Rat Paw Edema Research Articles

Design, synthesis, biological evaluation, and in silico studies of quinoxaline derivatives as potent p38α MAPK inhibitors.

A new series of quinoxaline derivatives possessing the hydrazone moiety were designed, synthesized, and screened for in-vitro anti-inflammatory activity by the bovine serum albumin (BSA) denaturation technique, and for antioxidant activity, by the (2,2'-diphenyl-1-picrylhydrazyl(DPPH) radical scavenging assay. The synthesized compounds were also tested for p38α mitogen-activated protein (MAP) kinase inhibition. The in-vivo anti-inflammatory activity was assessed by the carrageenan-induced rat paw edema inhibition method. All the compounds (4a-n) exhibited moderate to high in-vitro anti-inflammatory activity. Compound 4a displayed the highest inhibitory activity in the BSA assay (83.42%) in comparison to the standard drug diclofenac sodium (82.90%), while 4d exhibited comparable activity (81.87%). The DPPH assay revealed that compounds 4a and 4d have free radical scavenging potential (74.70% and 74.34%, respectively) comparable to the standard butylated hydroxyanisole (74.09%). Furthermore, the p38α MAP kinase inhibition assay demonstrated that compound 4a is highly selective against p38α MAP kinase (IC50 = 0.042) in comparison to the standard SB203580 (IC50 = 0.044). The five most active compounds (4a-4d and 4f) with good in-vitro profiles were selected for in-vivo anti-inflammatory studies. Compounds 4a and 4d were found to display the highest activity (83.61% and 82.92% inhibition, respectively) in comparison to the standard drug diclofenac sodium (82.65% inhibition). These compounds (4a and 4d) also exhibited better ulcerogenic and lipid peroxidation profiles than diclofenac sodium. The molecular docking and molecular dynamics simulation studies were also performed and found to be in agreement with the p38α MAP kinase inhibitory activity.

Exploring the therapeutic potential of Prinsepia utilis Royle seed oil: A comprehensive study on chemical composition, physicochemical properties, anti-inflammatory, and analgesic activities

Ethnopharmacological relevancePrinsepiautilis (PU) Royle, native to the Himalayan region, is a deciduous thorny shrub with numerous traditional uses of its roots, leaves and seeds for treatment of conditions such as rheumatic pain, joint pain, arthritis, and inflammation. Aim of the studyKeeping in mind the growing demand of products of natural origin as alternate medicine, the present study was undertaken to scientifically validate for the first time the traditional claims of healing pain and inflammation by evaluating the fatty oil isolated from the seeds using established in vitro and in vivo models. Materials and methodsPU Seeds were Soxhlet extracted using n-hexane and fatty oil was isolated. Chemical composition of the oil was established with the aid of Gas Chromatography-Flame Ionization Detection (GC-FID) and Gas Chromatography-Mass Spectrometry (GC-MS). The oil was then subjected to in vitro anti-inflammatory activity by following the established protocols of trypsin inhibitory and bovine serum albumin denaturation assays. The acute toxicity of the oil was also studied using OECD guidelines 423. The anti-inflammatory property of the oil was further evaluated using carrageenan-induced and formalin-induced edema in the rat paw. Moreover, hot plate latency and tail immersion assay were employed to evaluate analgesic activity of the oil. To establish the quality of the oil, various physicochemical properties were also studied. ResultsGC-FID and GC-MS analysis of the oil revealed the presence of linoleic acid (59.06 ± 0.00%), oleic acid (28.11 ± 0.01%), palmitic acid (9.51 ± 0.01%) and stearic acid (3.32 ± 0.01%). In vitro trypsin inhibitory and bovine serum albumin denaturation assay revealed dose-dependent notable activity of the oil with IC50 value of 63.57 μg/mL and 518.14 μg/mL, respectively. The physico-chemical characterization demonstrated that the oil possesses a low acidity and a high oxidative stability index. The oil was found to be non-toxic and displayed effective anti-inflammatory activities with significant inhibition till 4 h in carrageenan-induced and formalin-induced rat paw edema at maximum tested dose of 200 mg/kg b.w. The oil also exhibited significant results in hot plate latency and tail immersion assay with positive effects showing up to 4 h after dose administration. ConclusionThese findings, besides supporting the traditional claims, suggest that P. utilis seed oil has potential therapeutic applications as a natural anti-inflammatory and analgesic agent. Further studies are warranted to explore its mechanisms of action and potential use in pharmaceutical and nutraceutical industries.

