Rat Paw Research Articles

Evaluation of analgesic, antioxidant, and anti-inflammatory potential of Dianthus crinitus using mice as a research animal

In the past, natural resources were used as best therapeutic sources for different diseases. Among several herbal resources, certain plant families are known for their analgesic activities, such as Dianthus crinitus, which showed a good curative potential. The mentioned plant has been used traditionally for the healing of several illnesses such as pain, inflammation, injuries, etc. The current study, therefore, evaluated the analgesic and anti-antioxidant activities of ethanolic extracts of leaves, flowers, and seeds of Dianthus crinitus in mice. For analgesic activity, acetic acid and a hot plate thermal stimulation method were used to induce writhes in mice, followed by a tail emersion process. Results showed that the extract demonstrated analgesic potential in mice, signifying both peripheral and central modes of action. Furthermore, extract also significantly inhibited the rat paw edema triggered by carrageenan seaweed and dextran as revealed by neutrophil migration toward the peritoneal cavities of animals and enhanced vascular permeability. The data suggested that the extract exhibited a dose-dependent antioxidant action. These preliminary observations provided support for further exploration and justification for the potential development of a new class of analgesic and anti-inflammatory medicines from the constituents of Dianthus crinitus extract.

Broad spectrum antimicrobial, anti-inflammatory and peripheral analgesic activities of heteroaryl nitazoxanide analogs

Background The antiparasitic drug nitazoxanide possesses diverse biological activity. However, very few investigation was accomplished with nitazoxanide analogs. Therefore, herein we focused on the screening of bioactivities using some nitazoxanide-like synthesized molecules. Objectives Four heteroaryl nitazoxanide analogs synthesized in our laboratory were investigated for antimicrobial, anti-inflammatory, and analgesic activity. Materials and methods Disc diffusion method was used for assessing antimicrobial potency against several Gram-positive bacteria, Gram-negative bacteria, and fungi. Carrageenan-induced rat paw edema model was performed to evaluate anti-inflammatory activity. The analgesic property was evaluated using the acetic acid-induced writing inhibition method in the mice model. Molecular docking simulations against cyclooxygenase-1, cyclooxygenase-2, phospholipase A2, NF-κB inducing kinase, and interleukin-1 receptor-associated kinase 4 were also performed. Results and conclusion All the synthesized compounds exhibited broad spectrum antimicrobial property against a number of Gram-positive, Gram-negative species and unicellular fungi. Compound 4 or N-(5-nitrothiazol-2-yl)-furan-3-carboxamide emerged as the most prominent antimicrobial agent exhibiting zone of inhibition ranging in 14–22 mm. These zone diameters are sometimes greater than that displayed by nitazoxanide. Compounds 2 and 3 also showed remarkable broad-spectrum antimicrobial activity with a zone of inhibition 10–20 mm and 12–20 mm, respectively. Compound 4 also displayed potential anti-inflammatory activity which is comparable to standard aceclofenac. Compound 4 also showed mild analgesic effects. The compounds also exhibited moderate binding affinities against the selected target receptors and enzymes during in silico molecular docking. Heteroaryl nitazoxanide analogs showed prominent broad-spectrum antimicrobial, anti-inflammatory, and mild analgesic properties. This study indicates that heteroaryl nitazoxanide analogs might be interesting candidates for new drug discovery.

Design, synthesis of new 2,4-thiazolidinediones: In-silico, in-vivo anti-diabetic and anti-inflammatory evaluation

