Intramuscular compatibility of an injectable anti-inflammatory nanodispersion from a standardized Bixa orellana oil (Chronic®): a toxicological study in Wistar rats.

Bixa orellana L. is a plant popularly known as "ucurum", "annatto", and "achiote". It is native to South America, and its seeds are an abundant source of geranylgeraniol and tocotrienols. Nanoencapsulation is a valuable technique that can decrease the drug needed to achieve an effect, decreasing potential toxicity, side effects and potentiate the anti-inflammatory effect. This study aimed to evaluate the acute toxicity of an intramuscular application of a nanodispersion containing a standardized extract from the seeds of Bixa orellana (NBO) in Wistar rats. The chemical evaluation showed δ-tocotrienol at 0.725 ± 0.062 mg/mL (72.6 ± 0.9%). The stability study showed the nanoparticles had an average size from 53.15 ± 0.64 to 59.9 ± 3.63 nm, with a polydispersity index ranging from 0.574 ± 0.032 to 0.574 ± 0.32, Zeta potential from 18.26 ± 0.59 to 19.66 ± 1.45 mV. After testing the intramuscular application of NBO with doses from 1 to 5 mg/kg in animals, it was observed that the acute treatment did not elicit any toxic effects within this range. The dose of 10 mg/kg, although not affecting hematological and biochemical parameters (CPK, LDH, myoglobin, AST, ALT, TC, TG, glucose levels, creatinine, and urea), could induce some muscle tissue changes, including leukocyte infiltration, morphological chances, and potentially necrosis. In conclusion, the results showed that the treatments devoided toxicity between 1 and 5 mg/kg.

Potential of the Compounds from Bixa orellana Purified Annatto Oil and Its Granules (Chronic®) against Dyslipidemia and Inflammatory Diseases: In Silico Studies with Geranylgeraniol and Tocotrienols.

Some significant compounds present in annatto are geranylgeraniol and tocotrienols. These compounds have beneficial effects against hyperlipidemia and chronic diseases, where oxidative stress and inflammation are present, but the exact mechanism of action of such activities is still a subject of research. This study aimed to evaluate possible mechanisms of action that could be underlying the activities of these molecules. For this, in silico approaches such as ligand topology (PASS and SEA servers) and molecular docking with the software GOLD were used. Additionally, we screened some pharmacokinetic and toxicological parameters using the servers PreADMET, SwissADME, and ProTox-II. The results corroborate the antidyslipidemia and anti-inflammatory activities of geranylgeraniol and tocotrienols. Notably, some new mechanisms of action were predicted to be potentially underlying the activities of these compounds, including inhibition of squalene monooxygenase, lanosterol synthase, and phospholipase A2. These results give new insight into new mechanisms of action involved in these molecules from annatto and Chronic®.

Co-Treatment of Purified Annatto Oil (Bixa orellana L.) and Its Granules (Chronic®) Improves the Blood Lipid Profile and Bone Protective Effects of Testosterone in the Orchiectomy-Induced Osteoporosis in Wistar Rats.

This study aimed to evaluate and compare the effects of co-treatment with purified annatto oil (PAO) or its granules (GRA, Chronic®) with that of testosterone on the orchiectomy-induced osteoporosis in Wistar rats. After surgery, rats were treated from day 7 until day 45 with testosterone only (TES, 7 mg/kg, IM) or TES + PAO or GRA (200 mg/kg, p.o.). The following parameters were evaluated: food/water intake, weight, HDL, LDL, glucose, triglycerides (TG), total cholesterol (TC), alkaline phosphatase levels, blood phosphorus and calcium contents, femur weight, structure (through scanning electron microscopy), and calcium content (through atomic absorption spectrophotometry). Our results show that orchiectomy could significantly change the blood lipid profile and decrease bone integrity parameters. Testosterone reposition alone could improve some endpoints, including LDL, TC, bone weight, and bone calcium concentration. However, other parameters were not significantly improved. Co-treatment with PAO or GRA improved the blood lipid profile and bone integrity more significantly and improved some endpoints not affected by testosterone reposition alone (such as TG levels and trabeculae sizes). The results suggest that co-treatment with annatto products improved the blood lipid profile and the anti-osteoporosis effects of testosterone. Overall, GRA had better results than PAO.

Actions of Cannabis sativa L. fixed oil and nano-emulsion on venom-induced inflammation of Bothrops moojeni snake in rats.

