Reduced Paw Edema Research Articles

Application of Box-Behnken design for the optimization of Khellin-loaded ethosomes formulation for the management of psoriasis in mice

The objective of the present study was to develop and optimize Khellin-loaded ethosomes formulation to enhance the topical delivery of Khellin for the management of psoriasis. Based on vesicle size, polydispersity (PdI) and encapsulation efficiency, the formulation was optimized using the "3-factor 3-level", Box-Behnken design (BBD). Antioxidant, Anti-inflammatory and Anti-psoriatic activity were further assessed for the optimized formulation. The optimized formulation carried vesicles with a size of 214.64 ± 0.04 nm, PdI 0.387 ± 0.001 and an encapsulation efficiency of 68.38 ± 0.01%. Rhodamine-B loaded formulation was applied to mice skin, and the penetration depth was measured using confocal laser scanning microscopy (CLSM). It was found that the Rhodamine-B solution penetrated mice’s skin to a depth of 20.0 µm. However, the Rhodamine-B loaded ethosomes formulation penetrated mice’s skin to a depth of 55.0 µm. Further, the Khellin-loaded ethosomes formulation possessed strong antioxidant activity, presented a good reduction in paw edema, and showed good anti-inflammatory activity. In addition, the prepared Khellin-loaded ethosomes formulation exhibited considerable effects against psoriasis.

Oilseed Cakes: A Promising Source of Antioxidant, and Anti-Inflammatory Agents-Insights from Lactuca sativa.

This study evaluated the antioxidant and antibacterial properties of methanolic extracts derived from oilseed cakes of Lactuca sativa (lettuce), Nigella sativa (black seed), Eruca sativa (rocket), and Linum usitatissimum (linseed). Lettuce methanolic extract showed the highest potential, so it was selected for further investigation. High-performance liquid chromatography (HPLC-DAD) analysis and bioassay-guided fractionation of lettuce seed cake extract led to the isolation of five compounds: 1,3-propanediol-2-amino-1-(3',4'-methylenedioxyphenyl) (1), luteolin (2), luteolin-7-O-β-D-glucoside (3), apigenin-7-O-β-D-glucoside (4), and β-sitosterol 3-O-β-D-glucoside (5). Compound (1) was identified from Lactuca species for the first time, with high yield. The cytotoxic effects of the isolated compounds were tested on liver (HepG2) and breast (MCF-7) cancer cell lines, compared to normal cells (WI-38). Compounds (2), (3), and (4) exhibited strong activity in all assays, while compound (1) showed weak antioxidant, antimicrobial, and cytotoxic effects. The anti-inflammatory activity of lettuce seed cake extract and compound (1) was evaluated in vivo using a carrageenan-induced paw oedema model. Compound (1) and its combination with ibuprofen significantly reduced paw oedema, lowered inflammatory mediators (IL-1β, TNF-α, PGE2), and restored antioxidant enzyme activity. Additionally, compound (1) showed promising COX-1 and COX-2 inhibition in an in vitro enzymatic anti-inflammatory assay, with IC50 values of 17.31 ± 0.65 and 4.814 ± 0.24, respectively. Molecular docking revealed unique interactions of compound (1) with COX-1 and COX-2, suggesting the potential for targeted inhibition. These findings underscore the value of oilseed cakes as a source of bioactive compounds that merit further investigation.

Methanol Extract of Thottea siliquosa (Lam.) Ding Hou Leaves Inhibits Carrageenan- and Formalin-Induced Paw Edema in Mice

Inflammation is a physiological condition that when unattended causes serious health concerns over the long term. Several phytocompounds have emerged as promising sources of anti-inflammatory agents. Thottea siliquosa is a traditional medicine for inflammatory and toxicity insults; however, this has not been scientifically confirmed. The purpose of this study is to evaluate the anti-inflammatory properties of T. siliquosa methanol leaf extract in a mouse model. This study investigates the anti-inflammatory activities of a plant extract obtained from leaves of T. siliquosa (TSE) with a focus on carrageenan- and formalin-induced paw oedema in mice. The extract’s efficacy was assessed using well-established inflammation models, and the results showed a considerable reduction in paw edema in both cases. In the case of carrageenan model TSE at 50 mg/kg showed a 53.0 ± 2.5% reduction in edema, while those treated with TSM at 100 mg/kg exhibited a 60.0 ± 1.8% reduction (p < 0.01). In the case of a formalin model when a higher dose of TSE (100 mg/kg) was given, paw thickness decreased by 47.04 ± 1.9% on the fifth day and by 64.72 ± 2.2% on the tenth day. LC-MS analysis reported the presence of gallic acid, quinic acid, quercetin, clitorin, myricitrin, retronecine, batatasin II, gingerol, and coumaric acid in the extract. Overall, this study confirms that T. siliquosa extract exerts anti-inflammatory effects in animals and is possibly mediated through the combined effects of these phytochemicals.

