Paw Edema Volume Research Articles

Self-Nanoemulsifying Drug Delivery System (SNEDDS) of piroxicam

Piroxicam is a non-steroidal anti-inflammatory drug (NSAID) that is commonly used for arthritis, gout, and other musculoskeletal disorders. Piroxicam is poorly soluble in water and according to the biopharmaceutical drug classification system (BCS) is classified as a Class II drug with good permeability but poor dissolution. The self-nanoemulsifying drug delivery system (SNEDDS) has been extensively employed to improve the dissolution and absorption of water-insoluble drugs within the gastrointestinal tract, leading to enhanced oral bioavailability and increased therapeutic effect of the loaded drugs. Therefore, the present study aims to evaluate the anti-inflammatory activity of piroxicam-loaded SNEDDS as compared to conventional piroxicam suspension that was observed in male Wistar strain rats. The SNEDDS was tailored from a mixture of oleic acid, tween 80, and propylene glycol. Twenty male Wistar strain rats (aged 2-3 months, weighed 150-250g) were selected and were divided equally into 4 different groups receiving 1% PVP, SNEDDS carrier, piroxicam suspension (1.8 mg/Kg BW), and SNEDDS piroxicam (1.8 mg/Kg BW). Acute inflammation was induced by a carrageenan-induced paw edema model where the carrageenan was injected sub plantar in the hind paw of the rats to induce edema. Several parameters including paw edema volume, AUC 0-6 , and percent anti-inflammatory effect, were measured to evaluate the anti-inflammatory activity experienced in each group. At the end of this study, the piroxicam SNEDDS group significantly demonstrated better protection from paw edema compared to the piroxicam suspension group (ρ<0.05), suggesting that SNEDDS may enhance the anti-inflammatory activity of piroxicam.

Anti-inflammatory activities of a new VEGF blocker, Conbercept

Background Angiogenesis and inflammation exhibit a mutually reinforcing relationship in many human diseases. Vascular endothelial growth factor (VEGF) is one of the most important proangiogenic mediators. Conbercept is a novel VEGF inhibitor. Method Type II collagen-induced rat rheumatoid arthritis (CIA) model was established to evaluate the anti-chronic inflammation activities of Conbercept. ELISA was used to measure the concentrations of immune factors in the blood of arthritis rats. The xylene-induced ear edema was conducted to evaluate the effect of Conbercept on acute inflammation. Result and discussion Our results showed that Conbercept significantly reduced the paw edema volume and the arthritis index in CIA rats. Furthermore, we found that Conbercept decreased the serum levels of vascular endothelial growth factor (VEGF), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in CIA rats. Xylene-induced ear edema is a widely used method to study acute inflammation. Conbercept significantly inhibited xylene-induced ear edema. Conclusion All results indicate that Conbercept exhibits significant inhibition of acute and chronic inflammation.

EVALUATION OF ANTI-INFLAMMATORY (IN VIVO) ACTIVITY OF ARIFLEX LINIMENT IN COMPARISON WITH DICLOFENAC GEL IN CARRAGEENAN INDUCED RAT PAW EDEMA MODEL

Objective: The present study was conducted to evaluate anti-inflammatory activity of Ariflex liniment (conceptualized and developed by Ari Healthcare Pvt. Ltd) in comparison with Diclofenac gel in carrageenan induced rat paw edema model.
 Methods: Wistar rats of either sex weighing 150-180 g were taken and divided into 3 groups with 6 animals in each group i.e. Group 1 (Controlled Group), Group 2 (Diclofenac gel) and Group 3 (Ariflex liniment). The study drugs were topically applied 30 min prior to carrageenan injection. After 30 min 1% w/v of 0.05 ml carrageenan was injected subcutaneously in the paw. The paw was marked with ink at the level of lateral malleolus and immersed in mercury up to the lateral malleolus mark. The paw volume was measured plethysmographically, immediately after injection i.e. on 0 min, and then on 30 min,1h, 2h,3h, 4h and 5hr after injection.
 Results: Diclofenac gel sodium treated group showed significant inhibition (p<0.01) of paw edema at 30 min, 1, 2, 3, 4 and 5th hrs as compared to control group. Ariflex Liniment showed significant inhibition (p<0.05) of paw edema at 30 min, 1, 2, 3, and 4th hrs as compared to the control group. Group treated with Ariflex Liniment did not show any significant decrease in paw edema volume at 5th hrs when compared to the control group.
 Conclusion: Ariflex Liniment possesses anti-inflammatory activity.

