylates. ChemChemTech [Izv. Vyssh. Uchebn. Zaved. Khim. Khim. Tekhnol.]. 2024. V. 67. N 5. P. 17-23. DOI: 10.6060/ivkkt.20246705.6939.

Synthesis and anti-inflammatory activity of S-oxides of pyridinyloxy substituted imidazo[2,1-b][1,3]thiazines

Here derivatives of imidazo[2,1-b][1,3]thiazines are attractive objects for organic and medicinal chemists. In the present work chemoselective conditions for oxidation of the sulfur atom in the 6-(2-pyridinyloxy)substituted (benzo)imidazo[2,1-b][1,3]thiazines to the corresponding sulfoxides were proposed and their synthesis was performed. Synthesized sulfoxides exist in the diastereomeric mixture and individual diastereomers 2a-e and 3a-e were obtained using a chromatographic technique. The structure of compounds 2a-e and 3a-e were characterized using 1H, 13C NMR, LC-MS spectra, and X-ray analysis for derivative 2b. The anti-inflammatory activity screening in vivo was performed using the carrageenan model of inflammatory paw edema in white rats for all the diastereomeric mixtures and individual diastereomers. Diastereomer 2c possessed an anti-inflammatory effect with an inflammation inhibition index of 46.1% which was equal to the activity of the reference drug diclofenac sodium.

Free Radical Scavenging and Antinociceptive Activities of the Aqueous Extract from Matricaria chamomilla L. Flowers.

Background: Matricaria chamomilla L. (M. chamomilla) is a famous medicinal plant distributed worldwide. It is widely used in traditional medicine to treat all kinds of diseases, including infections, neuropsychiatric, respiratory, gastrointestinal, and liver disorders. It is also used as a sedative, antispasmodic, antiseptic, and antiemetic. Our aims in this study was thus to quantify the phenolic, flavonoids contents in the flower of this plant, and also to evaluate the in vitro antioxidant potential and the in vivo analgesic activity. Methods: The total phenolic and flavonoid contents of the plant aqueous extract (MCAqE) were estimated using the Folin–Ciocalteu and AlCl3 colorimetric methods, respectively. However, DPPH method was used to evaluate the in vitro antioxidant activity. Analgesic activity was tested by acetic acid induced writhing model in mice. Results: Quantitative determination of total polyphenols and flavonoids revealed that this extract contained 158.41±1.6 mg gallic acid equivalent/g of dry extract and 37.06±0.56 mg quercetin equivalent/g of dry extract, respectively. The antioxidant activity of the plant extract was important (IC50=3.08±0.25 mg/mL). MCAqE extract, at 400 mg/kg, showed analgesic activity (39.60±8.70%) against acetic acid induced pain in mice while the standard reference drug Diclofenac sodium exhibited 90.44±2.80% activity at 10 mg/kg dose.

Carboxyl-containing quinazolines and related heterocycles as carriers of anti-inflammatory activity

