Carrageenan In Rats Research Articles

Study of Antioxidant, Anti-inflammatory, Antinociceptive Activities and Toxicity of Stigmata of Zea mays Extracts

This study aims to investigate phytochemical screening, total polyphenol and flavonoids content, antioxidant activities and to examine toxicity, anti-inflammatory and antinociceptive effects of different extracts of stigmata of Zea mays from Morocco. The flavonoids and total phenols content were performed for both extracts. The aqueous and hydro-ethanolic extracts were screened for their possible antioxidant activities by three test systems, namely DPPH free radical-scavenging, reducing power and molybdenum system. Oral and Sub-acute toxicity of the hydro-ethanolic extract was evaluated in vivo. Anti-inflammatory activity of the hydro-ethanolic extract was evaluated by Carrageenaninduced rat paw edema method. The antinociceptive effect was tested by using the formalin test. Phytochemical screening of the extracts revealed a presence of flavonoids, leucoanthocyans, heterosid sterodic, coumarins, alkaloids, cardiac glycosides, anthocyanins and tannins. The flavonoids and total phenols content show higher content of flavonoids and total phenols in the hydro-ethanolic extract. It showed better antioxidant activity than the aqueous extract in the three methods used. Furthermore, the hydro-ethanolic extract with a concentration of 250 and 500 mg/kg body weight inhibited the inflammation induced by carrageenan in rats at 66.67% and 86.67% compared to 60.8% for indomethacin at 10 mg/kg after 5 h of inflammation induction. However, at dose of 500 mg/kg extract showed a pro-inflammatory effect. In the formalin test, the tolerance time of the rats was significantly higher compared to the control group. These initial results tend to support the traditional use in the treatment of cystitis, oliguria, nephritis, renal lithiasis edema, albuminuria, heart disease, slimming cures of stigmata of Zea mays in Morocco.

New thiopyridine complexes: design, electrochemical preparation and biological assessment

AbstractNovel complexes of Ru (III), Cu (II) and Au (III) (2–4) were prepared using 6-phenyl-2-thioxo-4-(trifluoromethyl)-1,2-dihydropyridine-3-carbonitrile (HL,1) adopting either electrochemical or traditional chemical methods. The electrochemical method is preferred in the synthesis of the complexes than the chemical one because it affords pure products with higher yields in shorter reaction time. The novel thiopyridine complexes were characterized by elemental analyses, IR,1H,19F-NMR, TGA and DTA measurements. The antimicrobial activity evaluation revealed that the complex bearing copper metal3has nearly the same activity as the reference drug ciprofloxacin. Anti-inflammatory activity evaluation showed that complex4containing gold displayed anti-inflammatory activity higher than the reference drug celecoxib upon using carrageenan rat hind paw edema method.

Mechanisms of the antiplatelet and analgesic effects of dextromethorphan and its metabolites.

Objective:In the present study, we investigated the effects of dextromethorphan (DM) and its metabolites, including dextrorphan (LK2), 3-methoxymorphinan (LK3), and 3-hydroxymorphinan (LK4), on platelet aggregation in vitro and the inflammatory pain caused by carrageenan in rats, and their underlying mechanisms.Materials and Methods:Rabbit platelets were pretreated with DM or its metabolites to assess their effects on platelet aggregation and related target mediators. In addition, the analgesic activity and the underlying mechanisms of DM and LK3 were investigated in a carrageenan-evoked thermal hyperalgesia rat model.Results:The inhibitory potency of DM and its metabolites on platelet aggregation induced by arachidonic acid or collagen was LK3> DM > LK4>> LK2 as demonstrated by the half-maximal inhibitory concentration values. Moreover, the mechanisms of the antiplatelet effect of DM and LK3 may involve the inhibition of intracellular calcium mobilization, expression of platelet surface glycoprotein IIb/IIIa, the formation of thromboxane B2, and elevation of platelet membrane fluidity. DM and LK3 also exhibited analgesic effects on carrageenan-evoked thermal hyperalgesia by suppressing the production of pro-inflammatory cytokines, nitric oxide, prostaglandin E2, and neutrophil infiltration in inflammatory sites.Conclusion:DM and its metabolites, especially LK3, exhibit both antiplatelet and analgesic effects, and may, therefore, potentially ameliorate platelet hyperactivity and inflammatory-related diseases.

