Discovery of a new pyrido[2,3-d]pyridazine-2,8-dione derivative as a potential anti-inflammatory agent through COX-1/COX-2 dual inhibition.

In this paper, we present the design and synthesis of a novel series of pyrido[2,3-d]pyridazine-2,8-dione derivatives via the annulation of the 2-pyridone pattern. The synthesized derivatives were evaluated for in vivo anti-inflammatory activity using an ear edema model. Compound 7c, which showed a greater inhibition of ear edema (82%), was further tested for its in vitro COX-1/COX-2 inhibitory activity. Compound 7c showed similar inhibitory activities against COX-1 and COX-2 isoenzymes. The structural features that ensure the dual inhibition of COX-1 and COX-2 were elucidated using molecular docking studies. Overall, the ring closing of 2-pyridone pattern I transformed this highly selective COX-2 inhibitor into a dual COX inhibitor (7c), which could serve as a model for determining selectivity for COX-2.

Resveratrol biotransformation and actions on the liver metabolism of healthy and arthritic rats.

AIMS: to investigate the effects of resveratrol on glycogen catabolism and gluconeogenesis in perfused livers of healthy and arthritic rats. The actions of resveratrol-3-O-glucuronide (R3G) and the biotransformation of resveratrol into R3G was further evaluated in the livers. MAIN METHODS: arthritis was induced with Freund's adjuvant. Resveratrol at concentrations of 10, 25, 50, 100 and 200 µM and 200 µM R3G were introduced in perfused livers. Resveratrol and metabolites were measured in the outflowing perfusate. Respiration of isolated mitochondria and activity of gluconeogenic enzymes were also evaluated in the livers. KEY FINDINGS: resveratrol inhibited glycogen catabolism when infused at concentrations above 50 µM and gluconeogenesis even at 10 µM in both healthy and arthritic rat livers, but more sensitive in these latter. Resveratrol above 100 µM inhibited ADP-stimulated respiration and the activities of NADH- and succinate-oxidases in mitochondria, which were partially responsible for gluconeogenesis inhibition. Pyruvate carboxylase activity was inhibited by 25 µM resveratrol and should inhibit gluconeogenesis already at low concentrations. Resveratrol was significantly metabolized to R3G in healthy rat livers, however, R3G formation was lower in arthritic rat livers. The latter must be in part a consequence of a lower glucose disposal for glucuronidation. When compared to resveratrol, R3G inhibited gluconeogenesis in a lower extension and glycogen catabolism in a higher extension. SIGNIFICANCE: the effects of resveratrol and R3G tended to be transitory and existed only when the resveratrol is present in the organ, however, they should be considered because significant serum concentrations of both are found after oral ingestion of resveratrol.

Alpha-tocopherol-loaded polycaprolactone nanoparticles improve the inflammation and systemic oxidative stress of arthritic rats.

Background and aim: The present study investigated the effects of orally administered α-tocopherol-loaded polycaprolactone nanoparticles on the articular inflammation and systemic oxidative status of middle-aged Holtzman rats with Freund's adjuvant-induced polyarthritis, a model for rheumatoid arthritis. Intraperitoneally administered free α-tocopherol provided the reference for comparison. Experimental procedure: Two protocols of treatment were followed: intraperitoneal administration of free α-tocopherol (100 mg/kg i.p.) or oral administration of free and nanoencapsulated α-tocopherol (100 mg/kg p.o.). Animals were treated during 18 days after arthritis induction. Results: Free (i.p.) and encapsulated α-tocopherol decreased the hind paws edema, the leukocytes infiltration into femorotibial joints and the mRNA expression of pro-inflammatory cytokines in the tibial anterior muscle of arthritic rats, but the encapsulated compound was more effective. Free (i.p.) and encapsulated α-tocopherol decreased the high levels of reactive oxygen species in the brain and liver, but only the encapsulated compound decreased the levels of protein carbonyl groups in these organs. Both free (i.p.) and encapsulated α-tocopherol increased the α-tocopherol levels and the ratio of reduced to oxidized glutathione in these organs. Conclusion: Both intraperitoneally administered free α-tocopherol and orally administered encapsulated α-tocopherol effectively improved inflammation and systemic oxidative stress in middle-aged arthritic rats. However, the encapsulated form should be preferred because the oral administration route does not be linked to the evident discomfort that is caused in general by injectable medicaments. Consequently, α-tocopherol-loaded polycaprolactone nanoparticles may be a promising adjuvant to the most current approaches aiming at rheumatoid arthritis therapy.

