Paw Edema Rat Model Research Articles

Tailoring of Novel Bile Salt Stabilized Vesicles for Enhanced Transdermal Delivery of Simvastatin: A New Therapeutic Approach against Inflammation.

Simvastatin (SMV), a cholesterol-lowering agent, has antioxidant and anti-inflammatory effects. Nevertheless, the oral use of SMV is linked with poor systemic bioavailability owing to its limited aqueous solubility and extensive first-pass metabolism. The aim of this study was to evaluate the feasibility of transdermal delivery of SMV using bile salt stabilized vesicles (bilosomes) for enhancing the anti-inflammatory potential of SMV. SMV-loaded bilosomes (SMV-BS) were prepared by the thin film hydration technique and optimized by 33 Box-Behnken design. The fabricated SMV-BS were assessed for vesicle size, entrapment efficiency (% EE) and cumulative drug release. The optimized formula was incorporated into HPMC gel and investigated for physical properties, ex vivo permeation, in vivo pharmacokinetic study and anti-inflammatory potential in inflamed paw edema rat model. The optimized SMV-BS showed vesicle size of 172.1 ± 8.1 nm and % EE of 89.2 ± 1.8%. In addition, encapsulating SMV within bilosomal vesicles remarkably sustained drug release over 12 h, compared to plain drug suspension. Furthermore, SMV-loaded bilosomal gel showed a three-fold enhancement in SMV transdermal flux, compared to plain drug suspension. Most importantly, the relative bioavailability of SMV-BS gel was ~2-fold and ~3-fold higher than those of oral SMV suspension and SMV gel, respectively. In carrageenan-induced paw edema model, SMV-BS gel induced a potent anti-inflammatory effect, as evidenced by a remarkable reduction in paw edema, which was comparable to that of the standard anti-inflammatory drug, indomethacin. Collectively, bilosomes might represent a plausible transdermal drug delivery system that could enhance the anti-inflammatory activity of SMV by boosting its skin permeation and its systemic bioavailability.

Evaluation of Different Surface Coating Agents for Selenium Nanoparticles: Enhanced Anti-Inflammatory Activity and Drug Loading Capacity.

BackgroundInflammation is the keystone in the disease’s pathological process in response to any damaging stimuli. Therefore, any agent that inhibits the inflammatory response is under focus, either a drug or a bioactive compound. Selenium nanoparticles have drawn attention in various biomedical applications, including the anti-inflammatory activity.PurposeIn the current study, we aimed to evaluate the capacity of different surface coating materials (soybean lecithin, PEG 6000, and β-cyclodextrin) to enhance the anti-inflammatory activity of the synthesized selenium nanoparticles (SeNPs). The capability of the coated SeNPs to adsorb indomethacin (IND) on their surfaces compared to the uncoated SeNPs was also evaluated.MethodsSeNPs were synthesized, coated with different materials, and characterized in vitro using X-ray diffraction, UV-Vis spectrophotometer, FTIR, SEM, TEM, and particle size and zeta potential measurements. The in vivo anti-inflammatory activity of the uncoated/coated SeNPs loaded into hydrogel was evaluated using a carrageenan-induced paw edema rat model. The effect of SeNPs surface coatings was further evaluated for IND loading capacity.ResultsOur findings proved the superior anti-inflammatory activity of all coated SeNPs compared to the uncoated SeNPs, especially with β-cyclodextrin surface coating. Regarding the IND loading capacity of the prepared uncoated/coated SeNPs, the amount of drug loaded was 0.12, 1.12, 0.3, and 0.14 µg IND/µg SeNPs for the uncoated, lecithin-, PEG- and β-CD-coated SeNPs, respectively.ConclusionSurface functionalization of SeNPs can provide a synergistic therapeutic activity. Our results are promising for further investigation of the in vivo anti-inflammatory synergistic activity of the IND-loaded surface-coated SeNPs.

