Search

Objective: To investigate the acute effects of ingesting a beverage containing guarana ( Paullinia cupana ) seed powder on performance during field tests related to physical capacities that are determinants of soccer performance, such as lower limb power, sprint, agility, and the capacity to carry out intermittent exercise., Methods: The study was conducted using a randomized, crossover, and counterbalanced design, with a beverage containing guarana or placebo administered in a double-blind manner. Twenty-seven under-17 soccer players of a professional soccer club performed a battery of tests 60 min after the ingestion of guarana (3 g of the fruit seed powder) or placebo. Trials were performed with a 7-day washout period. The battery of tests included a countermovement jump test, sprints of 10 and 20 m, an Illinois agility test, and a Yo-Yo Intermittent Recovery Test level 1 (YYIR1)., Results: Guarana ingestion did not improve countermovement jump, sprints, or agility ( p  > 0.05). However, guarana ingestion increased the distance covered in the YYIR1, compared with placebo ingestion ( p  = 0.01)., Conclusion: Acute ingestion of guarana improves the capacity to perform intermittent exercise in soccer players but seems to be ineffective to improve lower limb power, sprint, and agility.

This study characterized a nanosupplement based on coenzyme Q10 containing guarana (Paullinia cupana) and Brazil nuts oil (Bertholetia excelsa) (G-Nut). Determined cytotoxic and oxi-immunomodulatory effects on human peripheral blood mononuclear cells (PBMCs) and its effect on mortality of red Californian earthworms (Eisenia fetida) and on the immune efficiency of its coelomocytes immune by in vitro exposure to yeast dead microorganism. The cytotoxic and immunomodulatory effects of G-Nut and the GN-Free extract (0.25-3 mg/mL) were determined in PBMC cultures. Apoptotic, oxidative, and inflammatory markers were determined using biochemical, immunological, and molecular protocols. The effects of G-Nut and GN-Free extracts on mortality and immune efficiency were investigated in earthworms. G-Nut and GN-Free did not induce cytotoxic events in PBMCs, triggering the decrease in apoptotic (caspases 3 and 8) gene expression, lipid and protein oxidation levels, or pro-inflammatory cytokine levels. G-Nut and GN-Free did not trigger earthworm mortality and improved coelomocyte immune efficiency by increasing Eisenia neutrophil extracellular DNA traps and brown body formation when exposed to dead yeasts. The G-Nut nanoformulation is safe and can be used as a new form of food supplement by oral or transdermal delivery., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Mesenchymal stromal cells (MSCs) have therapeutic potential due to their abilities of differentiation, immunomodulation, and migration to injured tissues, potentiating such effects when cells are activated. Guarana (Paullinia cupana) is a tropical plant species found in South America that is known for its antioxidant, stimulant, and cicatricial effects. The guarana extract is composed of many substances and caffeine is the main component. The objective was to evaluate the effects of guarana and caffeine on MSCs. After the initial characterization, MSCs were treated with Paullinia cupana (10, 100, and 1000 μg/mL) or caffeine (0.4, 4, and 40 μg/mL) for 24 h. MSCs treatment with 1000 μg/mL guarana increased cell polarity, viability, cell migration to chemoattractant, antioxidant potential, and liberation of extracellular vesicles (EVs), while it reduced the levels of autophagy. MSCs treated with 100 and 1000 μg/mL guarana or 40 μg/mL caffeine showed a decrease of cell proliferation. No treatment affected the cellular area and cell cycle of MSCs. The study shows in vitro evidence that guarana could be a promising alternative for activating MSCs to promote better cellular products for future clinical therapies.

Bisphenol A (BPA) may adversely affect human health by inducing oxidative stress and irreversible damage to cells. Bioactive compounds found in some functional foods, individually or in combination, can attenuate the negative effects of BPA exposure; an example is the multi-supplement containing guarana (Gua), selenium (Se), and L-carnitine (LC) -GSC- which has already demonstrated antioxidant, genoprotective, and immunomodulatory activities. This study aimed to determine the effect of GSC and its constituents on oxidative and genotoxic alterations triggered by BPA exposure in the retinal epithelial cell line. The cells exposed to BPA (0.001, 0.01, 0.1, 1, 3, and 10 µM) to determine the lowest concentration required to induce cyto-genotoxicity. ARPE-19 cells were then concomitantly exposed to the selected BPA concentration, GSC, and its components (Gua, 1.07 mg/mL; Se, 0.178 µg/mL; and LC, 1.43 mg/mL). Flow cytometry, biochemical assays, qRT-PCR, genotoxicity, apoptosis, and cellular proliferation. Based on our results, 10 µM of BPA could induce cyto-genotoxic and oxidative alterations. BPA did not alter the Bcl-2/BAX expression ratio but induced Casp3 and Casp8 overexpression, suggesting that apoptosis was induced mainly via the extrinsic pathway. GSC partially reversed the alterations triggered by BPA in ARPE-19 cells. However, Se had unexpected negative effects on ARPE-19 cells. The multi-supplement GSC may attenuate changes in oxidative and genotoxic markers related to exposure of ARPE-19 cells to BPA. our results revealed that the antioxidant, anti-apoptotic, and genoprotective properties of GSC were not universally shared by its individual, once Se did not exhibit any positive impact.