In this study, a series of nine novel heterocyclic compounds were synthesized through a concise three-step reaction process. The synthesis involved Knoevenagel condensation at the 5th position of the 2,4-thiazolidinedione or rhodanine ring-system. Comprehensive physicochemical and spectral analyses, including FTIR, Mass, 1H NMR and 13C NMR, were performed to characterize the synthesized compounds. The synthesized derivatives were subjected to evaluation for their potential in various therapeutic domains. In-vivo anti-diabetic activity was assessed diabetes induced wistar rats, anti-inflammatory effects were gauged using the carrageenan and formalin induced rat paw edema model. Additionally, the in-vitro PPAR-γ modulatory activity, glucose uptake by using Saccharomyces cerevisiae and rat hemidiaphragm and cyclooxygenase inhibitory activity along with scavenge free radicals was tested by FRAP and DPPH method. According to the potential binding patterns of the most potent anti-diabetic compounds, namely 7a and 13a with the active sites of target PPAR-γ (PDB ID: 5U5L), was obtained through molecular docking using Schrodinger’s Glide model. Among the tested compounds, the compound 13a demonstrated significant antidiabetic activity with reduction in blood glucose levels (108.5 ± 2.171 mg/dL), comparable to the effect of pioglitazone (101.66 ± 0.95 mg/dL), similarly anti-inflammatory activity at fourth hour paw volume 93.6% and thickness at 3.99 ± 0.076 mm, respectively closer to that of standard drug diclofenac sodium (91.2% and 4.7 ± 0.057 mm) in carrageenan-induced paw edema in rat. The compound 13a displayed promising COX-2 inhibitory activity (IC50 = 7.82 μM) and DPPH antioxidant activity showcasing its multifaceted therapeutic potential. This study not only presents multi-targeting approach and highlights the significant potential compounds as a lead molecule for further therapeutic development.

Phytochemical characterization and biological activities evaluation of Opuntia sp. cladodes

The prickly pear is a plant belonging to the Cactaceae family, and it is the best-known species that has gained significant recognition in recent years. Opuntia sp. cladodes have been traditionally utilized as a functional food and in traditional medicine for treating chronic diseases. Therefore, this study aims to evaluate the antioxidant, antimicrobial, and pharmacological activities of cladode extracts from Opuntia microdasys (Cl1) and Opuntia macrorhiza (Cl2), as well as to identify their phytochemical compounds. The chemical composition of the cladode extracts was analyzed using spectrophotometric methods, while the antioxidant activity was determined through DNA nicking assays. Microdilution assays were employed to assess the antimicrobial activity. Analgesic and anti-inflammatory activities were determined using the acetic acid writhing test in mice and the carrageenan-induced Wistar rat paw edema test. The results revealed that the two extracts of cladodes from Cl1 and Cl2 were characterized by a high phenolic content (58.13 and 44.58 GAE/g of extract, respectively). All the tested extracts exhibited antimicrobial activity against the strains tested, with Minimum Inhibitory Concentration (MIC) values ranging from 0.312 to 5 mg/mL and Minimum Bactericidal Concentration (MBC) values ranging from 1.25 to 10 mg/mL. The cladode extracts of Cl1 and Cl2 at a dose of 300 mg/kg showed a dose-dependent inhibition of acetic acid-induced writhing in mice, with respective values of 64.76 % and 61.91 %. The maximum anti-inflammatory activity of all doses of cladode extracts was observed 5 h after carrageenan-induced paw edema, and all tested doses significantly inhibited the induced inflammation.

Fabrication and In-Vivo Evaluation of Polyvinyl pyrrolidone/Poloxamer 188 Hybrid Nanofibers of Deflazacort

The superior flexibility, efficient drug loading, high surface-to-volume ratio, ease of formulation, and cost-controlled production are considered exceptional advantages of nanofibers (NFs) as a smart delivery system. Deflazacort (DEF) is an anti-inflammatory and immunosuppressant agent. It is categorized as a poorly soluble class II drug. In this study, DEF-loaded polymeric nanofibrous using the electrospinning technique mats, Polyvinyl pyrrolidone (PVP) with or without Poloxamer 188 (PX) were used as mat-forming polymers. Microscopical imaging, drug content (%), and in vitro dissolution studies were conducted for all NFs formulae (F1-F7). All NFs improved the DEF dissolution compared to the unprocessed form, with the superiority of the PVP/PX hybrid. The optimized formula (F7) exhibited an average diameter of 655.46 ± 90.4 nm and % drug content of 84.33 ± 5.58. The dissolution parameters of DEF loaded in PVP/PX NFs (F7) reflected a release of 95.3 % ± 3.1 and 102.6 % ± 1.7 after 5 and 60 min, respectively. NFs (F7) was investigated for drug-polymer compatibility using Fourier-Transform Infrared Spectroscopy (FTIR), Powder X-ray diffraction analysis (PXRD), and Differential Scanning Calorimetry (DSC). In vivo anti-inflammatory study employing male Sprague-Dawley rats showed a significant reduction of rat paw edema for F7 (p < 0.05) compared with unprocessed DEF with a normal epidermal and dermal skin structure comparable to the healthy negative control. Immunohistochemical and morphometric data displayed similarities between the immune reaction of F7 and the negative healthy control. The finding of this work emphasized that DEF loaded in PVP/PX NFs could be considered a useful strategy for enhancing the therapeutic performance of DEF.