BACKGROUND: Bothrops moojeni snake venom (VBm) has toxins that cause pronounced tissue damage and exacerbated inflammatory reaction. Cannabis sativa L. is a plant species that produces an oil (CSO) rich in unsaturated fatty acids. Nano-emulsions have several advantages, such as better stability and higher penetrating power in membranes. Therefore, this study evaluated the effect of a nano-emulsion based on this herbal derivative (NCS) against VBm-induced inflammation in Wistar rats. METHODS: The CSO and NCS were submitted to physicochemical characterization. The inflammatory process was induced by the VBm (0.10 mg/kg) as follows: rat paw edema, peritonitis, analysis of leukocyte infiltrate in gastrocnemius muscle of rats and formation of granulomatous tissue. RESULTS: No significant changes were observed when the NCS was submitted to the centrifugation and thermal stress tests. There was no phase separation, changes in density (0.978 ± 0.01 g/cm3) and viscosity (0.889 ± 0.15). The droplet diameter ranged from 119.7 ± 065 to 129.3 ± 0.15 nm and the polydispersity index ranged from 0.22 ± 0.008 to 0.23 ± 0.011. The results showed that treatments with CSO (200 and 400 mg/kg) and NCS (100 mg/kg) were able to decrease significantly (p < 0.001) the formation of edema and granulomatous tissue. The CSO and NCS groups significantly attenuated (p < 0.001) the recruitment of inflammatory cells in the tests for peritonitis and leukocyte infiltrate. The histopathological analysis of the gastrocnemius muscle showed a reduction in tissue damage caused by VBm. CONCLUSION: The results obtained in this study showed anti-inflammatory activity of the CSO which may be due to a high UFA content. The nanosizing, as evidenced by the incorporation of the CSO in the NCS improved the effect and opens the perspective for the obtainment of a nanomedicine in which a kinetic stable phytotherapic can be used at low doses.

Sphaerospora festivus n. sp., a parasite of the flag cichlid, Mesonauta festivus (Teleostei: Cichlidae) from eastern Amazon, Brazil / Sphaerospora festivus n. sp., um parasito do ciclídeo bandeira, Mesonauta festivus (Teleostei: Cichlidae) da Amazônia oriental, Brasil

Abstract The present study describes a new species of the genus Sphaerospora found in the urinary bladder of the flag cichlid, Mesonauta festivus collected in Corre Água district of the municipality of Macapá, Amapá State (Brazil). The study includes morphological and phylogenetic analyses of the new parasite, to determine the relationship of the new species with related myxosporean species. The new species has polysporous plasmodia, which vary in size and shape. The mature myxospores are subspherical shape in valvar view. In the sutural view, the myxospores are 5.3±0.2 (5.2-5.6) μm in length and 7.0±0.7 (6.3-7.7) μm in width, with two piriform polar capsules equal size, 2.5±0.2 (2.3-2.8) μm in length and 1.8±0.2 (1.6-2.0) μm in width. The phylogenetic analyses of a partial sequence of the 18S rRNA gene confirmed the status of the new species and determined the relationship of the new species and related myxosporean species.The sum of the evidence indicates that, Sphaerospora festivus n. sp. belongs to the family Sphaerosporidae, and is the first record of the genus Sphaerospora from Brazil.

Resumo O presente estudo tem como objetivo descrever uma nova espécie de Sphaerospora encontrado na bexiga urinária de Mesonauta festivus, coletado no distrito Corre Água, no município de Macapá, estado do Amapá (Brasil). Foram realizadas análises morfométricas e filogenéticas, nas quais se avaliou a relação entre as espécies de mixosporídeos já descritas. A nova espécie possui plasmódio poliespórico, que varia em tamanho e forma. Os esporos maduros são subesféricos. Na visão sutural, apresentam 5,3 ± 0,2 (5,2-5,6) μm de comprimento e 7,0 ± 0,7 (6,3-7,7) μm de largura, com duas cápsulas polares piriformes de tamanhos iguais, 2,5 ± 0,2 (2,3-2,8) μm de comprimento e 1,8 ± 0,2 (1,6-2,0) μm de largura. As análises filogenéticas das sequências parciais do gene 18S rDNA confirmam ser uma nova espécie e determinou a relação desta com outros myxozoários já relatados. Conclui-se que a espécie em estudo pertence à família Sphaerosporidae, gênero Sphaerospora, e nova espécie, Sphaerospora festivus n. sp. e primeira ocorrência de parasitos desse gênero no Brasil.

Nano-emulsification of Aeollanthus suaveolens Mart. Ex Spreng essential oil modifies its neuroeffects?