Eugenia supra-axillaris Essential Oil and Its Nanoemulsion: Chemical Characterization, In Vivo Anti-Inflammatory, Analgesic, and Antipyretic Activities

The use of standard synthetic medications to treat inflammatory illnesses is associated with several negative effects. It has been shown that medicinal plants and their by-products are useful for safely treating inflammation. Herein, the essential oil of Eugenia supra-axillaris (family: Myrtaceae, ESA-EO) was isolated and further chemically characterized by GC-MS, and then, its nanoemulsion (ESA-EO-NE) was prepared. In addition, the anti-inflammation against the carrageenan-induced rats, the analgesic, and antipyretic activities of ESA-EO and ESA-EO-NE were evaluated in rats. Forty-three compounds were identified via GC-MS and categorized as mono- (61.38%) and sesquiterpenes (34.86%). d-limonene (32.82%), α-pinene (24.33%), germacrene-D (4.88%), α-humulene (4.73%), α-cadinol (3.39%), and trans-caryophyllene (3.15%) represented the main components. The administration of ES-EO and ES-EO-NE (50 and 100 mg/kg) demonstrated strong, dose-dependent inflammation inhibition capabilities in the model of rat paw edema, in comparison with both the reference drug and control. Reduced levels of malondialdehyde (MDA), increased levels of glutathione (GSH), and decreased levels of the proinflammatory cytokines (TNF-α), nitrosative (NO), and prostaglandin E2 (PGE2) in paw tissues all contributed to these substantial reductions in inflammation. Moreover, the oral administration of ESA-EO and ESA-EO-NE (50 and 100 mg/kg) exhibited potent analgesic and antipyretic activities in rats. Although the higher dose of ESA-EO and ESA-EO-NE (100 mg/kg) displayed delayed anti-inflammatory activity, they have long-lasting inflammation inhibition with fast onset and long-standing analgesic effects better than reference drugs. Furthermore, the most effective antipyretic efficacy was provided by ESA-EO-NE (100 mg/kg). These results provide insight into the possible therapeutic application of ESA-EO and its nanoemulsion against various inflammatory and painful illnesses as well as hyperthermia ailments.

Isolation of curcumin from Lakadong turmeric of Meghalaya and development of its PLGA-Cur-NS loaded nanogel for potential anti-inflammatory and cutaneous wound healing activity in Wistar rats

BackgroundLakadong turmeric (LKD) from Meghalaya, India, boasts high curcumin levels, but lacks scientific study. Moreover, Curcumin's poor solubility hinders its clinical use in inflammation and wound healing. This study isolated curcumin from LKD, forming a PLGA nanosuspension-based nanogel and explored for its potential anti-inflammatory and cutaneous wound healing activity in Wistar rats.MethodologyThe LKD rhizome was successively extracted by soxhlet using chloroform, hexane, ethyl acetate and methanol and their total phenolic content and antioxidant property was determined. Chloroform extract was loaded in column chromatography and curcumin was isolated, purified and characterized by FTIR, NMR, DSC, MS and HPTLC and its purity was analyzed by HPLC. The isolated curcumin was loaded into PLGA nanosuspensions by nanoprecipitation method followed by conversion to carbopol based Nanogel. The nanogels were characterized physicochemically and the drug permeation was observed. The optimized nanogel was evaluated for its anti-inflammatory and cutaneous wound healing activity by carrageenan-induced paw edema and excision wound model in albino Wistar rats divided in five groups and treated with plain carbopol gel, marketed turmeric cream and Cur NS nanogel (0.6% w/w equivalent curcumin each).ResultsResults depicted that the chloroform extract showed the presence of a considerable amount of phenolics with 50-60% yield of curcumin. HPLC analysis depicted that the LKD curcumin had higher purity when compared to standard curcumin. Homogenous curcumin nanosuspensions were obtained with size 150 ± 50 nm and PDI 0.2 ± 0.1. The Cur-NS-nanogel showed satisfactory physical property, drug loading and stability. Ex vivo permeation studies in rats showed controlled permeation with steady state flux of 21.28 ± 0.23 µg/cm2/hr in 24 h. Topical intervention with Cur-NS-nanogel (0.6%) significantly (p < 0.05) decreased the paw volume by 43.97% in the 3rd hour and 72.19% on the 4th hour. Furthermore, the cutaneous wound healing property of Cur-NS-nanogel when compared to negative control rats showed a substantial (p < 0.05) reduction in the percentage wound contraction from 5 to 20th days.ConclusionLKD showed high curcumin content with significant antioxidant effects. LKD curcumin loaded into stable nanogel depicted safe and controlled skin permeability with promising cutaneous wound healing and anti-inflammatory activity in experimental rats.

