Antinociceptive, anti-inflammatory and hypoglycemic activities of the ethanolic Turnera subulata Sm. flower extract in adult zebrafish (Danio rerio).

Turnera subulata Sm. belongs to the family Turneraceae and is found in Brazil. The present study evaluated the antinociceptive, anti-inflammatory, and hypoglycemic potential of T. subulata flower extract (EtFloTsu) in zebrafish (Danio rerio). The total phenol and flavonoid contents of EtFloTsu were determined and identified using the Folin Ciocalteu reagent and aluminum chloride (AlCl3), respectively. The constituents of the extract were identified by HPLC-DAD, and the in vitro antioxidant activity (DPPH) was determined, toxicity in brine shrimp, and acute toxicity of 96 h in adult zebrafish. In addition, adult zebrafish (n = 6/fish) were treated orally with EtFloTsu (4, 20, or 40 mg/kg; vo) and subjected to formalin-induced nociception tests (with its possible mechanism of action with camphor), carrageenan-induced inflammation, and D-glucose-induced hyperglycemia (111 mM). Oxidative stress in the liver and brain tissues was assessed. EtFloTsu showed high levels of phenolic and flavonoid compounds with antioxidant activity. The phytochemicals chlorogenic acid, luteolin-7-o-glucoside, vitexin, and apigenin-7-o-glucoside were also identified in EtFloTsu. The synergism between these constituents was possibly responsible for the antinociceptive (via TRPA1), anti-inflammatory, and hypoglycemic effects of EtFloTsu in adult zebrafish, without causing toxicity in animals. Therefore, T. subulata flowers have therapeutic agents that could treat pain, inflammation, diabetes, and related complications.Communicated by Ramaswamy H. Sarma.

Combretum lanceolatum extract reverses anxiety and seizure behavior in adult zebrafish through GABAergic neurotransmission: an in vivo and in silico study.

Combretaceae are reported in the literature for presenting neuroprotective and anxiolytic effects in animal models. Combretum lanceolatum Pohl. has few scientific reports on its pharmacological effects. The aim of this study was to evaluate the anxiolytic and anticonvulsant effects of the ethanol extract from the leaves of C. lanceolatum Pohl. (EtFoCl) and its possible mechanism of GABAergic action in adult zebrafish. EtFoCl was subjected to determination of the total phenol concentration, identification of phytochemical flavonoids by HPLC and in vitro antioxidant activity test, open field test and 96-hour acute toxicity in zebrafish. Anxiolytic doses were tested for pentylenetetrazole-induced seizures in adult zebrafish. To study the mechanisms of action, molecular docking simulations were performed between the main phytochemicals and the GABAA receptor (anxiolytic activity) and carbonic anhydrase II (anticonvulsant). The non-toxic doses that caused motor impairment were assessed in acute and chronic anxiety using the light and dark test. EtFoCl had altered the animals' locomotion, presenting an effect similar to the anxiolytic and anticonvulsant. These effects were prevented with flumazenil (GABAA antagonist). The phytochemicals homoorientin and quercetin-3-O-galactoside coupling in a region close to that of the inhibitor diazepam (GABAA receptor). Regarding the anticonvulsant mechanism, Homoorientina and Isovitexina were identified as the most favorable for the complex form with the carbonic anhydrase enzyme. C. lanceolatum has pharmacological potential for the treatment of acute and chronic anxiety and seizures, which can be partially explained by an interaction with the GABAA receptor.Communicated by Ramaswamy H. Sarma.

Hypolipidemic and reduced nitrergic effects of p-hydroxycinnamic diesters extracted from Copernicia prunifera in mice challenged by a high-fat diet.

