Anti-inflammatory Effects In Rats Research Articles

The combination of red palm oil and rooibos show anti-inflammatory effects in rats.

BackgroundRed palm oil (RPO) and rooibos have been shown to exhibit cardioprotective properties. RPO is rich in essential fatty acids and fat soluble antioxidants while rooibos contains polyphenolic compounds with a unique composition of flavonoids. They exert their biological effects in different cellular compartments. Therefore the combination of these two natural food compounds has the potential to enhance the spectrum of available dietary antioxidants in different cellular compartments, which could result in an enhanced protection against certain pathological conditions such as inflammation.MethodsMale Wistar rats weighing 150-200 g were supplemented with RPO, rooibos or their combination for 28 days. The Langendorff system and the lipoposaccharide (LPS)-induced inflammatory model were used to establish if RPO and rooibos, when supplemented alone or in combination, will reverse the negative effects of LPS on cardiac function at baseline. The effect of dietary intervention was also investigated on modulation of pro-inflammatory and anti-inflammatory cytokines in plasma and myocardial tissue.Results and discussionThe LPS resulted in induction of systemic inflammation as evidenced by increased levels of IL-1β in plasma of LPS-treated rats compared to their non-treated control counterparts. Dietary supplementation and LPS treatment did not have an effect on baseline cardiac functional parameters. However, the elevation of IL-1β levels in plasma of LPS-induced rats consuming either RPO or rooibos alone were paralleled with increased levels of the anti-inflammatory cytokine, IL-10. The combination of rooibos and RPO was associated with enhanced endogenous production of myocardial IL-10 in LPS-induced rats.ConclusionThe results of this study indicate that RPO and rooibos when supplemented individually showed anti-inflammatory effect at systemic level while their combination exhibited an enhanced anti-inflammatory effect in the myocardial tissue. Therefore, the findings in the current study argue that the combination of these two natural food substances could be beneficial in clinically relevant conditions where inflammation plays a role.

Dipeptidyl Peptidase-4 Inhibitor Alogliptin Prevents Further Dilatation of Abdominal Aortic Aneurysm Through Anti-oxidant and Anti-inflammatory Effect in Rats

landing zone, of whom 3 with concomitant extra-anatomic debranching of the supra-aortic vessels. Technical success was achieved in 100%. The 30-day mortality rate was 16.7% (n 1⁄4 4). Two patients had paraplegia. Neither stroke nor renal insufficiency requiring new dialysis occurred. During a mean follow-up of 28 months, another death in relation with dissection occurred and 8 patients (33%) required reintervention. All reintervention were managed by endovascular means. At last follow up CT-scan, 8 patients (33%) had complete remodeling of the aortic wall. Conclusion: This study confirms the feasibility of TEVAR for R-BAD and its lower perioperative morbidity and mortality rate compared to open surgery, reducing by more than 2 third the 30-day mortality. However the rate of reintervention is high and a long term follow up is mandatory.

Comparison of piroxicam pharmacokinetics and anti-inflammatory effect in rats after intra-articular and intramuscular administration.

This study evaluated the pharmacokinetic profile and therapeutic efficacy of piroxicam (PX), a long acting non-steroidal anti-inflammatory drug for the treatment of arthritis, following intra-articular (IA) injection in comparison to the pharmacokinetic profile and therapeutic efficacy of PX after intramuscular (IM) injection. In the pharmacokinetic study in rats, systemic exposure and pharmacokinetic parameters of PX after a single IA dose were compared with systemic exposure and pharmacokinetic parameters of PX after administration of the same dose IM (0.6 mg/kg). The anti-inflammatory and analgesic effects of IA PX were evaluated simultaneously in a monoiodoacetate-induced osteoarthritis rat model. The plasma PX concentration rapidly rose following IA injection, and it was comparable to the plasma PX concentration following IM injection, suggesting the rapid efflux of the drug molecule from the joint cavity. However, in the efficacy study, the IA PX administration significantly reduced the knee swelling by reducing the level of prostaglandin E2 in the joint, compared to that following administration of IA vehicle and after administration of the IM PX dose. In addition, we found that the anti-inflammatory and anti-nociceptive efficacies of IA PX were synergistically increased upon co-treatment with hyaluronic acid (HA), a potent agent for the treatment of osteoarthritis, at the weight ratio of 1:1 or 1:2, and these effects were more pronounced than those following administration of HA or PX alone. In conclusion, this study demonstrated the efficacy of the IA use of PX alone and/or in combination with HA in osteoarthritis.