Active pharmaceutical ingredients whose structure combines aromatic or heterocyclic fragments with pharmacophore carboxylic group are widespread on pharmaceutical market. The isolation of COX-NSAIDs complexes and following X-ray studies allowed to explain the key role of pharmacophore carboxylic group in the formation of enzyme-ligand interactions and the effect of its presence on the activity and selectivity. The introduction of selective COX-2-inhibitors to medicinal practice resulted in a significant decrease of side effects and complication frequencies. However, the problem of NSAIDs toxicity has not been solved. Thus, the search for the novel anti-inflammatory drugs using in silico methods and approaches including structural modification of known NSAIDs by “bioisosteric” replacements of aromatic and heterocyclic fragments with other structural elements with carboxylic group as the carrier of pharmacological effect, is a current trend of medicinal chemistry. The aim of present study is to purposefully search for anti-inflammatory agents among carboxyl-containing quinazolines and related heterocycles using in silico and in vivo methods, as well as to evaluate carboxylic group effect on the level of anti-inflammatory activity. Materials and methods. Quinazoline-4(3H)-ylidene)hydrazides of mono-(di-)carboxylic acids, 2-R-[1,2,4]triazolo[1,5-c]quinazolines, 3-R-5-(2-aminophenyl)-1H-1,2,4-triazoles, 5-carboxyalkyl[1,2,4]triazolo[1,5-c]quinazolines and 2-R-7-oxo-6,7-dihydropyrrolo[1,2-a][1,2,4]triazolo[1,5-c]quinazoline-4a(5H)-carboxylic acids were screened for their anti-inflammatory activity. MarvinSketch 20.19.0, AutoDock Vina and AutoDockTools 1.5.6, HyperChem 7.5, Discovery Studio were used for in silico research. “Drug-like” characteristics were evaluated using an online service. Prediction of toxicity and Ames mutagenicity of the studied compounds were performed in silico using Test software. Evaluation of the anti-inflammatory activity of the synthesized compounds was carried out on white Wistar rats (150–160 g of weight) using carrageenan induced paw edema model. Phlogogen (1 % aqueous solution of λ-carrageenan) was subplantarly injected in the dose of 0.1 ml in the rats’ hind right paw. The left one was used as a control. The studied compounds were intragastrically administered with atraumatic probe as water solution or finely dispersed suspension stabilized by Tween-80 in the dose of 10 mg/kg 1 hour before the injection of phlogogen. The reference drug Diclofenac sodium was administered intragastrically in a recommended for pre-clinical studies dose of 8 mg/kg. The paw volume was measured before the experiment and in 4 hours after phlogogen injection. The activity of these substances was determined by their ability to reduce the swelling compared with control group and was expressed in percentage. The experiments were carried out with respect to Bioethical rules and norms. Results. The search for anti-inflammatory agents among carboxylic-containing quinazolines and related heterocycles was theoretically substantiated using results of molecular docking, druglike criteria calculations and predicted parameters of toxicity. Experimental in vivo methods (“carrageenan” test) confirmed the anti-inflammatory activity of studied compounds and showed that (quinazoline-4(3H)-ylidene)hydrazides of dicarboxylic acids inhibit edema by 17.0–50.0 %, 2-carboxyalkyl-(phenyl-)-[1,2,4]triazolo[1,5-c]quinazolines – by 0.00–40.63 %, 2-(5-(2-aminophenyl)-1H-1,2,4-triazol-3-yl)alkyl-(phenyl-)carboxylic acids – by 2.43–49.65 %, 2-R-5-carboxyalkyl[1,2,4]triazolo[1,5-c]quinazolines – by 0.47–22.93 % and 2-R-7-oxo-6,7-dihydropyrrolo[1,2-a][1,2,4]triazolo[1,5-c]quinazoline-4a(5H)-carboxylic acids – by 0.94–17.16 %. Among them, there are compounds that compete with the reference drug “Diclofenac sodium”. The SAR analysis showed that both conformation of the molecule and the nature of the “pharmacophore” moiety (carboxyalkyl residue length) at the corresponding positions of the heterocycle have a significant effect on the anti-inflammatory activity. It was shown that the test compounds, according to molecular docking visualization data, have other enzyme-ligand interactions and probably a different mechanism of activity. Conclusions. The predicted affinity values, calculated “drug-like” criteria and toxicity parameters, visualization of the docking of studied molecules in active site of biological targets as well as experimental studies results showed that investigated compounds are promising in scope of purposeful search for anti-inflammatory drugs. The conducted in vivo screening of anti-inflammatory activity among carboxyl-containing quinazolines and related heterocyclic compounds allowed to detect series of substances that by the level of anti-inflammatory activity compete with reference-compound “Diclofenac sodium” on the carrageenan-induced paw edema model. Presented data may be considered as a theoretical basis for further structural modification of studied compounds aimed on elaboration of novel anti-inflammatory agents and evaluation of their activity mechanism (lipoxygenase inhibitors, phospholipase inhibitors, etc.).