Study of anti-inflammatory and antinociceptive properties of new derivatives of condensed 3-aminothieno[2,3-b]pyridines and 1,4-dihydropyridines

Background. α-сyanothioacetamide derivatives are promising targets for the search for effective and safe antinociceptive agents with antipyretic and antiexudative activity. The aim. To conduct in vivo experimental study of anti-inflammatory and analgesic effects of new thienopyridines and 1,4-dihydropyridines derivatives. Materials and methods. The synthesized cyanothioacetamide derivatives were subjected to virtual bioscreening using Swiss Target Prediction online service. 140 laboratory rats were randomly distributed into intact and control (dextran edema) groups, reference groups (acetylsalicylic acid and nimesulide) and ten experimental groups for the investigated derivatives of thieno[2,3-b]pyridine and 1,4-dihydropyridine. The anti-inflammatory activity of the compounds at a dose of 5 mg/kg was evaluated by modeling acute dextran edema of rat paw. Determination of analgesic activity was carried out in the hotplate analgesic assay on 130 rats in comparison with sodium metamizole. Results. 1,4-dihydropyridines AZ331 and AZ420, as well as thienopyridine derivative AZ023 were determined to have strong anti-inflammatory activity (2.5 times more effective than nimesulide and 2.2 times more effective than acetylsalicylic acid). Compounds AZ023, AZ331 and AZ383 showed pronounced analgesic activity. The time of stay on the heated plate for rats of experimental groups that were fed with AZ331 and AZ383 for prophylactic purpose was respectively 9.56 and 9.93 times more than the same index in the reference group. The animals receiving AZ023 were characterized by an increase in the latent reaction time up to 241.2 seconds, which is 14.53 times higher than that in the rats received sodium metamizole. Conclusion. New thienopyridine and 1,4-dihydropyridine derivatives with high antiinflammatory and analgesic activity were synthesized and studied; they were recognized as promising targets for further preclinical studies.

Effect of Panzeria Alaschanica Kupr. on Carrageenan-Induced Acute Inflammation in Rats

Objectives: In the present study, we aimed to investigate the effect of Panzeria alaschanica Kupr. (P. alaschanica) on carrageenan-induced acute inflammation in rats. Method: Carrageenan-induced rat paw edema was used to evaluate the anti-inflammatory activity. P. alaschanica extract (32, 64, and 160 mg/kg/ BW) or vehicle was given orally 60 minutes before the subplantar injection of carrageenan. Ibuprofen (100 mg/kg) was used as a standard drug. The carrageenan-injected paw was measured 30, 60, 120, 180, and 240 minutes after the carrageenan injection. The levels of serum tumor necrosis factor (TNF)-α, interleukin (IL)-ELISA measured 1β, and IL-6. Results: The P. alaschanica at all given doses significantly (p˂0.01) inhibited carrageenan-induced rat paw edema. Moreover, it significantly reduced TNF-α, IL-1β, and IL-6 serum levels at different doses (p˂0.01). The anti-inflammatory effect of P. alaschanica was comparable to ibuprofen. Conclusion: P. alaschanica has an anti-inflammatory impact on carrageenan-induced paw edema in rats. The mechanism of action may partly be via reducing the levels of pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6.

Synthesis of 1,3-substituted 1H-indazole derivatives and evaluation of anti-inflammatory activity in Sprague Dawley rats

Indazole is a very significant group of heterocyclics. Aim of the research was thus planned to synthesize novel derivatives of indazole and evaluate their anti-inflammatory activity. Novel compounds of indazole were first synthesized from reaction of 2-chlorobenzonitrile with phenylhydrazine in presence of catalyst potassium t-butoxide (t-BuOK) and the solvent diglyme. Synthesized derivatives of indazole were analyzed by 1H-NMR and MS spectroscopic techniques. All the synthesized derivatives of indazole were evaluated for their anti-inflammatory activity in Sprague Dawley rats by carrageenan-induced rat paw edema method. All the synthesized derivatives of indazole had shown very good activity in both docking and anti-inflammatory activity in rats in comparison to the standard etoricoxib. Compound 1a in a dose of 30 ​mg/kg body weight had shown most significant inhibition of edema as compared to toxic group and the inhibition was comparable to that of the standard drug, etoricoxib in a dose of 10 ​mg/kg body weight. A convenient means for the synthesis of derivatives of indazole was developed which may find applications in heterocyclic synthesis of derivatives of indazole. Compound 1a i.e., 3-(4-carboxyphenyl)amino-1-phenyl-1H-indazole had shown best anti-inflammatory activity amongst all the synthesized compounds.

Unveiling the Chemical Profiling Antioxidant and Anti-Inflammatory Activities of Algerian Myrtus communis L. Essential Oils, and Exploring Molecular Docking to Predict the Inhibitory Compounds against Cyclooxygenase-2.

