Paw Edema In Mice Research Articles

Phytochemical and Anti-Inflammatory Analysis of Prunus africana Bark Extract

Background and objectives: Inflammation is associated with various diseases; Prunus africana (Hook f.) is commonly used in Meru community of Kenya in management of inflammation. Medicinal plants contain phytochemicals associated with pharmacological activities; so, the aim of the present study was evaluating the anti-inflammatory activity of Prunus africana bark extract and qualitative analysis phytochemical of its phytochemicals. Methods: Five hundred mg of the powdered P. africana stem bark was extracted using 1.5 liters of dichloromethane for 24 h. The anti- inflammatory activity was evaluated against carrageenan paw induced edema in mice. The ability of the extracts to suppress the paw inflammation was expressed as a percentage inhibition of paw edema in five groups each comprising of five mice. Group I was treated with DMSO, group II with diclofenac (100 mg/Kg) and experimental groups III, IV and V with 50, 100 and 150 mg/Kg of the plant extract. The ability of the extracts to suppress the paw inflammation was expressed as a percentage inhibition of paw edema in mice. The qualitative phytochemical analysis was conducted using the standard protocols. Results: The percentages paw edema inhibition after the 4th h in the positive control and the experimental groups I, II and III were 13.61, 32.85, 25.15 and 5.92%, respectively. The qualitative evaluation of stem bark extract illustrated presence of tannins, saponins, flavonoids, alkaloids, quinones, cardiac glycosides, terpenoids, phenolics and coumarins. Conclusion: Dichloromethane stem bark extract of the P. africana presented anti-inflammatory activity hence a possible candidate for extraction of active anti-inflammatory compounds.

Antinociceptive, antiinflammatory, and antipyretic effects induced by the venom of Egyptian scorpion Androctonus amoreuxi

BackgroundScorpion venom is a very complicated mixture of various peptides/proteins which could induce toxicological and pharmacological responses. This investigation was conducted to evaluate the possible pharmacological properties (analgesic, antipyretic, and antiinflammatory effects) of the Egyptian scorpion venom Androctonus amoreuxi in mice and rats injected intraperitoneally with 1/10 and 1/5 LD50 (0.11 and 0.22 mg/kg for mice; 0.385 and 0.77 mg/kg for rats, respectively).ResultsThe peripheral and central analgesic effect of A. amoreuxi venom was determined using the tests of mice-abdominal writhing and tail immersion of rats, respectively. The antipyretic and antiinflammatory activities were examined using the pyrexia rats model induced by Brewer’s yeast and the paw mice edema induced by carrageenan, respectively. The venom of A. amoreuxi produced significant (p < 0.05) peripheral and central analgesic activity in both animal models. Also, treatment with the scorpion venom showed significant (p < 0.05) dose-independent reduction in pyrexia of rats. More importantly, the venom significantly inhibited mice paw edema induced by carrageenan.ConclusionAccordingly, the present results showed that the venom of this scorpion possesses remarkable pharmacological properties (analgesic, antipyretic, and antiinflammatory activities) on animal models, and might be contain certain peptides responsible for the reported activities.

Phyto-compounds and pharmacological activities of Lygodium lanceolatum Desv. (Schizaeaceae)