Guarana (GUA), a Brazilian seed extract, contains caffeine and other bioactive compounds that may have psychoactive effects. To assess the acute effects of GUA compared to a low dose of caffeine (CAF) on cognitive and mood parameters, twenty participants completed a double-blind, crossover experiment where they ingested capsules containing the following: (1) 100 mg CAF, (2) 500 mg GUA containing 130 mg caffeine, or (3) placebo (PLA). Cognitive tests (Simon and 2N-Back Task) were performed at the baseline (pre-ingestion) and 60 min after ingestion. The response time for the cognitive tests and heart rate variability were unaffected ( p > 0.05) by treatment, although 2N-Back was overall faster ( p = 0.001) across time. The accuracy in the 2N-Back Task showed a significant interaction effect ( p = 0.029) due to higher post-ingestion versus pre-ingestion levels ( p = 0.033), but only with the PLA. The supplements also had no effect on cognitive measures following physical fatigue ( n = 11). There was an interaction effect on perceived mental energy, where the pre-ingestion of GUA had lower mental pep ratings compared to post-ingestion ( p = 0.006) and post-exercise ( p = 0.018) levels. Neither the acute ingestion of GUA nor low dose of CAF influenced cognitive performance or provided consistent benefit on mood or mental workload through vagal modulation. Additional investigations are beneficial to determining the lowest effective dose for CAF or GUA to influence mood and/or cognitive performance.

Strawberry (Fragaria x ananassa Duch.) is a highly perishable fruit whose characteristics make it susceptible to developing microorganisms. Plant extracts have been studied as an alternative to pesticides to control spoilage microorganisms, responding to the expectation of the population seeking a healthier way of life. The fungus Botrytis cinerea is a facultative pathogen of vegetables, which can affect all stages of the development of several fruits, such as the strawberry, where it causes gray rot. Trichilia catigua (catuaba), Paullinia cupana (guarana), Stryphnodendron barbatiman (barbatimão), and Caesalpinia peltophoroides (sibipiruna) are planted in the Brazilian flora and have demonstrated pharmacological properties in their extracts. This work aimed to treat strawberries with a biodegradable film containing extracts of these species to evaluate strawberry conservation. There were notable distinctions in mass loss between the extract-treated and control samples. The pH, total acidity (TA), and soluble solids parameters exhibited consistently significant means across both sets of samples. Luminosity increased over the course of days in the color parameters, with the exception of strawberries coated with guarana. The red color showed greater intensity, except for those coated with barbatimão extract. Considering the results, it is possible to conclude that the coatings used can become an alternative to enhance the conservation of strawberries.

The extraction of valuable compounds from dried fruits and vegetables by microwave hydrodiffusion and gravity (MHG) requires previous hydration of the plant material. In this work, ultrasound was used to speed up the hydration of guarana powder before MHG extraction and increase caffeine recovery. The humidification step was speeded up with ultrasound taking only 15 min over 60 min without ultrasound. Water and 50% (v/v) ethanol were evaluated as green solvents for humidification, with a higher concentration of caffeine obtained for the hydroalcoholic solution. Ultrasound pretreatment allowed guarana extracts from MHG with two times more caffeine for both solvents evaluated. Therefore, ultrasound can be used in the hydration step before MHG extraction to reduce time and increase caffeine recovery from guarana powder.