Considering the large spectrum of side effects caused by synthetic drugs and the development of natural alternatives utilizing Algerian flora, this study aimed to place a spotlight on the chemical profile and antioxidant and anti-inflammatory activities of Myrtus communis L. essential oils (MCEOs). In this study, essential oils (EOs) were collected via hydro-distillation of the plant's leaves, and a chemical constituent analysis was performed using gas chromatography-mass spectrophotometry (GC-MS). The in vitro antioxidant activity was evaluated using DPPH, ABTS, and hydroxyl radical scavenging tests. The in vitro anti-inflammatory capacity was estimated by studying the antidenaturation effect using bovine serum albumin (BSA) as a protein model. The in vivo anti-inflammatory activity was carried out by utilizing the classical model of carrageenan-induced paw edema in rats, using diclofenac (DCF) as the reference drug. Moreover, the molecular interaction of the compounds obtained from the GC-MS analysis was studied within the binding site of cyclooxygenase-2 (COX-2) using an in silico approach as the confirmatory tool of the in vitro and in vivo experiments. The GC-MS analysis revealed that MCEOs were mainly composed of oxygenated monoterpenes (70.56%), oxygenated sesquiterpenes (3.1%), sesquiterpenes (4.17%), and monoterpenes (8.75%). Furthermore, 1,8-cineole was the major compound (19.05%), followed by cis-geranyl acetate (11.74%), methyl eugenol (5.58%), α-terpineol (4.62%), and β-myrcene (4.40%). MCEOs exhibited remarkable concentration-dependent free radical scavenging activity, with an IC50 of 15.317 ± 0.340 µg/mL, 18.890 ± 2.190 µg/mL, and 31.877 ± 0.742 µg/mL for DPPH, ABTS, and hydroxyl radical, respectively. The significant in vitro anti-inflammatory activity due to the inhibition of BSA denaturation was proportional to the EO concentration, where the highest value was recorded at 100 μg/mL with an approximately 63.35% percentage inhibition and an IC50 of 60.351 ± 5.832 μg/mL. MCEOs showed a good in vivo anti-inflammatory effect by limiting the development of carrageenan-induced paw thickness. The in silico study indicated that, among the 60 compounds identified by the GC-MS analysis, 9 compounds were observed to have a high binding energy to cyclooxygenase-2 as compared to diclofenac. Our study revealed that EOs from Algerian Myrtus communis L. can be considered to be a promising candidate for alleviating many debilitating health problems and may provide new insights in the fields of drug design, agriculture, and the food industry.

Ethnopharmacological analysis based on Thai traditional medicine theory and anti-inflammatory activity of Sa-Tri-Lhung-Klod remedy as a post-partum anti-inflammatory drug

Ethnopharmacological relevanceSa-Tri-Lhung-Klod (ST) remedy is a Thai traditional remedy used in obstetrics and gynecology to reduce inflammation and nourish the body post-partum. In Thai traditional medicine (TTM), there is a theory of formulating drugs based on the four elements and the tastes of herbs for use in treating diseases. Aims of studyTo determine relationships between taste theory and pharmacological properties for the anti-inflammatory effect of ST remedy and its chemical constituent components. To evaluate anti-inflammatory activity and also investigate the HPLC fingerprint of ST extracts. Materials and methodsST remedy was extracted by maceration in 95% ethanol (STE) and decoction in distilled water (STW). ST extracts were evaluated for anti-inflammatory activity by nitric oxide inhibitory assay in RAW264.7 cells, carrageenan-induced rat paw edema, and prostaglandin E2 inhibitory assay in inflamed rat paw tissue. In addition, the chemical constituent fingerprints of ST extracts were examined using HPLC. ResultsSTE contained seven main chemical compounds, and STW demonstrated only one identifiable chemical compound. The STE and STW displayed potent NO inhibitory activity with an IC50 value of 20.59 ± 0.03 and 52.93 ± 0.90 μg/mL, respectively. Moreover, the STE and STW (at doses of 100 - 400 mg/kg) promoted significant inhibition of inflammation in carrageenan-induced paw edema in rats (20.81 - 38.25%). Additionally, the STE (200 - 400 mg/kg) and STW (100 - 400 mg/kg) significantly reduced PGE2 levels in inflamed rat paw tissue. ConclusionThese findings suggest that the spicy, astringent, sweet, and fragrant taste of the ST remedy used to treat post-partum inflammation encompass constituents with potent anti-inflammatory activity. STE and STW possess anti-inflammatory properties and effectively inhibit the production of NO and PGE2. Results confirm the use of the ST remedy for treating inflammatory diseases in the post-partum period according to TTM knowledge.

Fucoidan from Ericaria crinita Alleviates Inflammation in Rat Paw Edema, Downregulates Pro-Inflammatory Cytokine Levels, and Shows Antioxidant Activity.

Fucoidans are sulfated polysaccharides detected mainly in the cell walls of brown seaweeds. Here, we examined the effects of single doses of fucoidan derived from Ericaria crinita (formerly Cystoseira crinita) on carrageenan-induced paw inflammation in rats. The serum levels of TNF-α, IL-1β, IL-6, and IL-10 of rats with LPS-induced systemic inflammation after 14 days of treatment were also evaluated. Subchronic treatment with fucoidan from E. crinita attenuated the inflammation during the late phase of the degraded carrageenan-induced paw edema (3rd to 5th hour after carrageenan injection) with peak activity at the 3rd hour after the application. Both doses of fucoidan from E. crinita (25 and 50 mg/kg bw) significantly decreased the levels of all tested pro-inflammatory cytokines (IL-1β, TNF-α, and IL-6) in the serum of rats with a model of system inflammation but had no effect on the anti-inflammatory cytokine IL-10. The results showed that the repeated application of fucoidan has a more prominent effect on the levels of some pro-inflammatory cytokines in serum in comparison to a single dose of the sulfated polysaccharide. This reveals the potential of E. crinita fucoidan as an anti-inflammatory agent. Furthermore, E. crinita fucoidan exhibited in vitro antioxidant capacity, determined by 2,2-diphenyl-1-picryl-hydrazyl radical scavenging and ferric reducing antioxidant power assays as follows: IC50 = 412 µg/mL and 118.72 μM Trolox equivalent/g, respectively.