Cedrol from Ginger Ameliorates Rheumatoid Arthritis via Reducing Inflammation and Selectively Inhibiting JAK3 Phosphorylation.

Ginger, as a food spice, is widely applied due to its extensive effects. Cedrol (CE) found in ginger is a sesquiterpene with anti-inflammatory activity. The objective of this research is to discuss the efficacy of CE on ameliorating rheumatoid arthritis (RA). CE inhibited chronic inflammation and pain in a dose-dependent manner accompanied by rapid onset and long duration. Besides, CE treatment effectively ameliorated the paw edema volume and arthritis score with no significant effect on body weight. Organ index, T-cell and B-cell proliferation, histopathology, and immunohistochemistry demonstrated that CE had immunological enhancement and attenuated RA effects. Remarkably, inhibition of phosphorylated-JAK3 protein, thereby abating the secretion of pro-inflammatory cytokines and inflammation-related mediators, was involved in the potential mechanism of CE efficiency through forming a hydrogen bond with ARG953 and ILE955 in the JAK3 active pocket. At the same time, the pharmacokinetic results showed that the absolute bioavailability of CE at 20, 40, and 80 mg/kg was 30.30, 23.68, and 16.11%, respectively. The current results offered clues for mastering the ameliorated RA of CE and further perfected the effective substance basis on the anti-inflammatory effect of ginger, which was beneficial for further applications.

In vivo anti-inflammatory effects of Prasiola japonica ethanol extract

Abstract The aim of this study was to investigate the efficacy of Prasiola japonica ethanol extract (Pj-EE) in various mouse inflammation models. For edema mice models, eight-week-old female ICR mice were orally administrated with Pj-EE (25 and 50 mg/kg) for one week, before ear edema induction with carrageenan or xylene. The weight, thickness, and volume of paw and ear edema were decreased in Pj-EE-treated mice after 3 h of edema induction. The mRNA expression levels of iNOS, COX-2, IL-6, IL-1β, and IFN-γ were decreased in Pj-EE-treated conditions. The phosphorylation forms of IκBα and IKKα/β were suppressed by Pj-EE at 50 mg/kg. The effect of Pj-EE on gastrointestinal disorder was examined in HCl/EtOH-induced gastritis model. Oral administration of Pj-EE ameliorated HCl/EtOH-stimulated gastric ulcers. In addition, Pj-EE reduced gene expressions of iNOS, COX-2, IL-6, and IL-1β. Alverine, one of ingredient compounds in Pj-EE, was also confirmed to show anti-edema activity, in vitro, and in vivo. Conclusively, therapeutic effects of Pj-EE were demonstrated in various inflammatory mouse models, suggesting a possibility as a promising anti-inflammatory functional food.

Anti-inflammatory, anti-nociceptive and anti-oxidant activities of carvacrol containing leaf extracts of edible Indian borage plant Plectranthus amboinicus: an in vivo and in vitro approach