Pomegranate supplementation attenuates inflammation, joint dysfunction via inhibition of NF-κB signaling pathway in experimental models of rheumatoid arthritis.

Incisive search of innovative compounds for regulating pain, inflammation, and bone damage, with nominal side effects has focused on nutritional supplements. The endeavor of this research work was to investigate, for first time, the inhibitory effect of pomegranate rind extract in established models of nociception and inflammation. Pomegranate (50, 100, and 200mg/kg) and indomethacin (3mg/kg) was assessed in eddy's hot plate-induced algesia, carrageenan, and Complete Freund's adjuvant-induced models in Wistar rats. Results of study conclude that pomegranate at a dose of 200mg/kg showed significant (p<0.001) reduction in paw swelling in both inflammatory experimental models. In addition, observations recorded a significant (p<0.05) increase in nociceptive threshold. Henceforth, we might say that pomegranate (200mg/kg) decline pain and inflammation by downregulating the activation of TNF-R1, TNF-α, IL-1β, IL-6, NF-κB, oxidative stress markers, and tissue histology. PRACTICAL APPLICATIONS: The research work represents the first report on inhibitory mechanism of NF-κB by pomegranate rind extract, enriched in tannins and flavanoids. The findings of the study provide satisfactory evidence of pomegranate rind in amelioration of adjuvant-induced arthritis. Pomegranate rind, being enrich in bioactive compounds like phenolics and flavanoids possess potent antioxidant activity that might contribute in attenuating rheumatoid arthritis.

Acute anti-inflammatory and anti-nociceptive activities of crude extracts, alkaloid fraction and evolitrine from Acronychia pedunculata leaves

Ethnopharmacological relevanceAcronychia pedunculata (family: Rutaceae) is one of the commonly used medicinal plants in Sri Lankan traditional medicine. Different parts of this plant are used for the treatment of inflammatory conditions in the form of medicinal oils and herbal porridge. Aim of the studyThe present study aimed to evaluate the anti-nociceptive activity and anti-inflammatory activity with their mechanisms and the acute toxicity of crude extracts of the fresh leaves of A. pedunculata for scientific validation of the ethnopharmacological claims for this plant. Further, attention has been focused on the isolation of active compounds from active fractions of the crude extracts. Materials and methodsThe acute anti-inflammatory effect of the aqueous (AELA) and 70% ethanol crude extracts (EELA) and alkaloid fraction of A. pedunculata leaves were evaluated by the determination of inhibition of hind paw oedema induced by carrageenan in Wistar rats. Evolitrine was identified as the major alkaloid with significant bioactivities by column chromatography and NMR. The anti-nociceptive and anti-histamine activities of EELA and evolitrine were evaluated by acetic acid induced writhing and wheal formation tests respectively. In addition, in-vitro (2, 2-diphenyl-1-picrylhydrazyl (DPPH) assay) and in-vivo (lipid peroxidation assay) anti-oxidant activity, nitric oxide (NO) inhibitory activity and acute toxicity of EELA were evaluated. ResultsAcute anti-inflammatory activity of AELA and EELA were dose-dependent. EELA was more active than AELA. The 200 mg/kg body weight (b. w.) dose of EELA was found as the minimum effective dose with maximum inhibition (78%) of oedema at 5th hour compared to the negative control (p < 0.05). Evolitrine was isolated and identified as an active anti-inflammatory and analgesic compound from active alkaloid fraction of EELA. Evolitrine showed activity enhancement when compared with crude EELA. The anti-inflammatory and analgesic activities of evolitrine (50 mg/kg b. w.) were comparable to that of reference drugs indomethacin (5 mg/kg b. w) and acetylsalicylic acid (100 mg/kg b. w.). The significant (p < 0.05) anti-histamine activity, DPPH scavenging in-vitro anti-oxidant activity, in-vivo lipid peroxidation inhibitory activity in-vivo, NO inhibitory activity of EELA as compared with relevant negative controls, were identified as probable mechanisms which mediated its anti-inflammatory action. Further, EELA showed a high safety margin in the limited dose acute toxicity study. ConclusionThe findings of the current study rationalize the usage of leaves of A. pedunculata in Sri Lankan traditional medicine as an analgesic and anti-inflammatory agent. Possible mechanisms mediating this activity included anti-histamine, anti-oxidant and NO inhibitory activities. Evolitrine is the major analgesic and anti-inflammatory compound isolated from the active alkaloid fraction of EELA.