New investigation of anti-inflammatory activity of Polycladia crinita and biosynthesized selenium nanoparticles: isolation and characterization

BackgroundMarine macroalgae have gained interest recently, mostly due to their bioactive components. Polycladia crinita is an example of marine macroalgae from the Phaeophyceae class, also known as brown algae. They are characterized by a variety of bioactive compounds with valuable medical applications. The prevalence of such naturally active marine resources has made macroalgae-mediated manufacturing of nanoparticles an appealing strategy. In the present study, we aimed to evaluate the antioxidant and anti-inflammatory features of an aqueous extract of Polycladia crinita and biosynthesized P. crinita selenium nanoparticles (PCSeNPs) via a carrageenan-induced rat paw edema model. The synthesized PCSeNPs were fully characterized by UV–visible spectroscopy, FTIR, XRD, and EDX analyses.ResultsFTIR analysis of Polycladia crinita extract showed several sharp absorption peaks at 3435.2, 1423.5, and 876.4 cm−1 which represent O–H, C=O and C=C groups. Moreover, the most frequent functional groups identified in P. crinita aqueous extract that are responsible for producing SeNPs are the –NH2–, –C=O–, and –SH– groups. The EDX spectrum analysis revealed that the high percentages of Se and O, 1.09 ± 0.13 and 36.62 ± 0.60%, respectively, confirmed the formation of SeNPs. The percentages of inhibition of the edema in pretreated groups with doses of 25 and 50 mg/kg, i.p., of PCSeNPs were 62.78% and 77.24%, respectively. Furthermore, the pretreated groups with 25, 50 mg/kg of P. crinita extract displayed a substantial decrease in the MDA levels (P < 0.00, 26.9%, and 51.68% decrease, respectively), indicating potent antioxidant effect. Additionally, the pretreated groups with PCSeNPs significantly suppressed the MDA levels (P < 0.00, 54.77%, and 65.08% decreases, respectively). The results of immune-histochemical staining revealed moderate COX-2 and Il-1β expressions with scores 2 and 1 in rats pre-treated with 25 and 50 mg/kg of free extract, respectively. Additionally, the rats pre-treated with different doses of PCSeNPs demonstrated weak COX-2 and Il-1β expressions with score 1 (25 mg/kg) and negative expression with score 0 (50 mg/kg). Both antioxidant and anti-inflammatory effects were dose-dependent.ConclusionsThese distinguishing features imply that this unique alga is a promising anti-inflammatory agent. Further studies are required to investigate its main active ingredients and possible side effects.

Standardized seed extract of Cajanus cajan (L) Millsp. produced antinociceptive and anti-inflammatory actions through inhibition of inflammatory mediators and activation of opioidergic signaling

Background and PurposePeripheral tissue damage and diseases could lead to persistent pain beyond possible resolution suggestive of disease-promoting condition which gives rise to chronic pain. The inability of current medications to manage some chronic inflammatory and painful conditions necessitate the need for better treatment options. Natural products have been a veritable source for the discovery of more efficacious and safer therapeutics. Cajanus cajan (L) Millsp, (Fabaceae) is used in traditional African medicines for the treatment of painful, gut disturbance and inflammatory conditions. Hence, the current study aims to investigate the anti-inflammatory and antinociceptive actions of the ethanol seed extract of Cajanus cajan (CC) in rodents and possible mechanisms of action. MethodsHigh performance liquid chromatography coupled with diode-array detection (HPLC-DAD) was used to identify 8 major flavonoids in CC. Antinociceptive activity was investigated using the acetic acid-induced writhing reflex, biphasic formalin-induced flinching behaviour and supraspinal hot plate-evoked nociception in mice. Carrageenan-induced rat paw oedema test was used to evaluate the anti-inflammatory action of CC in rats. Possible mechanism of antinociception and anti-inflammatory actions were examined using both in vivo model and molecular docking procedures against µ-opioid receptor (MOR), cyclooxygenase-2 (COX-2) and phospholipase A2 (PLA2) proteins, respectively. ResultsThe chromatographic procedure qualitatively and quantitatively confirmed the presence of rutin, quercetin, gallic acid, luteolin, pinostrobin, BiochaninA, formononetin and apigenin in CC. The in vivo nociceptive assay, showed that CC (50, 100, or 200 mg/kg, p.o.) significantly decreased mean number of writhing reflex with peak effect at 50 mg/kg (72% inhibition) when compared with vehicle control in mouse writhing test. Similarly, the biphasic formalin-induced nociception was significantly reduced by CC (50 mg/kg) with 24.61 and 66.73% inhibition of nociceptive reactions in both the early and late phases of formalin-induced inflammatory pain, respectively. In addition, CC significantly increased supraspinal thermally mediated pain threshold with maximum possible effects of 42.25 and 52.16% at CC 50 and 100 mg/kg, respectively, in hot-plate test. Similarly, CC100mg/kg caused time course inhibition of carrageenan-induced paw oedema in rat with peak effect (65.78%, CC 100 mg/kg; 6 h). Interestingly, the antinociceptive action of CC was blocked by the pre-treatment of mice with l-NG-nitro arginine methyl ester (L-NAME) or naloxone. The molecular docking analysis revealed prominent interactions of pinostrobin, physcion and lupeol with MOR, COX-2, and PLA2, respectively. ConclusionFindings from this study showed that Cajanus cajan seeds extract possesses anti-nociceptive and anti-inflammatory through inhibition of inflammatory mediators (PLA2/COX-2) and activation of opioidergic signalling.