Inflammation remains a complex process in host defense system and the pathology caused by it remains unsolved till date. Several steroidal and non-steroidal anti-inflammatory drugs in current use to treat inflammatory diseases elicit side effects in longer run. Hence, in order to counteract these outcomes, a pharmacognistic study using a Lamiaceae plant, Plectranthus amboinicus has been focused in the present study. P. amboinicus commonly known as Indian borage has been used in folk medicine for years in treating numerous diseases. It is well known for the presence of major phytochemical constituents which possess anti-inflammatory properties. Assessment of biochemical constituents and molecular mechanisms behind the anti-inflammatory property of P. amboinicus leaves were carried out in in vivo and in vitro conditions. In vivo studies of formalin-induced nociception and paw edema in mice and for in vitro condition lipopolysaccharide-induced inflammation using IC-21 macrophage cells were performed. Aqueous and ethyl acetate leaf extracts of P. amboinicus were analyzed for its phytochemical constituents. Variations in phytochemical components were noticed in GC-MS analysis. The carvacrol containing ethyl acetate extract exhibited higher anti-nociception in terms of lower paw licking time in the later phase of nociception and lowered hind paw edema volume up to 35%. The biochemical analysis revealed that the oxidative stress markers such as malondialdehyde and antioxidant enzymes have been modulated upon pretreatment with both extracts and also modulated the expression of inducible nitric oxide synthase, cyclooxygenase 2, Interleukin-1β, histamine 1 receptor genes and nuclear factor kappa B protein. In addition, nitric oxide inhibitory effect was observed in P. amboinicus treated IC-21 macrophages. Therefore, the molecular mechanism put forth in this study provides insights that the presence of carvacrol in ethyl acetate extract enhances anti-inflammatory activity.

Anti Inflammatory Potential of Euphoria Hirta L. Leaves In Jaipur Region

Introduction: Euphorbia hirta Linn. (E.hirta L.) is a medicinal herb belonging to the family Euphorbiaceae. It is commomly known as Asthma plant, Duddhi, Bara duddhi. It has been claimed for the various medicinal properties such as inflammation, diarrhoea, bronchitis, kidney stones, peptic ulcer, menstrual problems etc.
 Objective: the goal of our research work is to assessing the anti inflammatory activity of E.hirta L. leaves in regards to phytochemical studies.
 Methods: The method carragennan induced paw edema in rats was used to assess the anti inflammatory activity of aqueous extract of E.hirta L. leaves. The extract was obtained by maceration method and the analysis of phytochemicals was carried out by performing different chemical test in laboratory. Crude aqueous extract was given orally at different doses of 100mg/kg, 300mg/kg and 500mg/kg in wistar albino rats 30mins before carragennan injection. Ibuprofen (50mg/kg) was taken as reference drug. The volume of paw edema was measured by using plethysmometer at 1, 2 and 3 hr after carragennan administration.
 Results: The preliminary phytochemical study reveals the availibility of flavonoids, terpenoids, sterols, glycosides, tannins etc in different solvents of crude drug extract. The anti inflammatory effect of crude drug extract was exhibited a remarkable dose dependent reduction in paw edema volume. The inhibitory effect was highest at 500mg/kg dose of drug. Extract and ibuprofen showed 52% and 66% inhibition of paw edema respectively, at 3hr after carragennan administration.
 Conclusion: E.hirta L. leaves aqueous extract has a strong anti inflammatory activity. These consequences help in the traditional uses of the plants and in the development of new treatments.

Syzygium cumini(L.),Skeels fruit extracts: In vitro and in vivo anti-inflammatory properties