Chemical profile, antioxidant and anti-inflammatory properties of Miconia albicans (Sw.) Triana (Melastomataceae) fruits extract.

ETHNOPHARMACOLOGICAL RELEVANCE: Miconia albicans (Sw.) Triana has been widely used in Brazilian popular medicine for the treatment of several diseases. Aerial parts are used as an infusion to treat arthrosis and arthritis, to relieve rheumatic and stomach pains, and intestinal disorders due to its anti-inflammatory, anti-mutagenic anti-nociceptive, digestive and hepatoprotective properties. AIM OF THE STUDY: This study aimed to characterize the of M. albicans (Sw.) Triana fruits extract (MAFRE) chemical profile and to evaluate its antioxidant, anti-inflammatory and antitumor activities, as well as its toxicity. MATERIALS AND METHODS: Maceration with methanol as liquid extractor was used to prepare MAFRE. M. albicans (Sw.) Triana fruits chemical composition was characterized by UHPLC-QTOF-MS/MS and GC-FID (fatty acid methyl esters composition from lyophilized fruits). MAFRE antioxidant potential was evaluated in vitro using a combination of assays: Folin-Ciocalteu reducing capacity, DPPH• and ABTS radical scavenging ability and ferric reducing antioxidant power (FRAP). In vitro antiproliferative activity was investigated in four human tumor cell lines (U251, 786-0, HT29 and MDA-MB-231) while the effect on the non-tumor cell viability was assessed in the VERO cell line using the on-step MTT assay. In addition, in vivo anti-inflammatory effect was assessed by Croton oil-induced ear edema in mice followed by myeloperoxidase (MPO) activity evaluation. RESULTS: Thirty-five compounds were identified by UHPLC-QTOF-MS/MS. Among it flavonoids derived from quercetin (8), myricetin (1), kaempferol (2), terpenoids (6) and other compounds (18). GC-FID analysis identified and quantified nine fatty acids: palmitic, stearic, arachidic, behenic, elaidic, oleic, eicosenoic, and linoleic acids. The most abundant fatty acids were polyunsaturated fatty acids (5.33 ± 0.17 mg g-1), followed by saturated fatty acids (2.38 ± 0.07 mg g-1) and monounsaturated fatty acids (1.74 ± 0.09 mg g-1). The extract revealed high content of phenolic compounds (43.68 ± 0.50 mg GAE/g of extract), potent antioxidant, and ferrous chelating capacities. Morever, it proved to be non-toxic to the VERO cells, not affecting cells viability (95% of viable cells). No antiproliferative effect against human tumor cell lines were found. Furthermore, MAFRE significantly (p<0.05) reduced ear edema (≈35%) and MPO activity (84.5%) having a statistical effect similar to traditional steroidal and non-steroidal anti-inflammatory drugs. CONCLUSIONS: Taken together, the results evidenced that M. albicans fruit extract has antioxidant properties, a higher concentration of phenolic compounds, flavonoids, fatty acids, and also topical anti-inflammatory activity with low toxicity of extract on VERO cells. Through the ethnomedicinal study, these findings supporting the popular use of M. albicans, but also highlight that not only aerial parts and leaves deserve attention, but the fruits also have anti-inflammatory proprieties and can be a source of phenolic compounds and other substances with potential health benefices.

Cytotoxicity and anti-inflammatory effects of the extract, fractions and alkaloids from Palicourea minutiflora (Rubiaceae).