Oil in water nano-emulsions are drug delivery systems constituted by liquid lipophilic nano-droplets dispersed through the external aqueous phase, often reaching the kinetic stability with surfactant as stabilizers. Essential oils can be the oily phase or the source of bioactive compounds. In this study, the essential oil of Aeollanthus suaveolens-a plant used in folk medicine due to its psychopharmacological effects-was used for preparation of fine nano-emulsions by a low-energy titrating method. Monodisperse small nano-droplets (ca. 70 nm; PdI 0.200) were assembled by using blends of non-ionic surfactants, indicating modulation on surfactant system lead to altering the physical property. In a separate set of experiments, we investigated the role of this modulation on biological properties of the optimal nano-emulsion. The zebrafish embryos were more susceptible to the nano-emulsion than the bulk essential oil, showing the improved bioactivity due to nano-sizing. Therefore, adult zebrafish was treated, and paralysis was observed in the groups treated with the nano-emulsion, being this finding in accordance with hypnosis. At the same essential oil dose, another behavior was observed, suggesting that expected dose-dependent effects associated to sedative-hypnotics can be achieved by nano-sizing of psychoactive essential oils. This paper contributes to the state-of-art drug delivery systems by opening perspectives for novel sedative-hypnotics nano-emulsified essentials oils that can reach hypnotic effects at considerably lower dose, when compared with bulk materials, being useful for further completed dose-response studies.Graphical abstract.

Nano-emulsification Enhances the Larvicidal Potential of the Essential Oil of Siparuna guianensis (Laurales: Siparunaceae) Against Aedes (Stegomyia) aegypti (Diptera: Culicidae).

Siparuna guianensis (Laurales: Siparunaceae) has a terpene-rich essential oil with great potential for larvicides. The poor water miscibility of their compounds makes nano-emulsions of great interest for novel bioactive systems, including for control of Aedes aegypti (Diptera: Culicidae). This species is adapted to urban environments with important role in the epidemiology of some arboviruses such as dengue, chikungunya fever, zika, and urban yellow fever. The aim of the present study was to evaluate the feasibility of nano-emulsification to affect Ae. aegypti larvae. An optimal system was achieved by using a nonionic single surfactant, highlighted by its satisfactory size distribution profile. Moreover, improved larvicidal activity in comparison to bulk essential oil can be observed for the nano-emulsions. The estimated LC50 and LC90 values after 24 h of treatment of larvae with the essential oil were, respectively, 86.5232 and 134.814 µg/ml, while the estimated LC50 and LC90 value after treatment with the nano-emulsion were 24.7572 and 75.2452 µg/ml, respectively. The utilization of a simple technique to produce a fine nano-emulsion opens perspective for further integrative practices of mosquito control and giving value to this Amazon plant species may encourage its sustainable use and contribute to conservation policies.

Endopleura uchi (Huber) Cuatrec.: A medicinal plant for gynecological treatments - A reproductive toxicity assessment in zebrafish (Danio rerio).

ETHNOPHARMACOLOGICAL RELEVANCE: Endopleura uchi (Huber) Cuatrec is a plant species from the Brazilian Amazon. The barks of this tree are used in folk medicine - mainly as a decoction - for dyslipidemia, uterine infection, fibroids, polycystic ovary, menstrual disorders, as a contraceptive and abortive agent, among others. However, the data available about its developmental toxicity are still insufficient. AIM OF THE STUDY: This study aimed to evaluate the reproductive toxicity and teratogenic effects in embryos from zebrafish treated with the hydroethanolic extract from the barks of Endopleura uchi (EEu). MATERIALS AND METHODS: Both sexes of zebrafish (Danio rerio) were treated with EEu either through immersion (1.2, 2.5, and 5 mg/L) or orally (75, 200, and 500 mg/kg) over 21 consecutive days. Next, we assessed their fertility and gonads' histopathology; in their embryos were assessed teratogenesis, lethalities, and heart rate during daily observations (24, 48, 72, and 96 hpf). RESULTS: The phytochemical analysis of EEu through HPLC/MS shows bergenin as the major compounds. After 21 days of treatment were detected minor histopathological changes in parental fishes, such as atretic oocytes, interstitial fibrosis, and decreased the percentage of early vitellogenic oocytes, but without impairing the reproduction of treated animals. However, in the embryos was observed significantly increased frequency of malformation in all the groups treated through immersion, and in the group treated orally with the highest concentration (500 mg/kg). CONCLUSION: Based on the results, EEu caused no adverse effects in the progenitors on both treatments (immersion and oral). However, it was observed that the concentrations 1.2, 2.5, and 5 mg/L (immersion), and the dose 500 mg/kg (oral) caused malformations in the offspring (F1 generation). These results emphasize the need for attention when using preparations from E. uchi, mainly for pregnant women. Further studies are needed to compare its effects with the extract's primary compound (bergenin).