Anti-Inflammatory Effects of the Bioactive Compound Ferulic Acid Contained in Oldenlandia diffusa on Collagen-Induced Arthritis in Rats.

Objectives. This study aimed to identify the active compounds in Oldenlandia diffusa (OD) decoction and the compounds absorbed into plasma, and to determine whether the absorbed compounds derived from OD exerted any anti-inflammatory effects in rats with collagen induced arthritis (CIA). Methods. The UPLC-PDA (Ultra Performance Liquid Chromatography Photo-Diode Array) method was applied to identify the active compounds both in the decoction and rat plasma. The absorbable compound was administered to the CIA rats, and the effects were dynamically observed. X-ray films of the joints and HE stain of synovial tissues were analyzed. The levels of IL-1β and TNF-α in the rats from each group were measured by means of ELISA. The absorbed compound in the plasma of CIA rats was identified as ferulic acid (FA), following OD decoction administration. Two weeks after the administration of FA solution or OD decoction, the general conditions improved compared to the model group. The anti-inflammatory effect of FA was inferior to that of the OD decoction (P < 0.05), based on a comparison of IL-1β TNF-α levels. FA from the OD decoction was absorbed into the body of CIA rats, where it elicited anti-inflammatory responses in rats with CIA. Conclusions. These results suggest that FA is the bioactive compound in OD decoction, and FA exerts its effects through anti-inflammatory pathways.

Evaluation of Anti-Inflammatory and Anti-Nociceptive Effects of Defatted Fruit Extract of Olea europaea.

Fruits of Olea europaea L. have been used for centuries in folk medicine to treat many inflammatory diseases. In order to evaluate the anti-nociceptive activities of the methanolic and aqueous extracts of defatted fruits of O. europaea, formalin test was used and for evaluation of anti-inflammatory effects of the extract, the volume of paw edema was measured. The results revealed that both extracts did not exhibit significant analgesic activity in the first phase of formalin test, whereas methanolic extract at the 600 mg/Kg dose and aqueous extract at the 450 and 600 mg/Kg doses could inhibit induced pain in the second phase of formalin test. Furthermore, the results of paw edema volume measurement indicated that the aqueous extract has anti-inflammatory effects at dose of 600 mg/Kg. Induced anti-nociception by aqueous olive extract was not reversed by naloxone, which indicates that the opioid receptors are not involved in the analgesic effects of the extracts. The present data pointed out that the extracts of olive defatted fruit have anti-nociceptive and anti-inflammatory effects in rats but further studies are needed to elucidate the mechanism(s) of action and active components which are involved in analgesic and anti-inflammatory effects.

Pharmacokinetic/pharmacodynamic modeling of antipyretic and reducing plasma concentration of NO effects of Rheum palmatum in rat

Pharmacokinetic-pharmacodynamic (PK-PD) modeling was used to characterize the antipyretic and anti-inflammatory effects in rats of Rhein, a major component in rhubarb. Twenty-four healthy male Sprague-Dawley (SD) rats were randomly into four groups, of 6 each. The rats in first group were injected intravenously with lipopolysaccharide (LPS, 100 microg x kg(-1)). The second group rats were given rhubarb decoction (RD, 1.54 g x kg(-1)) by oral administration alone. The rats belonging to third group were administered orally RD 30 min after LPS injection. The rest rats were given normal saline only as control group. Orbital sinus blood sampling was collected at different time points. The Rhein and NO concentration in plasma and body temperature (BT) were measured. Relevant data of PK-PD modeling were performed with Kinetica 5. 0. 11. RD could suppress the rise in BT and plasma NO concentration. The antipyretic and anti-inflammatory responses were best described by a Sigmod-E(max) model. Delay between exposure and response was accounted for by a transit compartment model with two parallel transit compartment chains. The results showed that some parameters such as t1/2, C(max) and AUC were significantly increased in rats treated with LPS, compared to those in rats treated with normal saline. The EC50 for antipyretic effect and decrease of plasma NO concentration was respectively equal to 114.1, 90.80 microg x L(-1). The E(max) for antipyretic effect was about 111% of that for increase in BT after LPS injection. The E(max) for anti-inflammatory action was close to 8.399% of that for elevated NO level after modeling. Meanwhile, there was a difference in pharmacokinetic process of Rhein between the impact of normal saline and LPS. So, it can be concluded that the targets of regulating NO production and BT after RD administration may be at the same location. Not only do that, the antipyretic effect induced by RD maybe completely manifest through reducing the plasma concentration of NO.

