Subcutaneous Injection Of Carrageenan Research Articles

Inhibition of synaptic transmission by anandamide precursor 20:4-NAPE is mediated by TRPV1 receptors under inflammatory conditions.

Transient receptor potential ion channel, vanilloid subfamily, type 1 (TRPV1) cation channel, and cannabinoid receptor 1 (CB1) are essential in the modulation of nociceptive signaling in the spinal cord dorsal horn that underlies different pathological pain states. TRPV1 and CB1 receptors share the endogenous agonist anandamide (AEA), produced from N-arachidonoylphosphatidylethanolamine (20:4-NAPE). We investigated the effect of the anandamide precursor 20:4-NAPE on synaptic activity in naive and inflammatory conditions. Patch-clamp recordings of miniature excitatory postsynaptic currents (mEPSCs) from superficial dorsal horn neurons in rat acute spinal cord slices were used. Peripheral inflammation was induced by subcutaneous injection of carrageenan. Under naive conditions, mEPSCs frequency (0.96 ± 0.11 Hz) was significantly decreased after 20 μM 20:4-NAPE application (55.3 ± 7.4%). This 20:4-NAPE-induced inhibition was blocked by anandamide-synthesizing enzyme N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD) inhibitor LEI-401. In addition, the inhibition was prevented by the CB1 receptor antagonist PF 514273 (0.2 μM) but not by the TRPV1 receptor antagonist SB 366791 (10 μM). Under inflammatory conditions, 20:4-NAPE (20 μM) also exhibited a significant inhibitory effect (74.5 ± 8.9%) on the mEPSCs frequency that was prevented by the TRPV1 receptor antagonist SB 366791 but not by PF 514273 application. Our results show that 20:4-NAPE application has a significant modulatory effect on spinal cord nociceptive signaling that is mediated by both TRPV1 and CB1 presynaptic receptors, whereas peripheral inflammation changes the underlying mechanism. The switch between TRPV1 and CB1 receptor activation by the AEA precursor 20:4-NAPE during inflammation may play an important role in nociceptive processing, hence the development of pathological pain.

Evaluation of the anti-inflammatory, analgesic, anti-pyretic and anti-ulcerogenic potentials of synthetic indole derivatives

A large number of new synthetic compounds are synthesized in the field of heterocyclic chemistry having a variety of biological potentials. In the present study, some synthetic indole derivatives are used to check anti-inflammatory, analgesic, antipyretic and gastroprotective activity in albino mice. Albino mice of either sex of reproductive age were used for each study (n = 5). In anti-inflammatory activity, the negative control (NC) and positive control group animals were treated with normal saline and 10 mg/kg of indomethacin respectively. The treated groups received the twenty four different synthetic chemicals, after 30 min of sub cutaneous injection of carrageenan. In analgesic activity, hot-plate method is used and for each group the latency period was recorded at zero moment of the provision of required dose and after 30, 60, 90, 120 and 180 min. In anti-pyretic activity, Pyrexia was induced by using Brewer's yeast method. Before any treatment and then after duration of 18 h, the rectal temperatures were recorded. Among all the chemicals, only those chemicals which show any potential related to above mentioned activities were selected for gastroprotective activity. The gastroprotective activity was performed to check the gastric ulcers by using 300 mg/kg of single oral dose of indomethacin to animals of all groups except NC group. This study helped to screen out the most potent indole derivatives 3a-II and 4a-II from the 24 synthetic indole derivatives which demonstrated the best biological potential (anti-inflammatory, analgesic, antipyretic, and gastroprotection) as compared to the remaining ones. The micrometric and biochemical results also support the histological findings. Out of the twenty-four novel indole amines tested, 3a-II and 4a-II have shown the effective pharmacological capacity and additionally have not shown any overt and systemic toxicity. Thus these two indole amines need further in-depth pharmacokinetic and pharmacodynamics studies before they are recommended for any pre-clinical trial.