Anti-inflammatory activity of a dental gel based on Origanum vulgare raw material

Inflammatory and destructive diseases of parodontosis are one of the most complex and common forms of the teeth diseases of human population. Search of the herbal preparation with anti-inflammatory activity is a prospect way for development of new drugs on the base of local raw material. A prerequisite for this study has been the presence of a high antimicrobial and anti-caries activity of the essential oil of medicinal plant Origanum vulgare. The article presents for the first time the results on the anti-inflammatory activity of dental anti-caries gel with essential oil and ethanol extract of oregano. A sample of dental gel at a dose of 25 mg / kg has anti-inflammatory activity, which was expressed in a significant decrease by 41.4 % in the amount of inflammatory lymph in the abdominal teeth in rats compared to controls. The anti-inflammatory activity of this sample is comparable to the reference drug diclofenac sodium.

In-vitro Anti Arthritic Activity potentials of Erythroxylum monogynum leaves Hydro-alcoholic Extract

Rheumatoid arthritis (RA) is an evolving, enduring, and a crippling disorder categorized by puffiness, agony, and synovial joints arduousness. The exact reason of this devastating illness is mysterious. However, it is strongly linked to self-protection reaction triggered by various genetic and external factors. The current research work was designed to explore the anti-arthritic probable of the plant Erythroxylum monogynum. The plant leaves was collected, shade dried, blended and extracted (continuous hot percolation) with Hydro-alcoholic solvent. Preliminary phytochemical evaluation were carried out. Entirely the in-vitro models i.e. inhibition of protein denaturation, membrane stabilization and proteinase inhibition were carried out by using standard reference drug diclofenac sodium. In the present study there was significant (p<0.05) inhibition of protein denaturation in both standard and extract treated group and % inhibition of protein denaturation produced by extract at concentrations 100 and 300?g/ml exhibited improved activity than standard (Diclofenac sodium). From the results of the present study it can be stated that Erythroxylum monogynum may control the production of auto-antigens by preventing in-vivo denaturation of proteins in rheumatic diseases. Dose based and significant (p<0.05)of anti arthritic activity in in-vitro designs were found. The results disclose hopeful anti arthritic probables of the herb. However further pharmacological investigation using isolated active ingredients can be carried out to confirm its usefulness and effectiveness.

Anti-Arthritic Evaluation of Ginger, Colchicum and Detoxified Nux-Vomica combination for Poly Herbal Unani Formulation

Introduction: Arthritis (Wajaul Mafasil) is a condition which is growing worldwide due to lifestyle, environmental and genetic factors. In Unani literature, there are many herbs which are praised for treatment of Arthritis. So polyherbal formulation contains Ginger, Colchicum and Nux- Vomica is taken in combination for arthritis study. This combination is not previously reported but used by unani practitioners. Method: Three crude herbs (Ginger, Colchicum and Nux vomica) were extracted out in both aqueous and hydro-alcoholic solvent. LD-50 of all extracts (aqueous and hydro-alcoholic extract) was determined. Now respective extracts were mixed in effective dose ratio to obtain aqueous and hydro-alcoholic dosage form. Finally both effective combinations (aqueous and hydro-alcoholic) convert into tablet dosage form to determine its anti-arthritic activity by Carrageenan Induced Oedema Test, Cotton Pellet Induced Granuloma Test and Freund’s adjuvant Induced Arthritis Test. The efficacy of the Unani formulation was compared with reference drug (Diclofenac sodium). Result and Discussion: in Carrageenan Oedema Test, animals in high dose hydro-alcoholic, shows decrease in paw volume significantly after 3 hours of Carrageenan injection. In Cotton Pellet Induced Granuloma Test, animals in high dose hydro-alcoholic, shows reduction in granuloma formation significantly. In Freund’s Adjuvant Induced Arthritis Test, The significant reduction in paw volume was found in high dose hydro-alcoholic. Conclusion: Conclusively this study establishes anti-arthritic potential of polyherbal extract in unani literature. Thus these drugs possess synergistic anti-arthritic potential in combination against acute, sub-acute as well as chronic arthritis. So in future compatible dosages form may be prepared for treating arthritis.