Anti-rheumatoid arthritis potential of Halodule pinifolia: development, characterization and in vivo evaluation of H. pinifolia-based oral suspension and lipid nano-emulsion.

For treating chronic diseases like rheumatoid arthritis, herbal medicines are preferred due to their evident therapeutic effects and lesser side effects as compared to the long-term used conventional drugs. In this study, the anti-rheumatoid arthritis effect of an unexplored marine grass Halodule pinifolia (HP), and a combination of it with Glycyrrhiza glabra (liquorice; LQ), prepared as a conventional suspension (C1) and a lipid nano-emulsion (C1-N) was evaluated in Freund's complete adjuvant (FCA)- and collagen-induced arthritis (CIA) models. Formulations C1 and C1-N contained standardized extract HP (100mg/kg) as major active ingredient and liquorice LQ (50mg/kg) as both active ingredient (anti-inflammatory and anti-ulcer) and sweetening agent. Oral administration of HP and C1 to FCA-induced Sprague-Dawley rats significantly reduced the paw oedema, spleen index, controlled the haematological parameters, cytokine levels (IL-1β, IL-6, TNF-α estimated by ELISA), mRNA expression of cytokines and osteoclast markers (RANK, TRAP and cathepsin K measured by RTPCR). Histopathology and radiological scanning demonstrated lesser joint deterioration in sample-treated rats, as evident phenotypically. The downregulation of CD51 and MMP-3 (western blot) corroborated the anti-arthritic effect of HP and C1. HP showed better results among all. Further, under the CIA model, both C1 and C1-N were found to be potentially active as evidenced by their effect on rat paw oedema, spleen index, haematological parameters, rheumatoid factor, cytokines, osteoclast markers, histology and X-rays. The results proved the anti-arthritic effect of HP and the formulations, particularly the lipid nano-emulsion that showed improved stability as well as activity.

Duration of the preemptive analgesic effects of low- and high-frequency transcutaneous electrical nerve stimulation in rats with acute inflammatory pain.

Transcutaneous electrical nerve stimulation (TENS) activates various pathways to induce antinociceptive effects, based on the frequencies used. This study evaluates the preemptive analgesic effects and their duration of low- (LT: 4 Hz) and high-frequency TENS (HT: 100 Hz) using a rat model of acute inflammatory pain. Acute inflammation was induced by injecting 1% formalin into the hind paws of rats. LT or HT was applied for 30 min before formalin injection. Pain-related behaviors, such as licking, flinching, and lifting, were recorded for 60 min postinjection. Immunohistochemistry was used to assess the number of phosphorylated extracellular signal-regulated kinase (pERK)- and c-fos-positive cells in the spinal cord. Naloxone, a μ-opioid receptors (MORs) antagonist, and naltrindole, a δ-opioid receptors (DORs) antagonist, were administered before TENS application. Pain behavior duration and pERK- and c-fos-positive cell expression were then measured. LT and HT pretreatment significantly reduced both pain behaviors and the number of pERK- and c-fos-positive cells postformalin injection. Naloxone and naltrindole partially reversed the effects of LT and HT, respectively. Notably, HT's analgesic effect lasted up to 120 min whereas that of LT persisted for 90 min. LT and HT effectively exerted their preemptive analgesic effects on acute inflammatory pain by inhibiting pERK and c-fos expression in the spinal cord. HT presented a longer-lasting effect compared to LT. MOR and DOR activation may contribute to LT and HT's analgesic mechanisms, respectively.

Schisandrin B ameliorates adjuvant-induced arthritis in rats via modulation of inflammatory mediators, oxidative stress, and HIF-1α/VEGF pathway.