Analgesic and Anti-inflammatory Activities of Triterpenoid Molecules Isolated from the Leaves of Combretum glutinosum Perr. Ex DC (Combretaceae)

Combretum glutinosum Perr. Ex DC (COMBRETACEAE) is a traditional medicinal plant, widely distributed in Senegal and Africa. The aim of that study was to investigate the analgesic and anti-inflammatory activities of two triterpenes, betulonic acid (DN7) and cabraleone (DN12), isolated from the leaves of Combretum glutinosum. Experiments were performed in acetic acid-induced contortions in mice and carrageenan rat paw oedema. DN7 (3 mg/kg, per os) and DN12 (3 mg/kg, per os) significantly prevent contortions in mice. The number of contortions is respectively 30±10 and 32±7 versus 72.6±6.64 in control group (p&lt;0.05, n=5). DN7 (3 mg/kg, per os) significantly prevented the increased rat paw oedema (31.84±6.76 vs 92.72±6.05%) (p&lt;0.05, n=5). DN12 (10 mg/kg, per os) induced rat paw oedema prevention similar to that of acetylsalicylic acid (10 mg/kg, per os) administered in the same conditions (29.28±5.88 vs 30.96±7.25%; ns, n=5). The analgesic and anti-inflammatory activities of triterpenes isolated from C. glutinosum leaves are similar to those of non-steroidal anti-inflammatory drugs such acetylsalicylic acid, justifying the use of this plant in traditional medicine to manage pain and inflammation.

Antinociceptive and anti-inflammatory effects of the citrus flavanone naringenin.

Objective:Naringenin, a flavonoid found in citrus fruits, has notably diverse pharmacological properties. In the present study, we investigated the antinociceptive and anti-inflammatory effects of naringenin.Materials and Methods:The antinociceptive effects were evaluated using hot-plate, acetic acid-induced writhing, and tail-flick assays in mice and rats. The anti-inflammatory effects were examined by a carrageenan-induced paw edema test in rats.Results:Naringenin (100 or 200 mg/kg, oral administration) significantly delayed the reaction time of mice to thermal stimulation generated by a hot plate and a tail-flick unit and reduced the acetic acid-induced writhing response in mice. In addition, naringenin significantly decreased paw edema induced by carrageenan in rats, showing its anti-inflammatory effect.Conclusion:Our results show that naringenin has therapeutic potential with antinociceptive and anti-inflammatory properties and can further be exploited for the development of drugs for pain and inflammatory-related diseases.

Comparative anti-inflammatory activity of arils extracts of Punica granatum fruits

Anti-inflammatory is the property of a substance or treatment that reduces inflammation or swelling. The main objective of this study is to evaluate Anti-inflammatory activity of pomegranate arills extract on Rat’s Paw. Anti-inflammatory activity of pomegranate was tested on rats by employing induced Carrageenan rat Paw Edema Method. Various concentrations of the arils and arils mixture (1:1) prepared by dissolving in Hydroalcohol and alcohol to obtain a final concentration of 100mg/kg, 200mg/kg, 400mg/kg against the test organisms. The effectivity of Granatin B to aqueous and alcoholic extracts arils of Punica granatum calculated by measuring the increase in paw volume and percent inhibition by comparing with control And Standard drug.