Anti-rheumatic, and analgesic effects by the parent tuberous roots of Aconitum jaluense in adjuvant induced arthritis rats

The aim of this study was to test the anti-rheumatic effects of A. jaluense tubers in acute and chronic arthritis rats, and to assign its ingredients through UHPLC-TOF/MS. Subcutaneous injection of carrageenan for acute arthritis and complete Freund's adjuvant (CFA) for chronic arthritis was carried out in the hind paw of SD rats. The paw volume was measured by a plethysmometer thermal hyperalgesia was tested using a thermal plantar tester, and mechanical hyperalgesia was evaluated by ankle flexion evoked vocalizations. The expression of c-Fos in the brain hippocampus was measured with the avidin-biotin-peroxidase technique. The ingredients were assigned by UHPLC-TOF/MS, chromatography was performed by UHPLC system with DAD detector and BEH C18 column, and spectroscopy was conducted by ESI-MS system. The 80% ethanoic extract of A. jaluense tubers showed an acute anti-inflammatory effect by suppressing the edema volume in the hind paw of carrageenan-stimulated rats. In addition, A. jaluense tubers exerted an anti-rheumatic activity by reducing the secondary swelling volume from an immunological reaction in the left hind paw of CFA-induced chronic arthritis rats. Additionally, oral treatment with the 80% ethanoic extract -showed potent analgesic effects in the arthritis rats by recovering the paw withdrawal latency stimulated by the thermal hyperalgesia and by reducing the vocalization scores evoked by ankle flexion on both hind paws. Moreover, its treatment also indicated an anti-psychiatric effect by controlling the c-Fos protein expression of the brain hippocampus in CFA-stimulated arthritis rats. These results suggested that these therapeutic effects were exhibited by less toxic mono-esterified diterpenoid alkaloids (MDAs), and nontoxic non-esterified diterpenoid alkaloids (NDAs). A. jaluense tubers may act as viable therapeutic or preventive candidates for acute and chronic arthritis, particularly, for immune-inflammatory rheumatoid arthritis to suppress the pain and psychiatric condition.

Effects of subcutaneous injection of λ/κ-carrageenin on the immune and liver antioxidant status of gilthead seabream (Sparus aurata).

This study investigated the acute inflammatory response induced by subcutaneous injection of carrageenin (1%) or phosphate-buffered saline (control) in gilthead seabream (Sparusaurata). Skin mucus, serum, head kidney (HK) and liver were sampled at 1.5, 3 and 6hr post-injection (p.i.) to determine the immune and antioxidant status of this fish species. The skin mucus of the carrageenin group showed increased superoxide dismutase and peroxidase activities, lysozyme abundance, bactericidal activity against Vibrioanguillarum and Photobacteriumdamselae, and total immunoglobulins compared with those of the control group. However, the carrageenin-injected fish sampled at 6hr p.i. showed decreased protease activity in the skin mucus and peroxidase activity in the HK leucocytes compared with the control. Moreover, the carrageenin injection had no effects on the systemic immune system, but it reduced the liver catalase activities at both 3 and 6hr in the carrageenin group relative to those in the control group. The expression levels of several proinflammatory and cell marker genes in the HK and liver were also determined. In the HK, the expression levels of interleukin-1β and prostaglandin D synthase 1 were upregulated at 1.5 and 3hr, respectively, in the carrageenin group compared with those in the control group. Contrarily, the expression of the NADPH oxidase subunit phox40 (an acidophilic granulocyte marker) in the carrageenin group at 6hr was downregulated compared with that in the control group. These results suggested that subcutaneous injection of κ/λ-carrageenin in gilthead seabream triggered an acute skin inflammation characterized by the rapid recruitment of acidophilic granulocytes and the release of humoral mediators into the skin mucus.

In vivo anti-inflammatory activity of Lepidium sativum (L.) seeds

Lepidium sativum seeds have been used in traditional medicine for the treatment of liver dysfunction, jaundice, gastrointestinal disorders and spleen diseases. Furthermore, it was reported that these seeds have also an antioxidant, diuretic, antihypertensive, and anti-asthmatic activities. The present study aimed to explore the anti-inflammatory activity of the ethanolic ex-tract of L. sativum Linn. seeds (EELS) in vivo. The anti-inflammatory activity of EELS was tested in mice weighting (25±5) g. Either PBS vehicle (control group), ethanolic extract (50mg/kg) or diclofenac (50 mg/kg), were administered (p.o) for 60 min before an oedema was induced in the mice paw by subcutaneous injection of carrageenan. The mouse-paw volume was meas-ured from 1 h to 6 h after carrageenan injection. Plasma fibrinogen, serum albumin and C-reactive protein (CRP) levels were determined for each group. The EELS and the standard (diclofenac) reduced significantly (p < 0.05) paw oedema by 40.44 ± 16.36 % and 9.39 ± 1.99%, respectively compared to the control after the sixth hour after injection of carrageenan. Biomarkers of inflammation (serum albumin, CRP and plasma fibrinogen) levels were significantly (p <0.05) optimized in EELS group (assay) compared to the control. The obtained results revealed that the ethanolic extract of L. sativum Linn. seeds has a significant in vivo anti-inflammatory activity.