Schisandrin B (Sch B) has been shown to possess anti-inflammatory and antioxidant properties, however, its antirheumatoid arthritis properties and potential mechanism remain unexplored. This study evaluated the potential of Sch B in adjuvant-induced arthritic (AIA) rats. AIA was induced by injecting 0.1 ml of CFA into the paw of rats and the animals were administered with Sch B (50 mg/kg) for 28 days. The effects of Sch B were evaluated using arthritis severity, serum levels of oxido-inflammatory, and metabolic index parameters. Sch B eased arthritic symptoms by significantly reducing paw swelling and arthritic score and increased body weight gain. Moreover, Sch B alleviated the levels of oxido-inflammatory markers including interleukin-1 beta, interleukin-6, tumor necrosis factor alpha, nuclear factor kappa B, transforming growth factor β1, inducible nitric oxide synthase and malonaldehyde, as well as increased the levels of superoxide dismutase, glutathione, and Nrf2. Sch B also remarkably restored the altered levels of triglyceride, aspartate aminotransferase, lactic acid, pyruvate, phosphoenolpyruvate carboxylase, glucose, hypoxia inducible factor-1 alpha, and vascular endothelial growth factor. In addition, Sch B markedly alleviated p65 expression in the treated AIA rats. This study suggests that Sch B alleviated AIA by reducing oxidative stress, inflammation, and angiogenesis.

Evaluation of the Anti-Inflammatory and Antioxidant, Activities of Parinari Curatellifolia Planch. Ex Benth (Chrysobalanaceae) Methanol Stem Bark Extract

It is used as human food and beverage, and in traditional medicine it is used to treat pneumonia and fever. The aim of this was to investigate its anti-inflammatory and antioxidant activities of Parinari curatellifolia methanol stem bark extract. A 2kg of the dried and powdered plant material was extracted with 80% methanol through cold maceration to obtain the crude methanol extract. The crude methanol extract was sequentially fractionated using n-hexane, ethyl acetate and methanol to yield n-hexane, ethyl acetate and methanol fractions respectively. Acute toxicity study was conducted following the OECD guidelines. The anti-inflammatory activity of the fractions was evaluated was evaluated using inhibition of albumin denaturation, inhibition of egg albumin-induced paw edema in rats and phospholipase A2 (PLA2) inhibition assay models. In vitro antioxidant activity was evaluated using DPPH de-colourizing, Nitric oxide scavenging activity and Ferric Reducing Antioxidant Power (FRAP) assays. Oral acute administration of the extract revealed an LD50 dose &gt; 5000 mg/kg in rats. The extract caused a dose- and time-dependent inhibition of rat paw edema, and a concentration-dependent inhibition of Phospholipase A2 activity. IC50 of the extract for Albumin Denaturation inhibition was 37.22 ug/ml. In the antioxidant assays the IC50 of the extract against DPPH was 25.91 ug/ml, while the Nitric oxide Equivalence (mM)/mg was 42.38.

Evaluation of analgesic and anti-inflammatory activities of ethanolic fruit extract of Terminalia chebula

Analgesic and Anti-inflammatory activities of ethanolic fruit extract of Terminalia chebula was evaluated using tail-flick method, eddy’s hot plate method, acetic acid induced writhing responses and in-vivo anti-inflammatory property was determined using carrageenan rat paw edema. The ethanolic fruit extract of Terminalia chebula at different concentrations significantly inhibited the nociception in comparision with different standard drugs that showed anti-nociception. The test extract also reduced the edema induced in rats using carrageenan paw edema method as compared with the standard drug Diclofenac sodium 10mg/kg. The results obtained in this research study found to be very significant when compared to standard reference drug.