Propofol exerts anti-inflammatory effects in rats with lipopolysaccharide-induced acute lung injury by inhibition of CD14 and TLR4 expression

We investigated the effect of propofol (Prop) administration (10 mg kg-1 h-1, intravenously) on lipopolysaccharide (LPS)-induced acute lung injury and its effect on cluster of differentiation (CD) 14 and Toll-like receptor (TLR) 4 expression in lung tissue of anesthetized, ventilated rats. Twenty-four male Wistar rats were randomly divided into three groups of 8 rats each: control, LPS, and LPS+Prop. Lung injury was assayed via blood gas analysis and lung histology, and tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) levels were determined in bronchoalveolar lavage fluid using ELISA. Real-time polymerase chain reaction was used to detect CD14 and TLR4 mRNA levels, and CD14 and TLR4 protein expression was determined by Western blot. The pathological scores were 1.2 ± 0.9, 3.3 ± 1.1, and 1.9 ± 1.0 for the control, LPS, and LPS+Prop groups, respectively, with statistically significant differences between control and LPS groups (P < 0.05) and between LPS and LPS+Prop groups (P < 0.05). The administration of LPS resulted in a significant increase in TNF-α and IL-1β levels, 7- and 3.5-fold, respectively (P < 0.05), while treatment with propofol partially blunted the secretion of both cytokines (P < 0.05). CD14 and TLR4 mRNA levels were increased in the LPS group (1.48 ± 0.05 and 1.26 ± 0.03, respectively) compared to the control group (1.00 ± 0.20 and 1.00 ± 0.02, respectively; P < 0.05), while propofol treatment blunted this effect (1.16 ± 0.05 and 1.12 ± 0.05, respectively; P < 0.05). Both CD14 and TLR4 protein levels were elevated in the LPS group compared to the control group (P < 0.05), while propofol treatment partially decreased the expression of CD14 and TLR4 protein versus LPS alone (P < 0.05). Our study indicates that propofol prevents lung injury, most likely by inhibition of CD14 and TLR4 expression.

Antinociceptive and anti-inflammatory effects of Aloe saponaria Haw on thermal injury in rats

Ethnopharmacological relevanceIn Brazil, the plant Aloe saponaria Haw, popularly known as “babosa pintadinha”, has been empirically used for its potential effect on thermal injury. Because there are no scientific data confirming its popular use, the aim of the present study was to investigate the effects of Aloe saponaria on nociceptive and inflammatory parameters in a rat model of thermal injury. Materials and methodsAdult male Wistar rats were subjected to a thermal injury or sham procedure (immersion in water at 70 or 37°C, respectively, for 5 or 8s). Burned animals were topically treated with vehicle (base cream), sulfadiazine 1% (positive control) or Aloe saponaria cream (0.3%–30%) once a day for 2 or 6 days. Each day, 30min before the treatment, we measured nociceptive (static and dynamic mechanical allodynia, thermal allodynia and spontaneous pain) and inflammatory (paw edema) parameters. Moreover, enzymatic indicators of leukocyte infiltration into burned tissue were also determined 2 or 6 days after the thermal injury. ResultsThe thermal injury (fist and second-degree) procedure, but not the sham procedure, induced nociception and inflammation from 1 to 6 days after the injury. The topical treatment with Aloe saponaria cream (10%) reduced nociceptive behaviors from day 1 to 6 (peak at day 2), edema at days 5 and 6 (peak at day 6) and myeloperoxidase, N-acetyl-glucosaminidase and eosinoperoxidase activities at day 6. The antinociceptive and anti-inflammatory effects of Aloe saponaria were obtained with doses of 3%–30%, with maximal inhibition obtained with a dose of 10% (reductions of 39±9%, 41±9%, 31±7%, 83±7% and 23±2% for static and dynamic mechanical allodynia, thermal allodynia, spontaneous pain and paw edema, respectively). ConclusionOur results demonstrate that topically applied Aloe saponaria presented antinociceptive and anti-inflammatory effects in rats subjected to a thermal injury, which supports its traditional use for burn injuries.