ЭКСТРАКТ СТРОБИЛОВ ЕЛИ ОБЫКНОВЕННОЙ КАК ПЕРСПЕКТИВНОЕ СРЕДСТВО ДЛЯ МИНИМИЗАЦИИ РИСКОВ РАЗВИТИЯ ВОСПАЛЕНИЯ

The article is devoted to examining anti-inflammatory activity of dry aqueous extract of European spruce (Picea abies) strobiles using different routes of administration. Strobiles of European spruce for extracts were harvested on the territory of the Perm region of the Russian Federation in a mixed forest with a predominance of European spruce and Scots pine (Pinus sylvestris). Dry aqueous extract was obtained according to the original patented method. Procyanidins content in spruce strobiles and dry extracts was determined by using acid cleavage of procyanidins to anthocyanidins according to the Porter method. Anti-inflammatory activity was established by using carrageenan-induced paw edema in rats. White laboratory outbred Wistar rats were used in the experiment. According to the results of the study, the procyanidin content was found to equal approximately 13 % in the samples of spruce strobiles. Intraperitoneal administration of dry extract of strobile spruce at a dose of 100 mg/kg was established to induce a pronounced anti-inflammatory activity. Intraperitoneal administration of smaller doses of strobile extract resulted in a pronounced anti-inflammatory activity at a dose of 50 mg/kg. A dose of 10 mg/kg successfully suppressed inflammation (50 % edema suppression) 1 and 3 hours after carrageenan administration (p &lt; 0.05) according to hydrometric data, but this was not confirmed by photometric data. Oral administration of the extract showed no anti-inflammatory activity. With the rectal route of administration, no pronounced anti-inflammatory activity was found in the studied extract. The extract of spruce strobiles obtained by the original method contains 56 % procyanidins and exhibits pronounced anti-inflammatory activity when administered intraperitoneally. The use of the extract in oral and rectal routes of administration requires more in-depth study.

Extract of european spruce strobiles as a promising tool to minimize the risks of inflammation

The article is devoted to examining anti-inflammatory activity of dry aqueous extract of European spruce (Picea abies) strobiles using different routes of administration. Strobiles of European spruce for extracts were harvested on the territory of the Perm region of the Russian Federation in a mixed forest with a predominance of European spruce and Scots pine (Pinus sylvestris). Dry aqueous extract was obtained according to the original patented method. Procyanidins content in spruce strobiles and dry extracts was determined by using acid cleavage of procyanidins to anthocyanidins according to the Porter method. Anti-inflammatory activity was established by using carrageenan-induced paw edema in rats. White laboratory outbred Wistar rats were used in the experiment. According to the results of the study, the procyanidin content was found to equal approximately 13 % in the samples of spruce strobiles. Intraperitoneal administration of dry extract of strobile spruce at a dose of 100 mg/kg was established to induce a pronounced anti-inflammatory activity. Intraperitoneal administration of smaller doses of strobile extract resulted in a pronounced anti-inflammatory activity at a dose of 50 mg/kg. A dose of 10 mg/kg successfully suppressed inflammation (50 % edema suppression) 1 and 3 hours after carrageenan administration (p &lt; 0.05) according to hydrometric data, but this was not confirmed by photometric data. Oral administration of the extract showed no anti-inflammatory activity. With the rectal route of administration, no pronounced anti-inflammatory activity was found in the studied extract. The extract of spruce strobiles obtained by the original method contains 56 % procyanidins and exhibits pronounced anti-inflammatory activity when administered intraperitoneally. The use of the extract in oral and rectal routes of administration requires more in-depth study.