Antihyperuricemic, Anti-Inflammatory and Antihypertensive Effect of a Dry Extract from Solidago virgaurea L. (Asteraceae)

Solidago virgaurea L. is a perennial plant used in European traditional medicine as a diuretic or a remedy for inflammatory conditions of the urinary tract but also for gout, especially in the Balkans. The present study was focused on a preclinical, in vivo evaluation of antihyperuricemic, anti-inflammatory, and antihypertensive effects of a dry extract from S. virgaurea L. (ESV). Colorimetric and HPLC–MS techniques were used to identify the main chemical constituents of ESV. Antihyperuricemic effect of ESV was assessed in a rat model of hyperuricemia induced by the administration of potassium oxonate. Antihypertensive effect of ESV was evaluated in hyperuricemic rats by monitoring systolic blood pressure with a non-invasive blood-pressure recording system. The anti-inflammatory effect of ESV was tested using a rat model of paw edema. The main chemical constituents of ESV were rutin and phenolic acids represented by chlorogenic and caffeic acid. ESV demonstrated significant antihyperuricemic effects in rats due to an uricosuric mechanism. Additionally, ESV reduced the progression of arterial hypertension in hyperuricemic rats and also showed anti-inflammatory properties slightly inferior to diclofenac. The results suggest that ESV could be a natural remedy for the treatment of gout and protection against endothelial dysfunction caused by hyperuricemia.

Anti-inflammatory effect of Ganluyin, a Chinese classic prescription, in chronic pharyngitis rat model

BackgroundGanluyin (GLY) is a famous classical prescription with a long history of use as a treatment for inflammatory conditions such as chronic pharyngitis (CP) in many parts of China. However, it has not been developed as a modern pharmaceutic and its anti-inflammatory mechanisms remain unclear. The aim of this study was to assess the anti-inflammatory efficacy of GLY and potential mechanisms in a rat model of CP.MethodsThe chemical profile of GLY was analyzed by HPLC-UV. We used a mouse model of ear edema and a rat model of paw edema. Specifically, xylene was used to induce edema on the surface of one ear in mice, and carrageenan was injected subcutaneously into the right hind paws of rats to induce paw edema. The paw thickness, ear weight, and ear perfusion were measured and recorded. The CP model in rats was induced by irritating the throat with 5% ammonia and was used to evaluate the therapeutic efficacy of GLY. Levels of interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor (TNF-α), and prostaglandin E2 (PGE2) were measured by ELISA in serum, and protein expression of cyclooxygenase-2 (COX-2) and nuclear factor kappa-B p65 (NF-κB p65) in the throat were detected by immunohistochemistry and Western blot to evaluate the anti-inflammatory mechanism of GLY. Hematological assays were also conducted.ResultsThere were four flavonoids identified in GLY: naringin, neohesperidin, baicalin, and wogonoside. The oral administration of GLY showed a significant inhibitory effect on xylene-induced ear swelling and ear blood flow in mice and significantly ameliorated rat right hind paw edema at doses of 6.2 and 12.4 g/kg. Mechanistic studies found that the anti-inflammatory activity of GLY was related to the inhibition of pro-inflammatory cytokines such as IL-1β, IL-6, TNF-α, and PGE2 and that GLY reduced the expression of COX-2 and NF-κB p65 proteins in the throat, attenuated throat injury, and reduced inflammatory exudates. Hematological analysis showed that treatment with GLY prevented increases in white blood cell (WBC), neutrophil (NEUT), lymphocyte (LYMPH) and monocyte (MONO) levels.ConclusionsThese studies indicated that GLY has beneficial anti-inflammatory effects on CP and that it acts through reducing pro-inflammatory factors such as IL-1β, IL-6, TNF-α, and PGE2, as well as decreasing WBC, NEUT, LYMPH and MONO levels and decreasing the expression of COX-2 and NF-κB p65 proteins. These findings may lay the groundwork for further studies of GLY as a suitable candidate for the treatment of inflammatory diseases such as CP.

Rhoifolin Alleviates Inflammation of Acute Inflammation Animal Models and LPS-Induced RAW264.7 Cells via IKKβ/NF-κB Signaling Pathway.