Low-level laser therapy improves the inflammatory profile of rats with heart failure

Following heart failure (HF), immune activation leads to an imbalance between pro-inflammatory and anti-inflammatory cytokines. Low-level laser therapy (LLLT) has been used as an anti-inflammatory treatment in several disease conditions. However, the effect of LLLT on the skeletal muscle of rats with HF remains unclear. The present report aimed to evaluate the influence of LLLT on the inflammatory profile of rats with HF. The left coronary artery was ligated to induce HF and a sham operation was performed in the control groups. Male Wistar rats (n=49) were assigned to one of six groups: placebo sham rats (P-Sham; n=8), LLLT at a dose of 3 J/cm(2) sham rats (3 J/cm(2)-Sham; n=8), LLLT at a dose of 21 J/cm(2) sham rats (21 J/cm(2)-Sham; n=8), placebo HF rats (P-HF; n=9), LLLT at a dose of 3 J/cm(2) HF rats (3 J/cm(2)-HF; n=8), and LLLT at a dose of 21 J/cm(2) HF rats (21 J/cm(2)-HF; n=8). Four weeks after myocardial infarction or sham surgery, rats were subjected to LLLT (InGaAlP 660 nm, spot size 0.035 cm(2), output power 20 mW, power density 0.571 W/cm(2), energy density 3 or 21 J/cm(2), exposure time 5.25 s and 36.75 s) on the right gastrocnemius for 10 consecutive days. LLLT reduced plasma IL-6 levels (61.3 %; P<0.01), TNF-α/IL-10 (61.0 %; P<0.01) and IL-6/IL-10 ratios (77.3 %; P<0.001) and increased IL-10 levels (103 %; P<0.05) in the 21 J/cm(2)-HF group. Moreover, LLLT reduced the TNF-α (20.1 % and 21.3 %; both P<0.05) and IL-6 levels (54.3 % and 37.8 %; P<0.01 and P<0.05, respectively) and the IL-6/IL-10 ratio (59.7 % and 42.2 %; P<0.001 and P<0.05, respectively) and increased IL-10 levels (81.0 % and 85.1 %; both P<0.05) and the IL-10/TNF-α ratio (171.5 % and 119.8 %; P<0.001 and P<0.05, respectively) in the gastrocnemius in the 3 J/cm(2)-HF and 21 J/cm(2)-HF groups. LLLT showed systemic and skeletal muscle anti-inflammatory effects in rats with HF.

Efecto antiinflamatorio del extracto hidroalcohólico de Oenothera rosea (Yawar Socco) en ratas con inducción a la inflamación aguda y crónica

El presente estudio de diseño experimental tuvo como objetivo determinar el efecto antiinflamatorio de Oenothera rosea (Yawar socco) en ratas con inducción de inflamación aguda y crónica. La planta fue secada a 38°C en estufa de aire circulante, se molió, y maceró con etanol/agua (70:30)1. Para evaluar el efecto agudo, se utilizó el modelo experimental de Winter, edema subplantar inducido con carragenina y el edema auricular inducido con xilol. Para la actividad antiinflamatoria crónica se uso el modelo del granuloma inducido por carragenina utilizando una modificación de la técnica descrita por Sedwick y Lees. Se utilizaron 132 ratas albinas con peso promedio 300 g, distribuidas al azar en grupos de 8 cada uno, considerando un grupo control con suero fisiológico de 5 mL/kg, uno con el agente inductor de inflamación (AI), grupos con AI más extracto en tres dosis y grupos con AI, dexametasona e ibuprofeno; siendo 56 ratas para evaluación frente a la carragenina donde se consideró mililitros de volumen de la subplantar porcentaje de eficacia antiinflamatoria, nivel de PCR en sangre y observación histológica del proceso inflamatorio; primero en 56 ratas frente al xilol expresándose en miligramos de una porción del lóbulo (oreja derecha). Se utilizaron 50 ratones para evaluar toxicidad aguda, 20 ratas normales para la observación de efectos por administración a dosis repetidas durante 28 días. Los resultados mostraron un 60% de reducción de la inflamación aguda (p&lt;0,01), así como 60% la inflamación crónica (p&lt;0,05) y la PCR se redujo en 45% (p&lt;0,03); no hubo evidencia de efectos adversos, un 60% del efecto antiinflamatorio en ratas y 60% del efecto en edema auricular crónico; determinándose una DEM de 61 mg/kg y sin efectos adversos. Se concluye que en las condiciones experimentales se demostró que el extracto hidroalcohólico de Oenothera rosea en ratas presenta efecto antiinflamatorio y sin cambios hematológicos e histopatológicos en ratas.