Locally injected ivabradine inhibits carrageenan-induced pain and inflammatory responses via hyperpolarization-activated cyclic nucleotide-gated (HCN) channels.

BackgroundRecently, attention has been focused on the role of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in the mechanism of and as a treatment target for neuropathic and inflammatory pain. Ivabradine, a blocker of HCN channels, was demonstrated to have an effect on neuropathic pain in an animal model. Therefore, in the present study, we evaluated the effect of ivabradine on inflammatory pain, and under the hypothesis that ivabradine can directly influence inflammatory responses, we investigated its effect in in vivo and in vitro studies.MethodsAfter approval from our institution, we studied male Sprague–Dawley rats aged 8 weeks. Peripheral inflammation was induced by the subcutaneous injection of carrageenan into the hindpaw of rats. The paw-withdrawal threshold (pain threshold) was evaluated by applying mechanical stimulation to the injected site with von Frey filaments. Ivabradine was subcutaneously injected, combined with carrageenan, and its effect on the pain threshold was evaluated. In addition, we evaluated the effects of ivabradine on the accumulation of leukocytes and TNF-alpha expression in the injected area of rats. Furthermore, we investigated the effects of ivabradine on LPS-stimulated production of TNF-alpha in incubated mouse macrophage-like cells.ResultsThe addition of ivabradine to carrageenan increased the pain threshold lowered by carrageenan injection. Both lamotrigine and forskolin, activators of HCN channels, significantly reversed the inhibitory effect of ivabradine on the pain threshold. Ivabradine inhibited the carrageenan-induced accumulation of leukocytes and TNF-alpha expression in the injected area. Furthermore, ivabradine significantly inhibited LPS-stimulated production of TNF-alpha in the incubated cells.ConclusionThe results of the present study demonstrated that locally injected ivabradine is effective against carrageenan-induced inflammatory pain via HCN channels. Its effect was considered to involve not only an action on peripheral nerves but also an anti-inflammatory effect.

Analgesic and anti-inflammatory effects and molecular mechanisms of Kadsura heteroclita stems, an anti-arthritic Chinese Tujia ethnomedicinal herb

Ethnopharmacological relevanceRheumatoid arthritis (RA) is a chronic autoimmune disease characterized by failure of spontaneous resolution of inflammation. The stem of Kadsura heteroclite (KHS) is a well-known anti-arthritic Tujia ethnomedicinal plant, which named Xuetong in folk, has long been used for the prevention and treatment of rheumatic and arthritic diseases. Aim of the studyThe analgesic and anti-inflammatory effects and the potential mechanisms behind such effects of KHS would be investigated by using different animal models. Materials and methodsThe abdominal writhing episodes of mice induced by intraperitoneal injection of acetic acid and the tail-flick response induced by radiant heat stimulation were used to evaluate the analgesic effect of KHS. The number of abdominal writhing episodes of mice and the latency of tail-flick in rats were measured and recorded. In acute inflammatory models, the ear edema of mice was induced by applying xylene on the ear surface, while the paw edema of male and female rats was induced by subcutaneous injection of carrageenan into the right hind paws of animals. The carrageenan-induced paw swelling in rats were selected as an anti-acute inflammatory mechanism of KHS. Serum levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor (TNF-α) were measured by ELISA, and protein expression of cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) were detected by Western blot. ResultsThe maximal tolerated single dose of KHS was determined to be 26 g/kg in both sexes of mice. Pharmacological studies showed that KHS at the dose of 200 mg/kg significantly prolonged the reaction time of rats to radiant heat stimulation and suppressed abdominal writhing episodes of mice induced by intraperitoneal injection of acetic acid. KHS at the dose of 200, 400, and 800 mg/kg, showed dose-dependent inhibition of xylene-induced ear swelling in mice. KHS at the dose of 100, 200, 400, and 800 mg/kg demonstrated dose- and time-dependent suppression of paw edema induced by subcutaneous injection of carrageenan in both all rats. Mechanistic studies revealed that the anti-inflammatory effect of KHS was associated with inhibition of the production of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α and effectively decreased the expression of COX and iNOS proteins in the carrageenan-injected rat serum, paw tissues and inflammatory exudates. The positive reference drug, rotundine at a dosage of 100 mg/kg and indomethacin at a dosage of 10 mg/kg were used in both mice and rat models. ConclusionThese results suggested that KHS has significant effects on analgesia and anti-inflammation with decreasing the pro-inflammation cytokines of IL-1β, IL-6, and TNF-α and inhibiting the proteins expression of COX-2 and iNOS.