Effect of solvents on anti-inflammatory and analgesic activities of leaves extract of Mussa paradisiaca Linn

The present study was undertaken to evaluate anti-inflammatory and analgesic activities of two different solvated leaves extracts of Mussa paradisiaca Linn (MP) on experimental animals. Anti-inflammatory activity was carried out using formalin induced rat paw edema and cotton pellet induced granuloma models. Analgesic activity was evaluated using acetic acid induced writhing and tail immersion models. Acute toxicity studies were carried out for the extracts and the test drug doses for screening were selected depending upon LD50 values. Aqueous and ethanolic leaves extracts of MP Linn in the dose of 200 &amp; 400 mg/kg b.w, by oral route were used after confirmation of acute toxicity. Aspirin at a dose of 100 mg/kg, b.w was used as standard analgesic drug. Both doses of the extract inhibited the rat paw edema significantly (P&lt;0.001) and significant (P&lt;0.001) decrease in granuloma formation. It also suppressed the pain threshold of rat in tail immersion model (P&lt;0.001), as well as inhibited the acetic acid induced writhing (P&lt;0.001) when compared to the control group. It is concluded that the administration of aqueous and ethanolic leaves extracts of MP produced significant anti-inflammatory and analgesic effects in experimental animals by dose dependent manner but the ethanol leaves extract showed more significant activity than former solvent.

DOCKING STUDIES OF INDOLE ASSIMILATED PYRAZOLINE MOLECULAR HYBRIDS: DESIGN, SYNTHESIS AS ANTIINFLAMMATORY AGENTS AND ANTICANCER AGENTS

A series of novel compounds (4a-4l) have been synthesized by Claisen-Schmidt condensation, Schiff’s base and Cyclization mechanism. All the molecule structures were affirmation by IR, 1H NMR and Mass spectral data. The synthesized hybrids were screened for in vivo anti-inflammatory and invitro anticancer activities. Ant inflammatory activity was performed using carrageenan induced rat paw edema method using Diclofenac as standard drug. The anticancer activity has been assessing by using MTT assay against MCF7 and SKOV3 cell lines and Doxorubicin was used as reference standard. Among the compounds compound 4l exhibited the highest % inhibition of 98.4 when compared with the standard Diclofenac 94.2%.Compound 4f exhibited the lowest IC50 at concentration of 20.01µg against MCF7 cell lines and 32.87µg against SKOV3 cell lines. The molecular docking studies was performed using the Ligprep tool of Schrodinger suite. This study revealed that novel thiazolidne-4-one-pyrazole hybrids(4a-4j) had good interaction with the active site of EGFR receptor. Among the docked compounds, dock score of the compounds ranged from from -3.186 to -5.212. The highest score was exhibited by 4f with -5.212 with Glide binding energy of -34.697 Kcal/mol.

Anti-inflammatory Activity and Cyclooxygenase-2 Inhibitory effect of Peperomia pellucida (L.) Kunth Extract

Inflammation is an adaptive response underlying a wide variety of physiological and pathological processes mediated by the Cyclooxygenase (COX) enzyme. Cyclooxygenase-2 (COX-2) is an important enzyme that catalyzes the production of prostaglandins from arachidonic acid and has a crucial role in various pathologies including inflammation, neurological disorders, and cancer. The selective suppression of COX-2 over COX-1 is thought to be a useful approach for treating inflammation. Peperomia pellucida (L.)Kunth has been traditionally used as an anti-inflammatory and antioxidant, thus giving scope for anti-inflammatory studies. Since the action of Ethanol extract of Peperomia pellucida (EEPp) on COX-2 has not been previously described, in this study, we further investigated the effect of Cyclooxygenase-2 inhibitory effects spectrophotometrically in ELISA readers and evaluated of anti-inflammatory activity in the carrageenan-induced rat paw edema model. The edema volume was measured using a plethysmometer. The results showed that the EEPp (100, 200, and 400mg/kg BW) had significant anti-inflammatory activity and the EEPp demonstrated a COX-2 Inhibitory effect. The percentage of COX-2 inhibition was 10.87%, 47.04%, 56%, and the percentage of inhibition of paw edema was 34.93%, 46.61%, and 64.04%, respectively. These findings suggest that Peperomia pellucida extracts possess promising and remarkable anti-inflammatory activity, which is directed against the enzymatic activity of COX-2.