Kirenol exerts a potent anti-arthritic effect in collagen-induced arthritis by modifying the T cells balance

Rheumatoid arthritis is characterized by the imbalance of T cells, which leads to increased pro-inflammatory and reduced anti-inflammatory cytokines. Modulating the balance among T cells is crucial for the treatment of RA. Kirenol is a major diterpenoid components of Herba Siegesbeckiae, which has been applied for arthritic therapy for centuries. Since prior research showed Kirenol exhibited anti-inflammatory effect in rats, in this study we have evaluated the effect and mechanism of bioactive Kirenol in a rat model of collagen-induced arthritis (CIA) on modulation of T cells. After immunization with bovine type II collagen (CII), Wistar rats were orally administered saline (CIA group), 2mg/kg Kirenol or 2mg/kg prednisolone daily for 30 days. The severity of arthritis was clinically and histologically assessed. The numbers of CD4+CD25+Foxp3+ T regulatory cells (Tregs) and IFNγ+CD4+ and IL4+CD4+ T cells were determined by flow cytometry, the mRNA expression level of Foxp3 was quantified by RT-PCR, cytokine levels were measured by ELISA and CII-induced cell proliferation was quantified in vitro. Kirenol significantly delayed the occurrence and reduced the disease severity of CIA. Histological analysis confirmed Kirenol suppressed joint inflammation and inhibited cartilage and bone destruction, compared to the CIA group. Kirenol also upregulated the mRNA expression of Foxp3, increased the numbers of CD4+CD25+Foxp3+ and IL4+CD4+ T cells, and reduced the number of IFNγ+CD4+ T cells. Kirenol reduced the levels of TNF-α, IL-17A and IL-6 in synovial fluid and TNF-α, IL-17A and IFN-γ in serum, and increased the serum levels of IL-4, IL-10 and TGF-β1. In addition, Kirenol inhibited the ability of CII to induce splenocyte, PBMC and lymph node cell proliferation in vitro, compared to cells from CIA rats. In conclusion, these results suggest that Kirenol may be a potential immunosuppressant for the treatment for rheumatoid arthritis.

Evidence for the Safe Use of the Extract from the Brazilian Arnica, &amp;lt;i&amp;gt;Solidago chilensis&amp;lt;/i&amp;gt; Meyen, in Primary Health Care

In Brazil, the National Policy on Medicinal Plants has stimulated the use of plants in primary health care, validating the traditional medicine and pointing to the lack of a consistent set of evidence that supports their uses and indications by ethnobotany and ethnopharmacology. This paper aims to make a systematic review of the scientific literature to gather evidence on indications and safety of use of extracts of Solidago chilensis. The bibliographic research was carried out using terms derivate from the title, and all the published papers were downloaded, covering at least the last five years, and it was focused on preclinical and clinical studies with extracts of S. chilensis in the databases of Web of Science, BIREME, SciELO, PubMed, Scirus and Highwire. Phytochemical analysis carried out on many studies showed that among the chemical constituents of S. chilensis are sesqui- and diterpenes, flavonoids and other substances, and the diterpene solidagenone was identified as a marker of the extract that has demonstrated gastroprotective activity in different experimental models of ulcer induced in animals without signs of toxicity at doses above 600 mg/kg. Another studies show that the anti-inflammatory effect in rats has been given by inhibiting the exudation of leukocytes, especially neutrophils, as well as through inhibition of myeloperoxidase, adenosine deaminase, and tumor necrosis factor-α (TNF-α), decreased induction of nitric oxide synthesis and levels of interleukin-1β. Studies show that solidagenone at a concentration of 100 mg/kg showed activity similar to lansoprazole (20 mg/kg), the effect occurs without changes in the gastric mucosa or on acid secretion. The aqueous and alcoholic extracts showed anti-inflammatory activity and may act in a satisfactory way in cases involving the inflammatory response, such as injuries due to trauma, repetitive stress, pain, and healing. The inhibition of anti-inflammatory response is on the base of all these described effects. In spite of the fact that S. chilensis has been used since ancient times in Brazilian traditional medicine, and the existence of preclinical pharmacological end toxicological evidence for its efficacy as an inhibitor of anti-inflammatory response, we could find only a single clinical trial study carried out in treating lumbago. In this lack of clinical pharmacology and toxicology evidence for its uses, its safety and therapeutic indications are guaranteed, up to this moment, by traditional knowledge.