Evaluation of the in vitro anti-inflammatory and cytotoxic potential of ethanolic and aqueous extracts of Origanum syriacum and Salvia lanigera leaves.

In this study, the chemical compositions of the ethanolic and aqueous extracts of the leaves of Origanum syriacum and Salvia lanigera were identified based on GC-MS spectrometric analyses. The in vitro anti-inflammatory potential of the different extracts was evaluated by determining the membrane stabilization of human red blood cells and the percent inhibition of the COX1/2, 5LOX, and sPLA2-V enzymes. Both ethanolic extracts showed maximum membrane stabilization (≤ 91%, at 100 μg/mL) compared to the aqueous extracts (≤ 45%) and the reference drug diclofenac sodium (90.75%). The membrane-stabilizing effects of the ethanolic extracts could be directly correlated to their anti-inflammatory activity. While both ethanolic fractions strongly inhibited the 5LOX and COX-1 enzymes at 100 μg/mL, only the O. syriacum ethanolic extract selectively inhibited sPLA2-V (99.35%, at 50 μg/mL). The differences in the pharmacological efficiencies of the different extracts could be attributed to the variation in their chemical compositions particularly the content of oxygenated monoterpenoids. Additionally, none of the ethanolic extracts demonstrated cytotoxicity to human colorectal cancer cell lines (HCT-116 and Lovo), even at the highest concentration tested (200 μg/mL). The safe profiles of these extracts towards the tested cell lines may be due to the absence of the toxic phthalic acid ester substances. Collectively, these findings clearly suggest that the studied ethanolic extracts of O. syriacum and S. lanigera can be considered interesting candidates for the treatment of human inflammatory diseases related to oxidative stress and microbial infections.

Pharmacological and ADMET-based pharmacokinetic properties of Syzygium samarangense var. parviflorum leaf extract in in vitro, in vivo and in silico models

This research investigated pharmacological properties mainly the anti-inflammatory, anthelmintic, thrombolytic and anxiolytic potential of methanol extract of Syzygium samarangense (MESS) var. parviflorum. Anti-inflammatory action by bovine serum albumin, egg albumin denaturation and membrane stabilization, anthelmintic by live parasites, thrombolytic by clot lysis and anxiolytic by elevated plus maze (EPM) and light and dark box (LDB) tests were measured. The four targeted pharmacological properties were further justified using the most prevalent compounds, isolated from this plant, to be undergone for their pharmacokinetic property’s analyses, sitemap analyses and lignad-receptor interactions by computational models through SwissADME and Schrödinger, 2018 softwares against PDB 6COX, 6D6T, 1JFF receptors. MESS was found to display statistically significant (P < 0.05) inhibition of Bovine Serum albumin and Egg albumin denaturation compared to reference drug diclofenac sodium. Remarkable vermicidal effect on the paralysis and death of anthelmintic parasites was observed at MESS concentration 200 mg/dL. A nondescript clot lysis of MESS compared to streptokinase was evident in in vitro thrombolytic assay. MESS increased the number of times the animal crossed from one compartment to the other and the time spent in the brightly-lit chamber of the LDB. Three-methylchalcone derivatives out of seven MESS compounds were undertaken, based on cut off value and sitemap prediction score, for further ligand-receptor binding efficiency. All these three compounds showed promising docking score, glide emodel and glide energy against PDB 6COX, 6D6T and 1DDJ, plasmin proteins demonstrating the prospects of MESS to be materialized for anti-inflammatory, anthelmintic, and thrombolytic therapeutics with further clarification.