Assessing the aversive nature of pain with an operant approach/avoidance paradigm

Preclinical pain assessments can be criticized for failing to adequately characterize the human clinical pain experience. Although recent assessments have improved upon this shortcoming, there are still significant limitations. One concern is that current procedures fail to examine underlying motivational drives related to pain. Therefore, we used a novel approach-avoidance paradigm that allowed a rat to either satisfy hunger or avoid noxious stimulation to reveal prioritizing of motivational drives. The operant paradigm utilized a single lever that the animal pressed for appetitive reward (approach). The lever press was associated with mechanical stimulation of an inflamed paw induced by subcutaneous injection of carrageenan (avoidance). The results revealed that carrageenan-injected animals had a significant suppression of lever pressing and, in addition, had a longer latency to approach and press a lever for appetitive reward. The pattern of operant behavioral responses indicates that the motivation to avoid pain superseded the motivation to alleviate hunger. Utilization of approach-avoidance paradigms, such as this one, can allow researchers to unravel the complexities of the pain experience with the goal of enhancing translation to clinical efficacy.

Anti-inflammatory, antinociceptive and antioxidant properties of Schinopsis brasiliensis bark

Ethnopharmacological relevanceSchinopsis brasiliensis is a native plant from Brazil, popularly used in folk medicine to relieve pain and treat inflammation. This study evaluated the antinociceptive and anti-inflammatory activities and antioxidant properties of the hydroethanol extract (HEE) and ethyl acetate fraction (EAF) obtained from S. brasiliensis bark. Materials and methodsThe HEE and EAF of S. brasiliensis bark (10, 30 and 100mg/kg, p.o.) were evaluated using models of analgaesia (formalin-induced licking and hot-plate models) or inflammation (licking response by formalin-induced and carrageenan-induced cell migration into the subcutaneous air pouch). The antioxidant activities of HEE and EAF (50, 100 and 200µg/ml) were evaluated using the lipoperoxidation method induced in egg yolk by 2′-azobis(2-amidinopropane) dihydrochloride (AAPH) and FeSO4. ResultsHEE and EAF presented a central antinociceptive effect (at 100mg/kg dose), increasing the baseline and area under the curve in the hot plate model. EAF (100mg/kg) significantly reduced (p< 0.005) the pain response in the first (45%) and second (35%) phases of the formalin-induced licking model, while HEE (100mg/kg) reduced (38%) only the pain response in the second phase. Regarding anti-inflammatory activity, EAF (100mg/kg) also inhibited the inflammatory process induced by subcutaneous carrageenan injection in the SAP model, reducing the amount of the cytokine TNF-α produced. ConclusionHEE and EAF from S. brasiliensis bark show pharmacological interest because they were able to inhibit the peripheral and central transmission of pain. Our data also suggest that the anti-inflammatory activity caused by EAF exposure occurs through the inhibition of the pro-inflammatory cytokine TNF-α, also reducing the spreading of the inflammatory processes by neutralizing reactive oxygen species, which are by-products in the biosynthesis of pain mediators.

Revealing anti-inflammation mechanism of water-extract and oil of forsythiae fructus on carrageenan-Induced edema rats by serum metabolomics