Experimental Researches on the Effects of Some Antibiotics on Carrageenan-induced Rat Paw Inflamation

The aim of our study was to evaluate the effects of some antibiotics on hepatic and renal integrity in rats with acute paw inflammation. Acute inflammation was induced after sub-plantar administration of carrageenan in rats. The substances: prednisone (PDN), indomethacin (IND), cefotaxime (CEF), gentamicin (GEN) and sulfamethoxazole (SMT) were injected intraperitoneally, 30 min before carrageenan administration. Saline was intra-paw administered in control group. Prednisone and indomethacin were injected in a single daily dose, and the antibiotics every 12 hours, during 3 days. Specific biochemical parameters, liver and kidney tissues were examined after 3, 24 and 72 hours. Experimental protocol was conducted according to the recommendation of our University Committee for Research and Ethical Issues. The use of GEN, SMT and CEF resulted in exacerbation of hepatic enzymes activity, increasing in serum creatinine, blood urea and uric acid levels, statistically significant comparing with control group. Histopathological examination revealed the alteration of liver and kidney architecture in groups treated with GEN and SMT. The effects of GEN were more accentuated than those of SMT and CEF. The treatment with GEN and SMT manifested hepatic and renal toxicity in rats with experimental carrageenan-induced acute paw inflammation.

CARRAGEENAN INDUCES CELL DEATH IN RATS BLOOD

Background. Because of its physical and chemical properties, carrageenan is fairly widely used. About 70 % of the carrageenan produced in the world is used in the food industry. Previous studies point to the development of oxidative stress in rats, by means of which carrageenan chronic enterocolitis was modeled.Objective. The aim of our study was to investigate the level of apoptosis and necrosis in the suspension of leukocytes in rats using 0.5 % and 1.0 % solutions of carrageenan.Methods. Annexin V (V) binding assays were performed using Annexin V Apoptosis Kit (Sigma Aldrich, USA), caspase rate in leukocyte-lymphocyte blood fractions was determined by spectrofotometry.Results. It was established that in the experimental application of carrageenan, the percentage of leukocytes with signs of apoptosis in both experimental groups statistically significantly increased. It was detected by the increased activity of effector caspase-3 in 1 month after the experiment in 1.5 times in the 2nd group and in 2.8 times in the 3rd group vs control data that point to caspase-dependent apoptotic pathway in case of carrageenan usage in rats.Conclusions. Oral use of carrageenan in rats was accompanied by the increase in the number of leukocytes with signs of apoptosis. The animals that consumed 1.0 % solution of carrageenan had more obvious increase in the activity of caspase-3 in serum relative to a group of rats consuming 0.5 % of carrageenan, proving the increase in the severity of apoptotic processes in intestine with the increase of the dose of carrageenan.

Protection from Glucocorticoid-Induced Thymus Atrophy by Dihydromyricetin Via Up-Regulation of PPARγ and Anti-Oxidation

T lymphocytes produced by the thymus are essential mediators of immunity. Accelerated thymic atrophy appears in the patients with administration of glucocorticoids (GCs) which are commonly-used drugs to treat autoimmune and infectious diseases, leading to dysregulation of immunity with manifestation of progressive diminution of new T cell production. However, there is no ideal method to overcome such side effects of GCs. In the current study, we proposed a composition of dexamethasone (DEX) and dihydromyricetin (DMY) derived from a medicinal plant, which could protect from DEX-induced thymus damage and simultaneously enhance the anti-inflammatory effect of DEX. Dexamethasone (DEX)-induced thymus atrophy was effectively prevented by co-treatment with dihydromyricetin (DMY) via activating PPARγ in thymic tissues of mice with delayed type hypersensitivity (DTH) induced by 2,4- dinitrofluorobenzene (DNFB). Simultaneously, DMY demonstrated a synergistic effect on suppressing DTH with co-administration of DEX in the mouse model of DTH and the paw edema induced by carrageenan in rats. Increase of PPARγ expression was found in the thymic tissues of animals treated with DMY plus DEX than the animals treated with DEX alone, which was validated by agonist and antagonist of PPARγ. DMY protected thymus from atrophy induced by DEX via regulation of PPARγ-associated fatty acid metabolism and anti-oxidation in thymic tissues. Our findings may provide a new strategy on protection of thymus from damage caused by GCs by using appropriate co-remedies of GCs together with suitable adjuvant natural agents through up-regulation of PPARγ expression and anti-oxidation. Funding Statement: This work was supported by FDCT grants from the Science and Technology Development Fund of Macao (Project code 081/2013/A3). Declaration of Interests: The authors declare that they have no conflict of interests. Ethics Approval Statement: Animal care and experiments were conducted in accordance with the Laboratory Animal Research Committee Guidelines of Guangdong Provincial Hospital of Chinese Medicine.