Anti-Inflammatory Activity of Mangosteen (Garcinia Mangostana Linn.) Rind Extract Nanoemulgel and Gel Dosage Forms

Mangosteen (Garcinia mangostana Linn.) rind is known for its anti-inflammatory activity. Inflammation of local tissue can be overcome by topical administration of dosage forms. In an effort to improve the quality of topical drug delivery, nanoparticle technology can be an option.The purpose of this study is to determine the activity of gel and nanoemulgel dosage forms containing fractions of mangosteen rind extract (n-hexane: ethyl acetate). The gel dosage form of mangosteen rind fractions was successfully prepared. Its physical and chemical properties were evaluated, and the results were within the expected range. The spreadibility of the formulations was between 5-7cm and the pH was between 4.5 and 6.5.The 0.0625% and 0.125% mangosteen rind fraction concentrations are the formulas by which nanoemulgel was successfully formed, resulting in non-separating phases, percent transmittance of 96.997 ± 0.137% and 94.253 ± 0.134% respectively, particle size of 17.437 ± 0.427 and 17.240 ± 0.276 nm; potential zeta of 5.183 ± 0.202 and -10.143 ± 0.238. In the inflammatory test of carrageenan induced laboratory mice, nanoemulgel containing 0.0625% and 0.125% mangosteen rind fraction concentrations produced better percent inhibition (p<0.05) compared to gel containing 0.1%, 0.5%, and 1% mangosteen rind fraction concentrationsin the 90th minute, but the difference was not significant in the 120thminute through the end of thetest. The nanoemulgel containing 0.0625% and 0.125% mangosteen rind fraction concentrations have an unsignificant difference in results (p>0.05) when compared to the reference drug (diclofenac sodium) in the 90th minute.

Biochemical Confirmation of Anti-Inflammatory Activity of Oxicam-Based Pharmaceutical Compositions

Biochemical confirmation of anti-inflammatory activity of oxicam-based pharmaceutical compositions was performed by the determination of the level of one of the main markers of inflammation-C-reactive protein. Biochemical studies were carried out on laboratory animals (white WAG rats) to study the anti-inflammatory effects of meloxicam, piroxicam, caffeine, and pharmaceutical compositions consisting of meloxicam and caffeine, piroxicam and caffeine compared to the reference drug - sodium diclofenac. The content of CRP in serum of rats was determined using the CRP latex test kit (State registration number 1248/2002, Kharkiv, Ukraine). It was shown that composition of meloxicam and caffeine reduced the content of CRP by 16 times compared with formalin-induced edema, and by 2 times in comparison with the reference drug diclofenac sodium, which is statistically significantly different from the control, i.e. caffeine increases and potentiates anti-inflammatory action of meloxicam.

Methanolic Extract of Peel of Citrus maxima Fruits Exhibit Analgesic, CNS Depressant and Anti-inflammatory Activities in Swiss Albino Mice

Objectives: This study investigates analgesic, CNS depressant and anti-inflammatory activities of crude methanolic extract of Peel of Citrus maxima fruits. Materials and Methods: Methanolic extracts of Citrus maxima peel with different concentration were tested for analgesic activity in mouse model of acetic acid induced writhing and formalin induced licking and biting. Anti-inflammatory effect was tested by carrageenan induced paw edema model and the CNS depressant activity was evaluated by observing the reduction of locomotors activity by hole cross and open field test. Results: The extract, at 500 mg/kg, showed higher analgesic activity (73.34%) against acetic acid induced pain in mice while the standard reference drug Diclofenac sodium exhibited 87.13% activity at 10 mg/kg dose. The test dose at 500 mg/kg produced 48.23% protection in formalin induced hind paw licking and biting compared to 54.11% protection by the reference drug (10 mg/kg Diclofenac sodium). The antiinflammatory effect of the extract was comparable to reference drug Ibuprofen and the effect was sustained for 2-4 hr. However, the extract also showed significant dose dependent CNS depressant activity. Conclusion: Methanolic extract of peel of Citrus maxima fruits has CNS depressant effect with moderate analgesic and anti-inflammatory properties.

Investigation of anti-arthritic activity (in-vitro models) of Hibiscus hispidissimus Griffith

Aim of the experiment: The present study was designed to investigate the anti-arthritic potential of the plant Hibiscus hispidissimus. Materials and Methods: The aerial parts of the plant was collected, dried and extracted (maceration) with ethanol. Preliminary phytochemical studies were carried out. All the in-vitro models i.e. inhibition of protein denaturation, membrane stabilization and proteinase inhibition were carried out with standard reference drug diclofenac sodium. Result: Dose dependent and significant (p<0.05) anti arthritic activity in in-vitro models were found. Conclusion: The results reveal promising anti arthritic potential of the plant. However further pharmacological investigation using isolated active ingredients can be carried out to confirm its efficacy and mechanism of action.