Dyslipidemia is a chronic non-transmissible condition that has increased due to an unhealthy lifestyle. Statins have been used as the standard treatment to control hyperlipidemia. However, side effects and high costs may be associated with its prolonged treatment, so plants derivatives have been an attractive therapy to overcome these problems. Among the compounds extracted from plants, the p-hydroxycinnamic diesters (HCE), present in carnauba wax (CW), have been found with good pharmacological properties. Therefore, this study aimed to evaluate the potential anti-hypercholesterolemic and possible toxicological effects of HCE in C57BL/6J mice under a high-fat (HF) diet. Male C57BL/6J mice were fed during 60 days under the HF diet and therefore were either treated with HCE (200 and 400 mg/kg) or simvastatin (20 mg/kg) or received saline (controls) by gavage for 30 days under the same diet. HCE treatment was able to reduce serum total cholesterol and LDL levels. Besides, this compound increased liver X receptor (LXR) and but not significantly affected IL-1ß and TNF-α liver mRNA transcription activity. In conclusion, HCE treatment was found safe and may attenuate the deleterious effects of dyslipidemia due to chronic feeding with western diets.

Alpha Lipoic Acid Supplementation Improves Ovarian Tissue Vitrification Outcome: An Alternative to Preserve the Ovarian Function of Morada Nova Ewe.

This study evaluated the effect of adding alpha lipoic acid (ALA) to the vitrification solution of sheep ovarian tissue on 7 days of in vitro culture or 15 days of xenotransplantion. ALA was used at two different concentrations (100 µM: ALA100 and 150 µM: ALA150). Ovarian tissue was evaluated by classical histology (follicular morphology, development, and stromal cell density); immunohistochemistry for forkhead box O3a (FOXO3a); Ki67 (cell proliferation); cluster of differentiation 31 (CD31); and alpha smooth muscle actin (α-SMA). Reactive oxygen species (ROS) levels in ovarian tissue, as well as malondialdehyde (MDA) and nitrite levels in the culture medium, were assessed. Similar percentage of morphologically normal follicles was found in the vitrified ovarian tissue in the presence of ALA100 or ALA150 after in vitro culture or xenotransplantation. Follicular development from all treatments was higher (P < 0.05) than the control group. Moreover, an activation of primordial follicles was observed by FOXO3a. Stromal cell density and immunostaining for Ki67 and CD31 were significantly higher (P < 0.05) in ALA150 vitrified tissue. No difference (P > 0.05) was found in α-SMA between ALA concentrations after in vitro culture or xenograft. ROS levels in the ovarian tissue were similar (P > 0.05) in all treatments, as well as MDA and nitrite levels after 7 days of culture. We concluded that the addition of ALA 150 is able to better preserve the stromal cell density favoring granulosa cell proliferation and neovascularization.

Unbalance of Se and nutritional status in male infertility.

OBJECTIVE: To evaluate the selenium status and oxidative stress in male infertility cases selected from a private human reproduction center in the state of Ceará, Brazil. METHODS: The present study had a cross-sectional quantitative approach, carried out between January and October 2013 at a Human Reproduction Center. The studied population was composed of 49 male individuals seen at the clinic, aged between 18 and 60 years. Blood samples were collected to measure serum selenium concentrations, erythrocyte activity and glutathione peroxidase. After medical diagnosis, the participants were divided into fertile and infertile groups. Blood samples were collected for establishing Se concentrations in plasma and erythrocytes, and measurements of the enzymatic activity of glutathione peroxidase in the erythrocytes. RESULT: it resulted in 53.1% of fertile men and 46.9% of infertile men. The average age of the fertile group was 34.1 years and the infertile group was 37.3 years. Regarding the assessment of nutritional status, the scatter diagram of the infertility group showed a higher body mass index and waist circumference, showing that this group has a higher risk of global and abdominal obesity compared to the fertile group (p<0.0001, respectively). There were similarities between the groups regarding caloric intake, macronutrient and selenium intake. CONCLUSION: We can conclude that the serum values of selenium, in excess and in deficiency, can be harmful to male fertility.

Orally hypoglycemic activity of an insulin mimetic glycoprotein isolated from Cnidoscolus quercifolius Pohl. (Euphorbiaceae) seeds, Cq-IMP.