Palicourea species has been used in folk medicine in the treatment of some diseases including cancer and inflammatory disorders. This work aimed to evaluate the in vitro antiproliferative and in vivo topical anti-inflammatory activities of the methanolic extract, fractions and two major alkaloids isolated from Palicourea minutiflora. Methanolic extract, non-alkaloidal and alkaloidal fractions exhibited strong growth inhibition for ovarian cell lines (OVCAR-3, GI50 = 3.8 at 16.3 µg mL-1) and the vincosamide alkaloid revealed selective effect on the growth of glioma cell lines (U251, GI50 = 33.0 µg mL-1) compared with doxorubicin (DOX, GI50 = 0.42 and 0.025 µg mL-1, respectively) anticancer drug. Methanolic extract, fractions and strictosidinic acid showed significant inhibitory effect with 62.7% at 77.5% (p < 0.05) to ear edema induced by croton oil and 81% at 100% (p < 0.05) to myeloperoxidase assay compared with indomethacin (positive control) 68.4% and 91.3% (p < 0.05), respectively.

Anti-inflammatory and Antioxidant Activity of Nanoencapsulated Curcuminoids Extracted from Curcuma longa L. in a Model of Cutaneous Inflammation.

The present study evaluated the anti-inflammatory effect of nanoencapsulated curcuminoid preparations of poly(vinyl pyrrolidone) (Nano-cur) and free curcuminoids (Cur) in an experimental model of croton oil-induced cutaneous inflammation. Male Swiss mice, weighing 25-30 g, received oral treatment by gavage 1 h before CO application or topical treatment immediately after CO application (200 µg diluted in 70% acetone) with a single dose of Cur and Nano-cur. After 6 h, the animals were anesthetized and euthanized. The ears were sectioned into disks (6.0 mm diameter) and used to determine edema, myeloperoxidase (MPO) activity, and oxidative stress. Photoacoustic spectroscopy (PAS) was used to evaluate the percutaneous penetration of Cur and Nano-cur. Topical treatment with both preparations had a similar inhibitory effect on the development of edema, MPO activity, and the oxidative response. The PAS technique showed that the percutaneous permeation of both topically applied preparations was similar. Oral Nano-cur administration exerted a higher anti-inflammatory effect than Cur. Topical Cur and Nano-cur application at the same dose similarly inhibited the inflammatory and oxidative responses. Oral Nano-cur administration inhibited such responses at doses that were eight times lower than Cur, suggesting the better bioavailability of Nano-cur compared with Cur.Graphical abstract.

Synthesis of novel 3,5,6-trisubstituted 2-pyridone derivatives and evaluation for their anti-inflammatory activity.

The inflammatory response is the reaction of living tissue to an injury of a foreign nature, such as infection and irritants, and occurs as part of the body's natural defence response. Compounds capable of inhibiting cyclooxygenase (COX) enzymes, especially COX-2, have great potential as anti-inflammatory agents. Herein we present the regioselective synthesis of 49 novel compounds based on the 2-pyridone nucleus. The topical anti-inflammatory activity of seventeen compounds was evaluated in mice by croton oil (CO) induced ear edema assay. Most of the compounds exhibited a high level of in vivo anti-inflammatory activity, reducing ear edema and myeloperoxidase (MPO) activity. The most active compounds (2a and 7a) were inhibitors of COX enzymes. Compound 2a selectively inhibited the COX-2, while 7a was nonselective. Further, the compound 2a showed effective binding at the active site of COX-2 co-crystal by docking molecular study.

Methyl Jasmonate Reduces Inflammation and Oxidative Stress in the Brain of Arthritic Rats.

Methyl jasmonate (MeJA), common in the plant kingdom, is capable of reducing articular and hepatic inflammation and oxidative stress in adjuvant-induced arthritic rats. This study investigated the actions of orally administered MeJA (75-300 mg/kg) on inflammation, oxidative stress and selected enzyme activities in the brain of Holtzman rats with adjuvant-induced arthritis. MeJA prevented the arthritis-induced increased levels of nitrites, nitrates, lipid peroxides, protein carbonyls and reactive oxygen species (ROS). It also prevented the enhanced activities of myeloperoxidase and xanthine oxidase. Conversely, the diminished catalase and superoxide dismutase activities and glutathione (GSH) levels caused by arthritis were totally or partially prevented. Furthermore, MeJA increased the activity of the mitochondrial isocitrate dehydrogenase, which helps to supply NADPH for the mitochondrial glutathione cycle, possibly contributing to the partial recovery of the GSH/oxidized glutathione (GSSG) ratio. These positive actions on the antioxidant defenses may counterbalance the effects of MeJA as enhancer of ROS production in the mitochondrial respiratory chain. A negative effect of MeJA is the detachment of hexokinase from the mitochondria, which can potentially impair glucose phosphorylation and metabolism. In overall terms, however, it can be concluded that MeJA attenuates to a considerable extent the negative effects caused by arthritis in terms of inflammation and oxidative stress.