Synthesis and Evaluation of Amide Codrug of Ibuprofen and Amlodipine for Dual Inhibition of Inflammation and Hypertension

The codrugs approach showed as an effective strategy for targeting diseases synergistically, hence improving the quality of life of patients. The main goal is to address comorbid conditions of hypertension and osteoarthritic pain and inflammation in geriatric patients, eliminate the adverse gastrointestinal adverse effects of the drug, reducing dose with significant reduction of polypharmacy and improve patient compliance. The present study aimed to synthesize amide linked codrugs of Ibuprofen (nonsteroidal anti-inflammatory drug) and Amlodipine (Calcium channel Blocker), its biopharmaceutical study and evaluation of anti-inflammatory and antihypertensive activity. Codrug conjugates were synthesized by a one-pot amidation reaction of Amlodipine with Ibuprofen using DCC as coupling agent and DMAP as catalyst. The obtained compound Ibuprofen-Amlodipine amide linked codrug (IBAM) was characterized by determination of melting point, TLC, DSC, FT-IR, NMR, and mass spectroscopy. The solubility, partition coefficient, plasma protein binding and in vitro hydrolysis study in SGF and SIF were studied to determine biopharmaceutical properties.The anti-inflammatory and antihypertensive activity of synthesized compounds were tested in a carrageenan-induced rat paw oedema model and Fructose induced diabetic hypertensive model and it was discovered that the codrugs underwent significant hydrolysis in SIF (pH 7.4) and IBAM showed effective reduction in hypertension, inflammation in comparison to parent drug. Finally, it is concluded that the codrug approach could be successfully used in drug design and development for overcoming undesirable difficulties without losing the desired activities of the parent drugs.

Integrating Chemical Profiling, In Vivo Study, and Network Pharmacology to Explore the Anti-inflammatory Effect of Pterocarpus dalbergioides Fruits and Its Correlation with the Major Phytoconstituents.

The purpose of this study is to explore the anti-inflammatory activity of Pterocarpus dalbergioides fruit extract (PFE) and the underlying mechanism. Chemical profiling using ultraperformance liquid chromatography/mass spectrometry identified 28 compounds in PFE (12 flavonoids, 5 fatty acids, 4 phenolic compounds, 3 alkaloids, 2 sesquiterpenes, and 2 xanthophylls). PFE (2 g/kg) significantly inhibited carrageenan-induced rat paw edema after 4 h of administration (42% inhibition). A network-based strategy and molecular docking studies were utilized to uncover the anti-inflammatory mechanism. Out of the identified compounds, 16 compounds with DL ≥ 0.18 and F ≥ 30% were selected using bioavailability (F) and drug-likeness (DL) metrics. The network analysis revealed that 90 genes are considered key targets for the selected compounds and linked to the anti-inflammatory effect. Among all compounds, linoleic acid was found to be the top-most active constituent as it targets maximum genes. Four targets (TNF, IL6, AKT1, and CCL2) among the top 10 genes were found to be the main target genes that may contribute to the anti-inflammatory potential of PFE. Furthermore, KEGG (Kyoto encyclopedia of genes and genomes) pathway analysis revealed that PFE might regulate inflammation through five pathways: neuroactive ligand-receptor interaction, lipid and atherosclerosis, fluid shear stress and atherosclerosis, TNF signaling pathway, and rheumatoid arthritis. The docking study predicted the significant binding affinity between the top four active constituents (linoleic acid, 9-octadecenoic acid, 11,12,13-trihydroxy-9-octadecenoic acid, and rhamnetin-3-O-rhamnoside) and the selected target proteins (TNF and AKT1). The findings highlight PFE as a promising drug lead for controlling inflammation.

Topical Analgesic and Anti-Inflammatory Properties of Bioengineered Juglans regia L. Silver Nanoparticles.

&lt;b&gt;Background and Objective:&lt;/b&gt; Research has demonstrated the antibacterial, anti-angiogenetic, antiviral, anti-inflammatory, anticancer and antioxidant properties of colloidal silver due to its biological, optical and electrical properties. The aim of this study was the anti-inflammatory effect of the silver bioengineered nanoparticles by using the acetonitrile-unripe fruit extract of &lt;i&gt;Juglans regia&lt;/i&gt; L., on experimental animal model. &lt;b&gt;Materials and Methods:&lt;/b&gt; The study uses various techniques to characterize nanoparticles, including ultraviolet spectra, dynamic light scattering and Fourier transform infrared. The study used carrageenan-induced rat paw edema as an induction model for inflammation and assessed its antinociceptive effects in mice using the formalin test. As well as evaluation of proinflammatory cytokines IL-6, TNF and IL-1. &lt;b&gt;Results:&lt;/b&gt; The produced AgNPs were more compact and stable, according to physical characterization methods compared to chemical prepared nanoparticles. The formulation combining unripe fruit bio-reduced nanoparticles and extract, UF, shows a greater acute anti-inflammatory effect, while leaf extract has a better late anti-inflammatory effect. These bioengineered nanoparticles show efficient &lt;i&gt;in vivo&lt;/i&gt; anti-acute inflammation, reducing skin inflammation through decreased cellular infiltrates and cytokine release. &lt;b&gt;Conclusion:&lt;/b&gt; &lt;i&gt;Juglans regia&lt;/i&gt; L., extract and silver nanoparticles show notable effects in both the early and late stages of the antinociceptive formalin test. While, bioengineered NP/UF and NP/LV can be used as topical analgesics. The potent topical anti-inflammatory and analgesic effects of these medications provide a sufficient basis for the use of this plant material in dermatological products.