Ethnopharmacological relevanceSyzygium cumini (L.) Skeels is an important medicinal plant utilized in the health care systems of Pakistan, India, Sri Lanka, and Bangladesh. S. cumini have been used to treat renal issues, indigestion, diabetes, dysentery, and employed in folk medicine to treat inflammations. It is known to anticipate antioxidant, anti-inflammatory, anticancer, anti-diabetic, anti-bacterial, antifungal, activities, and radioprotective activities. Material and methodsWe examined the in vitro anti-inflammatory activities of S. cumini fruit extracts, evaluated using membrane stabilization, egg albumin denaturation, and bovine serum albumin denaturation assays. In vivo anti-inflammatory activity was also assessed, using murine models of carrageenan, formaldehyde, and PGE2 induced paw edema. Fractionation of active extracts was performed using HPLC, followed by LC-ESI-MS/MS analysis to identify the bioactive compounds responsible for anti-inflammatory activity. ResultsThe crude methanolic extract showed stronger in vitro and in vivo anti-inflammatory activities compared to other extracts. The most potent effects were observed in the formaldehyde induced paw edema assay wherein methanolic extract and standard indomethacin induced 72% and 88% inhibition against paw edema volume in comparison to control (normal saline) respectively. In the bovine serum albumin denaturation assay the methanolic extract induced 82% inhibition against denaturation as compared to control (phosphate buffer) while standard diclofenac sodium induced 98% inhibition. In contrast, 50% v/v MeOH:H2O or 100% dichloromethane extracts displayed moderate to weak effects in the anti-inflammatory models. HPLC fractionation provided 6 active sub-fractions, four (MF2, MF3, MF6, MF7) from the 100% methanolic extract and two (HAF1, HAF3) from the 50% methanolic extract. The MF2, MF7, and HAF1 sub-fractions displayed potent activity in all studied in vitro assays. LC-ESI-MS-MS analysis tentatively identified delphinidin 3-glucoside, peonidin-3,5-diglucoside, gallic acid, liquitrigenin, scopoletin, umbelliferon, and rosmanol from the 100% methanolic fractions. Myricetin, catechin, quinic acid, chlorogenic acid, ellagic acid, gallic acid, and caffeic acid were identified in the 50% methanolic fractions. ConclusionsThese results demonstrate that S. cumini fruit extracts are a rich source of bioactive compounds that are worthy of further investigation as leads for anti-inflammatory drug discovery.

Scientific Evaluation of anti-inflammatory potential of Macrotyloma uniflorum seeds extracts

Phytochemicals possessing the antioxidant properties naturally present in food attract a greater interest to healthcare researchers due to their desirable health effects on human health as they can be explored for protection against oxidative deterioration. Macrtotyloma uniflorum is a leguminous plant belonging to the family Fabaceae and commonly known as Horse gram. Aqueous and ethanol extracts of seeds of Macrotyloma uniflorum were evaluated for their anti-inflammatory effects using the scientific protocol on experimental rats. Extraction was carried out using the cold maceration method, and the anti-inflammatory activity was evaluated using a digital plethysmometer in the experimental rats injected with carrageenan to produce paw edema. Preliminary phytochemical studies confirmed the presence of various bioactive compounds such as alkaloids, glycosides, carbohydrates, proteins and amino acids, terpenoids, tannins, and phenolic compounds in both extracts while flavonoids were found only in ethanol extract. Both extracts of M. uniflorum seeds (200 mg/ml) significantly (p<0.01) reduced the paw edema volume induced by carrageenan. The ethanol extract of M. uniflorum seeds exhibited more potent anti-inflammatory activity than water extract, that might be due to the presence of flavonoids in ethanol extract. The activity of the extracts was compared with diclofenac sodium (10mg/kg b.wt.) as a reference drug. From the results, it may be suggested that the antioxidative potential of phenolic constituents and flavonoids is the primary factors for the anti-inflammatory activity of M. uniflorum seeds extracts.

Antioxidant, Anti-Inflammatory, and Analgesic Activities of Aqueous Extract of Diploknema butyracea (Roxb.) H.J. Lam Bark.

Diploknema butyracea (Roxb.) H.J. Lam is a multipurpose tree used by the Nepalese indigenous people for medicinal purposes such as rheumatism, asthma, and ulcer and other purposes such as cooking and lighting. However, there is no scientific evidence for the medicinal uses of this plant. The present study aimed to explore the phytochemical constituents, estimate the total phenolic content, evaluate antioxidant activity, and investigate the in vivo anti-inflammatory and analgesic activities of aqueous extract of Diploknema butyracea (Roxb.) H.J. Lam bark (ADBB). Phytochemical screening was performed using standard methods. The total phenolic content was determined using the Folin–Ciocalteu method. The in vitro antioxidant activity was determined using 2, 2-diphenyl-1-picrylhydrazyl radical scavenging assay and nitric oxide radical scavenging assay. For the in vivo studies, the plant extract was given in three different doses (50, 100, and 200 mg/kg body weight) to male albino Wistar rats. Anti-inflammatory and analgesic studies were carried out using the carrageenan-induced rat paw edema and the hot plate method, respectively. Results revealed the presence of different phytoconstituents such as flavonoids, tannins, glycosides, terpenoids, and carbohydrates together with a considerable amount of phenolic compounds. Antioxidant assays indicated the potent antioxidant activity of the plant extracts. The higher dose of D. butyracea (200 mg/kg) exhibited a maximum and significant inhibition (53.20%) of rat hind paw edema volume at 4 h and showed a greater increment in latency time (12.15 ± 1.81 sec) in the hot plate test at 120 min. The present study demonstrated the antioxidant, anti-inflammatory, and analgesic potential of ADBB, which supports its traditional medicinal use.