Apodanthera glaziovii (Cucurbitaceae) Shows Strong Anti-Inflammatory Activity in Murine Models of Acute Inflammation.

Background/objectives:Apodanthera glaziovii is an endemic species from the semi-arid Brazilian, which has limited toxicological and pharmacological studies. This species belongs to a well-studied family known for its bioactive compounds used in treating inflammatory. This study aimed to identify secondary metabolites in the stems from A. glaziovii, evaluate toxicity, and investigate the anti-inflammatory potential of the stem hydroalcoholic extract (SHE-Ag). Methods: qualitative and quantitative assays were employed to identify secondary metabolites, along with chromatographic analyses and 1H and 13C NMR. Toxicity was assessed through in vitro hemolytic toxicity, in vivo genotoxicity, and oral acute toxicity tests before the pharmacological assays were conducted. Results: phytochemical screening, HPLC and NMR analyses suggested the presence of saponins of the norcucurbitacin class. The SHE-Ag exhibited no hemolytic activity and no mutagenic potential. However, in vivo toxicity at a dose of 2000 mg/kg revealed hematological and biochemical alterations, while the 500 mg/kg dose was safe. In the anti-inflammatory assays, SHE-Ag at 100 mg/kg reduced paw edema by 55.8%, and leukocyte and neutrophil migration by 62% and 68% in the peritonitis model, respectively; inflammatory cell migration by 70% in the air pouch model, outperforming indomethacin, which showed a 54% reduction. Conclusions: these findings indicate that SHE-Ag is rich in saponins, confirmed through HPLC and 1H and 13C NMR analyses. The SHE-Ag also demonstrated low toxicity. The inflammation models used showed a reduction in inflammation, pro-inflammatory cells, and edema, highlighting the significant anti-inflammatory activity of hydroethanolic extract A. glaziovii stems.

Topical Anti-Inflammatory Formulations from Medicinal Plant Extracts: Stability, Efficacy, and Cytokine Modulation in a Carrageenan-Induced Paw Edema Model

Background: Traditional anti-inflammatory drugs, like NSAIDs, often cause side effects, which has fueled interest in plant-based alternatives with fewer adverse effects. Medicinal plants such as turmeric (Curcuma longa), ginger (Zingiber officinale), frankincense (Boswellia serrata), ashwagandha (Withania somnifera), and gotu kola (Centella asiatica) are known for their bioactive compounds with anti-inflammatory properties. This study aimed to evaluate the anti-inflammatory efficacy of these plant extracts in topical formulations. Methods: Ethanol extracts of the selected plants were prepared and formulated into topical gel and cream forms. Stability testing was conducted over a 30-day period to confirm the formulations' consistency, color, and pH. Anti-inflammatory efficacy was assessed using a carrageenan-induced paw edema model in Wistar rats. The animals were divided into six groups, including control, standard drug (indomethacin), and plant-based formulations at two extract concentrations (5% and 10%). Edema reduction was measured using a plethysmometer, and serum cytokine levels (TNF-α and IL-6) were quantified via ELISA. Histopathological analyses of tissue samples further evaluated the anti-inflammatory effects. Results: Both gel and cream formulations demonstrated stability over 30 days. The 10% extract cream formulation achieved the highest reduction in paw edema (70%) and reduced inflammation levels comparable to indomethacin. The 10% extract gel showed similar results (65% reduction). Biochemical analysis revealed significant reductions in TNF-α and IL-6 levels, especially in the 10% cream and gel groups, aligning with histopathological findings that indicated reduced tissue damage and inflammatory cell infiltration in treated groups compared to controls. Conclusion: The findings suggest that these plant extracts possess potent anti-inflammatory effects when formulated into stable, topical products. The 10% extract cream formulation was particularly effective, offering a promising alternative for managing inflammation with fewer side effects.