Pattern recognition receptors involved in the inflammatory attenuating effects of soybean isoflavone in β-amyloid peptides 1-42 treated rats

Pattern recognition receptors (PRRs) play important roles in the inflammatory responses to Alzheimer's disease (AD). Our previous study indicated that soybean isoflavone (SIF) exhibited anti-inflammatory effect in rats treated by β-amyloid peptides1-42 (Aβ1-42). In present study, we further detected the effects of SIF against inflammation caused by Aβ1-42 treatment in rats. Serum inflammatory mediators and neurotrophic factors including transforming growth factor-β (TGF-β), inducible nitric oxide synthase (iNOS), brain-derived neurotrophic factor (BDNF) and S100β were detected by enzyme-like immunosorbent assay (ELISA). Reverse transcription-polymerase chain reaction (RT-PCR) and western blot methods were applied for detecting mRNA and protein expression of interleukin-1β (IL-1β), iNOS, tumor necrosis factor-α (TNF-α), TGF-β, BDNF, S100β, myeloid differentiation factor88 (Myd88), Toll-like receptor2 (TLR2), formyl peptide receptors (FPRs), inhibitor κB kinase (IKK) and inhibitor κB-α (IκB-α) in rat's brain tissue. Our results indicated that SIF could reduce the production of IL-1β, TNF-α and iNOS induced by Aβ1-42 in serum and brain of rats. SIF also significantly reversed Aβ1-42-induced up-regulation of TLR2, FPR, Myd88, IKK and decreased IκB-α mRNA and protein expressions in rats. These results suggested that TLR2 and FPR might involve in the inflammatory process induced by Aβ1-42 treatment, and SIF was an efficiency compound in reversing the inflammation caused by Aβ1-42 treatment.

Evaluation Of Analgesic And Anti-Inflammatory Activity Of &lt;i&gt;Diospyros Cordifolia&lt;/i&gt; Extract

In this study we evaluated the analgesic and anti-inflammatory activities of the methanol extract of stem bark of Diospyros cordifolia (MEDC) Roxb. The analgesic effects of the stem bark of the plant was assessed in mice using the tail-flick method while carrageenan, histamine and dextran induced paw oedema was used to study the antiinflammatory effects in rats. The MEDC exhibited significant (p<0.01) analgesic effects comparable to the reference drug diclofenac sodium. MEDC also was evaluated for its anti-inflammatory potential against carrageenan, histamine and dextran induced rat paw edema. The methanol extract (25 and 50 mg / kg body weight) exhibited significant (p<0.01) activity against all phlogistic agents used in a dose dependent manner. All these effects were compared with reference drug phenylbutazone (100 mg/kg body weight).

Huang-Lian-Jie-Du-Tang exerts anti-inflammatory effects in rats through inhibition of nitric oxide production and eicosanoid biosynthesis via the lipoxygenase pathway

Abstract Objectives Huang-Lian-Jie-Du-Tang (HLJDT) is a traditional Chinese medicine with a long history of anti-inflammatory use, but its pharmacological effects have not been thoroughly investigated. This study aimed to evaluate the anti-inflammatory activity of HLJDT in vivo and in vitro. Methods The carrageenan rat air pouch model was used to investigate the anti-inflammatory action of HLJDT after oral administration. Moreover, we exploited a modified method based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) technique to assay the effects of HLJDT on arachidonic acid metabolites. Key findings Our data demonstrate that oral administration of HLJDT significantly inhibited the inflammatory responses in carrageenan-injected rat air pouches, and also significantly reduced the production of nitric oxide (NO) and leukotriene B4 (LTB4) in vivo, without any influence on biosynthesis of cyclooxygenase (COX)-derived eicosanoids. Similar behaviour of HLJDT was also observed by using calcium ionophore A23187-stimulated peritoneal macrophages, where HLJDT markedly inhibited eicosanoids derived from different lipoxygenases. The NO production and the mRNA expression of inducible nitric oxide synthase (iNOS) and chemotactic factors (CCL3, CCL4, CCL5 and CXCL2) were also inhibited by HLJDT in RAW 264.7 macrophages stimulated by lipopolysaccharide. Conclusions Our data revealed, for the first time, that HLJDT could inhibit biosynthesis of eicosanoids derived from different lipoxygenases. Also, HLJDT may exert its anti-inflammatory effects by its suppression on eicosanoid generation, NO production and gene transcription of chemotactic factors, which supports its effectiveness in the treatment of inflammatory diseases.