The growing interest in health and well-being has spurred the evolution of functional foods, which provide enhanced health benefits beyond basic nutrition. Guaraná seeds ( Paullinia cupana ) have been widely studied and used as a functional food due to their richness in caffeine, phenolic compounds, amino acids, and other nutrients. This has established guaraná as a significant food supplement, with Brazil being the largest producer of the world. This study aims to propose a set of analytical methods to chemically evaluate fifty-six different guaraná clones, from the Guaraná Germplasm Active Bank, to accommodate the diverse requirements of the food industry. Metabolomic approaches were employed, in which a non-target metabolomic analysis via UPLC-QTOF-MS E led to the annotation of nineteen specialized metabolites. Furthermore, targeted metabolomics was also used, leading to the identification and quantification of metabolites by NMR. The extensive data generated were subjected to multivariate analysis, elucidating the similarities and differences between the evaluated guaraná seeds, particularly concerning the varying concentration levels of the metabolites. The metabolomics approach based on the combination of UPLC-QTOF-MS E , NMR and chemometric tools provided sensitivity, precision and accuracy to establish the chemical profiles of guaraná seeds. In conclusion, evaluating and determining the metabolic specificities of different guarana clones allow for their application in the development of products with different levels of specific metabolites, such as caffeine. This caters to various purposes within the food industry. Moreover, the recognized pharmacological properties of the annotated specialized metabolites affirm the use of guarana clones as an excellent nutritional source.

A previous optimization of supercritical extraction from guarana seeds was performed applying orthogonal array design (OA9(34)). The antioxidant and antimicrobial activities of these extracts, as well as metabolomic profiling and correlations from the compounds by statistical analysis were determined. Extracts 1 (40% ethanol; 20 min; 40 °C and 100 bar), 2 (40% methanol; 60 min; 40 °C and 200 bar), and 8 (40% methanol; 40 min; 60 °C and 100 bar) had the highest combined values of antioxidant capacity for the DPPH, FRAP, ABTS and xanthine oxidase system methods, and were identified by chemometric analysis. Similar chemical profiles of the extracts were obtained by LC-DAD-MS, and were identified: methyl-xanthine, (epi)catechin and dimers and trimers of type A and B proanthocyanidins. The heat map analysis showed positive correlation between antioxidant methods DPPH, FRAP and ABTS and with flavan-3-ols and proanthocyanidins. Extract 3 was active against Gram-negative and -positive bacteria and Candida tropicalis .

Guarana [Paullinia cupana var. sorbilis (Mart.) Ducke] is a species of great economic and social important in Brazil, as it is the only commercial guarana producer in the world. The vegetative propagation method indicated for the culture is stem cuttings, which aims at productivity, tolerance, and uniformity of clonal cultivars, because reproduction by seeds has slow germination and high genetic variability, which in traditional varieties is an undesirable factor. Genetic factors can interfere with the rooting capacity of the crop. Studies seek alternatives that can improve this condition and enhance the production system. Use of growth regulators, microorganisms that promote plant growth, variation of substrates and fertilization, have been strategies used. Preliminary tests on the rate of stem rooting and seed germination with the use of exogenous phytohormone did not demonstrate in relation to the non-application of these inducers. The use of rhizobacteria, which presents itself as a promising activity in many cultures, has not yet been demonstrated in the culture of guarana. On the other hand, the influence of different substrates on rooting has already shown consistent results as a function of rooting rate. Fertilizing the mother plants as recommended by the production system for the crop has proven to be an efficient procedure. There are still few studies aimed at improving the spread of guarana, demonstrating that new protocols need to be explored, or that the protocols already used are reviewed from another perspective.

Guarana ( Paullinia cupana Kunth var. sorbilis ) is a typically Amazonian plant of high economic value due to the compounds found in its seed. For guarana to reach the maximum productive potential, management practices such as weed control are necessary. The use of herbicides is a viable alternative, however, its drift may lead to adverse effects on the primary and secondary plant metabolisms and cause losses in crop production. This study evaluated the differential drift effects of glyphosate doses on the physiology of guarana plants and the production of compounds of economic interest in their seeds. Glyphosate doses (57.6, 115.2, 230.4, 460.8 g ae ha -1 ) were applied to adult guarana plants after the flowering period. The photosynthetic functions and metabolism effects were evaluated. Herbicide treatments led to oxidative stress due to increased lipid peroxidation and increased carbohydrate and amino acid in their leaflets. Despite this, glyphosate showed no effect on fruit production or the content of secondary metabolites of commercial interest in seeds.

Guarana (Paullinia cupana) is a widely consumed nutraceutical with various health benefits supported by scientific evidence. However, its indirect health impacts through the gut microbiota have not been studied. Caenorhabditis elegans is a useful model to study both the direct and indirect effects of nutraceuticals, as the intimate association of the worm with the metabolites produced by Escherichia coli is a prototypic simplified model of our gut microbiota. We prepared an ethanoic extract of guarana seeds and assessed its antioxidant capacity in vitro, with a 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, and in vivo, utilizing C. elegans. Additionally, we studied the impact of this extract on C. elegans lifespan, utilizing both viable and non-viable E. coli, and assessed the impact of guarana on E. coli folate production. The extract showed high antioxidant capacity, and it extended worm lifespan. However, the antioxidant and life-extending effects did not correlate in terms of the extract concentration. The extract-induced life extension was also less significant when utilizing dead E. coli, which may indicate that the effects of guarana on the worms work partly through modifications on E. coli metabolism. Following this observation, guarana was found to decrease E. coli folate production, revealing one possible route for its beneficial effects.