Evaluation of anti-inflammatory and anti-arthritic property of ethanolic extract of Clitoria ternatea

ObjectiveClitoria ternatea is a well-known bioactive plant used to treat several inflammatory ailments in Ayurvedic system of medicine in India. The present investigation aimed to determine the anti-inflammatory and anti-arthritic activity of ethanolic extract of Clitoria ternatea roots (EECT) in animal models. MethodsThe anti-inflammatory activity of the EECT was evaluated by carrageenan and histamine-induced paw edema. ResultsEECT showed a significant reduction in mean paw edema volume in both carrageenan and histamine-induced inflammation. The efficacy of EECT in rheumatoid arthritis was tested against Freund’s complete adjuvant (CFA) induced arthritic model in Wistar rats. The anti-arthritic effect of EECT was determined by systematic scoring of arthritis symptoms and measuring paw edema. A considerable decrease in paw diameter was observed in the EECT (200 and 400 mg/kg) and diclofenac (10 mg/kg) treated groups after day 7. Diclofenac (10 mg/kg) and EECT (400 mg/kg) showed a significant reduction in paw diameter from day 14 compared with CFA control (P < 0.001). The anti-arthritic activity was also confirmed from the altered biochemical, haematological (Hb, RBC and WBC) and anti-oxidant parameters (SOD, MDA, CAT, and GSH). EECT (400 and 200 mg/kg) also showed a marked inhibition of joint destruction. ConclusionThis study provides a pharmacological rationale for the traditional use of C. ternatea against inflammation and rheumatoid arthritis in India.

Oral delivery of fish oil in oil-in-water nanoemulsion: development, colloidal stability and modulatory effect on in vivo inflammatory induction in mice

To improve the oral absorption of fish oil and test its anti-inflammatory effect, a fish oil nanoemulsion was developed using cis-4,7,10,13,16,19-docosahexaenoic fatty acid as a biomarker for oral administration. The colloidal stability tests of the fish oil nanoemulsion showed an average size of 155.44 nm ± 6.46 (4 °C); 163.04 nm ± 9.97 (25 °C) and polydispersity index 0.22 ± 0.02 (4 °C), 0.21 ± 0.02 (25 °C), indicating systems with low polydispersity and stable droplets. The fish oil nanoemulsion did not alter the cell viability of the RAW 264.7 macrophages and, at a concentration of 0.024 mg/mL, was kinetically incorporated into the cells after 18 h of contact. The nanoemulsion was maintained in the gastrointestinal region for a significantly shorter period of time (p ≤ 0.05) compared to the intake of fish oil in free form. Inflammatory tests demonstrated that nanoemulsion and fish oil showed less (p ≤ 0.05) neutrophil infiltration after 24h of sepsis induction and there was a significant reduction (p ≤ 0.05) in the volume of paw edema in female adult Balb/c mice who received the nanoemulsion diet compared to the other experimental groups (control, formalin, fish oil and sunflower oil). These results indicate that the fish oil nanoemulsion was significantly effective in the dietary conditions tested here, presenting satisfactory responses in the modulation of inflammatory disorders, demonstrating interesting and beneficial nutraceutical effects.