Curcumin Nanostructured Drug Delivery Induces the Anti-cancer and Anti-inflammatory activity In Vitro and In Vivo

Background: The therapeutic potential of plant-derived pharmaceuticals is often limited by poor bioavailability and rapid metabolism. This study aims to enhance the pharmacological effects of curcumin, a bioactive compound from plants, through the development of novel drug delivery systems (NDDS). Methods: Various NDDS, including liposomes, nanoparticles, and microspheres, were formulated to encapsulate curcumin. We evaluated their drug release characteristics, encapsulation efficiency, and particle size in vitro. The pharmacological effectiveness of these formulations was assessed using cytotoxicity assays on human cancer cell lines and anti-inflammatory models in rats. Results: The liposomal formulation achieved an encapsulation efficiency of 85% with an average particle size of 150 nm. The nanoparticle and microsphere formulations demonstrated encapsulation efficiencies of 78% and 90%, with particle sizes of 200 nm and 10 µm, respectively. All formulations exhibited a sustained release profile, with 70% of curcumin released over 24 hours. Cytotoxicity studies revealed that the NDDS formulations significantly increased cell death in cancer cells, with the liposomal formulation showing a 50% increase in apoptosis. In vivo experiments indicated a 60% reduction in paw edema with the nanoparticle formulation compared to the control group, highlighting enhanced anti-inflammatory effects. Conclusion: The findings of this study suggest that NDDS significantly improve the encapsulation efficiency, sustained release, and pharmacological activity of curcumin. This approach demonstrates the potential of NDDS to enhance the clinical efficacy of plant-derived drugs, leading to improved therapeutic outcomes.

Sulfated polysaccharide extracted from the alga Gracilaria domingensis modified with propionic anhydride negatively modulates acute inflammation and experimental hypernociception

Sulfated polysaccharides (PLSs) from marine algae represent a broad class of compounds with pharmacological interest, due to their therapeutic properties. PLSs have hydrophilic chains containing various chemical groups of several compositions that differ structurally and in their physicochemical and biological effects. However, this hydrophilic nature of PLSs is also responsible for some limitations in the use of these compounds. To overcome these disadvantages, PLSs can be chemically modified by grafting groups that can give the compound a more hydrophobic nature. In the present study, the PLS from Gracilaria domingensis was modified with propionic anhydride (PLS-AP) and underwent complementary characterizations by scanning electron microscopy, X-ray diffraction, infrared spectral analysis and elemental analysis. The reaction with propionic anhydride increased crystallinity and produced a chemically modified polysaccharide with new carbon, hydrogen and sulfur groups. The new characteristic of the compound may have added interesting properties to PLS, such as increased stability, amphiphilic nature and increased sulfate content, which in red marine algae SPSs produce biological activity. Regarding biological properties, PLS-AP (2.5 mg/kg) significantly reduced paw edema induced by carrageenan, histamine, serotonin, bradykinin and prostaglandin E2, as well as improved microscopic tissue damage criteria. The modified compound was also able to significantly decrease neutrophil migration, myeloperoxidase, and malondialdehyde concentrations and preserved glutathione levels in peritoneal fluid during induced peritonitis. Additionally, in antinociceptive tests, PLS-AP reduced the number of contortions induced by acetic acid and the response time to formalin-induced paw licking. Thus, PLS-AP may be a promising substance to treat inflammatory conditions.

Anti-inflammatory and antinociceptive effects of Aloysia gratissima leaves essential oil: An in vivo study

Background and aimAloysia gratissima is used in popular medicine as an analgesic and sedative. However, studies on its biological activities are still scarce. Therefore, this work aimed to evaluate the antinociceptive and anti-inflammatory effect of A. gratissima leaves essential oil (OAG) in mice. Experimental procedureThe OAG was obtained by hydrodistillation and its composition was determined by gas chromatography-mass spectrometry. The sesquiterpenes pinocamphone, β-pinene, and guaiol were the major constituents of OAG. The effect of OAG (1, 10, and 30 mg/kg, p.o.) was assessed by pre-treating male mice 1h before the formalin assay, carrageenan-induced peritonitis test, or the paw edema induced by arachidonic acid (AA). The acute toxicity of OAG (2000 mg/kg, p.o.) was also investigated. Results and conclusionThe minimum effective dose of OAG in the formalin test was 1 mg/kg. This dose did not affect the locomotor activity of mice. The OAG decreased the number of leukocytes/mm³ in the peritoneal exudate of mice and reduced paw edema 45 min after the arachidonic acid injection. OAG treatment elicited a reduction in NPSH levels in the paw tissue and increased NPSH levels in mice blood plasma and did not cause mice mortality. The OAG is devoid of acute toxicity and shows anti-inflammatory activity, which can be related to the presence of pinocamphone, guaiol, and β-pinene and is mediated, at least in part, by mechanisms that involve the participation of NPSH.