Rhoifolin (ROF) is a main effective component in Citrus grandis 'Tomentosa'. ROF has a potential anti-inflammatory activity, but its specific effects and mechanisms have not been studied. This study investigated the anti-inflammatory activity of ROF and searched for its possible molecular mechanisms. A mouse model of acute inflammation was induced by lipopolysaccharide, and the effects of ROF on pathological damages of the lung and liver were observed. Carrageenan-induced paw edema rat model was used to evaluate the effect of ROF on the volume of swelling paw. In LPS-induced RAW264.7 macrophages, the expression levels of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α were measured using ELISA. Real-time PCR was used to measure the mRNA levels of iNOS and CCL2. Western blot was used to detect the activation of IκBα and IKKβ in NF-κB signaling pathways. The results showed that ROF accelerated the recoveries of liver and lung tissue damages in acute inflammation mice and inhibited carrageenan-induced paw edema in rats; in addition, ROF significantly suppressed the secretion of TNF-α, IL-1β, and IL-6 in the serum of rats and mouse model. In LPS-induced RAW264.7 cells, 100 μmol/L ROF enhanced cell viability and suppressed the production of TNF-α, IL-6, and IL-1β significantly. ROF also decreased the mRNA expression of iNOS and CCL2 and inhibited IκBα and IKKβ phosphorylation. In summary, ROF had a potential therapeutic value for inflammation. Our research provided experimental basis for the further development of ROF as an anti-inflammatory drug and for clarifying the anti-inflammatory substance basis of Citrus grandis 'Tomentosa'. Graphical Abstract.

Formulation, characterization and pharmacological evaluation of anti-inflammatory polyphyto matrix tablet as a novel drug delivery system

Objective: To deal with the formulation, characterization and pharmacological evaluation of anti-inflammatory polyphyto matrix tablet containing Carica papaya, Vitex negundo, Moringa oleifera and Boswellia serrata used as a novel drug delivery system. An attempt has been made to develop polyphyto matrix tablets by using HPMC and ethyl cellulose. Methods: Pharmacological screening of polyphyto matrix tablet was evaluated by using the carrageenan-induced paw edema rat model and the study carried out by using various doses (100, 200 and 300 mg/kg body weight) of three different polyphyto matrix formulations. Diclofenac sodium was used as a standard drug, due to its considerable report on antiinflammatory importance. Data were expressed by mean±SD; statistical analysis was performed by using ANOVA and p less than 0.05 considered as statistically significant. Results: Physical and chemical evaluation parameters of polyphyto matrix formulation exhibits potent and dose-dependent anti-inflammatory activity in all the tested animal groups. Formulation F1 significantly (p less than 0.05) suppresses the inflammation in the rat paw and found to be preeminent and stable in comparison with standard and other two (F2 and F3) formulations. Conclusion: Study reveals that the polyphyto matrix formulation could be useful as either an alternative or a complementary therapy in the management of all types of inflammation. It may be due to presence of terpenoids, alkaloids, glycosides and other phytochemical in herbs.

In Vivo Evaluation of the Anti-Inflammatory Effect of Pistacia lentiscus Fruit Oil and Its Effects on Oxidative Stress.

In order to find new topical anti-inflammatory agents, we had recourse to a medicinal plant. This work was designed to determine the topical anti-inflammatory effect of Pistacia lentiscus fruit oil (PLFO), using carrageenan-induced paw edema rat model, and to evaluate its effects on oxidative stress. The topical anti-inflammatory activity of PLFO was compared to Inflocine® and estimated by measuring the diameter of paw edema, for 5 hours at a 1-hour interval. After that the rats were scarified and the inflamed paw tissue was removed for the exploration of some parameters of oxidative stress and histopathology. PLFO showed a significant anti-inflammatory activity in comparison with the Inflocine. The percentages of edema inhibition were 70% and % 51.5% (p < 0.01), respectively, after five hours. The treatment with PLFO and Inflocine led to significant increases (p ≤ 0.05) in the activities of CAT, SOD, and GPX and significant decreases in the MDA level and AOPP activity in the paw tissue after Carr injection, in comparison with the Carr group. Therefore, our findings demonstrate that PLFO might accelerate the development of new drugs which could be used scientifically as a source for natural health products in the treatment of topical inflammation.