Forsythiae Fructus is an important Chinese medicine which shows a significant effect against inflammation. This study aimed to investigate the preventive anti-inflammation mechanism of Forsythiae Fructus by serum metabolomics strategy and compare the difference of the metabolism pathways between Forsythia extract and Forsythia oil in rat. Four groups (control group, model group, Forsythia extract group and Forsythia oil group) were orally administered 10mL/kg 0.5% Tween 80 solution, 10mL/kg 0.5% Tween 80 solution, 5g/kg Forsythia extract and 0.48mL/kg Forsythia oil respectively. 30min after drug administration, rat acute inflammation was induced by subcutaneous injection of carrageenan in the right paw in model group, Forsythia extract group and Forsythia oil group. After being administered Forsythia extract and Forsythia oil, the percentage of rat paw edema was significantly decreased (P<0.05) compared with model group. Metabolomics based on UPLC-Q-TOF-MS/MS was used to analyze the collected serum sample. Multivariate analysis was established for metabolomics analysis. According to Principal component analysis (PCA) and partial least squares-discriminate analysis (PLS-DA) results, four groups were clearly separated. And thirteen alterative biomarkers were identified in the serum, namely PC (19:0/0:0), LysoPC (20:0), LysoPC (20:1), LysoPC (17:0), Sphingosine, Linoleic acid, 3R-hydroxy-butanoic acid (3-HB), 2-hydroxyhexadecanoic acid, Lactic acid, L-Threonine, L-Leucine, Maleic acid, Adipic acid. The change of biomarkers suggested that Forsythia extract affected Linoleic acid metabolism, Valine, leucine and isoleucine biosynthesis, Sphingolipid metabolism and Glycerophospholipid metabolism. Forsythia oil affected Sphingolipid metabolism and Glycerophospholipid metabolism. It indicated that Forsythia extract and Forsythia oil both showed significant preventive anti-inflammatory effect through acting on different metabolism pathways. Moreover, efficacy mechanism of Forsythiae Fructus could recover metabolites disturb in the body through affecting particular drug targets associated with the inflammatory pathway.

Metabonomic analysis of biochemical changes in the plasma and urine of carrageenan-induced rats after treatment with Yi-Guan-Jian decoction

The urinary and plasma metabonomics method based on a Agilent-1200 LC system coupled to an Agilent-6410 mass spectrometry (HPLC-MS/MS) had been established to investigate the anti-inflammatory activity of Yi-Guan-Jian (YGJ) decoction and explore its potential anti-inflammatory mechanism. Rat acute inflammation was induced by subcutaneous injection of carrageenan in hind paws. Multivariate statistical approaches, such as principal component analysis (PCA), partial least-squares discriminant analysis (PLS-DA) and XCMS online software were used to distinguish normal control group (NG), model group (MG), aspirin-treated group (AG) and Yi-Guan-Jian decoction group (YGJ), aimed at finding out the potential biomarkers. There was a clear separation among the four groups in PCA model. Twenty-five potential biomarkers had been identified using PCA, PLS-DA and XCMS online software. Lastly, we had an enrichment for the related metabolic pathways and screened out the pathways that influence the organism a lot in MetPA, then five mainly metabolism: tryptophan metabolism, lipid metabolism, oxidative stress, glyoxylate and dicarboxylate metabolism, taurine and hypotaurine metabolism were found. In this study, YGJ showed good anti-inflammatory effects and it could suppress the changes of pathologic inflammatory cytokines of carrageenan-induced rat paw edema (CIE). There might be a correlation between these results and the regulation of the disturbed metabolites in urine and plasma. This study demonstrates that metabonomics is a powerful methodology to gain insight into the mechanisms of traditional Chinese medicine (TCM) formula in therapy.

The investigation of anti-inflammatory activity of volatile oil of Angelica sinensis by plasma metabolomics approach

Angelica sinensis (AS) is an important medicinal plant, and volatile oil is the main pharmacologically active ingredient. This study was aimed to investigate the anti-inflammatory activity of the volatile oil of A. sinensis (VOAS) and explore its potential anti-inflammatory mechanism by plasma metabolomics approach. Rat acute inflammation was induced by subcutaneous injection of carrageenan in hind paws. Paw edema, histamine (HIS) and 5-hydroxytryptamine (5-HT) were detected. Then, we analyzed plasma metabolic profiling of acute inflammation and performed pathway analysis on the metabolite markers reversed after VOAS administration and further integration of metabolic networks. The results showed that VOAS could alleviate the paw edema and decrease plasma HIS and 5-HT levels. Fourteen metabolite markers of acute inflammation were screened, and the levels were all reversed to different degrees after VOAS administration. These metabolite markers mainly related to linoleic acid metabolism, ascorbate and aldarate metabolism, arachidonic acid metabolism, glyoxylate and dicarboxylate metabolism, and glycine, serine and threonine metabolism. In metabolic networks, glycine and arachidonic acid were node molecules. It indicated that VOAS could significantly inhibit systemic inflammatory response triggered by acute local stimulation and it exerted anti-inflammatory activity mainly through regulating the disturbed metabolic networks centered on glycine and arachidonic acid.