Therapeutic potential of sulfated glycosaminoglycan from seafood Asian green mussel (Perna viridis): Insights from an in vivo study

The Asian green mussel, Perna viridis, is widely consumed as seafood throughout the coastal regions of the Indo-Pacific area owing to its significant pharmaceutical and biomedical benefits. A pharmacologically active (1 → 3)/(1 → 4) linked sulfated glycosaminoglycan (PVP-2) with β-(1 → 3)-GlcNSp, and α-(1 → 4)-GlcAp units was isolated from P. viridis. PVP-2 (at 1–10 μg/mL) demonstrated a suppression of nitric oxide (NO) secretion in lipopolysaccharide-induced RAW 264.7 cells. Notably, PVP-2 at 5 μg/mL effectively restored NO levels (0.32 μg/mL) to homeostasis by downregulating excessive production (1.22 μg/mL). Furthermore, PVP-2 (at 22 mg/kg body weight) showed effective reduction of carrageenan-induced paw edema (82% inhibition at 5 h) in time dependent manner. This reduction was found to be comparable with standard treatment (87% inhibition of paw edema at 5 h). Treatment with PVP-2 (at 110 mg/kg body weight) resulted substantial inhibition of formalin-induced paw edema up to 10 days. At the end of the 10th day, the reduction in paw thickness was significantly greater (a four-fold increase) in the PVP-2 treated group compared to the formalin-induced group. Furthermore, PVP-2 displayed potent anti-inflammatory effect by attenuating cyclooxygenases (COX-1, 2) and 5-lipoxygenase (5-LOX) (IC50 < 2 mg/mL) enzymes with a higher selectivity index (IC50 COX-1/IC50 COX-2 ∼ 1.7) towards inducible pro-inflammatory COX-2. Therefore, inhibition of the NO production along with the reduction of paw edema, highlights the therapeutic potential of sulfated glycosaminoglycan from seafood Asian green mussel, as a naturally derived functional food to mitigate inflammation related disorders.

Exploration for the opioidergic, GABAergic and histaminergic potentials of synthesized Schiff’s base derivatives: An in-vivo approach

Herein, five Schiff’s base analogs (designated as AK1 to AK5) were synthesized and screened for their analgesic and anti-inflammatory efficacies. All compounds exhibited analgesic activity at selected doses from 45.31 % to 75.75 %, while the standard drug diclofenac sodium produced result as 86.33 %. Compounds AK1, AK3, AK4 and AK5 were found significantly P<0.001 effective at a dose of 25 mg/kg body weight (b.w). Similarly, in tail immersion test the produced percentage activity were in range from 40.19 % to 62.35 %. in which the compounds AK1, AK2, AK4 and AK5 were significantly P<0.01 effective at dose 12.5 mg/kg b.w, while at this dose significance level of efficacy of AK3 was P<0.05. Similarly, at administering doses of 25 mg/kg b.w all compounds were effective with significance level P<0.001, n = 8. Administration of the synthesized Schiff’s bases at the tested doses significantly reduced paw edema as compared to control. Results of paw edema at 3rd hour was significant P<0.001. AK4 and AK5 were subjected to mechanistic approaches by GABAergic, opiodergic and histaminergic pathways. In GABAergic pathway bicuculline caused a partial reversal of writhings responses indicating the involvement of GABA receptors and therefore the tested compounds may have act through GABAergic pathway. The naloxone caused a mild reversal in the tail immersion test and indicated that some other mechanisms are additionally involved in mode of action of these compounds. Additionally a mild response was observed while studying its action involving histaminergic pathway.