Tailored quinoline hybrids as promising COX-2/15-LOX dual inhibitors endowed with diverse safety profile: Design, synthesis, SAR, and histopathological study

Complications of the worldwide use of non-steroidal anti-inflammatory drugs (NSAIDs) sparked scientists to design novel harmless alternatives as an urgent need. So, a unique hybridization tactic of quinoline/pyrazole/thioamide (4a-c) has been rationalized and synthesized as potential COX-2/15-LOX dual inhibitors, utilizing relevant reported studies on these pharmacophores. Moreover, we extended these preceding hybrids into more varied functionality, bearing crucial thiazole scaffolds(5a-l). All the synthesized hybrids were evaluatedin vitroas COX-2/15-LOX dual inhibitors. Initially, series4a-cexhibited significant potency towards 15-LOX inhibition (IC50 = 5.454–4.509 μM) compared to meclofenamate sodium (IC50 = 3.837 μM). Moreover, they revealed reasonable inhibitory activities against the COX-2 enzyme in comparison to celecoxib.Otherwise, conjugates 5a-ldisclosed marked inhibitory activity against 15-LOX and strong inhibitory to COX-2. In particular, hybrids5d(IC50 = 0.239 μM, SI = 8.95), 5h(IC50 = 0.234 μM, SI = 20.35) and 5l (IC50 = 0.201 μM, SI = 14.42) revealed more potency and selectivity outperforming celecoxib (IC50 = 0.512 μM, SI = 4.28). In addition, the most potentcompounds, 4a, 5d, 5h, and 5l have been elected for further in vivoevaluation and displayed potent inhibition of edema in the carrageenan-induced rat paw edema test that surpassed indomethacin. Further, compounds5d, 5h, and 5l decreased serum inflammatory markers including oxidative biomarkersiNO, and pro-inflammatory mediators cytokines like TNF-α, IL-6, and PGE. Ulcerogenic liability for tested compounds demonstrated obvious gastric mucosal safety. Furthermore, a histopathological study for compound 5l suggested a confirmatory comprehensive safety profile for stomach, kidney, and heart tissues. Docking and drug-likeness studies offered a good convention with the obtained biological investigation.

Design, Synthesis and Evaluation of Antioxidant and NSAID Derivatives with Antioxidant, Anti-Inflammatory and Plasma Lipid Lowering Effects.

Amides containing methyl esters of γ-aminobutyric acid (GABA), L-proline and L-tyrosine, and esters containing 3-(pyridin-3-yl)propan-1-ol were synthesized by conjugation with 3,5-di-tert-butyl-4-hydroxybenzoic, an NSAID (tolfenamic acid), or 3-phenylacrylic (cinnamic, (E)-3-(3,4-dimethoxyphenyl)acrylic and caffeic) acids. The rationale for the conjugation of such moieties was based on the design of structures with two or more molecular characteristics. The novel compounds were tested for their antioxidant, anti-inflammatory and hypolipidemic properties. Several compounds were potent antioxidants, comparable to the well-known antioxidant, Trolox. In addition, the radical scavenging activity of compound 6 reached levels that were slightly better than that of Trolox. All the tested compounds demonstrated remarkable activity in the reduction in carrageenan-induced rat paw edema, up to 59% (compound 2, a dual antioxidant and anti-inflammatory molecule, with almost 2.5-times higher activity in this experiment than the parent NSAID). Additionally, the compounds caused a significant decrease in the plasma lipidemic indices in Triton-induced hyperlipidemic rats. Compound 2 decreased total cholesterol by 75.1% and compound 3 decreased triglycerides by 79.3% at 150 μmol/kg (i.p.). The hypocholesterolemic effect of the compounds was comparable to that of simvastatin, a well-known hypocholesterolemic drug. Additionally, all compounds lowered blood triglycerides. The synthesized compounds with multiple activities, as designed, may be useful as potential candidates for conditions involving inflammation, lipidemic deregulation and oxygen toxicity.

Lactobacillus species modulates TNF-α and Nrf2 expression in carrageenan-induced rat paw oedema