Lygodium lanceolatum Desv. (Schizaeaceae) is a native fern of Madagascar and Comoros. This species is widely used by the Malagasy population for the treatment of several diseases including different categories of pain. This work aims to determine the antioxidant capacity, the analgesic and anti-inflammatory properties of this plant and to report its phytochemical composition related to therapeutic properties. The methanol extract (MELL) and aqueous decoction (DLL) were prepared from the L. lanceolatum aerial parts. The isolation of compound 1 was carried out using exclusion chromatography. The total polyphenolic content (TPC) was evaluated using the Folin-Ciocalteu assay. Different HPLC methods were performed to quantify bioactive compounds in the L. lanceolatum aerial parts. The antioxidant capacity was determined using the DPPH free radical scavenging method and the Ferric Reducing Antioxidant Power (FRAP) assay. In vivo carrageenan-induced mice paw oedema was used to evaluate the anti-inflammatory activity, while the evaluation of the antalgic activity was carried out by the in vivo acetic acid-induced writhing test in mice. Acute toxicity was performed in mice to evaluate the toxicity of methanol extract and decoction of L. lanceolatum. The aerial parts of L. lanceolatum showed a high level of total polyphenolic content with a mean value of 10168.47 ± 1117.09 mgGAE/100 g of dry weight (DW). The HPLC total bioactive compound content (TBCC) showed a value of 4181.59 ± 1485.2 mg/100 g DW. Organic acids represent 79.12% of TBCC: malic acid (45.45%), succinic acid (12.02%), and quinic acid (11.47%) are the main quantified compounds. The isolated compound 1 was quercitrin which represents 1.12% of TBCC. Isolated quercitrin and MELL potently inhibited the free radical DPPH more than DLL. MELL antioxidant capacity was confirmed by the FRAP results. MELL, as well as DLL, inhibited in a dose-dependent manner the carrageenan-induced paw oedema and the acetic acid-induced writhing in mice. Quercitrin was 20 times more effective than DLL to decrease the number of writhes. MELL and DLL did not demonstrate toxicity during the acute toxicity test. These results indicate that L. lanceolatum possesses strong antioxidant, anti-inflammatory and antalgic properties thanks to phenolic compounds and organic acids, in particular quercitrin (the isolated compound) confirming the wide use of this species in the popular Malagasy medicine.

New insights on the arylpiperazinylalkyl pyridazinone ET1 as potent antinociceptive and anti-inflammatory agent

Pyridazine derivatives, such as arylpiperazinylalkyl pyridazinones, display antinociceptive effects to thermal and chemical stimuli. Here, we extended our previous knowledge on the pharmacological profile of 4-amino-6-methyl-2-(3-(4-(4-methylcyclohexa-1,3-dien-1-yl)piperazin-1-yl)propyl)-5-vinylpyridazin-3(2H)-one, here referred as ET1, paving the way for the comprehension of its complete mechanism of action. To this aim, we have evaluated the mouse behavioural responses in several animal models of pain, the effect of ET1 in the murine model of zymosan-induced paw oedema and air-pouch, assessing the cytokines and the cellular phenotype and finally, an in vitro radioligand binding study was performed on a panel of 30 different receptors. In the formalin test, ET1 reduced both neurogenic and inflammatory phase of nociception induced by the aldehyde. Similarly, ET1 strongly reduced paw licking response in the capsaicin test, the abdominal stretching in the writhing test and the carrageenan-induced thermal hyperalgesia. ET1 also evoked a long-lasting reduction of thermal hyperalgesia. Furthermore, ET1 produced a long-lasting anti-inflammatory effect in the zymosan-induced mouse paw oedema and air-pouch through the selective inhibition of inflammatory monocytes recruitment and the modulation of IL-1β, IL-6, TNF-α and MCP-1. Binding experiments confirmed an inhibitory effect on adrenergic α1A, α1B and α2A receptors subtypes and, for the first time, a moderate affinity was observed for the following receptors: histamine H1, imidazoline I2, sigma non-opioid intracellular receptor 1 and σ2. These results prompt ET1 as a potent analgesic and anti-inflammatory agent, and support the possibility that it may be suitable for clinical applications in a wide-range of inflammatory-based diseases.

Evaluation of Anti-Inflammatory and Analgesic Activities of Methanolic Extract of Aitchisonia Rosea in Albino Mice

Objective: Current analysis aims at in-vivo investigation of analgesic and anti-inflammatory activities of Aitchisonia rosea methanolic extract.&#x0D; Methods: Albino mice (20-30 g) were used in the study. Extract at 200, 400 and 800 mg/kg doses was tested against egg albumin and carrageenan induced mice paw edema along with formalin persuaded paw licking and acetic acid prompted writhing for analgesic activity.&#x0D; Results: Results depicted dose reliant and significant (p&lt;0.001) inhibition of carrageenan as well as egg albumin brought paw edema, abdominal constrictions/ hind limb stretching tempted by acetic acid and formalin instigated paw licking. Capability of crude extract to halt inflammatory and analgesic response was akin to that of ibuprofen in all models.&#x0D; Conclusion: The current findings support the use of Aitchisonia rosea for inflammatory conditions, which might be attributed to its previously proven high alkaloid, flavonoids, phenol, tannins content and free radical scavenging activity.