Anti-inflammatory activity of Choisya ternata Kunth essential oil, ternanthranin, and its two synthetic analogs (methyl and propyl N-methylanthranilates).

Choisya ternata Kunth (Rutaceae) is native to North America where it is popularly known as “Mexican orange”. In this study, the anti-inflammatory effects of the essential oil (EO) obtained from the leaves of C. ternata, one of its minor components (ternanthranin—ISOAN) and its two synthetic analogues (methyl and propyl N-methylanthranilate – MAN and PAN) were evaluated. Mice pretreated with the EO (EO) obtained from C. ternata leaves (3–100 mg/kg, p.o.), ISOAN, MAN or PAN (1–30 mg/kg, p.o.) and the reference drugs, morphine (1 mg/kg, p.o.) and acetylsalicylic acid (ASA, 100 mg/kg, p.o.), were evaluated in inflammation models such as formalin and subcutaneous air pouch models, with measurement of cell migration, exudate volume, protein extravasation, nitric oxide and pro-inflammatory cytokines. The EO from C. ternata significantly inhibited the time that the animals spent licking the formalin-injected paw in the second phase of the model at their higher doses (30 and 100 mg/kg, respectively). An inhibition of the inflammatory reaction induced after subcutaneous carrageenan injection into air pouch was also observed. In this model, the EO significantly reduced cell migration, exudate volume, protein extravased, and the increase in levels of inflammatory mediators (nitric oxide, TNF-α and IL-1β). ISOAN, MAN and PAN behaved in the same fashion at much smaller doses. Also, these molecules were able to show significant effects in the reduction of paw edema (at all tested doses) when the phlogistic agent was carrageenan, bradykinin, 5-HT, PGE2, C48/80 or 12-O-tetradecanoylphorbol-acetate (TPA). None of the tested doses had any effect in reducing histamine-induced edema. Our results indicate that the EO from C. ternata and anthranilate derivatives demonstrates an anti-inflammatory effect.

Involvements of galanin and its receptors in antinociception in nucleus accumbens of rats with inflammatory pain

This study tested the hypothesis that antinociceptive effects of galanin and its receptors in nucleus accumbens (NAc) of rats with inflammatory pain provoked by subcutaneous injection of 0.1ml of 2% carrageenin into the sole of the rat's left hindpaw. The hindpaw withdrawal latencies (HWLs) in response to thermal and mechanical stimulation significantly decreased in bilateral hindpaws at 3 and 4 hour after a subcutaneous injection of carrageenin. However intra-NAc injection of 2 and 3nmol, but not 1nmol of galanin markedly induced an increase in the HWLs in a dose-dependent way. Western blot also showed, that the expression of galanin receptor 1 (GalR1) and galanin receptor 2 (GalR2) were significantly upregulated in NAc at 3 hour after a subcutaneous injection of carrageenin. In addition, the rats were intra-NAc injected galanin, 5min later following by intra-NAc injection of galanin receptor antagonist galantide, the galanin-induce antinociceptive effects were suppressed by galantide. The results demonstrated that galanin and its receptors might be involved in antinociception in the NAc of rats with inflammatory pain.

Anti-inflammatory potential of carotenoid meso-zeaxanthin and its mode of action

Context: meso-Zeaxanthin (MZ) is a xanthophyll carotenoid with profound antioxidant activity.Objective: Oxidative stress plays a decisive role in numerous degenerative diseases including cancer. The present study evaluates anti-inflammatory effect of MZ.Materials and methods: Balb/c mice were treated with different doses of MZ (50 and 250 mg/kg b.wt, orally) 5 d before subcutaneous injection of carrageenan (1%), dextran (1%), and formalin (2%). Paw edema formation in MZ-treated and -untreated animals was measured using vernier calipers. Anti-inflammatory activity of MZ against lipopolysaccharide (LPS)-induced inflammatory model was studied by culturing macrophages in the presence and absence of LPS (5 μg/ml) and different concentrations of MZ (5, 10, and 25 μg/ml). After 24 h, the effect of MZ on pro-inflammatory cytokine levels in macrophages was analyzed by ELISA and its effect on various inflammatory genes was studied by RT-PCR.Results: MZ administration at different doses significantly (p < 0.001) inhibited paw edema induced by carrageenan, dextran, and formalin in mice. MZ also exhibited profound anti-inflammatory effect against LPS-induced inflammation in macrophages. Increased production of nitric oxide, C-reactive proteins, and various pro-inflammatory cytokines (TNF-α, interleukin-1β, and interleukin-6) in LPS-stimulated macrophages was significantly reduced by MZ treatment. Moreover, LPS-stimulated up-regulated mRNA expression of various inflammatory mediator genes like COX-2, TNF-α, and iNOS was down-regulated by MZ administration.Discussion and conclusion: MZ has potent anti-inflammatory effect which can be due to its down-regulated expression of various inflammatory mediator genes. Since cancer is considered as an inflammatory disease, the present study points towards the importance of MZ in chemo-preventive strategy.