The genus Cnidoscolus (Euphorbiaceae) is widely distributed in tropical areas. In the Northeast of Brazil, the species C. quercifolius is endemic and has been used in traditional medicine. In this study, a novel protein was isolated from C. quercifolius seeds and characterized by its molecular weight, primary structure, isoelectric point (pI), and carbohydrate content. The hypoglycemic activity of this protein was investigated by in vitro assay with the RIN-5F glucose-responsive cell line and in vivo test using alloxan-induced diabetic mice models. In addition, safe use of the protein was also investigated by cytotoxicity, hemagglutinating, and immunogenicity assays. The protein which was named Cq-IMP (Cnidoscolus quercifolius - Insulin Mimetic Protein) showed a single 11.18 KDa glycopolypeptide chain (16.4% of carbohydrates, m/m), pI of 8.0 and N-terminal sequence (TKDPELKQcKKQQKKqQQYDDDDKK) with similarity around 46-62% to sucrose binding protein-like and vicilin-like protein that was confirmed by mass spectrometry tryptic peptides analysis. Besides that, Cq-IMP presented anti-insulin antibody cross-reactivity as hypoglycemic activity in both in vitro and in vivo models. Additionally, it did not present any toxicity by methods tested. In conclusion, Cq-IMP is an insulin-mimetic protein, with a potent hypoglycemic activity and no toxicity showing great potential for therapeutic applications and drug development.

Metabolic profile of pitaya (Hylocereus polyrhizus (F.A.C. Weber) Britton & Rose) by UPLC-QTOF-MSE and assessment of its toxicity and anxiolytic-like effect in adult zebrafish.

Pitaya is a Cactacea with potential for economic exploitation, due to its high commercial value and its functional components - such betalains, oligosaccharides and phenolic compounds. Although the biological activities of pitaya have been studied using in vivo and in vitro models (anti-inflammatory and antiproliferative activities, as example), its anxiolytic-like effect is still unexplored. Therefore, the aim of this work was to perform a characterization of pulp and peel of pitaya (Hylocereus polyrhizus (F.A.C. Weber) Britton & Rose) using UPLC-QTOF-MSE, and to assess its toxicity and anxiolytic-like effect in adult zebrafish (Danio rerio). The results showed 16 and 15 compounds (in pulp and peel, respectively), including maltotriose, quercetin-3-O-hexoside, and betalains, putatively identified by UPLC-QTOF-MSE. Thus, pitaya pulp and peel showed no toxicity in both models tested (Vero cell lines and zebrafish model, LC50 ˃ 1 mg/mL); and a significant anxiolytic activity, since the treated fish reduced the permanence in the clear zone (Light & Dark Test) compared to that in the control, exhibiting anxiolytic-simile effect of diazepam. However, these effects were reduced by pre-treatment with the flumazenil suggesting that the pulp and peel of pitaya are anxiolytics agents mediated via the GABAergic system. These findings suggested that H. polyrizhus has the potential of developing an alternative plant-derived anxiolytic therapy. In addition, pitaya peel (which is a waste in the food industry) should be regarded as a valuable product, which has the potential as an economic value-added ingredient for anxiety disorders.

Carnauba wax uses in food - A review.

Carnauba wax is widely used in food, due to its physico-chemical characteristics with a predominance of esters and inert and stable components. Even with so many possibilities for the use of carnauba wax in food, there are still a large number of researchers around the world searching for new applications and a demand for new products with new technologies to improve existing ones. Recently, many parts of research which focus on the use of this wax in conservation and food processing have been carried out, some of which highlight the role of this wax in the microencapsulation of flavours, in preparing edible films and super hydrophobic and biodegradable packaging. This paper discusses the use of carnauba wax in food, including the extraction process of the wax, its chemical and physical characteristics, safety aspects, national and international law and permitted uses, along with the presentation of the main scientific research conducted.

Ethnobotanic, phytochemical uses and ethnopharmacological profile of genus Cnidoscolus spp. (Euphorbiaceae): A comprehensive overview.