Paullinia cupana Kunth., commonly named Guaraná, is a plant from Brazil used as stimulant. The aim of this study was to evaluate the potential of extracts and tannins-rich and methylxanthines-free fraction from guaraná in the anti-inflammatory and antioxidant effect in vitro. Extract 1 obtained good yields of tannins and methylxanthines and was used to identify a type-A procyanidin trimer by LC-ESI-MS. Fraction 4 was rich in tannins and absent of methylxanthines. The extracts and fraction exhibited strong capacity for scavenging DPPH radical with IC 50 between 5.88 and 42.75-µg/mL and inhibited TNF-α release by LPS-activated THP-1 cells when compared with control cells and did not present toxicity to THP-1 cells. The fraction 4, rich in tannins, was highly active, with IC 50 5.88 µg/mL by DPPH method and inhibited TNF-α release in 83.50% at 90 µg/mL. These results reinforced potential anti-inflammatory of guaraná and data for new therapeutic approaches., (Copyright © 2021. Published by Elsevier Ltd.)

Cold-adapted endo-β-1,4-glucanases hold great potential for industrial processes requiring high activity at mild temperatures such as in food processing and extraction of bioactive compounds from plants. Here, we identified and explored the specificity, mode of action, kinetic behavior, molecular structure and biotechnological application of a novel endo-β-1,4-glucanase (XacCel8) from the phytopathogen Xanthomonas citri subsp. citri. This enzyme belongs to an uncharacterized phylogenetic branch of the glycoside hydrolase family 8 (GH8) and specifically cleaves internal β-1,4-linkages of cellulose and mixed-linkage β-glucans releasing short cello-oligosaccharides ranging from cellobiose to cellohexaose. XacCel8 acts in near-neutral pHs and in a broad temperature range (10-50 °C), which are distinguishing features from conventional thermophilic β-1,4-glucanases. Interestingly, XacCel8 was greatly stimulated by cobalt ions, which conferred higher conformational stability and boosted the enzyme turnover number. The potential application of XacCel8 was demonstrated in the caffeine extraction from guarana seeds, which improved the yield by 2.5 g/kg compared to the traditional hydroethanolic method (HEM), indicating to be an effective additive in this industrial process. Therefore, XacCel8 is a metal-stimulated and cold-adapted endo-β-1,4-glucanase that could be applied in a diverse range of biotechnological processes under mild conditions such as caffeine extraction from guarana seeds., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Paullinia cupana Kunth, commonly known as guarana, is a native Brazilian plant species from the Amazon area that presents various biological effects, including antimicrobial action. The aim of this study was to chemically analyse the semipurified aqueous extract (AqF) of the plant and to evaluate the activity of crude (CE), ethyl-acetate (EAF), and AqF extracts against Helicobacter pylori . The chemical profile of AqF was determined based on solid analysis 13 C-NMR, direct infusion mass spectrometry (ESI-MS), and MALDI-TOF. The 13 C-NMR spectrum showed characteristics of flavan-3-ol and oligomeric proanthocyanidins. ESI-MS revealed the presence of procyanidin, caffeic acid and its derivatives. MALDI-TOF analysis detected procyanidins of up to 6 units and profisetinidins of up to 5 units. Whereas CE and EAF showed inhibitory activity against H. pylori , CE, EAF, and AqF presented not high inhibitory activity against urease. The results demonstrate the potential of P. cupana to control and prevent H. pylori infection.