Synthesis and investigation of anti-inflammatory and anticonvulsant activities of novel coumarin-diacylated hydrazide derivatives

A number of novel coumarin derivatives synthesized by the reaction of 3-carbonyl chloride coumarin with some substituted aryl acid hydrazides to investigate their anti-inflammatory and anticonvulsant activities. Carrageenan (0.1 ml of 1%, w/v) was injected subplantarly in the right paw of rats to induce an acute model of inflammation. Anti-inflammatory efficacy was evaluated for 5 hours at 3 different dosages 5, 10, 25 mg/kg. After that, the changes in the level of paw edema volumes and percentage inhibition of all groups were observed and the most effective coumarin derivative was found as N'-(2-hyroxybenzoyl)-2-oxo-2H-chromene-3-carbohydrazide. In addition, N’-(2-oxo-2H-chromene-3-carbonyl)nicotinohydrazide, (E)-N’-(3-(4-hydroxyphenyl)acryloyl)-2-oxo-2H-chromene-3-carbohydrazide, and N’-(5-amino-2-hydroxybenzoyl)-2-oxo-2H-chromone-3-carbohydrazide showed their anti-inflammatory effects in a dose-dependent manner. On the other hand, pentylenetetrazole (PTZ, 80 mg/kg, i.p.)-induced seizure model was used to investigate the anticonvulsant activities of six newly synthesized coumarin derivatives in mice. Hybrid compound of salicylic acid hydrazide and 3-carbonyl chloride coumarin (8d) was found the most promising anticonvulsant agent among all treatment groups according to the onset of seizure and survival rate. Moreover, (E)-N'-cinnamoyl-2-oxo-2H-chromene-3-carbohyrazide (8b) and (E)-N'-(3-(4-hyroxyphenyl)acryloyl)-2-oxo-2H-chromene-3-carbohydrazide (8c) has potential anticonvulsant efficiency in low doses (30 mg/kg). The anticonvulsant effect of these coumarin derivatives may be through enhanced GABA-mediated inhibition in the brain.

Evaluation of the curative role, Anti-inflammatory and anti-oxidative activity of some dietary spices on carrageenan induced paw edema in albino Wistar rats

Background: Inflammation is a major burning problem worldwide and billions of individuals are affected. Some of the spices used daily in Algerian cuisine have been known to possess major anti-inflammatory effects. Turmeric, red pepper, ginger, cinnamon and cumin etc. are a few of the wide spectrum of spices used in Algeria.&#x0D; The aim of the study was to investigate the antiinflammatory effect and anti actvity of some dietary spices in carrageenan induced models of inflammation on Wistar rats.&#x0D; Methods: Albino wistar rats were divided into four groups. Inflammation was induced on the animal by injecting the right hand paw with carrageenan (0.1 ml of 1%). Group 1 was fed with food and water and treated with carrageenan (control) whereas group 2 and 3 treated with different doses (100 and 200 mg/kg/bw) of aqueous extract of some dietary spices with carrageenan, respectively. Group 4 treated with standard drug diclofenac sodium (10 mg/kg b.w., reference drug for inflammation), once for 24 hrs.&#x0D; Results: The content of total phenolic was 137.2±21.6 mg/g and flavonoids 122.3±5.8 mg/g. After 60, 120, 180, 240 and 300 min, the data indicate that some dietary spices 100 and 200 mg/kg was significantly effective reducing paw edema volumes induced by carrageenan compared to control (p &lt;0.01). The levels of serum pro-inflammatory white blood cells, neutrophile, lymphocyte, monocyte, eosinophile, total protein and protein c reactive and total cephalin KADIN and platelts in the control group were significantly increased by carrageenan injection compared with the normal group. The rats pretreated with some spices 100 and 200 mg/kg had significantly lower levels of pro-inflammatory to compare control group. The paw edema in carrageenan-induced rats was considerably reduced by treating with 100 and 200 mg/kg aqueous extract of some dietary spices when compared to the untreated rats (p&lt;0.001).&#x0D; Conclusion : The present results clearly demonstarted that carrageenan significantly increased paw edema whereas some dietary treated rats significantly decreased the paw edema. The study underlines the importance of some of the frequently used spices (Turmeric, red pepper, ginger, cinnamon and cumin) in the treatment of inflammation.