Analgesia by fascia manipulation is mediated by peripheral and spinal adenosine A1 receptor in a mouse model of peripheral inflammation

The role of adenosine receptors in fascial manipulation-induced analgesia has not yet been investigated. The purpose of this study was to evaluate the involvement of the adenosine A1 receptor (A1R) in the antihyperalgesic effect of plantar fascia manipulation (PFM), specifically in mice with peripheral inflammation. Mice injected with Complete Freund’s Adjuvant (CFA) underwent behavioral, i.e. mechanical hyperalgesia and edema. The mice underwent PFM for either 3, 9 or 15 min. Response frequency to mechanical stimuli was then assessed at 24 and 96 h after plantar CFA injection. The adenosinergic receptors were assessed by systemic (intraperitoneal, i.p.), central (intrathecal, i.t.), and peripheral (intraplantar, i.pl.) administration of caffeine. The participation of the A1R was investigated using the 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), a selective A1R subtype antagonist. PFM inhibited mechanical hyperalgesia induced by CFA injection and did not reduce paw edema. Furthermore, the antihyperalgesic effect of PFM was prevented by pretreatment of the animals with caffeine given by i.p., i.pl., and i.t. routes. In addition, i.pl. and i.t. administrations of DPCPX blocked the antihyperalgesia caused by PFM. These observations indicate that adenosine receptors mediate the antihyperalgesic effect of PFM. Caffeine’s inhibition of PFM-induced antihyperalgesia suggests that a more precise understanding of how fascia-manipulation and caffeine interact is warranted.

Evaluation of wound healing and anti-inflammatory activity of hydro-alcoholic extract and solvent fractions of the leaves of Clerodendrum myricoides (Lamiaceae) in mice.

Wounds significantly affect people's quality of life and the clinical and financial burden of healthcare systems around the world. Many of the current drugs used to treat wounds have problems such as; allergies and drug resistance. Hence, the exploration of new therapeutic agents from natural origin may avert this problem. Clerodendrum myricoides have long been used to treat wounds in Ethiopia. Despite this, nothing has so far been reported about the wound healing and anti-inflammatory activity of C. myricoides. This study aimed to evaluate the wound healing and anti-inflammatory activity of 80% methanol extract and solvent fractions of C. myricoides leaves in mice. Leaves of C. myricoides were extracted using the maceration technique. The extract was formulated as 5% and 10% w/w ointments. The wound healing activity of the extract was evaluated using excision, incision, and burn wound models whereas the healing activities of solvent fractions were evaluated using the excision wound model. A carrageenan-induced paw edema model was used for the anti-inflammatory test. In the dermal toxicity test, 2000 mg/kg of 10% extract was found to be safe. In excision and burn wound models, treatment with 10% and 5% extract showed a significant (p<0.001) wound contraction. Solvent fractions of the extract significantly reduced wound contraction. A significant reduction in periods of epithelialization and favorable histopathology changes were shown by extract ointments. In incision wounds, 10% (p<0.001) and 5% (p<0.01) extracts significantly increase skin-breaking strength. After one hour of treatment, 400 mg/kg (p<0.001) and 200 mg/kg (p<0.05) showed significant reduction in paw edema. Results of this study indicate that 80% methanol extract and the solvent fraction of the leaves of C. myricoides possess wound-healing and anti-inflammatory activity and support traditional claims.

Development and Assessment of Helicteres isora Extract Loaded Phospholipid Complex for Anti-Nociceptive Activity

Its primary objective is to assess the efficacy of a phospholipid complex formulation containing an extract of Helicteres isora in reducing inflammation, to determine its progress and evaluation. An Indian Screw Tree, also known as Helicteres isora, is an extremely healing plant. In addition to improving solubility and stability, the phospholipid complex formulation also increases bioavailability and efficacy. This formulation was created by combining Helicteres isora extract with phospholipids using a technique known as phospholipid complexation. Several parameters were evaluated to evaluate the formulation, including particle size, zeta potential, encapsulation efficiency, and drug release profile. Using both in vitro and in vivo models, the anti-inflammatory properties of a phospholipid complex formulation of Helicteres isora were assessed. The experiments were conducted using a rat model of carrageenan-induced paw edema. In this work, phospholipid complex formulations were shown to have improved physicochemical properties, including smaller particle sizes and higher encapsulation rates. According to the results of the in vivo evaluation, phospholipid complex formulations significantly reduced paw edema compared with plain extracts, indicating improved anti-inflammatory activity. The bioavailability, anti-inflammatory activity, and bioavailability of Helicteres isora extract are enhanced by the phospholipid complex formulation.