Meloxicam formulations for transdermal delivery: hydrogels versus organogels

The objective of this work was to evaluate the efficacy and suitability of different organogel formulations as transdermal delivery systems of meloxicam (MX) compared to hydrogel formulations. Hydrogels and hydroalcoholic gels were prepared using either carbopol 940 or pluronic F-127 as gelling agents. The organogels used glyceryl monostrearate (GMS), a glyceryl fatty acid ester as organogelator in view of the good skin tolerability of this group of organogelators. The liquid phase was oleic acid, Mygliol 812 or Labrasol. In vitro drug release through cellophane membrane was studied. The effect of some formulation variables (organogelator concentration, type of liquid phase, drug concentration and method of drug incorporation) on the release patterns of meloxicam (MX) from different organogels was investigated. In vitro skin permeation through excised rat skin in phosphate buffer (pH 7.4) was carried out. The in vivo skin penetration was evaluated by measuring the anti-inflammatory effect in rats by the paw edema test. The highest drug release was obtained from Mygliol 812 organogel, Labrasol organogel and hydroalcoholic pluronic gel. The results revealed an inverse correlation between the drug release rate and organogelator concentration and direct correlation between the drug release rate and the initial drug concentration. The release rate of the drug was dependent on the nature of the gel's liquid component (which influences drug solubility), but not on the method of drug incorporation. Permeation across rat skin showed that Mygliol 812 and Labrasol organogels were superior to hydrogels and hydroalcoholic gels. The anti-inflammatory activity of the drug in different formulations was studied using carragenan-induced rat paw edema method. The results showed an excellent anti-inflammatory activity for the tested formulations, but the anti-inflammatory activity of organogels was significantly higher than that of hydroalcoholic gel. Histopathological examination of rat skin treated with the selected formulations showed normal skin histology. These findings suggest that these organogels could be effective vehicles for transdermal delivery of meloxicam.

Huang-Lian-Jie-Du-Tang exerts anti-inflammatory effects in rats through inhibition of nitric oxide production and eicosanoid biosynthesis via the lipoxygenase pathway

Huang-Lian-Jie-Du-Tang (HLJDT) is a traditional Chinese medicine with a long history of anti-inflammatory use, but its pharmacological effects have not been thoroughly investigated. This study aimed to evaluate the anti-inflammatory activity of HLJDT in vivo and in vitro. The carrageenan rat air pouch model was used to investigate the anti-inflammatory action of HLJDT after oral administration. Moreover, we exploited a modified method based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) technique to assay the effects of HLJDT on arachidonic acid metabolites. Our data demonstrate that oral administration of HLJDT significantly inhibited the inflammatory responses in carrageenan-injected rat air pouches, and also significantly reduced the production of nitric oxide (NO) and leukotriene B(4) (LTB(4)) in vivo, without any influence on biosynthesis of cyclooxygenase (COX)-derived eicosanoids. Similar behaviour of HLJDT was also observed by using calcium ionophore A23187-stimulated peritoneal macrophages, where HLJDT markedly inhibited eicosanoids derived from different lipoxygenases. The NO production and the mRNA expression of inducible nitric oxide synthase (iNOS) and chemotactic factors (CCL3, CCL4, CCL5 and CXCL2) were also inhibited by HLJDT in RAW 264.7 macrophages stimulated by lipopolysaccharide. Our data revealed, for the first time, that HLJDT could inhibit biosynthesis of eicosanoids derived from different lipoxygenases. Also, HLJDT may exert its anti-inflammatory effects by its suppression on eicosanoid generation, NO production and gene transcription of chemotactic factors, which supports its effectiveness in the treatment of inflammatory diseases.