Effectivity of Holothuria scabra and Spirulina platensis extract combination as an Antiinflammatory Agent Measured by Carrageenan-induced Rat Paw Edema

Sea cucumber, Holothuria scabra, can be found abundantly in Indonesian seas, which is also known to possess several medicinal properties. Spirulina platensis is another marine resources that has recently been extensively researched for its medicinal ability, such as anti-inflammatory effect. This study aims to evaluate the efficacy of H. scabra extract combined with S. platensis extract in reducing inflammation. This study uses male Wistar rats as the study animal. Inflammation was induced by injecting carrageenan solution into the mice paw. Combination of H. scabra and S. platensis extract with various combination ratio (1:1; 1:2; and 2:1) was applied to the mice paw. Diclofenac sodium was used as the standard control therapy. Edema inhibition rate and anti-inflammatory efficacy were measured by analyzing the edema size and calculating the edema difference. Combination of H. scabra and S. platensis with 1:1 ratio has the largest edema inhibition volume compared to the other treatments. H. scabra and S. platensis combination outperforms the positive diclofenac sodium control group in terms of edema inhibition. The highest anti-inflammatory effect is obtained in the combination of H. scabra and S. platensis with 1:2 ratio, however, the anti-inflammatory efficacy is not as potent as the positive control. The effectivity of Holothuria scabra and Spirulina platensis extract in reducing the edema might be caused by their ability to reduce the levels of several inflammatory markers, including IL-6, NO, MMP9, and COX-2. This result suggests that H. scabra and S. platensis combination has anti-inflammatory effect shown in mice paw edema model.

LALLT (Loxosceles Allergen-Like Toxin) from the venom of Loxosceles intermedia: Recombinant expression in insect cells and characterization as a molecule with allergenic properties

Bites evoked by Brown spiders (Loxosceles genus) are associated with skin injuries (cutaneous rash, itching, swelling, erythema and dermonecrosis) and systemic manifestations. Transcriptome analyses of Loxosceles venom glands showed that the venom has a complex composition containing toxins such as phospholipases-D, metalloproteases and hyaluronidases. Here, by screening the RNA from L. intermedia venom glands, we cloned a novel allergen toxin, and named LALLT (LoxoscelesAllergen-Like Toxin). Sequence analysis showed that LALLT is closely related to allergens from other spiders and RNA screening indicated the presence of LALLT orthologues in the venom of other Loxosceles spiders. Recombinant LALLT was expressed (~45 kDa) in baculovirus-infected insect cells and purified by affinity chromatography. Antibodies against different Loxosceles venoms cross-reacted with LALLT and antibodies against LALLT recognized three Loxosceles venoms, revealing epitopes identity. LALLT triggered paw edema in mice and erythema, edema and leukocyte infiltration into the dermis of rabbit skin. Also, LALLT induced vascular permeability in mice, degranulation of rat mesentery mast cells, as well as prompted degranulation and increased calcium influx in RBL-2H3 cells. Data reported suggest for the first time the existence of allergens in Loxosceles venoms and make LALLT available for clinical studies about allergenic events arisen by Loxosceles envenoming.