Wound healing and anti-inflammatory activities induced by a Plantago australis hydroethanolic extract standardized in verbascoside

Ethnopharmacological relevancePlantago australis is a popular plant found to be widely spread in Latin America. In folk medicine, the seeds and leaves are used mainly for anti-inflammatory, wound healing, among others. The verbascoside, a phenolic glycoside, is an active chemical component described in this species of plant, which has antioxidant, anti-inflammatory and healing effects. PurposeThe aim of the present study was to evaluate whether P. australis hydroethanolic extract (PAHE) standardized in verbascoside could promote wound healing associated with anti-inflammatory action within both in vitro and in vivo models. MethodsFor the wound healing activity, we used a Scratch Test, an assay capable of evaluating the migratory ability of keratinocyte cells (HaCat) in vitro and thereby confirming the activity in rats. For the anti-inflammatory activity, the inflammation was induced with LPS in microglial murine cells (N9). Inflammatory mediators (IL-6, IL-10, IL-12p70, INFγ, MCP-1 and TNFα) were measured and the activity of superoxide dismutase (SOD), catalase (CAT), and mitochondrial membrane potential were evaluated. In addition, using paw edema induced by carrageenan in rats, the anti-inflammatory activity in vivo was analyzed. ResultsThe PAHE and verbascoside, induced a significant increase in migration of keratinocytes, at all concentrations tested when compared to the negative control. The wound healing activity in vivo showed that the PAHE accelerated the process. The treatments with PAHE and verbascoside induce increases in the antioxidants enzymes, suggesting a possible activation of these enzymes. However, this did not result in an increase in the expression of inflammatory mediators in microglial cells. In LPS activated cells the verbascoside displayed a significant reduction of TNFα, IL-6, IL-12p70, MCP-1 and INFγ, while the PAHE only displayed statistically significant reduction in TNFα. Interestingly, both the compounds could reduce the oxidative parameters in N9 cells activated by LPS. Additionally, pretreatment with PAHE inhibited the paw edema in rats. ConclusionThe results suggest that PAHE has wound healing activity, improving cells migration and, as well as was able to reverse the oxidation effect in LPS-activated N9 cells. The wound-healing and anti-inflammatory activities of PAHE were confirmed in vivo. In addition, the presence of verbascoside can be related to PAHE effects, since this compound was capable of increase keratinocytes migration and inhibiting inflammation mediators.

Local administration of mangiferin prevents experimental inflammatory mechanical hyperalgesia through CINC-1/epinephrine/PKA pathway and TNF-α inhibition

Steroidal and non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to control inflammatory pain, but there is a risk of gastrointestinal bleeding and increased heart failure risk. The search for new drugs remains ongoing, and natural products are a source for potential new compounds. Mangiferin, a natural xanthone C-glucoside, has demonstrated biological activity, including anti-inflammatory and analgesic properties, but it's mechanisms are poorly understood. In this study, we investigated the mechanisms underlying the anti-inflammatory and analgesic effects of local administration of mangiferin. We employed an electronic von Frey apparatus to evaluate mechanical hyperalgesia induced by carrageenan in rats. Mangiferin (150–1200 µg/paw), administered locally into the hindpaw, prevented hyperalgesia in a dose-dependent – 150 µg (− 9%), 300 µg (− 27%, P < 0.01), 600 µg (− 77%, P < 0.001) and 1000 µg (− 93%, P < 0.001) – and local manner. Mangiferin showed decreased levels of TNF-α (P < 0.001) and CINC-1 (P < 0.001), but not IL-1β; it also prevented neutrophil migration (P < 0.01), but not the increased COX-2 expression in peripheral tissue challenged with carrageenan. To further explore the mechanisms of mangiferin actions, rats were injected with modulators of inflammation and nociception; mangiferin prevented hyperalgesia induced by IL-1β (P < 0.01), CINC-1 (P < 0.01), epinephrine (P < 0.01), 8-Br-cAMP (P < 0.01) or capsaicin (P < 0.01), but not that induced by PGE2 or α,β-MeATP. Our study shows that mangiferin has anti-inflammatory and analgesic properties when locally administrated. The control of the inflammatory response and mechanical hyperalgesia by mangiferin depends on the inhibition of TNF-α production/release and the CINC1/epinephrine/PKA pathway, supporting its marked inhibition of inflammatory mechanical hyperalgesia.