IN VITRO ANTI – INFLAMMATORY ACTIVITY OF THE FLOWERS OF NERIUM OLEANDER (WHITE)

Inflammation is a part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells or irritants. It is characterized by redness, swollen joints, joint pain, its stiffness and loss of joint function. Inflammation is currently treated by NSAIDs. Unfortunately these drugs cause increased risk of blood clot resulting in heart attacks and strokes. Therefore, the developments of potent anti-inflammatory drugs from the natural products are now under considerations. Natural products are rich source for discovery of new drugs because of their chemical diversity. A natural product from medicinal plants plays a major role to cure many diseases associated with inflammation. The conventional drug available in the market to treat inflammation produces various side-effects. In this present study anti-inflammatory potential of Nerium Oleander was investigated. Based on the resulted the ethonolic extract of the flowers showed the highest anti inflammatory activity. The increments in absorbance of test samples with respect to control indicated stabilization of protein i.e. inhibition of heat-induced protein (albumin) denaturation by Nerium oleander and reference drug diclofenac sodium.

English

Members of the genus Desmodium are widespread in the sub-tropics, tropics and used in traditional medicine, as part of recipes for treating fever, pains, cough and dysentery.  In this study, phytochemical screening and comparative anti-inflammatory activities of the methanol extracts, hexane and ethyl acetate fractions of the leaves of Desmodium velutinum and Desmodium scorpiurus were investigated using the egg-albumin induced oedema and protein denaturation methods.  The presence of flavonoids, saponins, tannins and sterols were detected in the leaves of D. velutinum and D. scorpiurus while, the extracts and fractions exhibited anti-inflammatory activities not significantly different (p<0.05) from the activities of the reference drug (Diclofenac Sodium).  The hexane fractions of D. velutinum and D. scorpiurus exhibited the most pronounced effects of 76.9 and 68.2% respectively at a dose of 2000 µg/ml in the in vitro model; 27.2 and 24.5% respectively in the in vivo model. This study has been able to report the anti-inflammatory activities of the leaves of D. velutinum and D. scorpiurus.  Key words:  Desmodium velutinum, Desmodium scorpiurus, anti-inflammatory activities, papilionaceae, in vivo, in vitro.

Synthesis of some new amide-linked bipyrazoles and their evaluation as anti-inflammatory and analgesic agents

Four series of new bipyrazoles comprising the N-phenylpyrazole scaffold linked to polysubstituted pyrazoles or to antipyrine moiety through different amide linkages were synthesized. The synthesized compounds were evaluated for their anti-inflammatory and analgesic activities. In vitro COX-1/COX-2 inhibition study revealed that compound 16b possessed the lowest IC50 value against both COX-1 and COX-2. Moreover, the effect of the most promising compounds on inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2) protein expression in lipopolysaccharide (LPS)-activated rat monocytes was also investigated. The results revealed that some of the synthesized compounds showed anti-inflammatory and/or analgesic activity with less ulcerogenic potential than the reference drug diclofenac sodium and are well tolerated by experimental animals. Moreover, they significantly inhibited iNOS and COX-2 protein expression induced by LPS stimulation. Compounds 16b and 18 were proved to display anti-inflammatory activity superior to diclofenac sodium and analgesic activity equivalent to it with minimal ulcerogenic potential.