Grape Pomace Polyphenols Reduce Acute Inflammatory Response Induced by Carrageenan in a Murine Model.

Grape pomace (GP), a by-product of wine production, contains bioactive polyphenols with potential health benefits. This study investigates the anti-inflammatory properties of a polyphenolic fraction derived from GP, obtained by ultrasound-microwave hybrid extraction and purified using ion-exchange chromatography. In the inflammation model, mice were divided into six groups: intact, carrageenan, indomethacin, and three GP polyphenols treatment groups. Paw edema was induced by subplantar injection of carrageenan, and the GP polyphenols were administered intraperitoneally at doses of 10, 20, and 40 mg/kg. The anti-inflammatory effect was evaluated by measuring paw volume, and expression of inflammatory markers: cyclooxygenase-2 (COX-2), myeloperoxidase (MPO), and cytokines (IL-1β and IL-6), along with lipid peroxidation levels. The GP polyphenols significantly reduced paw edema and expression levels of COX-2, MPO, and cytokines in a dose-dependent manner effect, with the highest dose showing the greatest reduction. Additionally, lipid peroxidation levels were also decreased by GP polyphenols treatment at doses of 10 and 20 mg/kg. These findings suggest that ultrasound-microwave extraction combined with amberlite purification proved to be effective in obtaining a polyphenolic-rich fraction from GP. Thus, GP polyphenols may serve as a natural anti-inflammatory and antioxidant agent for treating inflammation and oxidative stress-related diseases.

Assessment of acute toxicity, genotoxicity, and anti-inflammatory activity of SteLL, a lectin from Schinus terebinthifolia Raddi. Leaves, in mice

Ethnopharmacology relevanceSchinus terebinthifolia Raddi (Anacardiaceae), known as Brazilian pepper tree, stands out as a medicinal plant widely used in traditional medicine. The leaves are popularly used as anti-inflammatory agent and to relieve inflammatory conditions such as bronchitis, ulcers, and wounds, for example. Aim of the studyThe present study evaluated the acute toxicity, genotoxicity, and anti-inflammatory activity of S. terebinthifolia leaf lectin (SteLL) in mice (Mus musculus). Materials and methodsIn the acute toxicity assay, the animals were treated intraperitoneally (i.p.) or orally (per os) with a single dose of 100 mg/kg. Genotoxicity was assessed by the comet and micronucleus assays. Carrageenan-induced peritonitis and paw edema models were used to evaluate the anti-inflammatory effects of SteLL (1, 5 and 10 mg/kg, i.p.). ResultsNo animal died and no signs of intoxication or histopathological damage were observed in the acute toxicity assay. Genotoxic effect was not detected. In peritonitis assay, SteLL reduced in 56–69% leukocyte migration to the peritoneal cavity; neutrophil count decreased by 25–32%, while mononuclear cell count increased by 67–74%. SteLL promoted a notable reduction of paw edema after 4 h (61.1–63.4%). Morphometric analysis showed that SteLL also decreased the thickness of epidermal edema (30.2–40.7%). Furthermore, SteLL decreased MPO activity, plasma leakage, NO release, and modulated cytokines in both peritoneal fluid and paw homogenate. ConclusionSteLL did not induce acute toxicity or genotoxicity in mice and stands out as a promising candidate in the development of new phytopharmaceuticals with anti-inflammatory action.

Sub-acute toxicity, antinociceptive and anti-inflammatory effects of Mucuna pruriens L. leaves in experimental rodents