Extracts from the roots of Paullinia pinnata L. are used in West Africa as traditional remedies for a variety of diseases including infestations with soil-transmitted helminths. Based on the results of an ethnopharmacological survey in Ghana, an aqueous acetone (70%) extract was investigated for its anthelmintic and phytochemical properties. Partitioning of the crude extract followed by several fractionation steps of the ethyl acetate phase using Sephadex ® LH-20, fast centrifugal partition chromatography, RP-18-MPLC and HPLC led to isolation of six oligomeric A-type procyanidins ( 1 to 6 ). To determine the anthelmintic activity, the crude extract, fractions and isolated compounds were tested in vitro against the model organism Caenorhabditis elegans . A significantly better activity was observed for the trimeric A-type procyanidin ( 1 ) compared to a B-type trimer. However, this effect could not be generalized for the tetrameric procyanidins, for which the type of the interflavan-linkage (4→6 vs. 4→8) had the greatest impact on the bioactivity. Besides the procyanidins, three novel compounds, isofraxidin-7- O- α-l-rhamnopyranosyl-(1″→6')-β-d-glucopyranoside ( 17 ), 4-methoxycatechol-2- O -(5''- O -vanilloyl-β-apiofuranosyl)-(1''→2')-β-glucopyranoside ( 18 ) and a 6-(3-methoxy-4-hydroxyphenyl)-hexane-2,4-diol-2- O -hexoside ( 19 ) were isolated together with further ten known compounds ( 7 to 16 ), mainly coumarins and coumarinolignans. Except for 3-β-d-glucopyranosyloxy-4-methyl-2(5 H )-furanone ( 15 ), none of the isolated compounds has previously been described for P. pinnata . The anthelmintic activity was attributed to the presence of procyanidins, but not to any of the other compound classes. In summary, the findings rationalize the traditional use of P. pinnata root extracts as anthelmintic remedies.

Purpose: This study aimed to evaluate the impact of a topical lotion (CG428) on hair thickness and density in breast cancer survivors with permanent chemotherapy-induced alopecia (PCIA)., Methods: The study was a double-blind, randomized controlled trial which conducted from February 2016 to December 2016 at the Samsung Comprehensive Cancer Center in Seoul, South Korea. Breast cancer patients with PCIA were randomized on average of 3.5 years after chemotherapy. Topical lotion (Batch DT023) is a botanical drug under development containing a novel patented blend of 4 botanical ingredients: citrus, cocoa, guarana, and onion. Participants were asked to self-apply the study product or placebo twice per day for 6 months. Changes in hair density and thickness were assessed using a noninvasive bioengineering device, and patient-reported outcomes were evaluated at 3 and 6 months after randomization., Results: A total of 35 patients were randomized to intervention (N = 18) or placebo (N = 17). Patients in the intervention group were older than those in the placebo group (52.1 vs. 41.6 years; P < 0.001). The mean hair density (SD) at baseline was 97.6 (6.4) and 126.8 (30.3) hairs/cm 2 in the intervention and placebo group, respectively (P = 0.005). The corresponding values for hair thickness were 49.9 (12.7) and 48.1 (8.4) μm, respectively. After 6 months, hair density had increased by 34.7 and 24.9% compared with baseline in the intervention and control groups, respectively (P = 0.37). Corresponding values for hair thickness were 19.8 and 35.6%, respectively (P = 0.23). Similar findings were observed after age adjustment., Discussion: In this pilot randomized clinical trial, we observed safety, tolerability, and a trend toward the efficacy of CG428 vs. placebo, especially regarding hair density and self-reported improvement.

Background: Low-level laser therapy (LLLT) has several clinical applications; however, its benefits are not universal. Therefore, combination therapy with LLLT and extracts from the guarana (Paullinia cupana) plant may improve its effectiveness as guarana extracts exhibit anti-aging properties., Objectives: To evaluate the antioxidant, anti-inflammatory, anti-apoptotic, and proliferative effects of combined LLLT and guarana extract therapy on human dermal fibroblasts., Methods: Human dermal fibroblasts (HFF-1) were cultured and initially exposed to several concentrations (1, 3, 5, 10, 30 µg/mL) of guarana extract. The experimental concentration of guarana extract was selected by analyzing cytokine levels, DNA oxidation, and apoptotic markers in LLLT-exposed (4 J/cm 2 ) and LLLT-unexposed fibroblast cultures. After 72 hours, the cells were analyzed using spectrophotometric, fluorimetric, immunological, and gene expression (qRT-PCR) assays. Flow cytometry was used to evaluate the effect of each treatment on cell cycle., Results: Fibroblasts treated with guarana (5 µg/mL) exhibited anti-inflammatory and anti-apoptotic properties been used in complementary protocols. Combined guarana and LLLT treatment significantly decreased protein carbonylation, lipoperoxidation, and DNA oxidation, downregulated the mRNA and protein expression of pro-inflammatory molecules, and upregulated IL-10 gene and protein expression. Guarana plus LLLT also decreased the levels of caspases 1, 3, and 8, increased the percentage of S-phase cells, and decreased FGF-1 and KGF-1 levels. Some of these changes were also observed after treatment with guarana or LLLT alone., Conclusions: Our results suggest that concomitant treatment with guarana and LLLT may promote fibroblast biostimulation and thus is clinically relevant., (© 2019 Wiley Periodicals, Inc.)