Rosmarinus officinalis essential oil: A review of its phytochemistry, anti-inflammatory activity, and mechanisms of action involved.

ETHNOPHARMACOLOGICAL RELEVANCE: Plant species Rosmarinus officinalis L. (Lamiaceae; Synonyms: Salvia rosmarinus Schleid. and Rosmarinus angustifolius Mill.) is a herb widely used worldwide. In local and traditional medicine, its used for inflammation-related diseases. Currently, studies report anti-inflammatory activity in its essential oil (EORO). However, to better understand EORO's anti-inflammatory activity its necessary to understand its phytochemistry and the signaling pathways affected by it. Hence, this review aimed to describe EORO phytochemical profile, ethnopharmacological uses, some biological activities of EORO will be described but emphasizing its anti-inflammatory potential and possible mechanisms of action involved. MATERIALS AND METHODS: The research was performed using the databases Medline, Embase, BVS Regional Portal, Science Direct, CAPES Journals, and Scopus; using the keywords "Rosmarinus officinalis", "anti-inflammatory" and "essential oil". Additional information was gathered from related textbooks, reviews, and documents. RESULTS AND DISCUSSION: Until now about 150 chemical compounds were identified in EORO samples, more frequently reported molecules were 1,8-cineole, α-pinene, and camphor. Studies suggest that the anti-inflammatory activity of EORO occur mainly through inhibition of NF-κB transcription and suppression of arachidonic acid cascade. Its antioxidant activity also aids by preventing injury caused by the reactive species of inflammation; its smooth muscle relaxant activity contributes to ameliorating airway inflammatory diseases. Lastly, toxicity assessments indicate low toxicity to EORO. CONCLUSIONS: Current evidence indicates anti-inflammatory activity in EORO, supporting its ethnopharmacological uses in inflammatory-related diseases, and potential future applications. However, although considerable acute inflammatory models were tested, more chronic inflammatory models are needed; clinical studies are still absent, this may be due to the high doses needed for essential oils to exert pharmacological effects, but recent studies show this issue can be bypassed using the oil formulated as nanoemulsions to improve its bioavailability.

Effect of the treatment of Copaifera duckei oleoresin (copaiba) in streptozotocin-induced diabetic rats

ABSTRACT Diabetes mellitus is a syndrome that reaches more than 382 million people worldwide. It interferes with the metabolism of carbohydrates, causing chronic hyperglycemia. The objective of this study was to evaluate the effect of the Copaifera duckei, Dwyer, Fabaceae, oleoresin on streptozotocin-induced (STZ) diabetic rats. This study was based on the induction of diabetes mellitus by streptozotocin (55 mg/kg, i.p.) in Wistar rats and treated with doses of C. duckei oleoresin (250 and 500 mg/kg, p.o.). Subsequently, the clinical, biochemical and histopathological of the pancreas parameters were evaluated. Gas chromatographic analysis indicated that β-bisabolene (22.29%), β-caryophyllene (21.25%) and α-farnesene (15.58%) sesquiterpenes were the major components of the C. duckei oleoresin. In streptozotocin-induced diabetes mellitus, it was possible to observe that the C. duckei oleoresin treatment had a significant effect (p < 0.001) on the clinical parameters, and that there was a positive improvement. This was attenuated by the urea, creatinine, and transaminases alterations (p < 0.001) observed in animals with diabetes mellitus, as well as the significantly reduced (p < 0.001) values of total cholesterol, triacylglycerides, and glucose. In the histopathological analyses of the pancreas, it was observed that the C. duckei oleoresin was able to restore β-cells and to significantly increase the quantity and diameter of the Langerhans islets (p < 0.05), when compared to the diabetic group. The treatment with C. duckei oleoresin, employed under the conditions of this study, presented antidiabetic activity and can improve the complications found in this syndrome.