Antinociceptive and antiinflammatory effects of essential oil of Dennettia tripetala G.Baker (Annonaceae) in rodents.

In this study we evaluated the analgesic and anti-inflammatory activities of the essential oil (EO) of the fruits of Dennettia tripetala in rodents. The plant is a tropical African plant and the fruits are commonly eaten as spices and consumed as a stimulant, and its various parts are used in the treatment of fever, cough and as anti-emetics.The analgesic effects of the oil was assessed in mice using the hot plate, acetic acid-induced writhings and formalin test, while carrageenan-induced paw oedema was used to study the antiinflammatory effects in rats. The EO at 25-50 mg/kg exhibited significant (p<0.05) antinociceptive effects comparable to a potent opioid agonist, morphine (10 mg/kg) and non-steroidal anti-inflammatory drugs such as, aspirin (100 mg/kg) and indomethacin (80 mg/kg). The antinociceptive effect of the EO was also blocked by naloxone (2 mg/kg) in all the models used. The EO demonstrated significant (p<0.05) anti-inflammatory effect in the carrageenan-induced paw oedema model of inflammation that is also comparable to dexamethasone (1 mg/kg) The results showed that the essential oil of D. tripetala possesses significant antinociceptive and antiinflammatory effects in the animal models used. The results also suggest that the analgesic effects may be mediated both centrally as well as peripherally, while the antiinflammatory activity may be effective in both early and late phases of inflammation. The results obtained may therefore be used to rationalize the use of the plant in the treatment of pain and fever in traditional medicine.

Physalis angulata extract exerts anti-inflammatory effects in rats by inhibiting different pathways

Physalis angulata is a popular medicine used in Brazil due to its anti-inflammatory effects, but the pharmacological mechanisms underlying these actions remain to be better understood. In the present work, lyophilized aqueous extract from the roots of Physalis angulata Linneu (AEPa) was used to control the inflammatory response induced by the injection of 1% carrageenan into subcutaneous rat's air pouches. Adenosine deaminase (ADA) activity, nitrite level, and prostaglandin E 2 (PGE 2) level were used to evaluate the action of inflammatory mediators. Tumor growth factor-β (TGF-β) level was used as a bioindicator of immunomodulatory response. Rats were injected with vehicle, indomethacin, or AEPa (0.5 mg/kg, 1 mg/kg, and 5 mg/kg i.p.), 1 h before carrageenan administration. AEPa at 0.5 mg/kg had no effect. However, 1 mg/kg of AEPa showed significant anti-inflammatory effects, decreasing exudate volume, total number of inflammatory cells, ADA activity, nitrite level, and PGE 2 level in 50%, 41%, 20%, 60%, and 41%, respectively. The anti-inflammatory effects of 5 mg/kg AEPa appeared to be more effective than those of 1 mg/kg AEPa (84%, 80%, 43%, 70%, and 75%, respectively). In addition, TGF-β level was upregulated to 9700 pg/ml after 5 mg/kg AEPa, in comparison with 160 pg/ml in the vehicle-treated group, and 137 pg/ml in the indomethacin-treated group. The results indicate that AEPa exerts powerful anti-inflammatory and immunomodulatory activities, interfering with the cyclooxygenase pathway, lymphocyte proliferation, NO, and TGF-β production.

Final Report on the Safety Assessment of Glycyrrhetinic Acid, Potassium Glycyrrhetinate, Disodium Succinoyl Glycyrrhetinate, Glyceryl Glycyrrhetinate, Glycyrrhetinyl Stearate, Stearyl Glycyrrhetinate, Glycyrrhizic Acid, Ammonium Glycyrrhizate, Dipotassium Glycyrrhizate, Disodium Glycyrrhizate, Trisodium Glycyrrhizate, Methyl Glycyrrhizate, and Potassium Glycyrrhizinate1

Final Report on the Safety Assessment of Glycyrrhetinic Acid, Potassium Glycyrrhetinate, Disodium Succinoyl Glycyrrhetinate, Glyceryl Glycyrrhetinate, Glycyrrhetinyl Stearate, Stearyl Glycyrrhetinate, Glycyrrhizic Acid, Ammonium Glycyrrhizate, Dipotassium Glycyrrhizate, Disodium Glycyrrhizate, Trisodium Glycyrrhizate, Methyl Glycyrrhizate, and Potassium Glycyrrhizinate1