BackgroundThe buildup of activated immune cells at injury sites accelerates the production of free radicals and reactive oxygen species which further promotes oxidative stress, leading to an inflammatory response that can in turn intensify oxidative stress. This study evaluates the activity of three Lactobacillus species sourced from Nigerian locally fermented drink products for acute inflammatory regulation potentials in Wistar rats using paw oedema model induced by carrageenan. Material and methodsOedema was induced with 1% iota-carrageenan in experimental groups and thereafter received 5 × 107 CFU/mL of L. fermentum CIP 102980, L. fermentum NBRC 15885 and L. plantarum CIP 103151 treatments while positive control group received diclofenac sodium (150 mg/kg body weight of rats). The occurrence of inflammation, oxidative stress were assessed at intervals (t = 1, 4, 24, and 72 hrs) on rat paw tissues via biochemical estimation of NO, MPO, MDA and GSH. Routine haematoxylin and eosin stain was used to investigate neutrophil infiltration and immunostaining of tumour necrosis factor alpha (TNF-α) and nuclear factor erythroid 2–related factor 2 (Nrf2) was performed to evaluate inflammation and oxidative stress respectively. ResultsLactobacillus treated groups showed significant control to mitigate the influx of infiltrating neutrophils to rat paws, as well as interacting with non-enzymatic antioxidants (glutathione) to act as antioxidants by increasing their levels, regulating lipid peroxidation, nitric oxide and myeloperoxidase compared to diclofenac sodium group. LAB treatments also downregulated the production of TNF-α cytokine and upregulated Nrf2 compared to untreated group. ConclusionLactobacillus exert potent therapeutic benefits against oxidative stress damage and influx of neutrophil cells in inflamed rats.

Utilization of Suji Leaves Extract (Pleomele Angustifolia N.E Brown) in Inhibiting Carrageenan-Induced Inflammation on Rats

Suji leaf (Pleomele angustifolia N.E. Brown) has long been used as an ingredient for traditional medicines. This study seeks to evaluate the anti-inflammatory activity of suji leaf extract in terms of its ability to reduce oedema in the hind paws of rats. Six groups were treated: negative control, positive control given diclofenac sodium as anti-inflammatory medication, two groups of suji leaf extract powder (SEP) with doses of 300 and 800 mg/kg, acetone extract of suji leaf (AES), and a group of acetone extract of SEP (EA-SEP) at a dose of 500 mg/kg with oral administration. Injections of 1% carrageenan suspension into the right hind paw of rats induced inflammation. The results demonstrated that SEP administered at a dose of 800 mg/kg has an inflammatory capacity (80.56%), AES (56.94%), and AE-SEP (75.7%). Chlorophyll, total phenol, and antioxidant capacity in SEP (9.0809 mg /g sample; 3.7354 mg GAE/g sample; 3.04 mg AAE/g sample), AES (4.6471 mg /g sample; 0.9994 mg GAE/g sample; 3.26 mg AAE/g sample), and AE-SEP (6.4912 mg /g sample; 2.1703 mg GAE/g sample; 2.55 mg AAE/g sample). According to qualitative test results, Suji extract contains bioactive compounds of the flavonoid group, saponins, steroids, and triterpenoids. It is believed that phenolic compounds function as anti-inflammatory agents.

Novel Leflunomide Analog, UTLOH-4e, Ameliorates Gouty Arthritis Induced by Monosodium Urate Via NF-κB/NLRP3 Signaling Pathway.

Gouty arthritis (GA) is a common form of inflammatory arthritis caused by intra-articular deposition of monosodium urate (MSU) crystals; however, there is a tremendous lack of safe and effective therapy in the clinic. The goal of this work was to investigate a novel leflunomide analogue, N-(2,4- dihydroxyphenyl)-5-methyl-1,2-oxazole-3-carboxamide (UTLOH-4e), for its potential to prevent/ treat gouty arthritis. In this study, the anti-inflammatory activity of UTLOH-4e was evaluated by MSUinduced GA model in vivo and in vitro, and the molecular docking test was applied to estimate the affinity of UTLOH-4e/UTL-5g/b for MAPKs, NF-κB, and NLRP3. In vitro, UTLOH-4e (1~100 μM) treatment inhibited the inflammatory reaction with no obvious cytotoxicity in PMA-induced THP-1 macrophages exposed to MSU crystals for 24 h, involving the prominent decreased production and gene expression of IL-1β, TNF-α, and IL-6. Western blot analyses demonstrated that UTLOH-4e (1~100 μM) significantly suppressed the activation of NLRP3 inflammasomes, NF-κB, and MAPK pathways. Furthermore, the data from the experiment on gouty rats induced by intra-articular injection of MSU crystal confirmed that UTLOH-4e markedly ameliorated rat paw swelling, articular synovium inflammation and reduced the concentration of IL-1β and TNF-α in serum through down-regulating NLRP3 protein expression. These results manifested that UTLOH-4e ameliorates GA induced by MSU crystals, which contributes to the modulation of NF-κB/ NLRP3 signaling pathway, suggesting that UTLOH- 4e is a promising and potent drug candidate for the prevention and treatment of gouty arthritis.