Ethnopharmacological relevanceMucuna pruriens L is a wild and cultivated leguminous plant which have been used as an aphrodisiac, diuretic, nerve tonic, and antiarthritic agent. AimTo evaluate the toxicity, antinociceptive, and anti-inflammatory activities of M. pruriens (EEMP) ethanol extract in experimental models. MethodsM. pruriens dried leaves were extracted using aqueous ethanol (30:70). Tests for acute and subacute toxicity were conducted on rats and mice. Mice were used in hotplate, acetic acid, and formalin models to test the antinociceptive activity of EEMP. The anti-inflammatory properties of EEMP (25, 100, and 400 mg/kg) were assessed egg albumin, carrageenan, and formalin-induced oedema models. The study examined the anti-inflammatory mechanism of EEMP (25–400 mg/kg) in rats with an air pouch caused by carrageenan. Air pouch exudates were tested for total leucocytes and differential cell counts, TNF-α, IL-6, myeloperoxidase activity, malondialdehyde, nitrites, and reduced glutathione (GSH). ResultsThe acute oral toxic dose of EEMP is greater than 2000 mg/kg. There were no significant behavioral, hematological or biochemical alterations seen after 14-days repeated administration of EEMP (200, 400 and 800 mg/kg) in mice. The EEMP demonstrated significant antinociceptive activity in hotplate, acetic acid and formalin-induced nociception in mice. The EEMP significantly and dose dependently reduced paw oedema at 2, 4 and 96 h in the egg-albumin, carrageenan- and formalin-induced paw oedema, respectively. Exudates volume, inflammatory cell counts, TNF-α, IL-6, myeloperoxidase, malondialdehyde and nitrites were significantly reduced, while GSH increased in carrageenan-air pouch of EEMP-treated rats. ConclusionMucuna pruriens leaves ethanol extract demonstrated good safety profile as well as antinociceptive and anti-inflammatory activity through mechanisms related to inhibition of oxidative stress and pro-inflammatory cytokines as well as lysosomal membrane stability.

Anti-arthritic Activity and Anti-inflammatory Mediators Modulation Effect of Bioactive Traditional Chaturbeeja Churna on Arthritis Experimental Model

Objectives: The purpose of this research was to determine whether or not Chaturbeeja Churnam (CC) had anti-arthritic properties and the effect it has on Wistar rats that have been induced with arthritis using Complete Freund's Adjuvant (CFA). Methods: Injection of 0.2 milliliters of CFA into the sub-plantar surface of the left hind paw resulted in the development of arthritis. The test samples CC-1 and CC-2 were administered to the animals for a period of 21 days in a row. After the arthritis was induced, the rise in swelling that was noticed was observed. The blood samples that were taken were then used in additional testing with a hematology analyzer to determine the number of red blood cells (RBC), white blood cells (WBC), erythrocytes sedimentation rate (ESR), and hemoglobin (Hb). Using rat ELISA kits, the levels of IL-6 and TNF- that were found in the serum were also analyzed. Results: CC showed a significant inhibitory effect in the protein denaturation assay. Results showed that a significant reduction in paw edema was observed in CC-2 treated rats. The maximum anti-inflammatory activity (59.12%) of the CC was noticed at a dose level of 400 mg/kg. The paw edema was restored on day 21 was 4.52 mm for CC-2, which is near to the control group. The arthritis score in treated rats was found to be considerably lower than in the control group i.e. 0.92 for CC-2 and 1.61 for CC-1. A decrease in levels of RBC and hemoglobin was observed in arthritic rats. Inflammation was significantly reduced and serum levels of IL-6 and TNF-α were lowered after treatment with the test drug. Conclusion: It can be concluded from the study that CC possess significant anti-arthritic activity. Furthermore, this condition was linked to a reduction in abnormal humoral immune responses.

Immunomodulatory properties of cholecalciferol in rats with experimentally induced inflammation

The study aimed to investigate anti-inflammatory and immunomodulatory effects of cholecalciferol (vitamin D3) in rats with complete Freund’s adjuvant-induced arthritis (AIA) and lipopolysaccharide (LPS)-induced inflammation. In the first experiment, rats were treated with cholecalciferol 14 days before or from the day of induction of arthritis. In the second set-up, animals received cholecalciferol for 14 days which was followed by LPS injection. TNF (tumour necrosis factor)-alpha, IL (interleukin)-1β, TGF (transforming growth factor)-β1 levels were measured by enzyme linked immunosorbent assay (ELISA). Cholecalciferol treatment reduced paw oedema and ankle joint diameter in AIA. Significantly lower IL-1β concentrations were found in cholecalciferol-treated arthritic rats. In LPS-challenged rats, cholecalciferol markedly lowered serum TNF-α, whereas an elevation in IL-1β concentrations was observed. Cholecalciferol slightly increased TGF-β1 serum concentration in arthritic rats and non-significantly reduced its level in LPS-challenged animals. Our findings showed that cholecalciferol exerts immunomodulatory properties which probably contribute to its anti-inflammatory effect.