Fatty acids uptake and oxidation are increased in the liver of rats with adjuvant-induced arthritis.

Severe rheumatoid cachexia is associated with pronounced loss of muscle and fat mass in patients with advanced rheumatoid arthritis. This condition is associated with dyslipidemia and predisposition to cardiovascular diseases. Circulating levels of triglycerides (TG) and free fatty acids (FFA) have not yet been consistently defined in severe arthritis. Similarly, the metabolism of these lipids in the arthritic liver has not yet been clarified. Aiming at filling these gaps this study presents a characterization of the circulating lipid profile and of the fatty acids uptake and metabolism in perfused livers of rats with adjuvant-induced arthritis. The levels of TG and total cholesterol were reduced in both serum (10-20%) and liver (20-35%) of arthritic rats. The levels of circulating FFA were 40% higher in arthritic rats, possibly in consequence of cytokine-induced adipose tissue lipolysis. Hepatic uptake and oxidation of palmitic and oleic acids was higher in arthritic livers. The phenomenon results possibly from a more oxidized state of the arthritic liver. Indeed, NADPH/NADP+ and NADH/NAD+ ratios were 30% lower in arthritic livers, which additionally presented higher activities of the citric acid cycle driven by both endogenous and exogenous FFA. The lower levels of circulating and hepatic TG possibly are caused by an increased oxidation associated to a reduced synthesis of fatty acids in arthritic livers. These results reveal that the lipid hepatic metabolism in arthritic rats presents a strong catabolic tendency, a condition that should contribute to the marked cachexia described for arthritic rats and possibly for the severe rheumatoid arthritis.

Anti-Inflammatory and Antioxidant Actions of Methyl Jasmonate Are Associated with Metabolic Modifications in the Liver of Arthritic Rats.

Methyl jasmonate (MeJA) is a fatty acid-derived cyclopentanone which shares structural similarities with prostaglandins and has been under study as a promising anti-inflammatory agent. This study investigated the actions of MeJA on systemic inflammation and oxidative status in rats with adjuvant-induced arthritis, a model for rheumatoid arthritis. MeJA (75 to 300 mg·kg-1) was administrated orally during 18 days after arthritis induction with Freund's adjuvant. Articular and systemic inflammation was greatly increased in arthritic rats, likewise the oxidative stress in plasma and liver. The hepatic glucokinase activity and glycolysis were increased in arthritic rats. MeJA decreased most inflammatory parameters and abolished the increased protein carbonylation in plasma and liver, diminished the increased hepatic ROS content, and restored the hepatic GSH/GSSG ratio in arthritic rats. However, the MeJA treatment decreased the hepatic glucokinase activity and glycolysis and stimulated mitochondrial ROS production in healthy and arthritic rats. Oxygen uptake was increased by MeJA only in livers from treated arthritic rats. This action may bear relation to the increased activity of mitochondrial NADP+-dependent enzymes to provide reducing equivalents for the glutathione cycle. These beneficial effects, however, are associated with a decreased glucose flux through the glycolysis in the liver of arthritic and healthy rats.

ß-Caryophyllene, the major constituent of copaiba oil, reduces systemic inflammation and oxidative stress in arthritic rats.