Pharmacological Potential of Tetrahydrofurano/Pyrano Quinoline and Benzo[b]furoindolyl Derivatives in Acute Inflammation, Pain and Oxidative Stress.

Investigation of the pharmacological potential of Tetrahydrofurano/pyrano quinoline and Benzo [b]furoindolyl derivatives in acute inflammation, pain and oxidative stress. Tetrahydrofurano/ pyrano quinoline and Benzo[b]furoindolyl were evaluated for anti-inflammatory activity by carrageenan-induced hind paw edema in rats. Analgesic activity in mice was assessed by both peripheral and central analgesic models. The free radical scavenging activity of the synthetic compound was analyzed by the in vivo antioxidant assays, by measuring the antioxidant enzymes such as Superoxide dismutase (SOD), Catalase and Peroxidase from the liver homogenate and the in vitro antioxidant activity was evaluated by DPPH photometric assay, Hydroxyl radical scavenging and Lipid Peroxidation assay. The compounds had substantially inhibited the inflammation induced by subcutaneous carrageenan injection. The same compounds had demonstrated remarkable central and peripheral analgesic activity with potent free radical scavenging activity as evident from both in vitro and in vivo antioxidant assays. Tetrahydrofurano/pyrano quinoline and Benzo[b]furoindolyl derivatives exhibit varied pharmacological activities that include anti-inflammatory, analgesic and antioxidant activity.

Therapeutic potential of Polyalthia cerasoides stem bark extracts against oxidative stress and nociception.

Background:Polyalthia cerasoides is a medicinal plant known for its ethnopharmacological importance. Despite this, investigation related to its therapeutic benefit is still unexplored.Aim:To evaluate the stem bark extracts of Polyalthia cerasoides for pharmacological activities relating to inflammation, nociception and oxidative stress using in vivo and in vitro models.Materials and Methods:Pet ether, ethyl acetate and chloroform fractions of the stem bark were evaluated for anti-inflammatory activity by carrageenan-induced hind paw edema in rats. Anti-nociceptive activity in mice was assessed using thermally and chemically induced analgesic models. The free radical quenching potential of the extracts was initially analyzed using the in vitro DPPH photometric assay, Hydroxyl radical scavenging and Lipid Peroxidation assays. Then modulatory effect of the extracts on in vivo antioxidant system was evaluated by carbon tetrachloride induced hepatotoxicity and subsequent measurements of antioxidant enzymes such as Superoxide dismutase, Catalase and Peroxidase from the liver homogenate.Results:Among the tested fractions, ethyl acetate extract had substantially inhibited the inflammation by 68.5% that was induced by subcutaneous carrageenan injection whereas pet ether and chloroform extract showed only minimal inhibitory effect. Investigation of the anti-nociceptive activity revealed that the ethyl acetate fractions had significantly repressed the algesia in both the analgesic experimental models. In vitro and in vivo individual antioxidant assays demonstrated that the ethyl acetate fraction has strong free radical quenching potential which also restores the endogenous hepatic enzymes.Conclusion:The ethyl acetate fraction enriched with flavinoids and steroids from Polyalthia cerasoides stem bark has potent bioactivity to combat inflammation, ROS and pain. This needs further characterization for potential therapeutic applications.

Metabonomic analysis of the anti-inflammatory effects of volatile oils of Angelica sinensis on rat model of acute inflammation.