The application of medicinal plants are the most important biotechnological alternative in the treatment of numerous diseases, especially in developing countries, such as Brazil. Among them, we specified some specimens of the genus Cnidoscolus used as phytotherapies, with healing properties, analgesic, anti-inflammatory, antibiotic and diuretic, anticancer, among others. Such effects are possibly associated with the presence of terpenoids, alkaloids, coumarins, flavonoids phenolic compounds, among others. Thus, the objective of this work was to evaluate in the literature the studies on the phytochemical, ethnopharmacological and biotechnological applications of this genus, from 1998 to 2017. Among the sixty-one studies reported in this review, ten species are popularly utilized to pharmacological and/or biotechnological applications. Cnidoscolus aconitifolius and Cnidoscolus chayamansa are the most cited species, which were also supported by either animal or cellular investigations indicating some beneficial pharmacological actions like antioxidant, anti-inflammatory and potential cytotoxic activity. The plant parts of this genus under study are important as sources for the isolation and identification of bioactive molecules with biotechnological applications, among the many diseases treated with this phytotherapy. Given these verdicts, ethnopharmacological approaches are significant systematic tools in the determination of plant species that exhibit medicinal and nutritional purposes. The results presented here should further stimulate the development of validation studies to ensure the safe and effective use of these plant species.

Corrigendum to "Antihypercholesterolemic Effects of Fruit Aqueous Extract of Copernicia prunifera (Miller) H. E. Moore in Mice Diet-Induced Hypercholesterolemia".

[This corrects the article DOI: 10.1155/2017/6376173.].

Antihypercholesterolemic Effects of Fruit Aqueous Extract of Copernicia prunifera (Miller) H. E. Moore in Mice Diet-Induced Hypercholesterolemia.

The present objective of the investigation is to evaluate the antihypercholesterolemic activity of the aqueous fruit pulp extract (APE) of Copernicia prunifera (Miller) H. E. Moore (Arecaceae family). Various chemical characterization methods like thin layer chromatography, Fourier transform infrared spectroscopy, 1H and 13C NMR, and molecular weight by gel permeation chromatography have been employed to characterize the extracted pectin. The present study demonstrated that hypercholesterolemic diet (HD) created hypercholesterolemia, caused significant increases in body weight, total cholesterol, and low-density lipoprotein, and caused decreases in high-density lipoprotein in serum compared with SD group. Two doses (APE 150 and 300 mg/Kg b.w./day) were administered to hyperlipidemic mice for 90 days. APE reversed body weight changes, changed serum lipids to normal values, and significantly inhibited the changes of lipid peroxidation and inflammation in the liver tissues. The renal parameters analyzed (urea and creatinine) altered by diet were reverted to normal values. Our results revealed that aqueous fruit pulp extracts of carnauba reduced hypercholesterolemia showing a potential preventive effect against cardiovascular diseases without side effects cause.

Screening of Bioactivities and Toxicity of Cnidoscolus quercifolius Pohl.

The caatinga, an exclusively Brazilian biome, is one of the most endangered vegetation systems in the planet. To be exploited rationally, its potential needs to be scientifically demonstrated. Among these is the faveleira, used in northeastern Brazil. It stands out for its extraordinary drought resistance and medicinal properties. The objective of this study was to assess the therapeutic potential of compounds extracted from Cnidoscolus quercifolius Pohl in preventing disease and its rational use as a herbal therapeutic tool. The methodology began with the collection and herborization of the plant material, to obtain the chemical compounds, preliminary phytochemical analysis, and extraction of the constituents of the active extracts. To determine the biological activities the authors conducted investigation of antioxidant and antimicrobial activities, inhibition capacity of the acetylcholinesterase enzyme, and initial assessment of toxicity of the extracts. The results demonstrated great potential as an antimicrobial agent, an important antioxidant capacity, and acetylcholinesterase inhibition response with no significant difference compared with the reference drug. The authors expect to develop a new herbal product, resulting in lower production costs and that, consequently, could be commercialized in more accessible form to the population, highlighting the risk reduction of contraindication of this category of medications.

Carnauba wax p-methoxycinnamic diesters: Characterisation, antioxidant activity and simulated gastrointestinal digestion followed by in vitro bioaccessibility.