Synthesis and Anti‐Inflammatory Activity of a Novel Series of Diphenyl‐1,2,4‐triazoles and Related Derivatives

In the present investigation we have synthesized a series of new 1‐[3‐(4‐substitutedphenyl)‐5‐phenyl‐4H‐1,2,4‐triazol‐4‐yl]urea and 1‐[3‐(4‐substitutedphenyl)‐5‐phenyl‐4H‐1,2,4‐triazol‐4‐yl]thiourea derivatives (4Ia ‐ 4IId). The newly synthesised derivatives were characterized by using the data of IR, 1H NMR and Mass Spectral analysis. Thus synthesised and characterized targetted compounds were further screened for their anti‐inflammatory activity by using Carrageenan – induced paw edema rat model. Among all the newly synthesized derivatives, Compounds 4Ia‐4Ic and Compounds 4IIa‐4IId were reduced the inflammation very significantly (p&lt;0.0001), thus these compounds showed promising anti‐inflammatory activity and only one compound (4Id) showed moderate anti‐inflammatory activity (p&lt;0.05).

Experimental study on anti-inflammatory activity of a TCM recipe consisting of the supercritical fluid CO2 extract of Chrysanthemum indicum, Patchouli Oil and Zedoary Turmeric Oil in vivo

Ethnopharmacological relevanceChrysanthemum indicum (Compositae) Linné, Pogostemon cablin (Blanco) Benth and Curcuma wenyujin (Zingiberaceae) Y. H. Chen et C. Ling are three of the extensively used herbal remedies among traditional Chinese medicines for the purpose of anti-inflammation. A traditional Chinese medicine (TCM) recipe named CPZ consisting extracts of the above three herbs, has shown noteworthy anti-influenza activity, which is closely related to its anti-inflammatory feature. Aim of this studyTo investigated the anti-inflammtory activity of CPZ in vivo for a further exploration of the recipe's anti-inflammatory properties. Materials and methodsThe anti-inflammatory property of CPZ on acute inflammation was evaluated by inflammatory models of dimethylbenzene (DMB)-induced ear vasodilatation and acetic acid-induced capillary permeability enhancement in mice, as well as the carrageenan-induced paw edema rat model, in which inflammation-related cytokine including prostaglandin E2 (PGE2), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and nitric oxide (NO) in the edematous paw tissue were determined by enzyme linked immunosorbent assay (ELISA). Moreover, effect of CPZ on chronic inflammation was observed through granuloma formation in rats subjected to cotton pellet implantation. ResultsCPZ (340, 170, and 85mg/kg for mice, p.o.) not only decreased the DMB-induced ear vasodilatation but also attenuated capillary permeability under acetic acid challenge in mice. And the significant inhibition on carrageenan-induced paw edema was observed. Further more, the ELISA results showed that CPZ (170, 85, and 42.5mg/kg for rats, p.o.) could up-regulate the level of IL-1β in the edema paw tissue of rats significantly while down-regulate that of PGE2, but no apparent effect on TNF-α or NO was observed in the test. Besides, CPZ had a certain degree of restraining effect on the cotton pellet-induced granuloma formation in rats and the highest dose of 170mg/kg even showed a significant suppression on it. ConclusionThe above results indicated that CPZ possessed a potent anti-inflammatory activity, which is indicated to be closely associated with its regulation on IL-1β and PGE2 thereby mediating the inflammatory response acting at an appropriate level.