Illicium verum Extract Exhibited Anti-inflammatory Action in Rodents

Background: Illicium verum Hook. f. (Star anise) has been traditionally used for the treatment of abdominal colic, vomiting, pain, nervousness, insomnia and rheumatism. Objective: The present study was conducted to investigate the anti-inflammatory properties of Illicium verum extracts. Methods: Different extracts of I. verum (IV-Ext-1, IV-Ext-3 and IV-Ext-4) were screened for their anti-inflammatory potential using carrageenan-induced paw edema in mice. The mechanism of action was explored using paw edema tests (carrageenan, histamine, serotonin and prostaglandins) in rats and anti-oxidant activity (DPPH assay). Reverse phase HPLC was used for chemical characterization of extracts. Results: The IV-Ext-3 was found to be the most potent anti-inflammatory agent (38% inhibition) using carrageenan-induced paw edema. The anti-inflammatory effect was observed during both the initial (IC50: 260 mg/kg) and late phases (IC50: 200 mg/kg). Similar IC50 of 200 mg/kg was observed in both phases of histamine-induced paw edema. However, the extract failed to cause 50% inhibition in serotonin-induced edema (IC25: 400 mg/kg) and was also ineffective against Prostaglandin- E2 induced edema. Furthermore, the IV-Ext-3 appeared to be an effective antioxidant (IC50: 12 µg/ml). The HPLC chromatogram of IV-Ext-3 showed the presence of anti-inflammatory constituents such as shikimic acid (1.6%) and anethole (0.25%), 3, 4-dihydroxybenzoic acid (0.003%) and p-hydroxy methyl benzoate (0.117%) along with some polar hydroxyl derivatives of benzoic acids. Conclusion: Among all the extracts of I. verum, IV-Ext-3 was found to be the most effective antiinflammatory agent which can be attributed to multiple anti-inflammatory constituents, antihistamine and antioxidant potentials. Keywords: Star anise, anti-histamine, prostaglandins synthesis inhibitor, antioxidant, anti-inflammatory, edema.

New perspectives for natural triterpene glycosides as potential adjuvants

BackgroundTriterpene glycosides are a vast group of secondary metabolites widely distributed in plants including a high number of biologically active compounds. The pharmacological potential is evaluated by using many bioassays particularly in the field of cancerology, immunology, and microbiology. The adjuvant concept is well known for these molecules in vaccines, but there is little preclinical evidence to support this concept in the management of cancer, infections and inflammation. PurposeWe aim to review some examples of triterpene glycosides from natural sources which exhibit adjuvant activity when they are co-adminitered with anticancer drugs, targeted toxins, antimicrobial, anti-inflammatory drugs and with antigens in vaccines. MethodsThe scientific literature on the adjuvant potential of triterpene glycosides covering mainly the last two decades has been identified by using relevant key words in the databases, using the online service such as Medline/PubMed, Scopus, Web of Science, Google Scholar. ResultsWe divided these findings in four kind of examples, the combination of triterpene glycosides (1) with chemotherapeutic agents in conventional tumor therapies and with targeted toxins, (2) with antimicrobial drugs, (3) with antiinflammatory drugs, and (4) with an antigen in prophylactic and therapeutic vaccines. Pharmacological studies have revealed that some triterpene glycosides co-administered with anticancer drugs such as cisplatin, paclitaxel, cyclophosphamide, etoposide, 5-fluorouracyl, mitoxantrone exhibited increased cytotoxicity in tumor cells better than when the drugs were administered alone. However in vivo toxicological and pharmacokinetic studies are required before the combination strategy can be applied into clinical practice. Other studies showed that combined application of triterpene glycosides with targeted toxins resulted in the increased efficacy of the toxin, simultaneously reducing the dosage, and side effects. It was also shown that the co-administration of the triterpenoids with corticosteroids synergistically inhibited the inflammatory response induced by carrageenan in rats. The search for new alternative adjuvants in vaccines in comparison with the aluminium salts inducing only a Th2-type immune response resulted in the discovery of the promising purified fraction QS-21 from Quillaja saponaria, which has been used in the development of a variety of prophylactic and therapeutic vaccines. Over 120 clinical trials for around 20 vaccine indications in infectious diseases, cancer, degenerative disorders have been reported involving more than 50,000 patients. ConclusionThis review summarized the successfull in vitro and in vivo studies showing that this combination approach of triterpene glycosides co-adminitered with anticancer, antimicrobial and anti-inflammatory drug may provide an exciting road for further developments in the treatment of some cancers, parasitic and inflammatory diseases and in the rational design of vaccines against infectious diseases and cancer. From a clinical point of view, the potential benefit of QS-21, a promising triterpene glycoside from Quillaja saponaria has been highlighted in several vaccine clinical trials with a favorable ratio efficacy/toxicity.