The current study investigated the action of ß-caryophyllene, the major constituent of copaiba oil, on the systemic inflammation, oxidative status, and liver cell metabolism of rats with adjuvant-induced arthritis, a model for rheumatoid arthritis. This study also compared the actions of ß-caryophyllene with those previously reported for copaiba oil on arthritic rats. For this purpose, Holtzman healthy and arthritic rats received 215 and 430 mg·kg-1 ß-caryophyllene orally once a day during 18 days. Both doses of ß-caryophyllene reduced the adjuvant-induced paw edema, swollen of lymph nodes, and number of circulating and articular leukocytes. ß-Caryophyllene, at the dose of 430 mg·kg -1 , abolished the increases of protein carbonyl groups and myeloperoxidase activity in the liver and plasma of arthritic rats and, at both doses, it restored the increased levels of reactive oxygen species and reduced glutathione in the arthritic liver. These beneficial actions were of the same extension as those of copaiba oil ( Copaifera reticulata) and, therefore, ß-caryophyllene is possibly responsible for the anti-inflammatory and antioxidant actions of the oil. Hepatic gluconeogenesis was 40% lower in arthritic rats, which also presented a reduced number of hepatocytes per liver area (-23%) associated with increased hepatocyte area (+18%) and liver weight (+50%). None of these hepatic alterations were improved by ß-caryophyllene, but not even by ibuprofen. However, unlike copaiba oil, ß-caryophyllene did not modify the hepatic morphology and metabolism of healthy rats. These results reveal that ß-caryophyllene improves the systemic inflammation and oxidative status of arthritic rats and, in addition, it was not associated with hepatotoxicity.

Anti-inflammatory and antiproliferative activities of Ixora brevifolia Benth. (Rubiaceae).

The crude extract and fractions from the branches of Ixora brevifolia, a tree found in the Brazilian Cerrado, were tested for anti-inflammatory and in vitro antiproliferative effects. The crude extract and n-hexane fraction exhibited significant inhibition of ear oedema in mice, while n-hexane-precipitated and chloroform fractions strongly inhibited the myeloperoxidase activity in ear tissue. The n-hexane and n-hexane-precipitated fractions showed strong growth inhibition for glioma cell line and the hydromethanolic fraction inhibited the growth of leukaemia cell line.

Synthesis and Biological Evaluation of New Tyrosol-Salicylate Derivatives as Potential Anti-Inflammatory Agents.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most commonly used medications in inflammatory illnesses. However, the gastrointestinal bleeding and toxicity associated with NSAIDs long term use prompted the quest towards investigations for new anti-inflammatory agents. Natural and natural-derived molecules proved its anti-inflammatory efficacy in vitro as well as in vivo. Given this background, the scope of this research involves structural changes of the natural polyphenol (tyrosol) generating two new salicylate derivatives and testing their biological properties, focusing on anti-inflammatory effects assessed in vitro and in vivo assays. The first molecular modification was the introduction of a carboxylic acid group adjacent to the phenol group present in this compound, which creates a new salicylate-like tyrosol. In addition, the acetylation of phenol group in this molecule produced an acetylsalicylate derivative, which may be regarded as aspirin-like natural polyphenol. Interestingly, tyrosol and its novel derivatives attenuated the edema in acute inflammatory response on carrageenan- induced local inflammation in mice. In addition, our results demonstrated that tyrosol and its novel derivatives were able to reduce the chemotaxis of neutrophil assessed in vitro model by chemo attractant (fMLP). Furthermore, only derivative 2 was able to reduce this effect in the acute inflammatory model. In (DPPH)- scavenging activity, tyrosol derivatives demonstrated a minor antioxidant activity, which may suggest that radical scavenging is not a major pathway involved in the anti-inflammatory effects of these derivatives. Salicylate-like tyrosol derivatives are of particular interest for future studies.

Evidence of anti-inflammatory effect and percutaneous penetration of a topically applied fish oil preparation: a photoacoustic spectroscopy study.

