Carrageenan-induced Acute Edema Research Articles

A comprehensive tool in recycling plant-waste of Gossypium barbadense L agricultural and industrial waste extracts containing gossypin and gossypol: hepatoprotective, anti-inflammatory and antioxidant effects.

Improper management of agricultural and industrial cotton wastes causes environmental pollution and worsens the climate change challenge. Green recycling of cotton could contribute to a circular economy. One of the economic values of cotton wastes lies in their bioactive components. Two types of cotton wastes-agricultural and industrial-of the species Gossypium barbadense L. Giza 95 were targeted in the current study, aiming to maximize their medicinal value and investigate the anti-inflammatory, hepatoprotective, and antioxidant activities of their phytochemical extracts. Phytochemical extraction was performed using different solvents extraction. An anti-inflammatory effect was tested in carrageenan-induced acute edema in a rat paw model. A carbon tetrachloride chronic model of liver injury was used for the assessment of hepatoprotective potential. Liver enzymes (AST and ALT), oxidative stress markers (MDA and GSH), inflammatory biomarkers (C-reactive protein), and histopathological features were investigated. As a result, ethyl acetate proved to be the solvent of best choice to extract the gossypin polyphenolics, where the extracted amount reached 14,826.2µg/g, followed by butanol (8751.4µg/g extract). The chloroform (CHCL3) fraction showed the highest amounts of gossypol (190.7µg/g extract), followed by petroleum ether. Cotton waste's composition analysis showed a wide range of components, including 33 metabolites such as gossypetin, polyphenolics, and other metabolites that possess therapeutic effects. Both chloroform extract and industrial waste extracts showed superior anti-inflammatory and hepatoprotective effects in comparison to other extracts. All tested extracts (ethyl acetate, chloroform, and industrial waste) showed proper antioxidant activities.

Zinc and Calcium Cations Combination in the Production of Floating Alginate Beads as Prednisolone Delivery Systems.

The aim of this research was to verify the application of alginate in combination with Ca2+ and Zn2+ ions to produce a floating and prolonged release system for the oral administration of prednisolone. Hollow and floating gel-beads were designed using prilling/ionotropic gelation as the microencapsulation technique, zinc acetate in the gelling solution as the alginate external crosslinker, and calcium carbonate in the feed as the internal crosslinking agent able to generate gas when in contact with the acidic zinc acetate solution. To achieve this goal, drug/alginate solutions were opportunely combined with different amounts of calcium carbonate. The effect of the addition of calcium carbonate into the feed solution on buoyancy, encapsulation efficiency, morphology, size distribution, as well as in vitro drug release profile of the alginate particles was studied. Moreover, the ability of the floating beads to modulate in vivo the anti-inflammatory response was assayed using the carrageenan-induced acute oedema in rat paw. The proposed strategy allowed obtaining alginate beads with extremely high encapsulation efficiency values (up to 94%) and a very porous inner matrix conferring buoyancy in vitro in simulated gastric fluid up to 5 h. Moreover, in vivo, the best formulation, F4, resulted in the ability to prolong the anti-inflammatory effect up to 15 h compared with raw prednisolone.

Improvement of Resveratrol Effects When Combined with Rice Oil in Rat Models of Inflammation.

This study investigated the effects of systemic treatment with a new formulation of resveratrol (RSV) vehicled in rice oil (RSVO) in experimental rat models of inflammation. Male Wistar rats were evaluated in the following in vivo models: carrageenan-induced acute edema, complete Freund's adjuvant (CFA)-evoked sub-chronic edema, and CFA-induced polyarthritis. The animals were treated orally with RSVO (10-15 mg/kg) or RSV (100-200 mg/kg), depending on the experimental protocol. RSV was more effective than RSVO in carrageenan-elicited acute edema when dosed in either prophylactic or therapeutic schemes of administration. However, the repeated RSVO administration, at 10-fold lower doses, exhibited superior anti-inflammatory actions in either the sub-chronic edema or the chronic polyarthritis model elicited by CFA, when compared with RSV. The novel formulation RSVO displayed a lower plasma biotransformation when compared with the RSV-treated group-46% versus 88% of metabolites, respectively. RSVO also prevented polyarthritis-related cartilage destruction, an effect that might rely on the inhibition of the pro-inflammatory cytokine interleukin-6 (IL-6), associated with an increase of the anti-inflammatory cytokine interleukin-10 (IL-10). Noteworthy, the long-term administration of RSVO did not elicit any gastrointestinal harm. Our study revealed that RSVO was notably effective in the long-term inflammatory and degenerative responses triggered by CFA. This innovative formulation might well represent a promising alternative for treating chronic inflammatory diseases, such as arthritis.