Nanosuspension of quercetin: preparation, characterization and effects against Aedes aegypti larvae

Abstract Aedes aegypti (Diptera: Culicidae) is the main vector of some neglected diseases, including dengue. It is very important to develop formulations that increase effectiveness of vector control with low toxicity. Quercetin is a plant-derived flavonoid that modulates the development of some insects. The low water solubility of quercetin impairs the development of water-dispersible commercial products. To circumvent this problem, the preparation of nanoformulations is considered promising. Thus, this study aimed to evaluate the effect of bulk and quercetin nanosuspension against A. aegypti larvae and also to investigate their ecotoxicity. Quercetin nanosuspension was produced by a solvent displacement method followed by solvent evaporation and was maintained in two different temperatures (4 and 25 ºC). Its size distribution and zeta potential were monitored along 30 days. The influence of quercetin nanosuspension and bulk-quercetin was investigated at various concentrations against A. aegypti and the green algae Chlorella vulgaris. The quercetin nanosuspension presented higher stability at 4 ºC and negative zeta potential values. Quercetin nanosuspension and bulk-quercetin adversely affected the larvae development, especially at the highest concentrations. Larvae mortality was between 44% and 100% (48 h) for quercetin nanosuspension at 100 and 500 ppm, respectively. The bulk-quercetin induced around 50% mortality regardless the concentration used at this same time-period. Absence of emerging mosquitoes from water was observed on the survival larvae of all the treated groups. Quercetin nanosuspension was less toxic than bulk-quercetin against C. vulgaris, especially at higher concentrations. These data indicate that quercetin nanosuspension may represent a potential larvicide for A. aegypti control, once they induced larvae death and inhibited the survival ones to emerge from water. In addition, it did not demonstrated ecotoxicity against a non-target organism, highlighting its better properties, when compared to the bulk-quercetin.

Leaves of Spondias mombin L. a traditional anxiolytic and antidepressant: Pharmacological evaluation on zebrafish (Danio rerio).

ETHNOBOTANICAL RELEVANCE: Spondias mombin L. is a plant dispersed throughout the tropical regions of South America, Africa, and Asia, being found mainly in the North and Northeast of Brazil, where the leaves are used in preparations for neuropsychiatric disorders. Therefore, it is of great importance to carry out studies in different pharmacological models that can prove the traditional use of this plant species. MATERIALS AND METHODS: the hydroethanolic extract from S. mombin leaves (HELSm) was evaluated by oral administration (25 mg/kg) and by immersion (25 mg/l) in scototaxis test in zebrafish (Danio rerio). For this study, caffeine (100 mg/kg) and buspirone (25 mg/kg) were used as standard drugs. The antidepressant action of the HELSm was evaluated assessed in the novel tank diving test (NTDT). In this study, a group with 1% ethanol, one with unpredictable chronic mild stress (UCMS), and another with developmental, social isolation (DSI) were used as induction groups for depression-like behavior and fluoxetine (20 mg/kg) as a drug pattern. RESULTS: by the HPLC-UV fingerprint analysis, the HELSm presented several derivatives of polyphenolic compounds and flavonoids and identified ellagic acid and isoquercitrin, and by the gas-chromatographic, the majority of the identified compounds were fatty acids, esters, and alcohols. By immersion, the LC50 was 49.86 mg/l and by oral via the LD50 in 48 h, was 4.515 g/kg in zebrafish. For all spatiotemporal and behavioral variables (time spent, white compartment, latency, toggle, erratic swimming, freezing duration, thigmotaxis, and risk assessment), the treatment with HELSm produced a similar effect to buspirone and was significant when compared to the caffeine and control group (p < 0.01, Tukey-Kramer test). For all spatiotemporal and behavioral variables evaluated (time spent at the top of the apparatus, crossed quadrants, erratic swimming, and duration of freezing), treatment with HELSm produced a change in the depression-like behavior in the groups tested, with a similar effect to fluoxetine, both with a significant difference when compared to the control groups (p < 0.01). CONCLUSIONS: Our results suggest that the acute administration of the HELSm in the scototaxis and NTDT tests in a zebrafish model (Danio rerio) produced anxiolytic and antidepressant effects, devoid of hypnotic and sedative actions by immersion, and this action was improved when administered by oral via. Possibly, the presence of isoquercitrin in the leaves of Spondias mombin participates in the anxiolytic and antidepressant effects.

Oil from the fruits of Pterodon emarginatus Vog.: A traditional anti-inflammatory. Study combining in vivo and in silico.