This paper investigates the topical anti-inflammatory effect of a fish oil preparation (FOP) in a croton oil (CO) model of skin inflammation. The photoacoustic spectroscopy (PAS) was applied to estimate the percutaneous penetration of the FOP and as a model to evaluate the topical inflammatory response. After applying CO, the groups of mice received a topical application of a FOP on the left ear. The right ear received the vehicle that was used to dilute the CO. After 6 h, ear tissue was collected to determine the percent inhibition of edema, myeloperoxidase (MPO) activity, and cytokine levels and to perform PAS measurements. Treatment with FOP reduced edema and MPO activity, which was at least partially attributed to a decrease in the levels of tumor necrosis factor, interleukin- 1 ? , interleukin-6, keratinocyte-derived chemokine, and monocyte chemoattractant protein-1. The topically applied FOP penetrated into the tissue and decreased the area of the bands that characterize inflamed tissue. The present results demonstrated the topical anti-inflammatory effect of the FOP. PAS suggests that FOP anti-inflammatory activity is linked with its ability to penetrate through the skin.

Anti-Inflammatory and Antioxidant Actions of Copaiba Oil Are Related to Liver Cell Modifications in Arthritic Rats.

The present study investigated the action of copaiba oil (Copaifera reticulata) on the systemic inflammation, oxidative status, and liver cell metabolism of rats with adjuvant-induced arthritis. The later is an experimental autoimmune pathology that shares many features with the human rheumatoid arthritis. Holtzman rats were distributed into the following groups: control (healthy) rats; control rats treated with copaiba oil at the doses of 0.58 and 1.15 g · kg-1 , arthritic rats, and arthritic rats treated with copaiba oil (0.58 and 1.15 g · kg-1 ). The oil was administrated orally once a day during 18 days after arthritis induction. Both doses of copaiba oil improved the paw edema and the dose of 0.58 mg · kg-1 improved the swollen adrenals and lymph nodes besides decreasing the plasmatic myeloperoxidase activity (-30%) of arthritic rats. Copaiba oil (1.15 g · kg-1 ) abolished the increases of protein carbonyl groups and reactive oxygen species in the liver and both doses increased the liver GSH content and the catalase activity in arthritic rats. Copaiba oil (1.15 g · kg-1 ) decreased glycolysis (-65%), glycogenolysis (-58%), and gluconeogenesis (-30%) in the liver of arthritic animals. However, gluconeogenesis was also diminished by the treatment of control rats, which presented lower body weight gain (-45%) and diminished number of hepatocytes per liver area (-20%) associated to higher liver weight (+29%) and increased hepatocyte area (+13%). The results reveal that copaiba oil presented systemic anti-inflammatory and antioxidant actions in arthritic rats. These beneficial effects, however, were counterbalanced by harmful modifications in the liver cell metabolism and morphology of healthy control rats. J. Cell. Biochem. 118: 3409-3423, 2017. © 2017 Wiley Periodicals, Inc.

Acute toxicity, antiedematogenic activity, and chemical constituents of Palicourea rigida Kunth.

The phytochemical study of the leaves, roots, and flowers of Palicourea rigida led to the isolation of the triterpenes betulinic acid (1) and lupeol (2), the diterpene phytol (3), and the iridoid glycosides sweroside (4) and secoxyloganin (5). These compounds were identified using NMR 1H and 13C and comparing the spectra with published data. We studied the antiedematogenic activity of crude extracts from the organs, and of different fractions, in mice and found that the n-hexane fraction of the leaf extract significantly inhibited the ear edema resulting from croton oil administration. The crude extract from leaves was not acutely toxic to the mice.

Synergistic effects of anethole and ibuprofen in acute inflammatory response.

This study assessed the effect of the combination of anethole and ibuprofen in comparison with monotherapy by either drug alone, using two in vivo inflammatory models, namely the pleurisy and paw edema in rats. We also measured the levels of the TNF protein in plasma, and the ability of anethole to inhibit, in vitro, the activity of the cyclooxygenase 1 and cyclooxygenase 2 enzymes. The test drugs (anethole; ibuprofen; anethole + ibuprofen), at different doses, were administered once (p.o.) 60 min before the induction of the inflammatory response. The association of anethole + ibuprofen inhibited the development of the inflammatory response in both models used. This effect can be partially explained by the inhibitory action on the production of TNF and of COX isoforms. The isobologram analysis evidenced a synergistic effect between ibuprofen and anethole, because the combination of drugs showed a higher inhibitory potential than either drug alone.