Synthesis, in-vitro, in-vivo anti-inflammatory activities and molecular docking studies of acyl and salicylic acid hydrazide derivatives

Over the course of time several drugs have been synthesized and are available in market for the treatment of inflammation. However, they were unable to cure effectively and associated with side effects. To effectively deal with such diseases, heterocycles and their derivatives have gained their special position. For this reason 1,3,4-oxadiazole (15–16), 1,2,4-triazole (17–18), Schiff base (19–24) and 3,5-disubstituted pyrazole (25) derivatives were synthesized starting from salicylic acid and acyl acid hydrazides (12–14) as COX-1 and COX-2 inhibitors. In vivo anti-inflammatory activities were also tested by carrageenan-induced mice paw edema against albino mice of any sex. Structures of all the synthesized compounds were confirmed by FT-IR and 1H NMR analysis. Schiff base derivative of 4-amiontirazole (24) with IC50 value of 1.76 ± 0.05 (COX-2) and 117.8 ± 2.59 emerged as potent COX-2 inhibitor. Furthermore, we also performed in-vivo anti-inflammatory investigations by using carrageenan induced paw edema test. From in-vivo anti-inflammatory activities, it was found that after 1 h the maximum percentage inhibition 15.8% was observed by compound 14 which is comparable with that of the standard drug followed by the compound 18 with percentage inhibition of 10.5%. After 3 h, the maximum percentage inhibition was observed by compound 18 with 22.2% and compound 14 with 16.7%. After 5 h the maximum percentage inhibition was observed by compound 18 with 29.4% followed by compound 16 with 23.5%. We further explore the mechanism of the inhibition by using docking simulations. Docking studies revealed that the selective COX-2 inhibitors established interactions with additional COX-2 enzyme pocket residues.

Capsaicin-Cyclodextrin Complex Enhances Mepivacaine Targeting and Improves Local Anesthesia in Inflamed Tissues.

Acidic environments, such as in inflamed tissues, favor the charged form of local anesthetics (LA). Hence, these drugs show less cell permeation and diminished potency. Since the analgesic capsaicin (CAP) triggers opening of the TRPV1 receptor pore, its combination with LAs could result in better uptake and improved anesthesia. We tested the above hypothesis and report here for the first time the analgesia effect of a two-drug combination (LA and CAP) on an inflamed tissue. First, CAP solubility increased up to 20 times with hydroxypropyl-beta-cyclodextrin (HP-β-CD), as shown by the phase solubility study. The resulting complex (HP-β-CD-CAP) showed 1:1 stoichiometry and high association constant, according to phase-solubility diagrams and isothermal titration calorimetry data. The inclusion complex formation was also confirmed and characterized by differential scanning calorimetry (DSC), X-ray diffraction, and 1H-NMR. The freeze-dried complex showed physicochemical stability for at least 12 months. To test in vivo performance, we used a pain model based on mouse paw edema. Results showed that 2% mepivacaine injection failed to anesthetize mice inflamed paw, but its combination with complexed CAP resulted in pain control up to 45 min. These promising results encourages deeper research of CAP as an adjuvant for anesthesia in inflamed tissues and cyclodextrin as a solubilizing agent for targeting molecules in drug delivery.

Molecular Insight into the Anti-Inflammatory Effects of the Curcumin Ester Prodrug Curcumin Diglutaric Acid In Vitro and In Vivo.

Curcumin diglutaric acid (CurDG), an ester prodrug of curcumin, has the potential to be developed as an anti-inflammatory agent due to its improved solubility and stability. In this study, the anti-inflammatory effects of CurDG were evaluated. The effects of CurDG on inflammatory mediators were evaluated in LPS-stimulated RAW 264.7 macrophage cells. CurDG reduced the increased levels of NO, IL-6, and TNF- α, as well as iNOS and COX-2 expression in cells to a greater extent than those of curcumin, along with the potent inhibition of MAPK (ERK1/2, JNK, and p38) activity. The anti-inflammatory effects were assessed in vivo by employing a carrageenan-induced mouse paw edema model. Oral administration of CurDG demonstrated significant anti-inflammatory effects in a dose-dependent manner in mice. The effects were significantly higher compared to those of curcumin at the corresponding doses (p < 0.05). Moreover, 25 mg/kg curcumin did not exert a significant anti-inflammatory effect for the overall time course as indicated by the area under the curve data, while the equimolar dose of CurDG produced significant anti-inflammatory effects comparable with 50, 100, and 200 mg/kg curcumin (p < 0.05). Similarly, CurDG significantly reduced the proinflammatory cytokine expression in paw edema tissues compared to curcumin (p < 0.05). These results provide the first experimental evidence for CurDG as a promising anti-inflammatory agent.