Therapeutic effects of lornoxicam-loaded nanomicellar formula in experimental models of rheumatoid arthritis.

BackgroundRheumatoid arthritis (RA) is a chronic inflammatory disease treated by nonsteroidal anti-inflammatory drugs (NSAIDs) including lornoxicam (LX). Nanocarriers have been used to increase the efficacy and reduce the side effects of various drugs. The objective of the present study was to compare the therapeutic efficacy of systemic administration of lornoxicam-loaded nanomicellar formula (LX-NM) with that of free LX.Materials and methodsThe LX-loaded mixed polymeric nanomicellar formula was prepared by direct equilibrium technique. Two rat models were used in the study: carrageenan-induced acute edema and Freund’s complete adjuvant (FCA)-induced chronic arthritis.ResultsThe inhibitory effect of LX-NM on carrageenan-induced edema was higher than free LX for the same dose (1.3 mg/kg, i.p.). LX-NM (0.325 mg/kg, i.p.) produced effects comparable to that of diclofenac, which served as a standard. In the FCA model, daily treatment with LX-NM (0.325 mg/kg, i.p.) starting on day 14 significantly reduced the percentage of edema and increased weight growth. However, the same dose of LX failed to confer any significant change. Additionally, LX-NM significantly attenuated the rise of tumor necrosis factor-α (TNF-α), interleukin-1β, prostaglandin E2, nuclear factor-κβ, malondialdehyde and nitric oxide serum levels. In contrast, LX failed to show any significant reduction in elevated serum biomarkers except for TNF-α.ConclusionLX-NM is an alternative delivery system that is simply prepared at low costs. It showed a superior therapeutic efficacy against RA compared to free LX. Thus, LX-NM can be considered as a promising candidate for treatment of RA and similar inflammatory disorders.

In Vitro and In Vivo Anti-Allergic and Anti-Inflammatory Effects of eBV, a Newly Developed Derivative of Bee Venom, through Modulation of IRF3 Signaling Pathway in a Carrageenan-Induced Edema Model.

BackgroundBee venom (BV), a type of toxin extracted from honeybees (Apis mellifera), has been empirically and widely used to treat inflammatory diseases throughout Asia. Essential BV (eBV) was developed by removing phospholipase A2 (PLA2) and histamine to lower occurrence of allergic reaction. This study investigated the anti-allergic and anti-inflammatory activities of eBV in vitro and in vivo and its underlying mechanism of action.MethodsThe anti-inflammatory potential of eBV was assessed in vivo using a carrageenan-induced paw edema model. To further investigate the mechanism by which eBV exerts anti-allergic and anti-inflammatory effects, compound 48/80-stimulated RBL-2H3 cells and lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophage cells were studied in vitro.ResultsRelease of β-hexosaminidase and histamine was increased by eBV in a dose-dependent manner, but these levels were lower in eBV compared to original BV at the same concentration. In addition, eBV suppressed compound 48/80-induced expression of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in RBL-2H3 cells. eBV was also shown to suppress nitric oxide (NO) production by down-regulating mRNA expression and subsequent protein expression of inflammatory mediators in LPS-induced RAW 264.7 cells. Phosphorylation of activators and signal transducers of transcription 1/interferon regulatory factor 3 (STAT1/IRF3) was attenuated by eBV treatment. eBV significantly inhibited carrageenan-induced acute edema in vivo. Serum levels of prostaglandin E2 (PGE2), TNF-α, and IL-1β were also down-regulated by eBV.ConclusionsThese results demonstrate that eBV inhibits allergic and inflammatory response by reducing inflammatory mediator production via regulation of the STAT1/IRF3 signaling pathway, suggesting that eBV is a feasible candidate for regulation of allergic-inflammatory response in complementary and alternative medicine.