ETHNOBOTANICAL RELEVANCE: The oil obtained from the fruits of Pterodon emarginatus Vog. (OPe) is used orally and topically, in traditional medicine for some purposes, such as acute and chronic inflammatory states as rheumatoid arthritis. MATERIALS AND METHODS: In this work, the anti-inflammatory activity of the OPe was demonstrated based on several animal models and presented an in silico study based on the 6α,7ß-dihydroxy-vouacapan-17ß-oic acid (DHVA) majority compound of the OPe to evaluate the interaction this compound, with cyclooxygenase-2 (COX-2) in 4COX (Mus musculus) and 5KIR (Homo sapiens) and molecular dynamics simulation. RESULTS: The OPe (498 mg/kg, p.o) significantly inhibited (p < 0.05, Student t-test) the primary and secondary reactions of arthritis by Freund's Complete Adjuvant (FCA) and in dermatitis induced by croton oil in mice, OPe inhibited peak of edema. In vascular permeability test in rats, the treatment with OPe was able to block the response to PGE2, serotonin, and bradykinin (p < 0.05, Student t-test). In the writhing test in mice, the OPe at doses of 498 and 980 mg/kg (p.o) produced inhibition of 73% and 92%, respectively, and was not significantly effective in the hot plate test. In the evaluation of the potency in relation to gastric injury (gastric ulcer induced by stress) and combined assay in the assessment of anti-inflammatory potency and gastric damage, it was observed that indomethacin (10 mg/kg, p.o.) inhibited carrageenan edema by 51% and produced a higher number of gastric lesions when compared to the group treated with OPe, where only areas of hyperemia were observed, without the occurrence of ulcerative lesion, and which inhibited the edema by 47%. In the in silico study, it was found that the DHVA is capable of binding to two organisms (4COX - Mus musculus and 5KIR - Homo sapiens), however, with higher binding affinity to the organism Homo sapiens. CONCLUSIONS: As expected, all tested ligands were capable of forming hydrogen interactions with residues at their respective binding sites, but the DHVA ligand was capable of creating slightly more hydrogen bonds when docked to either 4COX or 5KIR than the other tested ligands, thus demonstrating the participation of this compound in the anti-inflammatory and antialgic responses observed in the in vivo assays as a COX-2 inhibitor. Therefore, the results obtained support the traditional use of OPe for inflammatory and gastric problems.

Anti-inflammatory activity of nanoemulsions of essential oil from Rosmarinus officinalis L.: in vitro and in zebrafish studies.

The essential oil from Rosmarinus officinalis L. (OERO) has bioactive compounds with anti-inflammatory activity. The objective of this study was to evaluate the anti-inflammatory potency of nanoemulsions containing essential oil of Rosmarinus officinalis L. (NOERO, NECHA, NECULT, and NECOM) in vitro and in vivo. This study was accomplished in a quantitative format through tests with diphenyl picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), cellular antioxidant activity (CCA), determination of nitric oxide production, cellular viability and anti-inflammatory activity in zebrafish. OERO's were submitted to the analysis-coupled gas chromatography-mass spectrometry (GC-MS), which highlighted 1,8-cineol and camphor as major compounds. NOEROs were obtained by a low-energy method and presenting the medium size smaller than 200 nm. The efficiency of encapsulation by spectrometry and gas chromatographic analysis was 67.61 and 75.38%, respectively. In the CCA assay, all of the samples presented percentage values of inhibition similar to the quercetin pattern, indicating antioxidant activity. In the test for determination of NO·, all of the samples inhibited the production of NO· when compared to LPS, and NOEROS were more effective than OEROS to 5 µg/mL. In the cell viability assay, the cells remained viable after contact with the samples, demonstrating an absence of cytotoxicity. This study showed that all nanoemulsions (NECHA, NECULT, and NECOM) showed no toxicity to macrophages, besides demonstrating antioxidant activity and potentiation of the essential oil effect in the proliferation of viable fibroblasts. Nanoemulsions has also shown the ability to potentiate the anti-inflammatory action of essential oils by exerting immunomodulatory activity by inhibiting the production of the pro-inflammatory mediator nitric oxide. The results obtained with NECHA in zebrafish confirm the hypothesis that prominent terpenic compounds, alpha-pinene, 1,8-cineole, and camphor, became more available at the target sites, inhibiting the inflammatory process in this animal species.

Anti-inflammatory and antialgic actions of a nanoemulsion of Rosmarinus officinalis L. essential oil and a molecular docking study of its major chemical constituents.