Antinociceptive and Anti-Inflammatory Activities of Mycetia longifolia (Wall.) O. Kuntze

Mycetia longifolia is used traditionally for the treatment of pain, inflammation, ulcers, and wounds. Phytochemical analysis revealed the presence of alkaloids, flavonoids, tannins, glycosides, and polyphenols. The ethanol extract of the plant was investigated for its antinociceptive and anti-inflammatory activities in mice models and compared to the reference drug diclofenac sodium and control. In the acetic acid-induced writhing model, the extract showed a good antinociceptive effect characterized by the reduction in the number of writhes. The percent inhibition of writhing response by the extract was 74.56% at 500 mg.kg−1 dose. The extract caused decrease in licking time and licking frequency in mice when placed on a hot plate. The extract at doses of 250 and 500 mg.kg−1 b.w. inhibited the formation of paw edema induced by carrageenan.

Exploration of Analgesic Activity of the Ethanolic Extract of Erythrina variegate Bark.

The aim of this study was to evaluate analgesic activity of the ethanolic extract of the bark of Erythrina variegata . The analgesic potential of the extract was evaluated using acetic acid-induced writhing test for peripheral analgesic activity and tail immersion, hot plate, formalin and glutamate test at 50, 100, and 200 mg/kg body weight doses. In analgesic activity tests, the extract at the doses of 50, 100, and 200 mg/kg b.w. produced a remarkable increase in pain threshold in a dose dependent manner. In acetic acid induced writhing test, the inhibitory effect was to be parallel to the reference drug diclofenac sodium. The extract showed 18.89% writhing inhibitory effect at the dose 200 mg/kg b.w., whereas diclofenac sodium showed 79.42% inhibition of writhing at a dose of 10 mg/kg b.w. The results of tail immersion and hot plate test also showed potential analgesic activity of the extract which is also comparable to the standard drug morphine (5 mg/kg b.w.). In formalin test, the bark extract at doses 200 mg/kg b.w. were found to exhibit the highest 47.80% inhibitory effect in late phase, whereas the reference drug morphine showed 63.64% inhibitory effect on licking of the hind paw. In glutamate test, the bark extract at doses 200 mg/kg b.w. were found to exhibit the highest 68.07% inhibitory effect in late phase, whereas the reference drug diclofenac sodium showed 61.53% inhibitory effect on licking of the hind paw. In conclusion, it can be said that the plant part have potential analgesic activity and may be used to relief pain.

Antinociceptive Activities of Acetone Leaves Extracts of Carissa Spinarum in Mice

Despite the progress that has occurred in recent years in the development of therapies for pain, there is still a need for effective and potent analgesics for pain. Pain is defined as unpleasant feeling essential for body’s defense system. It acts as a warning signal against disturbances in the body. Conventional antinociceptives are expensive and have many side effects. Continued use of these drugs may lead to tolerance and resistance. Medicinal plants have been used to relieve pain and form a better alternative. Herbal antinociceptives are affordable and have arguably fewer side effects. Carissa spinarum (Linn) is used to treat rheumatoid pain, fever and inflammation related disorders. This plant is used locally by people in Embu County as analgesics. This study was designed to bioscreen the acetone leaves extracts C.spinarum (Linn) for anti-nociceptive potential. The plant parts were collected from Siakago-Mbeere north sub-county, Embu County, Kenya. The samples were prepared and extraction of the active compounds carried out using organic solvent acetone in the ratio 1:2. Swiss albino mice were divided into five groups of five mice each: Normal, negative, reference and experimental group. Pain was induced experimentally using formalin and acetic acid. The experimental groups were treated with 50 and 100 mg/kg dose quantities of plant extract prepared. The acetone leaves extracts of the plants were evaluated for antinociceptive properties in mice compared to the reference drug diclofenac sodium. Mice were injected intraperitoneally with doses of the herbs, diclofenac and the vehicle. Thirty minutes later the animals were injected with 0.01ml of 2.5% formalin in the sub planter region of the left hind paw and the other set with 0.4 ml of 5% acetic acid. The total time spent lifting; biting, licking the paw and writhing were counted and scored. The acetone leaves extracts tested at different dose levels lowered paw licking time in a dose dependant manner, Further, the phytochemical screening results showed that the acetone leaves extracts of C. spinarum (Linn) possess anti-nociceptive activities. The study has established that acetone leaves extracts of C. spinarum (Linn) are effective in management of pain.

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

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