Astragalin attenuates oxidative stress and acute inflammatory responses in carrageenan-induced paw edema in mice.

Astragalin is a flavonoid existed in several edible and medicinal plants and was recorded to have multiple biological and pharmacological significances. This work aimed to assess the possible protective effect of astragalin administration against oxidative tension, acute inflammation and histopathological deformations in a mouse paw edema model induced following intra sub-plantar injection of carrageenan. Thirty-six male Swiss mice were divided into four groups: control, carrageenan, astragalin (75mg/kg) + carrageenan, and indomethacin (10mg/kg) + carrageenan. Astragalin administration for five consecutive days to carrageenan injected mice showed a significant reduction in the development of paw in a time dependent effect, inhibited lipoperoxidation by-product, malondialdehyde and increased superoxide dismutase and catalase activities. Astragalin was found also to suppress the inflammatory signaling in the inflamed tissue as exhibited by the decreased myeloperoxidase activity along with the decreased protein and transcriptional level of pro-inflammatory cytokines including tumor necrosis factor-alpha, interleukin-1 beta and interleukin-6. Moreover, inducible nitric oxide synthase and cyclooxygenase-2 expressions and their products (nitric oxide and prostaglandin E2) were downregulated. Additionally, astragalin decreased monocyte chemoattractant protein-1 and nuclear factor kappa B expression in the inflamed paw tissue. The recorded findings provide evidences for the potential application of astragalin as a plant-derived remedy for the treatment of acute inflammation due to its promising antioxidant and anti-inflammatory activities along with its ameliorative impact against the histopathological changes in the paw tissue.

Anti-inflammatory, Anxiolytic and Antioxidant Property of Lactuca sativa L and Formulation of Microspheres Loaded Sustained Release Anti-inflammatory Gel

Anti-inflammatory and anxiolytic properties of Lactuca sativa L extract was evaluated by formalin induced mice paw edema test, and elevated plus maze animal model respectively. Solid microspheres containing dispersed extract were obtained by water-in-oil-in-water multiple emulsion system followed by solvent evaporation method. Optimization was carried out using MINITAB 16 and optimized microspheres were loaded into a gel base. Anti-oxidant activity of optimized microspheres loaded gel was evaluated using DPPH (2,2-diphenyl-1-picrylhydrazyl) assay. The gel was also evaluated for its physical properties, drug release kinetics and anti-inflammatory activity using formalin induced mice-paw edema test where the anti-inflammatory potential was compared to marketed diclofenac gel (1.16% w/w). All doses of extract as well as microsphere loaded sustained release anti-inflammatory gel showed a dose and time dependent inhibition of edema (P&lt;0.05), the extract also showed a dose dependent inhibition of level of anxiety (P&lt;0.001). Potential anti-oxidant activity was seen with different concentration of crude extract and microsphere loaded gel. The anti-oxidant potential was compared using IC50 value which was 5.62 µg/mL, 6.34 µg/ml, 8.25 µg/mL for ascorbic acid, methanolic extract of L. sativa and microspheres loaded gel respectively.

Phytochemistry and anti-inflammatory activity of ethanolic root bark extract of Vepris nobilis Mziray (Rutaceae family)

Root bark powder of Vepris nobilis Mziray (family Rutaceae) collected from Mukura Sub-county, Ngora District, Eastern Uganda, about 300 km from the Capital City Kampala was extracted with 70% ethanol. Phytochemical analyses was carried out as well as in vivo anti inflammatory animal tests. The GC–MS analysis identified 37 compounds in the extract including fatty acids (45.08%), sesquiterpenes (40.38%), furaquinoline alkaloids (10.93%), a phenylpropanoid (2.37%) and a triterpenoid (1.31%). Interestingly, it revealed that at 400 and 600 mg of extract / kg of body weight, formalin induced paw oedema in mice was inhibited much better than by 25 mg of Diclofenac sodium /kg body weight. It was concluded that ethanolic root bark extract of V. nobilis has important phytochemicals that need to be evaluated for anti-inflammatory activity as potential lead compounds for anti-inflammatory drug development.