We evaluate the anti-inflammatory and antialgic potency of a nanoemulsion (NEORO) containing the essential oil of Rosmarinus officinalis L. (EORO), which is composed primarily of limonene, camphor and 1,8-cineole. The EORO and NEORO were administered orally 30 min prior to starting the experiments. In a test of rat paw oedema induced by carrageenan, NEORO was effective in doses of 498 µg/kg, and it inhibited 46% of the maximum peak of the oedema; in a dose of 300 mg/kg, EORO inhibited 50% of the maximum peak of the oedema. In an acetic acid-induced writhing test, NEORO yielded a dose-dependent effect, and a dose of 830 µg/kg inhibited 84% of the algesic process; a dose of 100 mg/kg of EORO inhibited 55%. In an assay for H2S production in rat stomachs, a dose of 498 µg/kg of NEORO inhibited H2S production in all of the measurement phases, and a dose of 100 mg/kg EORO inhibited 60% and influenced the effect of the ethanol significantly, reducing the production of H2S. We suggest that NEORO potentiated the effect of EORO, demonstrating effectiveness in doses 600 times lower than those applied with EORO. Among the major compounds of EORO, the camphor molecule exhibited the largest number of interactions with the therapeutic targets related to the inflammatory process, suggesting that it is responsible for EORO's anti-inflammatory and antialgic effects. This work paves the way for future investigations related to the therapeutic role of NEORO in the inflammation process.

Effect of Euterpe oleracea Mart. (Açaí) Oil on Dyslipidemia Caused by Cocos nucifera L. Saturated Fat in Wistar Rats.

Dyslipidemia is caused by disturbances in lipid metabolism that lead to chronic elevations of serum lipids, especially low-density lipoprotein (LDL)-cholesterol and triglycerides, increasing the risk of metabolic syndrome, obesity, diabetes, atherogenic processes, and cardiovascular diseases. The oil from the fruits of Euterpe oleracea (OFEO) is rich in unsaturated fatty acids with potential for treating alterations in lipid metabolism. In this study, we aimed to investigate the effect of OFEO on hyperlipidemia induced by Cocos nucifera L. saturated fat (GSC) in Wistar rats. Chromatographic profile showed that unsaturated fatty acids account for 66.08% in OFEO, predominately oleic acid (54.30%), and saturated fatty acids (palmitic acid 31.6%) account for 33.92%. GSC-induced dyslipidemia resulted in an increase in total cholesterol, LDL-cholesterol, triglycerides, glucose, and liver and abdominal fat, as well as atherogenic processes in the thoracic aorta. OFEO treatment did not reduce hypertriglyceridemia, but did reduce total cholesterol and LDL-cholesterol, thus contributing to the antiatherogenic action of OFEO. OFEO treatment inhibited the formation of atheromatous plaques in the vascular endothelium of the treated rats, as well as those who were treated with simvastatin. The results obtained suggest that OFEO has an antiatherogenic effect in a rat model of dyslipidemia.

Hypoglycemic effect of formulation containing hydroethanolic extract of Calophyllum brasiliense in diabetic rats induced by streptozotocin

ABSTRACT Diabetes mellitus is a chronic and severe metabolic dysfunction, it's slow and progressive evolution interferes directly in the metabolism of carbohydrates, fats and proteins, causing hyperglycemia, glycosuria, polydipsia, hyperlipidaemia, among others. The aim of this study was to evaluate the antidiabetic effect of hydroethanolic extract and granulated of Calophyllum brasiliense Cambess., Clusiaceae, species in diabetic rats as well as it's biochemical parameters. The results demonstrated that both the pharmaceutical forms, hydroethanolic extract and granulated, were able to reduce significantly (p < 0.001) hyperglycemia and glycosuria, in addition to improve polydipsia, polyuria, and weight loss. Treatments using hydroethanolic extract and granulated were also able to reduce significantly levels of triacylglycerides, cholesterol and low-density lipoprotein, as well as the transaminases, urea and creatinine levels. Therefore, it is concluded that these pharmaceutical forms have anti-diabetic effect and act improving the biochemical parameters, this effect is probably due to the high content of polyphenolic compounds found in the formulations.

Effects of a low-level semiconductor gallium arsenide laser on local pathological alterations induced by Bothrops moojeni snake venom.