The Brazilian Food Supplement Law recently recognized that guarana ( Paullinia cupana ) contains bioactive substances, hence supporting its role as a functional food ingredient. The health benefits of guarana are associated, at least in part, to its phenolic compounds. However, to the best of our knowledge, there is no literature addressing the presence of phenolic compounds in the fraction containing insoluble-bound compounds and its contribution in terms of alpha-glucosidase inhibition. The concentration of phenolic extracts released from the insoluble-bound fraction required to inhibit 50% of alpha-glucosidase (IC 50 ) activity was 5.8-fold lower than that present in the soluble counterpart. Both fractions exhibited a mixed inhibition mode. Fourteen proanthocyanidins (dimers to tetramers) present in the insoluble-bound fraction were tentatively identified by MALDi-TOF-MS. Future studies aiming at increasing the concentration of the soluble counterpart are deemed necessary. The results presented here enhance the phenolic database of guarana and have a practical impact on the procurement of nutraceuticals and functional ingredients related to the prevention and/or management of type 2 diabetes. The Brazilian normative on food supplements has been recently revised. This study lends support to the future inclusion of guarana powder in the list of sources of proanthocyanidins for the industry of food supplements., Competing Interests: The authors declare no conflict of interest.

The seeds of the guarana plant ( Paullinia cupana Kunth, family Sapindaceae) are well-known to many cultures as a stimulant, aphrodisiac, and astringent. Its rhizome was traditionally boiled into a tea by Amazonian cultures. Today, guarana seeds are ground to a fine powder and sold as powder, tablets, and capsules. This review focuses on the traditional uses, phytochemistry, and biological activities of the guarana seed to evaluate its safety as a dietary ingredient. A comprehensive review of published literature was conducted to identify articles that focused on the phytochemistry, pharmacology, and safety of guarana. On the basis of this review, guarana is not currently known to be associated causally with any serious health risks when consumed properly. Overall, guarana is generally recognized as safe as a dietary ingredient marketed for its flavor and caffeine content. If guidelines for caffeine intake are respected, guarana consumption is not likely to be associated with any serious health risks.