Isolation, Formulation and Assessment of Anti-inflammatory Properties of Ursolic Acid from&lt;i&gt; Nerium oleander&lt;/i&gt;

Purpose: The purpose of the research work was the extraction and isolation of Ursolic Acid (URA) from the leaves of Nerium oleander (N. oleander) and the assessment of its anti-inflammatory activity using an in-vitro model. Methods: Ursolic Acid (URA) is a bioactive molecule. It is a key component of N. oleander. The hydroalcoholic maceration method was used for extract preparation and was used to isolate the bioactive components of URA. The prepared extract, isolated URA were characterize and analyse by using pharmacognostic parameters, Fourier Transform Infrared (FTIR) and Thin Layer Chromatography (TLC) method. The carrageenan-induced inflammation rat paw oedema test in-vitro model was used for the assessment of anti-inflammatory properties of isolated bioactive compound URA. Results: The results of evaluation and characterization indicated that the extract’s ash value and extractive values were within the parameters specified in the Indian Ayurvedic Pharmacopoeia. The prepared hydroalcohalic extract has potential bioactive components such as flavonoids, saponins, and triterpinoids. The isolated compound was URA. The extract may be able to alleviate inflammation, according to the percentage inhibition. Conclusion: The URA was successfully removed from the leaves of N. oleander. The examination criteria revealed that the extract contained certain small contaminants, which may have anti-inflammatory effects.

Anti-inflammatory, analgesic, antitussive and antipyretic activities of polyphenol-enriched fraction from Nymphaea candida

Ethnopharmacological relevance“Snow-white waterlily” (Nymphaea candida) dried flower possesses various efficacy in Uighur medicine such as reducing fever and nourishing the liver, anti-inflammatory and cough relieving, moistening the throat and quenching thirst. Aim of the studyPolyphenols are characteristic component of N. candida as well as its quality markers, and the purpose of this study was to conduct investigations into anti-inflammatory, antitussive, antipyretic, and analgesic activities of the polyphenol-enriched fraction from N. candida (NCTP) in order to validate the traditional efficacy of this plant. Materials and methodsThe polyphenols in NCTP were analyzed by HPLC, and an acute oral toxicity study was conducted for NCTP. The anti-inflammatory activities of NCTP were evaluated using xylene induced ear edema, capillary permeability, cotton pellet granuloma, and carrageenan-induced rat paw edema, of which multiple biochemical indices were measured in carrageenan-induced rat paw edema such as prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2),5-lipoxygenase (5-LOX), interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) activities; the analgesic activities were investigated using acetic acid writhing, hot plate test, and formalin test; the anti-tussive and antipyretic effects were tested by ammonia induced cough in mice and yeast-induced fever respectively. ResultsNCTP with LD50 of 5222 mg/kg was low toxicity and safety. NCTP (200 mg/kg) could significantly reduce ear swelling and capillary permeability by 30.63% and 31.37%, respectively. NCTP revealed 15.76% inhibiting activities in cotton pellet granuloma in mice at a dosage of 200 mg/kg. Furthermore, NCTP (50, 100, and 200 mg/kg) substantially decreased carrageenin-induced paw edema in rats between 1 and 5 h, and NCTP could decrease PGE2, 5-LOX, COX-2 levels as well as IL-6, IL-1β, TNF-α activities compared with the control group; NCTP could decrease MDA contents in carrageenin-induced rise, and increase SOD and GSH activities. Furthermore, the dose-dependent inhibition effect of NCTP on pain was revealed in the hot plate experiment. In addition to reducing the amount of writhes brought on by acetic acid, NCTP (50, 100, and 200 mg/kg) significantly inhibited pain latency against both stages of the formalin test. Moreover, NCTP (50, 100, 200 mg/kg) showed the better antitussive activities in mice in a dose-dependent manner. In the yeast-induced pyrexia test, dosages of 50, 100, and 200 mg/kg resulted in a statistically significant drop in rectal temperature. ConclusionThe experimental results proved the analgesic, anti-inflammatory, anti-tussive and antipyretic activities of the polyphenol-enriched fraction from N. candida, and supported the traditional use of this plant as well.