Fruit Extract of Pithecellobium dulce (FPD) ameliorates carrageenan-induced acute inflammatory responses via regulating pro-inflammatory mediators.

Unravelling the precise mechanisms underlying the anti-inflammatory action of fruit extract of Pithecellobium dulce (FPD) is quite complex. Hence the prime approach of this particular study is to unveil intriguing insights to its possible anti-inflammatory mechanisms. Anti-inflammatory effects of FPD were determined against experimentally induced acute and chronic inflammation in mice paw edema models. Administration of FPD significantly reduced the acute and chronic inflammation via regulating pro-inflammatory mediators such as pro-inflammatory cytokines (TNF-α, IL-6, and IL-1ß), Cycloxygenase 2 (COX-2), and inducible nitric oxide synthase (iNOS) compared to control group. The overall results suggest that FPD mitigates inflammation by regulating the inflammatory mediators. PRACTICAL APPLICATIONS: Fruit of Pithecellobium dulce is comestible and has been widely distributed in Asian pacific region. Non-steroidal anti-inflammatory drugs (NSAIDS) are among the most conventional treatment strategy against pain and inflammation. Although, chronic use of NSAIDS are associated with severe side effects such as gastrointestinal irritation, hepatic injury, excessive bleeding, and cardiovascular disorders. Hence identification of more effective complementary and alternative therapeutic approach from natural resources with fewer side effects could improve the quality of life of those receiving NSAIDS. Administration of fruit extract of Pithecellobium dulce ameliorates carrageenan-induced acute inflammatory responses, as evidenced by paw edema measurement, expression of antioxidant enzymes such as glutathionine, super oxide dismutase, pro-inflammatory cytokine analysis (IL-1β, IL-6, and TNF-α), vascular permeability measurement, expression of COX-2 and iNOS. Further, confirmed the involvement of HO-1 pathway in anti-inflammatory action of FPD. The outcome of this present investigation could have a broad range of applications in alleviating inflammatory disorders.

Effect of Nectaroscordum koelzi Methanolic Extract on Acute and Chronic Inflammation in Male Mice.

The present study deals with the effect of Nectaroscordum koelzi fruit extract on acute and chronic inflammation. A total of 84 NMRI mice were used in this study. The effect of the extract on acute inflammation was analyzed by increasing vascular permeability via acetic acid and xylene induced ear edema among mice. The extract was evaluated in terms of effects on chronic inflammation by means of the cotton pellet test among mice. For the assessment of inflammation degree, the mice paw edema volume was measured by the plethysmometric test. The findings showed that the extract was effective on acute inflammation induced by acetic acid in mice. In the xylene ear edema, N. koelzi extract indicated a significant activity in mice. In the cotton pellet method, the methanol extract produced a significant reduction in comparison with the control and dexamethasone. Mice paw edema volume decreased with the extract. In general, the data from the experiments indicated that the methanol extract of N. koelzi has an anti-inflammatory effect on acute and chronic inflammation. However, the exact contributing mechanisms have not been investigated for the pharmacological effects.