Modulation of acute and chronic inflammatory processes by a traditional medicine preparation GCSB-5 both in vitro and in vivo animal models

Aim of this study GCSB-5 is a traditional medicine preparation composed with six oriental herbs which have been widely used for the inflammatory diseases in Asia. In the present study, we have demonstrated the anti-inflammatory effects of GCSB-5 in vivo and in vitro along with its underlying mechanism of action. Methods The acute and chronic inflammation models in animals were applied to investigate the anti-inflammatory effects of GCSB-5. To further investigate the mechanism of the anti-inflammatory activity, lipopolysaccharide (LPS)-induced murine macrophage RAW264.7 cells were also employed. Results In in vivo animal model, oral administration of GCSB-5 significantly inhibited TPA- and carrageenan-induced acute edema and adjuvant-induced arthritis. The vascular permeability, leukocyte migration, and granuloma formation were also inhibited by GCSB-5. In accordance, GCSB-5 suppressed the LPS-induced nitric oxide (NO) production by the downregulation of mRNA and protein expressions of inducible nitric oxide synthase (iNOS). GCSB-5 also suppressed the expressions of cyclooxygenase-2 (COX-2) and inflammatory cytokines such as interleukin-1β and interferon-β. The activation of NF-κB by LPS was also alleviated by GCSB-5, which correlated with its inhibitory effect on IkB degradation. The signaling pathway with the activation of Akt was also attenuated by the treatment by GCSB-5. Conclusions Taken together, our results demonstrate that GCSB-5 reduces the development of acute and chronic inflammation and its anti-inflammatory property might in part be a function of the inhibition of iNOS and COX-2 expression via down-regulation of the Akt signal pathway and inhibition of NF-κB activation. These findings suggest that GCSB-5 might be an applicable therapeutic traditional medicine in the regulation of the inflammatory response.

Prevention of arthritic inflammation using an oriental herbal combination BDX-1 isolated fromAchyranthes bidentata andAtractylodes japonica

An oriental herbal combination (BDX-1) was isolated from Achyranthes bidentata and Atractylodes japonica. We previously tested the clinical effectiveness of BDX-1 in rheumatoid arthritis (RA) patients and found that it has a beneficial therapeutic effect. Here, we provide experimental evidence for the effectiveness of BDX-1 on RA in murine models. The oral administration of BDX-1 was found to markedly inhibit collagen-induced arthritis, adjuvant-induced arthritis, and zymosan-induced inflammation. It also inhibited carrageenan-induced acute edema and acetic acid-induced writhing response. In addition, the biological activity of BDX-1 was found to be strongly increased by fermentation. Our results suggest that BDX-1 could be useful for the treatment of rheumatoid arthritis.

Antiarthritic effect of bee venom: Inhibition of inflammation mediator generation by suppression of NF‐κB through interaction with the p50 subunit

To investigate the molecular mechanisms of the antiarthritic effects of bee venom (BV) and melittin (a major component of BV) in a murine macrophage cell line (Raw 264.7) and in synoviocytes obtained from patients with rheumatoid arthritis. We evaluated the antiarthritic effects of BV in a rat model of carrageenan-induced acute edema in the paw and in a rat model of chronic adjuvant-induced arthritis. The inhibitory effects of BV and melittin on inflammatory gene expression were measured by Western blotting, and the generation of prostaglandin E(2) (PGE(2)) and nitric oxide (NO) and the intracellular calcium level were assayed. NF-kappaB DNA binding and transcriptional activity were determined by gel mobility shift assay or by luciferase assay. Direct binding of BV and melittin to the p50 subunit of NF-kappaB was determined with a surface plasmon resonance analyzer. BV (0.8 and 1.6 mug/kg) reduced the effects of carrageenan- and adjuvant-induced arthritis. This reducing effect was consistent with the inhibitory effects of BV (0.5, 1, and 5 mug/ml) and melittin (5 and 10 mug/ml) on lipopolysaccharide (LPS; 1 mug/ml)-induced expression of cyclooxygenase 2, cytosolic phospholipase A(2), inducible NO synthase, generation of PGE(2) and NO, and the intracellular calcium level. BV and melittin prevented LPS-induced transcriptional and DNA binding activity of NF-kappaB via the inhibition of IkappaB release and p50 translocation. BV (affinity [K(d)] = 4.6 x 10(-6)M) and melittin (K(d) = 1.2 x 10(-8)M) bound directly to p50. Target inactivation of NF-kappaB by directly binding to the p50 subunit is an important mechanism of the antiarthritic effects of BV.