Anti-Vasculogenic, Antioxidant, and Anti-Inflammatory Activities of Sulfated Polysaccharide Derived from Codium tomentosum: Pharmacokinetic Assay.

The purpose of this paper was to investigate the anti-inflammatory and anti-angiogenic activities of sulfated polysaccharide from C. tomentosum (PCT) using carrageenan (CARR)-induced paw edema in a rat model and anti-vasculogenic activity on a chorioallantoic membrane assay (CAM) model. Based on in vitro tests of anti-radical, total antioxidant, and reducing power activities, PCT presents a real interest via its antioxidant activity and ability to scavenge radical species. The in vivo pharmacological tests suggest that PCT possesses anti-inflammatory action by reducing paw edema and leukocyte migration, maintaining the redox equilibrium, and stabilizing the cellular level of several pro-/antioxidant system markers. It could significantly decrease the malondialdehyde levels and increase superoxide dismutase, glutathione peroxidase, and glutathione activities in local paw edema and erythrocytes during the acute inflammatory reaction of CARR. PCT pretreatment was effective against DNA alterations in the blood lymphocytes of inflamed rats and reduced the hematological alteration by restoring blood parameters to normal levels. The anti-angiogenic activity results revealed that CAM neovascularization, defined as the formation of new vessel numbers and branching patterns, was decreased by PCT in a dose-dependent manner, which supported the in silico bioavailability and pharmacokinetic findings. These results indicated the therapeutic effects of polysaccharides from C. tomentosum and their possible use as anti-proliferative molecules based on their antioxidant, anti-inflammatory, and anti-angiogenic activities.

The Nociceptive and Inflammatory Responses Induced by the Ehrlich Solid Tumor Are Changed in Mice Healed of Plasmodium berghei Strain ANKA Infection after Chloroquine Treatment.

Comorbidities that involve infectious and noninfectious diseases, such as malaria and cancer, have been described. Cancer and malaria induce changes in the nociceptive and inflammatory responses through similar pathophysiological mechanisms. However, it is unclear whether malaria and antimalarial treatment can change the inflammatory and nociceptive responses induced by solid cancer. Therefore, the present study experimentally evaluated the effect of infection by Plasmodium berghei strain ANKA and chloroquine treatment on the nociceptive and inflammatory responses induced by the solid Ehrlich tumor in male BALB/c mice. On the 1st experimental day, mice were infected with Plasmodium berghei and injected with tumor cells in the left hind paw. From the 7th to the 9th experimental day, mice were treated daily with chloroquine. The parasitemia was evaluated on the 7th and 10th days after infection. On the 11th experimental day, mice were evaluated on the von Frey filament test, the hot plate test, and the paw volume test. At the end of the experimental tests on the 11th day, the peripheral blood of all mice was collected for dosing of IL-1β and TNF-α. The blood parasitemia significantly increased from the 7th to the 10th day. The chloroquine treatment significantly decreased the parasitemia on the 10th day. The presence of the tumor did not significantly change the parasitemia on the 7th and 10th days in mice treated and nontreated with chloroquine. On the 11th day, the mechanical and thermal nociceptive responses significantly increased in mice with tumors. The treatment with antimalarial significantly reduced the mechanical nociceptive response induced by tumors. The hyperalgesia induced by tumors did not change with malaria. The mechanical and thermal hyperalgesia induced by the tumor was significantly reduced in mice treated and healed from malaria. On the 11th day, the volume of the paw injected by the tumor was significantly increased. The mice treated with chloroquine, infected with malaria, or healed of malaria showed reduced paw edema induced by the tumor. Mice with tumors did not show a change in IL-β and TNF-α serum levels. Mice with tumors showed a significant increase in serum levels of IL-1β but not TNF-α when treated with chloroquine, infected with malaria, or healed of malaria. In conclusion, the results show that malaria infection and chloroquine treatment can influence, in synergic form, the nociceptive and inflammatory responses induced by the solid tumor. Moreover, the mechanical antinociception, the thermal hyperalgesia, and the antiedema effect observed in mice treated with chloroquine and healed from malaria can be related to the increase in the serum level of IL-1β.