Anti-inflammatory activity of Codium elongatum on Carrageenan-induced paw edema in Wistar male rats

Inflammation is the physiological defence system of the body to initiate the healing mechanism for tissue and eliminate injurious stimuli. In the present study, the anti-inflammatory activity of Codium elongatum was evaluated. Water extract (250 mg/kg, b.w.) and isolated polysaccharide (500 mg/kg, b.w.) are investigated in the carrageenan-induced rat paw edema model using phenylbutazone as a standard drug. Both water extract and isolated polysaccharide showed significant anti-inflammatory activity by blocking the cyclooxygenase 2 pathway. This is the first report to demonstrate the in-vivo anti-inflammatory activity of Codium elongatum.

Rumex nervosus nanoparticles versus aqueous extract: introduction of novel immunomodulatory anti-inflammatory nano-preparation for management of paw oedema and gastritis in rats

BackgroundRumex nervosus is abundant in East African and Arabian countries, and is used in curing gastrointestinal diseases as well as in wound healing. The current study intends to assess Rumex nervosus aqueous extract's anti-inflammatory benefits compared to its nanoparticles on rat paw edema and its gastric mucosal protection against ulceration.Materials and methodsIn-vitro cytotoxicity effects and antioxidant activity of Rumex nervosus nanoparticles versus aqueous extract were studied, followed by a pilot in vivo pharmacological study to determine the suitable dose of nanoparticles that would be used in the safety and efficacy studies in comparison with the aqueous extract. Its protective effects on arthritis and soft tissue inflammation were studied in rat paw edema and gastric ulcer models. Rumex nervosus extract (250 and 500 mg/kg) and nanoparticles (3.3 and 6.6 mg/kg) were given to four groups of rats orally before induction of paw oedema with subplantar 0.2 ml (1% w/v) formaldehyde or gastritis with oral ethanol 1 ml (70%), besides negative, positive control and reference groups.ResultsPaw volumes and gastric ulcer indices, as well as the anti-inflammatory and antioxidant parameters (kappa β, Paraoxonase1, and Malondialdehyde) that were measured in sera showed a marked reduction in groups treated with high doses of Rumex nervosus extract, and nanoparticles. Histopathologic and histochemical assessment of the stomachs confirmed the other investigations. All results were significant compared to positive control untreated groups.ConclusionsMost studies demonstrated Rumex nervosus’s protective anti-inflammatory benefits with the superiority of large doses of nanoparticles, offering a promising natural solution for low cost against inflammation.

Chromone-based small molecules for multistep shutdown of arachidonate pathway: Simultaneous inhibition of COX-2, 15-LOX and mPGES-1 enzymes

As a new approach to the management of inflammatory disorders, a series of chromone-based derivatives containing a (carbamate)hydrazone moiety was designed and synthesized. The compounds were assessed for their ability to inhibit COX-1/2, 15-LOX, and mPGES-1, as a combination that should effectively impede the arachidonate pathway. Results revealed that the benzylcarbazates (2a-c) demonstrated two-digit nanomolar COX-2 inhibitory activities with reasonable selectivity indices. They also showed appreciable 15-LOX inhibition, in comparison to quercetin. Further testing of these compounds for mPGES-1 inhibition displayed promising activities. Intriguingly, compounds 2a-c were capable of suppressing edema in the formalin-induced rat paw edema assay. They exhibited an acceptable gastrointestinal safety profile regarding ulcerogenic liabilities in gross and histopathological examinations. Additionally, upon treatment with the test compounds, the expression of the anti-inflammatory cytokine IL-10 was elevated, whereas that of TNF-α, iNOS, IL-1β, and COX-2 were downregulated in LPS-challenged RAW264.7 macrophages. Docking experiments into the three enzymes showed interesting binding profiles and affinities, further substantiating their biological activities. Their in silico physicochemical and pharmacokinetic parameters were advantageous.