Metabonomics based on GC-MS was used to study the possible anti-inflammatory mechanisms of volatile oils of Angelica sinensis (VOAS) in rats with acute inflammation. Acute inflammation was induced by subcutaneous injection of carrageenan in rats. The levels of prostaglandin E2 (PGE2 ), histamine (HIS) and 5-hydroxytryptamine (5-HT) in the inflammatory fluid were detected. Principal component analysis and orthogonal partial least squares-discriminant analysis models were performed for pattern recognition analysis. After the administration of VOAS, the levels of PGE2 , HIS, and 5-HT returned to levels observed in normal group. According to GC-MS analysis, the intervention of VOAS in rats with acute inflammation induced substantial and characteristic changes in their metabolic profiles. Fourteen metabolite biomarkers, namely, lactic acid, malic acid, citric acid, trans-dehydroandrosterone, aldosterone, linoleic acid, hexadecanoic acid, pregnenolone, octadecenoic acid, myristic acid, l-histidine, octadecanoic acid, arachidonic acid (AA) and l-tryptophan, were detected in the inflammatory fluid. The levels of all biomarkers either increased or decreased significantly in model groups. VOAS possibly intervened in the metabolic process of inflammation by altering histidine metabolism, tryptophan metabolism, AA metabolism, steroid hormone biosynthesis, fatty acid metabolism and energy metabolism. Metabonomics was used to reflect an organism's physiological and metabolic state comprehensively, and it is a potentially powerful tool that reveals the anti-acute-inflammatory mechanism of VOAS.

In vivo antiinflammatory activity and chemical composition of Hypericum scabroides

To evaluate the methanolic extracts of aerial parts of Hypericum scabroides (HSM) (200 mg/kg, p.o.) for in vivo anti-inflammatory activity. The anti-inflammatory activity of HSM was tested in mice weighting (25±5) g. Either vehicle (control group), the methanolic extracts (200 mg/kg) or diclofenac (50 mg/kg), was administered (p.o.) for 60 min before an edema was induced in the mice paw by subcutaneous injection of carrageenin. The mouse-paw volume was measured 1 h, 3h and 6 h after injection of carrageenin. The HSM showed significant reduction of edema in carrageenan induced mice paw edema model at 1 h and 3 h for (78.03±15.54)% and (40.44±16.36)%, respectively. The diclofenac 50 mg/kg exhibited % reduction in paw volume (31.00±11.52)%, (0.80±0.09)% and (9.39±1.99)% after 1 h, 3 h and 6 h, respectively compared to control group. The obtained results revealed that HSM has significant anti inflammatory activity. Furethermore, the chemical composition of HSM was analyzed by using high performance liquid chromatography-diode array dedector. The plant contained pseudohypericin (trace) hypericin (trace), chlorogenic acid (0.014 0±0.000 5)%, rutin (0.005 0±0.000 6)%, hyperoside (0.016±0.005)%, isoquercitrin (0.034 0±0.000 5)% and kaempferol (trace). The obtained results of the present investigation revealed that methanol extract of Hypericum scarbroides has significant anti-inflammatory activity.

In vivo anti-inflammatory activity of Garcinia indica fruit rind (Kokum) in rats

The aqueous extract of Garcinia indica fruit rind (GIE) was studied for anti-inflammatory activity in carrageenan induced paw edema and cotton pellet induced granuloma in rats. Wistar rats were orally administered GIE (400 mg/kg and 800 mg/kg) and the standard drug diclofenac sodium (10 mg/kg) 60 min prior to a subcutaneous injection of carrageenan (0.1 ml of 1% w/v) into their right hind paws to produce edema. The paw volumes were measured at various time intervals to assess the effect of drug treatment. In the granuloma model, 4 sterile cotton pellets were implanted in the ventral region in each rat. GIE (400 mg/kg and 800 mg/kg) and the standard drug diclofenac sodium (10 mg/kg) were administered orally for 8 days to the pellet implanted rats. The granuloma tissue formation was calculated from the dissected pellets and the activities of the marker enzymes AST, ALT and ALP were assayed from the serum. A significant reduction in paw edema and cotton pellet granuloma was observed with GIE treatment when compared with the carrageenan treated and cotton pellet implanted animals respectively. GIE treatment significantly attenuated the AST, ALT &amp; ALP activities elevated by foreign body granulomas provoked in rats by the subcutaneous implantation of cotton pellets. It may be concluded that GIE possesses anti-inflammatory activity which may be due to an underlying antioxidant activity and/ or lysosomal membrane stabilization by virtue of its phenolic constituents.