Anti-inflammatory and immunosuppressive activity of mixture of Trachelospermum asiaticum and Paeonia suffruticosa extracts (novel herbal formula SI000902)

The present research aimed at determining the anti-inflammatory and immunosuppressive effect of novel herbal formula SI000902, ethanolic extract of Trachelospermum asiaticumvar. intermedium Nakai (TA) and Paeonia suffruticosa Andrews (PS) (TA and PS, mixed 1:1). The in vitro anti-inflammatory and immunosuppressive effect of SI000902 was investigated using cytokines and nitrogen oxide (NO) inhibition potency along with interferon(INF)-γ and interleukin (IL)-2, and IL-6 levels were evaluated in human T-cells. Furthermore, the in vivo anti-inflammatory effect was scrutinized by carrageenan-induced paw edema in rats. SI000902 strongly inhibited NO (91.3%), tumor necrosis factor (TNF) (31.5%), IL-6 (76.7%), and IL-1 (86.5%). In addition, it suppressed the expression of INF-γ (56.9%), IL-2 (37.1%), and IL-6 (44.3%) in human T-cells and also showed significant decrease in paw edema in carrageenan-induced paw edema rat model. These findings demonstrate that SI000902 has excellent anti-inflammatory and immunosuppressive activity and might be a potential natural source for the treatment of inflammatory diseases such as rheumatoid arthritis (RA). Key words: Trachelospermum asiaticum, Paeonia suffruticosa, anti-inflammatory,immunosuppressive, T-cell suppression.

An orally active natural product based anti-inflammatory small molecule (RNV-2005) (117.19)

Abstract RNV-2005 is a natural product based molecule originally designed based on its interaction with glucocorticoid receptor (GR). The effective dose of RNV-2005 was found to be in the range of 0.3-10 mg/kg in rodent models. Unlike most analgesic and NSAID compounds, RNV-2005 was non-ulcerogenic up to a tested dose of 200 mg/kg. In an acute toxicity study, RNV-2005 did not show any adverse effect at a highest tested dose of 2000 mg/kg. The LD50 dose of RNV-2005 is therefore not established. A 70-80% reduction in paw edema was observed in animals treated with RNV-2005 at a dose of 10 mg/kg in carrageenan induced paw edema rat model. The analgesic properties of RNV-2005 was measured using tail flick latency and acid induced writhing reflex in Albino mice at doses 0.3-3 mg/kg. In a LPS induced ex-vivo study in SW mice, reduction of cytokines such as TNFα, IL-1β, IL-6 and IL-12 was measured in plasma. Further studies of RNV-2005 in collagen-induced arthritis in DBA/1J mice, adjuvant induced arthritis in Lewis rats, PK studies and in vitro inhibition assays for COX-1 and COX-2 in cell based assays will be presented. Similarly, the molecular mechanisms underlying GR mediated inflammatory responses, with an emphasis on NF-κB and AP-1 and their respective signaling pathways will be discussed. These results with preliminary safety data encourage the clinical potential of RNV-2005 towards development of a novel anti-inflammatory molecule with high therapeutic index.

Submicron Emulsion Vehicle for Enhanced Transdermal Delivery of Steroidal and Nonsteroidal Antiinflammatory Drugs

Significant improvement is demonstrated for transdermal delivery of steroidal and nonsteroidal antiinflammatory drugs (NSAID), including betamethasone valerate and dipropionate, indomethacin, diclofenac, piroxicam, and naproxen, when formulated in a submicron Emulsion (SME) vehicle rather than in standard creams. SMEs comprise oil droplets, with mean size of ∼100nm (0.1 µm), dispersed in a continuous water phase. Hydrophobic drugs are incorporated into the oil phase of the SME, resulting in improved penetration and increased efficacy of the incorporated antiinflammatory drug. The performance of medicated topical SME was compared with that of regular topical cream formulations, as measured by the carrageenan‐induced paw edema rat model. Indomethacin in SME topical vehicle was 50% more active than in regular cream base, Diclofenac in SME proved to be 40% more active than Voltaren Emulgel. Improvement of steroidal antiinflammatory drugs action in topical SME cream was even more pronounced; that is, up to 3–4‐fold. Antiinflammatory drugs in SME also demonstrate noticeable systemic activity, but for regional edema treatment, local delivery is advantageous. The new SME delivery system was tested for primary irritation in humans in a 48‐h trial. Low irritancy and excellent human acceptance for SME placebo or diclofenac‐loaded SME cream make this novel transdermal/topical DDS attractive for further development.