Synthesis of Some Novel 2,6-Disubstituted Pyridazin-3(2H)-one Derivatives as Analgesic, Anti-Inflammatory, and Non-Ulcerogenic Agents.

Some novel 2,6-disubstituted pyridazine-3(2H)-one derivatives were synthesized and evaluated for in vitro cyclooxygenase-2 (COX-2) inhibitory efficacy. Compounds 2-{[3-(2-methylphenoxy)-6-oxopyridazin-1(6H)-yl]methyl}-1H-isoindole-1,3(2H)-dione (5a), 2-propyl-6-(o-tolyloxy)pyridazin-3(2H)-one (6a), and 2-benzyl-6-(3,5-dimethyl-1H-pyrazol-1-yl)pyridazin-3(2H)-one (16a) showed the most potent COX-2 inhibitory activity with IC50 values of 0.19, 0.11, and 0.24 μM, respectively. The synthesized compounds with the highest COX-2 selectivity indices were evaluated for their anti-inflammatory, analgesic, and ulcerogenic activities. Compounds 6a and 16a demonstrated the most potent and consistent anti-inflammatory activity over the synthesized compounds, which was significantly higher than that of celecoxib in the carrageenin rat paw edema model and with milder ulcer scoring than that of indomethacin in the ulcerogenicity screening.

Anti-nociceptive and anti-inflammatory effects of the methanolic extract of Opuntia humifusa stem.

Opuntia humifusa (O. humifusa) Raf. has been used for the prevention and treatment of rheumatoid arthritis, inflammation, and cancer. Our study was designed to unveil the anti-nociceptive and anti-inflammatory effects of the methanolic extract of O. humifusa Raf stem (OHS). The anti-nociceptive effect was measured by hot plate, acetic acid-induced writhing, and tail flick assays in mice and rats. Moreover, the anti-inflammatory effect was measured by vascular permeability and carrageenan and serotonin-induced paw edema tests in rats. Furthermore, anti-inflammatory effect was also measured using macrophage-like LPS-induced RAW 264.7 cells. OHS extract inhibited acetic acid-induced writhing (p<0.0001), and delayed the reaction time of mice to the hot plate-induced thermal stimulation (p<0.0001) and tail flick tests (p<0.05). OHS extract attenuated the carrageenan and serotonin-induced paw edema in rats (p<0.001). Similarly, OHS extract significantly decreased Evans blue concentration in acetic acid induced vascular permeability test (p<0.0001), revealing its strong anti-inflammatory effect. Finally, among four different fractions of OHS extract, n-butanol fraction strongly decreased NO production (p<0.0001) and iNOS expression in LPS-induced RAW 264.7 cells. Our results suggest that the methanolic extract of O. humifusa stem can be used to develop a therapeutic or supportive drug and/or functional food against pain and inflammation related diseases.

Evaluation of the protective effect of pentoxifylline on carrageenan-induced chronic non-bacterial prostatitis in rats.