Novel Quinolone Substituted Imidazol-5(4H)-ones as Anti-inflammatory, Anticancer Agents: Synthesis, Biological Screening and Molecular Docking Studies

Background: Quinolones and imidazolones are important heterocyclic moieties which have been reported to possess potent anti-inflammatory and anticancer properties. The activity of these compounds were related to inhibition of nuclear factor-kappaB (NF- κB) which is one of the important targets studied for designing of anti-inflammatory and antitumor drugs. Further, hybrid pharmacophore approach is used in the present study for designing potent molecules. Objectives: Aim of the study is to synthesis a series of quinolone substituted imidazolones and evaluation of their anti-inflammatory and anticancer activity. Methods: Quinolone substituted imidazolones were synthesized by aminolysis of 7-amino-4-methyl-quinoline-2(1H)-one with substituted oxazolones afforded quinolone substituted imidazolones. Structures of synthesized compounds were characterized by spectral techniques and were evaluated for anti-inflammatory activity by carrageenan-induced rat paw oedema test. Differences between control and treatment groups were tested using one way analysis of variance followed by Tukey’s test. Anticancer activity was assessed by evaluating the cytotoxicity of compounds on BT-549 and HeLa, human cancer cell lines by MTT assay. Results: Compounds 3-fluorobenzylidene substituted imidazolonyl quinolone (F3) and 4-phenoxybenzylidene substituted imidazolonyl quinolone (F12) were the most cytotoxic compounds against BT-549 and HeLa cell lines. While 2-chlorobenzylidene substituted imidazolonyl quinolone (F4) and 4-chlorobenzylidene substituted imidazolonyl quinolone (F5) exhibited the highest anti-inflammatory activity. Most of the test compounds exhibited statistically significant inhibition of paw oedema volume when compared to that of control. Conclusion: Molecular docking studies revealed that combination of two pharmacophores was crucial for binding of quinolone substituted imidazol-5(4H)-ones on NF-κB with good correlation between docking score and biological activity.

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.

Clitoria ternatea anthocyanin extract suppresses inflammation in carrageenaninduced rat paw edema via down-regulating genes of phosphoinositide 3-kinase signaling pathway

Inflammation is characterized by an increase in vascular permeability leading to edema formation. Phosphoinositide 3-kinase (PI3K) signaling pathway plays the main role to regulate several key events in the inflammatory response to damage and infection. Our previous in silico study showed that anthocyanin and ternatin flavonoids may offer antiinflammatory potential via molecular docking model. Here, we explored whether Clitoria ternatea anthocyanin extract (CTA) had protective activity against inflammation via regulating gene expression related to PI3Ks in rat edema. CTA was extracted in methanol and acetone using maceration and lyophilization. Edema model was done by injecting carrageenan into rat paw. Oral supplementation of CTA (100, 250, and 500 mg/kg BW) and ibuprofen standard (15 mg/kg BW) was given to rats daily for 7 days. After sample treatment, the right hind paw of the rat was injected with carrageenan to induce edema condition. The ability of CTA to suppress the inflammation in paw edema was measured by quantifying the increased percentage of rat paw volume at 1, 3, and 5 hrs after injection. Rat paw tissue was collected, and gene expression related to PI3Ks, i.e. Akt1, PKB, Ilk, Pdk2, Pik3Ca, and p53 was determined using quantitative PCR (qPCR). Carrageenan showed a time-dependent increase in volume of rat paw starting from injection until the next 5 hrs. It reached maximum volume increase of rat paw at 3 hrs after injection. CTA treatment had a dose-dependent pattern in reducing the edema volume in carrageenan-induced paw edema. At 500 mg/kg BW, CTA significantly suppressed the inflammation in paw edema compared to that of positive control, indicating by the low percentage of paw edema volume at 1, 3, and 5 hrs after carrageenan injection. At gene level, qPCR data showed that CTA significantly down-regulated the expression of genes involved in PI3Ks, such as Akt1, PKB, Ilk, Pdk2, Pik3Ca, and p53 in paw tissues. Thus, CTA may have a protective effect against edema via suppressing genes of PI3Ks.