New synthetic coumarinolignans as attenuators of pro-inflammatory cytokines in LPS-induced sepsis and carrageenan-induced paw oedema models

The aim of the study was to explore the inhibition efficacy of new synthetic coumarinolignans (SCLs) against the secretion of pro-inflammatory cytokines in two in vivo models of inflammation. Four SCLs 1-4 were screened for their pro-inflammatory cytokine inhibitory potential through oral administration at a dose of 50mg/kg body weight in lipopolysaccharide-induced mouse endotoxaemia and carrageenan-induced mouse paw oedema models. Levels of pro-inflammatory cytokines (IL-1β, TNFα and IL-6) in blood and paw tissue samples were estimated using ELISA. Paw oedema was measured using a plethysmometer. Results were compared with a natural coumarinolignan, cleomiscosinA (5), and the structure-activity relationship (SAR) was interpreted. Compound 2 had the greatest potential in the endotoxaemia model, exhibiting 66.41%, 62.56% and 43.15% inhibition of plasma IL-1β, TNFα and IL-6 secretions, respectively. Further dose-dependent study revealed its anti-inflammatory potential even at dose of 10mg/kg body weight with 24.42% decline in the level of IL-1β. Nevertheless, SCLs 1, 3 and 4 showed marked inhibitory activity with 57.54%, 51.48% and 62.46% reduction in the levels of IL-1β, respectively. Moreover, compound 2 decreased the plasma TNFα and IL-1β levels to 50.03% and 36.58% along with the reduction of paw oedema volume in the local inflammation induced by carrageenan. All compounds including cleomiscosinA (5) were more effective against IL-1β. By studying SAR, the presence of dihydroxyl groups in the phenyl ring of lignans was identified to be essential for the activity. Also, esterification of lignans and presence of a 4-methyl substituent in the coumarin nucleus were found to play some role in enhancing the activity. All four SCLs, especially compound 2, have shown vast potential to emerge out as promising anti-inflammatory drugs.

Diallyl Disulfide Suppresses Inflammatory and Oxidative Machineries following Carrageenan Injection-Induced Paw Edema in Mice.

Diallyl disulfide (DADS) is the major organosulfur constituent in garlic, with a variety of pharmacological activities including antioxidant and anti-inflammatory. Here, we examined the potential antiedematous impact of DADS- versus carrageenan-mediated paw edema in mice. Carrageenan injection potentiated an inflammatory reaction as presented by the elevated serological C-reactive protein (CRP) levels and transcription of tumor necrosis factor-alpha (TNF-α, Tnfα), interleukin-1 beta (IL-1β, Il1b), interleukin-2 (IL-2, Il2), inducible nitric oxide synthase (iNOS), nitric oxide (NO), cyclooxygenase-2 (COX-2, Ptgs2), prostaglandin E2 (PGE2), monocyte chemoattractant protein-1 (MCP-1, Ccl1), nuclear factor kappa B (NF-κB), and myeloperoxidase (MPO) activity, while interleukin-10 (IL-10) was declined in the injured paw tissue. Additionally, carrageenan elevated lipid peroxidation in terms of malondialdehyde (MDA) and decreased glutathione content (GSH). Remarkably, DADS was found to inhibit the inflammatory signaling, suppressed the developed oxidative damage, and protected the histopathological alterations in the inflamed paw tissue in response to carrageenan injection. Our findings suggest that DADS could be used as an alternative therapy used to alleviate the pathophysiological changes associated with the genesis of paw edema through its potent anti-inflammatory and antioxidant impacts.

Apamin from bee venom suppresses inflammation in a murine model of gouty arthritis

Ethnopharmacological relevanceBee venom (BV) has been used for the treatment of inflammatory diseases, such as rheumatoid arthritis, and for the relief of pain in traditional oriental medicine. Aim of studyThe aim of this study was to determine the anti-inflammatory effect of BV on monosodium urate (MSU)-induced gouty arthritis in a mouse model. Materials and methodsTo develop a mouse model of acute gouty arthritis, 4 mg 50 μL−1 of MSU crystal suspension was injected intradermally into the right paw. After MSU crystal injection, we evaluated inflammatory cytokine production in mice of the BV-treated (0.5 and 1 mg kg−1 body weight) and apamin (APM)-treated (0.5 and 1 mg kg−1 body weight) groups. The positive control group was administered a colchicine (1 mg kg−1 body weight) injection with MSU crystals. ResultsBV and APM treatment suppressed inflammatory paw edema in MSU-administered mice. It also exerted anti-inflammatory effects in mice with gouty arthritis by inhibiting proinflammatory cytokine production and inflammasome formation. Interestingly, MSU crystal formation was decreased by BV and APM treatment. ConclusionsThese results suggest that the APM from BV might be useful for the treatment of gouty arthritis due to its anti-inflammatory activities.