Pleiotropic consequences of Bruton tyrosine kinase deficiency in myeloid lineages lead to poor inflammatory responses

AbstractBruton tyrosine kinase (Btk), a non-receptor-associated tyrosine kinase of the Tec family, appears to participate in many myeloid cell functions. We show that macrophages from X-linked immunodeficient (XID) mice lacking functional Btk cannot generate efficient bursts of reactive oxygen intermediates (ROIs). The induction of apoptotic cell death by inflammatory stimuli is also enhanced in XID macrophages. Phagocytosis of bacterial particles is only marginally affected in them. In vivo, XID mice show reduced severity of inflammatory diseases in models of experimental autoimmune encephalomyelitis (EAE), dextran sulfate sodium (DSS)-induced colitis, and carrageenan-induced acute edema. Also, polymorphonuclear neutrophil granulocytes (PMNs) in XID mice show poor ROI and nitric oxide (NO) induction, along with a reduction in PMN recruitment to peritoneal inflammation. XID mice show reduction in PMN numbers in peripheral blood, and their bone marrow shows a reduction in the numbers of both monocytic and granulocytic lineages, extending to the earliest progenitor populations. Thus, Btk is likely to play a significant role at multiple points during the development and functioning of the myeloid lineages, affecting the outcome of many infectious as well as noninfectious inflammatory events in vivo. (Blood. 2004;104:1191-1197)

Anti-inflammatory and Analgesic Effects of Drypemolundein A, a Sesquiterpene Lactone from Drypetes molunduana

Previous pharmacological screening in our laboratory showed analgesic and anti-inflammatory effects of a crude stem bark extract of Drypetes molunduana. Phytochemical studies of this plant led to the isolation an structural elucidation of seven pentacylic triterpenes and one lignan, which were already known compounds, and a new furanosesquiterpene lactone, Drypemolundein A. The purpose of this study was to examine the anti-inflammatory and analgesic activities of drypemolundein A. The compound was studied against carrageenan-induced acute edema. At doses of 10 and 20 mg/kg, orally administered, it significantly reduced (57.57 and 66.66% inhibition at 1 h intervals, respectively) paw edema. At the same doses, this sesquiterpene lactone also exhibited significant analgesic action in force-induced pain in rat paw. These results indicate that drypemolundein A functions as an effective anti-inflammatory and analgesic agent.

Prolonged plasma levels of ketoprofen after oral administration of its α-cyclodextrin conjugate/ethylcellulose dispersion in rats

6A-O-[2-(3-benzoylphenyl)propinoyl]-α-cyclodextrin (KP/α-CyD conjugate), in which an anti-inflammatory drug, ketoprofen (KP), is covalently bound to one of the primary hydroxyl groups of α-cyclodextrin, was prepared, and the CyD conjugate-based prolonged-release system was designed by combining the KP/α-CyD conjugate (used as a delayed-release fraction) with the KP/ethylcellulose (EC) solid dispersion (used as a slow-release fraction). The conjugate showed a typical delayed-release pattern after oral administration to rats, i.e., plasma levels of KP increased after a lag time of about 3 h and reached a maximum concentration at about 9 h. The co-administration of the conjugate and the EC solid dispersion gave a sustained-release pattern of KP, i.e., a constant plasma KP level was maintained for at least 24 h. The long circulating release patterns in plasma KP levels after oral administration were reflected in the anti-inflammatory effect using with carrageenan-induced acute edema in rat paw.

Enhancement of the antiinflammatory effect of ethyl 4-biphenylyl acetate in ointment by beta-cyclodextrin derivatives: increased absorption and localized activation of the prodrug in rats.

Ethyl 4-biphenylyl acetate (EBA) is a prodrug of the antiinflammatory 4-biphenylyl acetic acid (BPAA). The inclusion complexes of EBA with beta-cyclodextrin (beta-CyD), heptakis(2,6-di-O-methyl)-beta-cyclodextrin (DM-beta-CyD), and 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CyD) at a molar ratio of 1:2 (EBA:cyclodextrin) were prepared and used to make hydrophilic antiinflammatory ointments. The in vitro release of EBA from the ointments was enhanced by complexation in the order of beta-CyD less than DM-beta-CyD less than or equal to HP-beta-CyD. The improvement correlated with the improved solubility and not with the decreased diffusibility observed to occur upon the complexation of EBA. In vivo the complexation with cyclodextrin derivatives increased both the release of EBA from the vehicle and its conversion in the underlying tissue to BPAA, but the total of EBA and BPAA in the tissue was decreased. In vitro studies confirmed that the effects of cyclodextrin derivatives on the conversion were exerted indirectly. The combination of the enhanced release and of the enhanced prodrug hydrolysis by esterases in the site where the antiinflammatory action is required resulted in increased therapeutic effects. In the model of carrageenan-induced acute edema in rat paw, the complexation improved the therapeutic effects over those of EBA alone in the order of beta-CyD less than DM-beta-CyD less than HP-beta-CyD. HP-beta-CyD may be a particularly useful cyclodextrin derivative since it improves the topical availability and does not irritate tissues.