The beneficial biological effects of cinnamic acid derivatives and the lack of studies on the antioxidant activity and bioavailability of cinnamic esters from carnauba wax, diesters were extracted from carnauba wax powder. Their structural, physical and morphological characteristics, antioxidant activity and in vitro bioaccessibility were measured. p-Methoxycinnamic diester (PCO-C) was identified, which has a crystalline, apolar structure and exhibited significant antioxidant activity (107.27 ± 3.92 µM Trolox/g of dry weight) before and after simulated in vitro gastrointestinal digestion and 32.46% bioaccessibility. In human cells, PCO-C (250 µg/mL) inhibited the production of intracellular reactive oxygen species, with an effect similar to that of Trolox (80 µM). Thermogravimetric analysis showed that PCO-C had high thermal stability and high UV absorption between 250 and 350 nm. These results indicate that this compound is promising as an antioxidant for pharmaceutical and food industry applications, such as the development of active packaging and functional foods.

Antiviral and Antioxidant Activities of Sulfated Galactomannans from Plants of Caatinga Biome.

Dengue represents a serious social and economic public health problem; then trying to contribute to improve its control, the objective of this research was to develop phytoterapics for dengue treatment using natural resources from Caatinga biome. Galactomannans isolated from Adenanthera pavonina L., Caesalpinia ferrea Mart., and Dimorphandra gardneriana Tull were chemically sulfated in order to evaluate the antioxidant, and antiviral activities and the role in the inhibition of virus DENV-2 in Vero cells. A positive correlation between the degree of sulfation, antioxidant and antiviral activities was observed. The sulfated galactomannans showed binding to the virus surface, indicating that they interact with DENV-2. The sulfated galactomannans from C. ferrea showed 96% inhibition of replication of DENV-2 followed by D. gardneriana (94%) and A. pavonina (77%) at 25 µg/mL and all sulfated galactomannans also showed antioxidant activity. This work is the first report of the antioxidant and antiviral effects of sulfated galactomannans against DENV-2. The results are very promising and suggest that these sulfated galactomannans from plants of Caatinga biome act in the early step of viral infection. Thus, sulfated galactomannans may act as an entry inhibitor of DENV-2.

Chemical composition, antioxidant and antibacterial activities of two Spondias species from Northeastern Brazil.

CONTEXT: The leaves of Spondias tuberosa Arr. Cam. (Anacardiaceae) and Spondias mombin L. have been traditionally used for medicinal purposes. Some studies reveal their antibacterial, antimicrobial, and antiviral properties. OBJECTIVE: Determine the chemical composition, antioxidant, and antimicrobial activities of Spondias species to justify its ethnopharmacological use. MATERIALS AND METHODS: Spondias species extracts were prepared with methanol:water 80:20 and analyzed by silica gel column chromatography and reversed phase liquid chromatography (HPLC). The antioxidant activity was evaluated by scavenging the radicals 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) and 2,2-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS•+) and measuring antimicrobial activity (agar well diffusion method, minimum inhibitory concentration and minimum bactericidal concentrations). RESULTS: The HPLC analysis of Spondias extracts demonstrated the occurrence of high yield of flavonoids. Found in S. mombin were quercetin (2.36 ± 0.01 mg/g) and ellagic acid (41.56 ± 0.01 mg/g) and in S. tuberosa species rutin (53.38 ± 1.71 mg/g), quercetin (24.46 ± 0.87 mg/g), and ellagic acid (169.76 ± 0.17 mg/g). The antibacterial activity of the extracts against the various bacteria strains varied from 8.8 to 20.1 mm. MIC values from 62.5 to 125 µg/mL were satisfactory when compared with other plant products. Medium DPPH scavenging activity IC50 for Spondias extracts varied from 0.042 to 0.558 mg/mL and for ABTS from 0.089 to 0.465 mg/mL. DPPH scavenging activity for constituent ellagic acid IC50 = 0.042 mg/mL and for quercetin IC50 = 0.081 mg/mL. DISCUSSION AND CONCLUSION: The chemical study of Spondias leaf extracts showed the occurrence of quercetin, rutin and ellagic acid, substances with relevant antioxidant and antimicrobial activities.