Guaraná is a native fruit of the Amazon rainforest, which presents high levels of phenolic compounds. However, these bioactive compounds may be unstable in food processing and gastrointestinal conditions. Thus, this work aimed to characterize guaraná seed extract (GSE) followed by microencapsulation using a spray-chilling method and with vegetable fat as carrier, as well as to evaluate the particles. Phenolic-rich GSE was produced using 50% (w/w) hydroalcoholic solution and dehydrated by spray drying and lyophilization. Powdered GSE was characterized in relation to its inhibitory activity on digestive enzymes. Solid lipid microparticles (SLM) were evaluated for the retention of bioactive compounds and the release profile of phenolic compounds in simulated gastrointestinal conditions. Powdered GSE showed anti-obesity potential due to the high inhibitory activity of lipase. Regarding the retention of phenolic compounds, at least 75% were detected after 90 days at 25 °C in SLM. Moreover, SLM loaded with 7.5% GSE released approximately 99% of phenolic compounds in simulated gastrointestinal conditions. These results show the efficiency of spray chilling for protection and release of phenolic compounds from GSE, allowing future application in food., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Catechins and methylxanthines are natural molecules in guarana (Paullinia cupana) that are associated with antioxidant and stimulatory effects in the human body. There are few natural sources of these antioxidants. The most popular molecule used in foods and beverages is caffeine, which, most of the time, is derived from synthetic sources. In this work, cold hydroalcoholic (CHM), hot hydroalcoholic (HHM), and aqueous enzymatic maceration (AEM) were applied to crude (CG) and waste guarana seeds (WG) to process these materials into natural added-value products with enhanced levels of catechin, epicatechin, epicatechin gallate, caffeine, theobromine and theophylline. The highest level of catechins and methylxanthines was extracted with HHM. Nevertheless, AEM enhanced the global yield in the extract, probably due to the solubilization of other substances. The maceration procedures applied to guarana contributed to the valorization of this plant crop by providing antioxidant sources with clear applications in food and nonfood industries., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Ethnopharmacological Relevance: Paullinia pinnata L. (Sapindaceae) is an African woody vine, traditionally used for the treatment of itch and pain-related conditions such as rheumatoid arthritis., Aim: This work evaluates, in vitro and in vivo, the anti-inflammatory and analgesic effects of aqueous (AEPP) and methanol (MEPP) extracts from Paullinia pinnata leaves., Methods: AEPP and MEPP (100, 200 and 300 mg/kg/day) were administered orally in monoarthritic rats induced by a unilateral injection of 50 μl of Complete Freund's Adjuvant (CFA) in the ankle joint. During the 14 days of treatment, pain and inflammation were evaluated alternatively in both ankle and paw of the CFA-injected leg. Malondialdehyde (MDA) and glutathione (GSH) levels were assessed in serum and spinal cord. Histology of soft tissue of the ankle was also analyzed. For in vitro studies, AEPP and MEPP (10, 30 and 100 μg/ml) were evaluated against nitric oxide (NO) production by macrophages that were either non-stimulated or stimulated with LPS, 8-Br-AMPc and the mixture of both substances after 8 h exposure. These extracts were also evaluated on TNF-α and IL-1β production in cells stimulated with LPS for 8 h. Finally, the ability of the extracts to bind to neuroactive receptors was evaluated in vitro using competitive binding assays with >45 molecular targets., Results: AEPP and MEPP significantly reduced by 20-98% (p < 0.001) the inflammation and pain sensation in both the ankle and paw. AEPP significantly increased glutathione levels (p < 0.05) in serum. Both extracts reduced MDA production in serum and spinal cord (p < 0.001), and significantly improved tissue reorganization in treated arthritic rats. P. pinnata extracts did not affect NO production in non-stimulated macrophages but significantly reduced it by 47-88% in stimulated macrophages. AEPP and MEPP also significantly inhibited TNF-α (35-68%) and IL-1β (31-36%) production in LPS stimulated macrophages. No cytotoxic effect of plant extracts was observed. MEPP showed concentration-dependent affinity for Sigma 2 receptors with an IC 50 of 50 μg/ml., Conclusion: These results demonstrate the analgesic and anti-inflammatory effects of P. pinnata extracts on monoarthritis and further support its traditional use for pain and inflammation. These activities are at least partly due to the ability of these extracts to inhibit the production of NO, TNF-α, IL-1β and to likely modulate Sigma 2 receptors., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Obesity is a metabolic disorder associated with adverse health consequences that has increased worldwide at an epidemic rate. This has encouraged many people to utilize nonprescription herbal supplements for weight loss without knowledge of their safety or efficacy. However, mounting evidence has shown that some herbal supplements used for weight loss are associated with adverse effects. Guarana seed powder is a popular nonprescription dietary herb supplement marketed for weight loss, but no study has demonstrated its efficacy or safety when administered alone. Wistar rats were fed four different diets (low-fat diet and Western diet with or without guarana supplementation) for 18 weeks. Metabolic parameters, gut microbiota changes, and toxicity were then characterized. Guarana seed powder supplementation prevented weight gain, insulin resistance, and adipokine dysregulation induced by Western diet compared with the control diet. Guarana induced brown adipose tissue expansion, mitochondrial biogenesis, uncoupling protein-1 overexpression, AMPK activation, and minor changes in gut microbiota. Molecular docking suggested a direct activation of AMPK by four guarana compounds tested here. We propose that brown adipose tissue activation is one of the action mechanisms involved in guarana supplementation-induced weight loss and that direct AMPK activation may underlie this mechanism. In summary, guarana is an attractive potential therapeutic agent to treat obesity., (© 2019 John Wiley & Sons, Ltd.)

Purpose : To investigate the effect of ingesting carbohydrate (CHO), caffeine  (CAF), and a guarana complex (GUAc) during a running exercise on cognitive performance, rating of perceived exertion (RPE), and shooting performance in high-level modern pentathlon athletes. Methods : A total of 10 athletes completed 4 counterbalanced sessions within a 2-wk period, corresponding to ingestions of CHO (30 g), GUAc (300 mg), CAF (200 mg), or placebo. The exercise involved a 40-min run on a treadmill at a steady speed, previously determined as a "somewhat hard" exercise (RPE 13). Shooting and cognitive performance (Simon task) were assessed in 3 phases: before exercise and ingestion, before exercise and after half ingestion, and after exercise and full ingestion. Drinks were consumed 40 min (250 mL) and 5 min (125 mL) prior to exercise and after 20 min of running (125 mL). RPE was assessed at 10-min intervals during exercise. Results : There was an interaction between drink and exercise on mean reaction time ( P  = .01, η p 2 = .41 ) and a drink effect on RPE ( P  = .01, η p 2 = .15 ). CHO, CAF, and GUAc enhanced the speed of information processing after exercise ( P  = .003, P  = .004, and P  = .04, respectively), but only CAF and GUAc decreased RPE ( P  = .002 and P  = .02, respectively). Conclusion : The results highlight a beneficial effect of nutritional supplements on information processing and RPE. This finding is particularly interesting as decision-making processes are crucial in the performance of many sports.