TO SYNTHESIZE, CHARACTERIZATION AND PHARMACOLOGICAL EVALUATION OF NOVEL SUBSTITUTED ISATIN DERIVATIVES

Series of novel Schiff bases of Isatin the equimolar amines and 5-Dicrboxymethyl (R=COO2Me) substituted isatins (1 mmol of each) were added to 96% w/w ethanol (20 mL) containing 8 drops of glacial acetic acid. The mixture was heated under reflux for 5 h and then cooled to room temperature. The resulting solid was collected by filtration, washed with cold ethanol and dried in open air. The derivatives thus prepared had sufficient analytical purity. anticonvulsant activity performed by method as Animals were weighed and numbered. Mice were divided into 7 groups of six animals each. Group 1 served as control which was treated with vehicle (2% v/v Tween 80), group 2 was treated with standard drug phenytoin (25 mg/kg, i.p.) and groups 3– 7 were treated with newly synthesized oxadiazole derivatives (25 mg/kg, i. p.). One hour after injection, the animals were subjected to electro shock through ear electrodes of 80 mA for 0.2 sec by electroconvulsiometer AND ANTI-inflammatory activity measured by Weigh the animals and number them. Mark the animals with picric acid for individual animal identification. Divide rats into 5 groups of 6 rats each. Note the initial paw volume of each rat by dipping just beyond tibio-tarsal junction by mercury displacement method. The pharmacological screening of the synthesized compounds showed anti convulsant activity ranging from 56.2 % to 76.3 % inhibition of epileptic seizures in mice, where as the standard drug Phenytoin showed 83.95 % inhibition of epileptic seizures in mice. The compound iiih4 from each group was found to be nearly potent to Phenytoin which is used as standard drug. Anti-inflammatory activity ranging from 31.09 to 63.11 % inhibition of rat paw edema volume after 3 hours, whereas the standard drug Indomethacin showed 62.06 % inhibition of rat paw edema volume after 4 hours. The compound iiih3 was found to be nearly more potent then indomethacin which is used as standard drug&#x0D; Keywords: Isatin; Schiff bases; Anti convulsant activity; Anti-inflammatory activity; Isatin.

Anti-Inflammatory Effect of Polyherbal Formulation (PHF) on Carrageenan and Lipopolysaccharide-Induced Acute Inflammation in Rats

Polyherbal formulation (PHF) is composed of Artemisia santolinifolia Turcz, Saussurea salicifolia L. and Hippophae rhamnoides L., which mainly used for inflammatory disorders in traditional Mongolian medicine. The aim of the study was to evaluate the anti-inflammatory effect of PHF in carrageenan and lipopolysaccharide (LPS) induced models of inflammation. The total active constituents of 20% ethanol extract of PHF was determined, using Folin-Ciocalteu reagent and aluminum chloride reagent, respectively. Inflammation models were induced by 1% carrageenan and LPS 7.5 mg/kg in the experimental groups. The levels of serum tumor necrosis factor- α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and high mobility group box 1 protein (HMGB-1) were measured in PHF pretreatment groups by enzyme-linked immunosorbent assay (ELISA). The lungs were harvested and evaluated for histopathological assessment on 12 hours after LPS administration. The content of total phenolic was 28.5±0.12 mg/g and flavonoids 12.4±0.42 mg/g. After 60, 120, 180, 240 and 300 min, the data indicate that PHF 75, 150 and 300 mg/kg was significantly effective reducing paw edema volumes induced by carrageenan compared to control (p&lt;0.01). PHF pretreatment significantly reduced levels of serum TNF-α, IL-1β and IL-6 at 300 minutes after carrageenan injection. Moreover, pretreated with PHF 150 mg/kg groups serum levels of TNF-α, IL-1β and HMGB-1 were significantly (p&lt;0.01) reduced compared with the control group after LPS injection. It showed less inflammation and change of pulmonary structure compared with the LPS group at 12 hours after LPS injection. From the results of the study, it was demonstrated that PHF had sufficient potential to treat inflammatory disorders by reducing pro-inflammatory cytokines.