Bradykinin Receptors Play a Critical Role in the Chronic Post-ischaemia Pain Model.

Complex regional pain syndrome type-I (CRPS-I) is a chronic painful condition resulting from trauma. Bradykinin (BK) is an important inflammatory mediator required in acute and chronic pain response. The objective of this study was to evaluate the association between BK receptors (B1 and B2) and chronic post-ischaemia pain (CPIP) development in mice, a widely accepted CRPS-I model. We assessed mechanical and cold allodynia, and paw oedema in male and female Swiss mice exposed to the CPIP model. Upon induction, the animals were treated with BKR antagonists (HOE-140 and DALBK); BKR agonists (Tyr-BK and DABK); antisense oligonucleotides targeting B1 and B2 and captopril by different routes in the model (7, 14 and 21days post-induction). Here, we demonstrated that treatment with BKR antagonists, by intraperitoneal (i.p.), intraplantar (i.pl.), and intrathecal (i.t.) routes, mitigated CPIP-induced mechanical allodynia and oedematogenic response, but not cold allodynia. On the other hand, i.pl. administration of BKR agonists exacerbated pain response. Moreover, a single treatment with captopril significantly reversed the anti-allodynic effect of BKR antagonists. In turn, the inhibition of BKRs gene expression in the spinal cord inhibited the nociceptive behaviour in the 14th post-induction. The results of the present study suggest the participation of BKRs in the development and maintenance of chronic pain associated with the CPIP model, possibly linking them to CRPS-I pathogenesis.

Citral Inhibits the Inflammatory Response and Hyperalgesia in Mice: The Role of TLR4, TLR2/Dectin-1, and CB2 Cannabinoid Receptor/ATP-Sensitive K+ Channel Pathways.

Citral ((2E)-3,7-dimethylocta-2,6-dienal), a bioactive component of lemongrass, inhibits oxidant activity, nuclear factor kappa B (NF-κB) activation, and cyclooxygenase-2 (COX-2) expression, even as it activates peroxisome proliferator-activated receptor (PPAR)-α and γ. Additionally, citral produces long-lasting inhibition of transient receptor potential (TRP) channels that are found in sensory neurons, such as TRPV1-3 and TRPM8, while it transiently blocks TRPV4 and TRPA1. Here, the effect of citral in experimental models of acute inflammation and hyperalgesia in mice, and the underlying citral mechanisms of action were investigated. ADMET properties and molecular targets were predicted using the online server. The immunomodulatory and antihyperalgesic effects of citral were evaluated, using mechanical and thermal stimuli, at different time-points on carrageenan, lipopolysaccharides (LPS), and zymosan-induced paw edema and hyperalgesia in mice. ADMET analysis ensures that the citral has not violated Lipinski's rule of five, indicating its safety consumption, and molecular target prediction software identified that citral is a potential fatty acid amide hydrolase (FAAH) inhibitor. Oral treatment with citral (50-300 mg/kg) significantly inhibited carrageenan-induced paw edema and thermal allodynia. Furthermore, citral modulated the inflammation induced by LPS and zymosan, toll-like receptor (TLR) 4, and TLR2/dectin-1 ligands, respectively. Moreover, pretreatment with cannabinoid receptor type 2 (CB2R) antagonists and ATP-sensitive K+ channel inhibitor, but not with a cannabinoid receptor type 1 (CB1R) antagonist, significantly reversed the anti-inflammatory effect of citral. Intriguingly, citral did not cause any relevant action in the central nervous system, and it was safe when assessed in a 14 day toxicity assay in male mice. Therefore, citral constitutes a promising, innovative, and safe molecule for the management of immunoinflammatory conditions and pain states.