A high performance liquid chromatography with ultraviolet method for Eschweilera nana leaves and their anti-inflammatory and antioxidant activities.

BACKGROUND: Eschweilera nana Miers is a tree widely distributed in Cerrado, Brazil. OBJECTIVE: In this study, we aimed to describe its phytochemical properties and antioxidant and topical anti-inflammatory effects for the first time, as well validate an high performance liquid chromatography with ultraviolet/visible (HPLC-UV-Vis) method for the separation and quantification of the main components (hyperoside and rutin) in the hydroalcoholic extract of E. nana leaves. MATERIALS AND METHODS: Structural identification of compounds in E. nana extract was performed by analysis of spectral data by (1)H nuclear magnetic resonance, (13)C nuclear magnetic resonance and/or ESI/EM. The HPLC-UV-Vis method was validated according International Conference on Harmonization (ICH) parameters. The 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) method were used for determination of in vitro antioxidant activities and the croton oil-induced inflammation for evaluation of in vivo anti-inflammatory effects. RESULTS: Hyperoside, rutin, α-amirin, ß-amirin, ß-sitosterol, and stigmasterol were identified in the hydroalcoholic extract of E. nana leaves. HPLC-UV-Vis was validated according to ICH parameters. Furthermore, in vitro and in vivo assays demonstrated that the hydroalcoholic extract and methanol fraction showed significant antioxidant and topical anti-inflammatory effects, as they were able to reduce ear edema induced by croton-oil application. CONCLUSIONS: This research showed the first phytochemical study of E. nana extract and their biological activities may be associated with the presence of flavonoids in the extracts.

Primary Characterization and Evaluation of Anti Ulcerogenic Activity of an Aqueous Extract from Callus Culture of Cereus peruvianus Mill. (Cactaceae).

In the current study we reported cultivation, extraction procedure, analysis and preliminary characterization of the aqueous extract from Cereus peruvianus callus culture and evaluated its anti ulcerogenic activity in vivo models of experimental ulcers in Wistar rats. The obtained aqueous extract from callus (AC) was dialyzed and subjected to freeze-thaw process, providing a possible polysaccharide. The carbohydrate and protein contents of the aqueous extract were estimated at 53.4% and 0.66%, respectively, composed primarily of galactose, arabinose and galacturonic acid, with minor amounts of glucose. This appeared heterogeneous when analyzed by high-performance size-exclusion chromatography and a multi-angle laser light scattering detector (HPSEC-MALLS). The AC was found to be significantly effective against ethanol-induced lesions but was ineffective against indomethacin-induced lesions. The callus culture of C. peruvianus is an alternative source for the synthesis of substances originally produced by plants. The calluses grown indefinitely in vitro under controlled conditions are stable tissues, and the aqueous extract from calluses may be used instead of fully developed plants using the protocols described in this study.

Primary characterization and evaluation of anti ulcerogenic activity of an aqueous extract from callus culture of Cereus peruvianus Mill. (Cactaceae).

In the current study we reported cultivation, extraction procedure, analysis and preliminary characterization of the aqueous extract from Cereus peruvianus callus culture and evaluated its anti ulcerogenic activity in vivo models of experimental ulcers in Wistar rats. The obtained aqueous extract from callus (AC) was dialyzed and subjected to freeze-thaw process, providing a possible polysaccharide. The carbohydrate and protein contents of the aqueous extract were estimated at 53.4% and 0.66%, respectively, composed primarily of galactose, arabinose and galacturonic acid, with minor amounts of glucose. This appeared heterogeneous when analyzed by high-performance size-exclusion chromatography and a multiangle laser light scattering detector (HPSEC-MALLS). The AC was found to be significantly effective against ethanol-induced lesions but was ineffective against indomethacin-induced lesions. The callus culture of C. peruvianus is an alternative source for the synthesis of substances originally produced by plants. The calluses grown indefinitely in vitro under controlled conditions are stable tissues, and the aqueous extract from calluses may be used instead of fully developed plants using the protocols described in this study.