Antivenom therapy has been ineffective in neutralizing the tissue damage caused by snakebites. Among therapeutic strategies to minimize effects after envenoming, it was hypothesized that a low level laser would reduce complications and reduce the severity of local snake venom effects. In the current study, the effect of a low-level semiconductor gallium arsenide (GaAs) laser on the local pathological alterations induced by B. moojeni snake venom was investigated. The experimental groups consisted of five male mice, each administered either B. moojeni venom (VB), B. moojeni venom + antivenom (VAV), B. moojeni venom + laser (VL), B. moojeni venom + antivenom + laser (VAVL), or sterile saline solution (SSS) alone. Paw oedema was induced by intradermal administration of 0.05 mg kg(-1) of B. moojeni venom and was expressed in mm of directly induced oedema. Mice received by subcutaneous route 0.20 mg kg(-1) of venom for evaluating nociceptive activity and the time (in seconds) spent in licking and biting the injected paw was taken as an indicator of pain response. Inflammatory infiltration was determined by counting the number of leukocytes present in the gastrocnemius muscle after venom injection (0.10 mg kg(-1)). For histological examination of myonecrosis, venom (0.10 mg kg(-1)) was administered intramuscularly. The site of venom injection was irradiated by the GaAs laser and some animals received antivenom intraperitoneally. The results indicated that GaAs laser irradiation can help in reducing some local effects produced by the B. moojeni venom in mice, stimulating phagocytosis, proliferation of myoblasts and the regeneration of muscle fibers.

Action of AferBio (fermented food) in a rat inflammatory model.

BACKGROUND: AferBio is a fermented prebiotic food that contains beta-glucans, which are oligosaccharides capable of stimulating the proliferation of beneficial bacteria in the gastrointestinal tract. The aim of this study was to evaluate the possible effects of this functional food on the inflammatory response in rats. METHODS AND RESULTS: AferBio (900 mg/kg) inhibited edema formation by 34% compared to the control group. We also observed inhibition of the primary and secondary reactions of inflammation after the injection of Freund's adjuvant in the animals fed AferBio. Daily administration of AferBio for 6 d inhibited the formation of granulomatous tissue by 37%; additionally, inhibition of 31% of neutrophil migration downstream of carrageenan-induced peritonitis was observed. An ulcerogenic potency assay revealed that indomethacin produced a higher number of lesions compared to treatment with AferBio. Anti-inflammatory potency analysis showed that indomethacin inhibited 39% of carrageenan-induced edema but produced a higher number of lesions. However, animals treated with AferBio had areas of hyperemia without ulcerative lesions and 21% of edema was inhibited. CONCLUSION: Based on the results obtained in this study, AferBio appears to have anti-inflammatory activity during acute and chronic inflammatory processes.

Antimicrobial activity of extracts obtained from the seeds of Vatairea guianensis (Aublet) / Actividad antimicrobiana de extractos obtenidos de las semillas de Vatairea guianensis (Aublet)

Medicinal plants are widely and culturally used in an empiric way to treat several diseases in the Amazon. Here, Vatairea guianensis, which is used in traditional medicine to treat skin infections, such as cutaneous mycoses, was studied. The present work evaluated the in vitro antibacterial activity of hydroethanolic, hexanic, chloroformic, and methanolic extracts, obtained from the seeds of V. guianensis by the broth microdilution method, to measure their minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) against Gram-positive (Staphylococcus aureus and Enterococcus faecalis) and Gram-negative (Pseudomonas aeruginosa and Salmonella sp.) bacteria. All extracts showed antimicrobial activity against both Gram-positive and Gram-negative bacteria, with MICs ranging from 3.12 ug/mL to 50 ug/mL and MBCs ranging from 6.25 ug/mL to 100 ug/mL. Finally, these results on antimicrobial activity might contribute to the study of V. guianensis and increase the medical interest in this genus, which is still poorly studied.

Las plantas medicinales son ampliamente utilizados y culturalmente de forma empírica para tratar varias enfermedades en la Amazonía. Aquí, fue estudiado Vatairea guianensis, que se utiliza en la medicina tradicional para tratar infecciones de la piel, como las micosis cutáneas. El presente trabajo se evaluó la actividad in vitro antibacteriana de los extractos hidroetanólico, hexánico, clorofórmico y metanólico, obtenido de las semillas de V. guianensis por el método de microdilución en caldo, para medir su concentración inhibitoria mínima (CIM) y la concentración mínima bactericida (CMB) contra las bacterias Gram-positivas (Staphylococcus aureus y Enterococcus faecalis) y Gram-negativas (Pseudomonas aeruginosa y Salmonella sp.). Todos los extractos mostraron actividad antimicrobiana frente a bacterias Gram-positivas y Gram-negativas, con los CIM que van desde 3,12 ug / ml a 50 ug / mL y CMB que van de 6,25 ug / ml a 100 ug / ml. Por último, estos resultados sobre la actividad antimicrobiana podrían contribuir al estudio de V. guianensis y aumentar el interés médico en este género, que todavía está poco estudiada.