Chronic non-bacterial prostatitis (CNP) is the most common type of prostatitis and oxidative stress (OS) was shown to be highly elevated in prostatitis patients. This study aimed to investigate the protective effect of pentoxifylline (PTX) on CNP induced by carrageenan in rats. Male adult Wistar rats (n=30) were divided into control, CNP and three treatment groups (n=6) including CNP+cernilton and CNP+PTX groups. CNP was induced by single intraprostatic injection of 1% carrageenan (100µl). Rats in treatment groups received orally cernilton 100mg/kg and PTX at 50 and 100mg/kg 1week after CNP induction for 21days. Prostatic index (PI), prostatic specific antigen (PSA), tumor-necrosis factor alpha (TNF-α), serum lipid peroxidation (MDA), blood urea nitrogen, creatinine and histopathological changes were compared between groups. There were significant increase of PI, serum levels of PSA, TNF-α and MDA in CNP group at 29day. In treatment groups, significant reduction in PI, serum levels of PSA, TNF-α, MDA and creatinine was observed especially in rats treated with dose of 50mg/kg of PTX. In CNP group, histopathological changes of the prostate such as leucocyte infiltration, large involutions and projection into the lumen and reducing the volume of the lumen were observed as well. Whereas PTX, especially at dose of 50mg/kg, could improve the above-mentioned changes remarkably in CNP treated rats. For the first time, our findings indicated that PTX improved CNP induced by carrageenan in rats.

Anti-inflammatory and membrane stabilizing properties of methyl jasmonate in rats

The present investigation was carried out to evaluate anti-inflammatory and membrane stabilizing properties of methyl jasmonate (MJ) in experimental rat models of acute and chronic inflammation. The effects of MJ on acute inflammation were assessed using carrageenan-induced rat's paw edema model. The granuloma air pouch model was employed to evaluate the effects of MJ on chronic inflammation produced by carrageenan in rats. The number of white blood cells (WBC) in pouch exudates was estimated using light microscopy. The levels of biomarkers of oxidative stress, such as malondialdehyde (MDA), glutathione (GSH) and activity of antioxidant enzymes in the exudates, were determined using spectrophotometry. The membrane stabilizing property of MJ was assessed based on inhibition of hemolysis of rat red blood cells (RBC) exposed to hypotonic medium. Our results indicated that MJ (25–100 mg·kg−1, i.p.) produced significant anti-inflammatory activity in carrageenan-induced paw edema in rats (P < 0.05). MJ reduced the volume of pouch exudates and the number of WBC in carrageenan-induced granulomatous inflammation. It also exhibited potent antioxidant and membrane stabilizing activities. In conclusion, these findings suggest the therapeutic potentials of methyl jasmonate in disease conditions associated with inflammation and its anti-inflammatory activity may be related to its antioxidant and membrane stabilizing activities.

English

Annona senegalensis leaves are used in African Traditional Medicine as analgesic and anti-inflammatory drugs. This study aimed to investigate the analgesic and anti-inflammatory activities of total ethereal leaf extract (TEE) of A. senegalensis and its methanolic fraction (MF). Experiments were performed in acetic acid induced contortions in mice and carrageenan rat paw edema. The preventive effect of TEE (100 mg/kg, per os) and MF (1 mg/kg, 3 mg/kg and 10 mg/kg, per os) was evaluated in carrageenan induced edema at 1, 3 and 5 h. The analgesic effect of MF (1, 3 and 10 mg/kg, per os) was tested in mice contortions. Oral administration of MF (3 mg/kg) showed an analgesic activity less similar than 100 mg/kg of acetylsalicylic acid (ASA) administered in the same conditions (17.60&plusmn;6.74 vs26.80&plusmn;4.66 contortions). The analgesic activity of MF is dose dependent at the lower doses (1 and 3 mg/kg, per os). However, the prevention of mice contortions with MF is less important at a higher dose (30 mg/kg, per os). In rat paw edema, TEE (100 mg/kg, per os) and MF (1 and 3 mg/kg, per os), significantly prevented carrageenan induced edema, as compared to the control and ASA groups. The dose of 3 mg/kg per os of MF induced an edema percentage inhibition similar to 100 mg/kg per os of ASA. Similarly to analgesic activity, the prevention of rat paw edema with MF is less important at a higher dose (10 mg/kg, per os). These results show an analgesic and anti-inflammatory activity of A. senegalensis leaf extracts, justifying the use of this plant leaves in African Traditional Medicine to prevent or treat pain and inflammation. &nbsp; Keys words: Annona senegalensis, leaves, pain, inflammation.