A microwave-assisted digestion procedure using diluted HNO 3 and H 2 O 2 was developed for multi-element determination in guarana samples by ICP OES. Optimization step was performed employing a mixture design with pseudocomponents using HNO 3 , H 2 O 2 and H 2 O. The analytical signal of each element, residual acidity and residual carbon content were optimized simultaneously using the desirability function. The best condition for digestion of a 250 mg sample mass resulted from a mixture constituted by 1.0 mL of HNO 3 , 3.0 mL of H 2 O 2 and 6.0 mL of H 2 O. This condition allowed final digests with residual acidity and residual carbon content of 0.4 mol L -1 and 6.5%, respectively. The method was validated and applied for the determination of K, Ca, Mg, S, P, Cu, Fe, Mn and Zn in 72 guarana seed samples from Bahia state. This work presents unpublished results about the mineral composition of guarana seed samples produced in Bahia state, Brazil., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

This work aims to analyze the thermal decomposition kinetics of guarana seed residue applying inert and oxidizing atmospheres. Thermal decomposition experiments were carried out in a thermogravimetric analyser using heating rates of 5, 10 and 15 °C/min. Three thermal decomposition stages were identified: dehydration; pyrolysis/oxidative pyrolysis, and carbonization/combustion, respectively. In order to obtain the estimation of the activation energies, the isoconversional method proposed by Vyazovkin (1997) was applied. Besides that, three and six independent parallel reactions schemes were applied for respective atmospheres. The ranges of activation energy were of 52-140 kJ/mol and 71-171 kJ/mol for inert and oxidizing atmosphere, respectively. The modeling of conversion rates presented a good agreement in relation to the experimental data (AD < 4%)., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The antioxidant and antimicrobial effects of guarana seed extracts (GSE) added to pork patties were evaluated for 18 days storage at 2 ± 1 °C. Five treatments were prepared: i) without natural antioxidant [control (negative control)], ii) with BHT at 200 mg/kg (positive control), and iii) with three different concentrations: 250  mg/kg (guarana seed low dose-GSL), 500  mg/kg (guarana seed medium dose-GSM) and 1000  mg/kg (guarana seed high dose-GSH) of guarana extracts, respectively. The pH, instrumental colour (CIE L*, a*, b*), total viable counts (TVC), Pseudomonas spp. counts and lactic acid bacteria (LAB) counts, 2-thiobarbituric acid reactive substances (TBARS) and carbonyl content were determined after 0, 7, 11, 15 and 18 days of storage period. The in vitro antioxidant activity together with the phenolic profile of GSE was also studied. Microbial analysis showed that GSE had no antimicrobial activity on pork patties. The untargeted UHPLC-ESI-QTOF approach confirmed the wide phenolic composition of GSE able to explain the antioxidant power (28.2 g/kg of phenolic equivalents). Low doses (GSL) of GSE were able to preserve the values of colour parameters, obtaining higher L*, a* and b* values during storage, which is reflected in the lowest colour differences during storage (ΔE* 0-18  = 4.56). TBARS and carbonyls values in GSE added samples were lower than control and BHT ones. GSL and GSM provided better results than the synthetic antioxidant (0.08 and 0.07 vs 0.18 mg MDA/kg; 2.47 and 3.13 vs 3.23 nmol/mg, for GSL and GSM vs BHT, respectively). These findings show that GSE are very effective against colour deterioration, lipid and protein oxidation in pork patties and possessing the potential to be used as natural antioxidants., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Microbiota alterations are observed in pathological conditions, and their regulation is a subject of great interest. Gut microbes are affected by diet, and plant polyphenols may have positive effect on gut microbiota; however, plant-derived extracts may have toxic effects. Guarana (Paullinia cupana Mart.) is a nontraditional medicinal plant applied worldwide. Guarana yields an alkaloid and polyphenol-rich seed with antimicrobial, antioxidant, and anti-inflammatory properties, where caffeine is the major compound. We evaluated the effects of guarana seed powder (GSP) and purified caffeine on gut microbial composition and redox and inflammatory parameters in Wistar rats after 21 days of treatment. Fecal microbiota was analyzed utilizing 16S rDNA sequencing. Antioxidant enzymes activities from liver, kidney, and colon, as well as oxidative damage markers, were evaluated. Total nonenzymatic antioxidant potential was also evaluated. Microbiota was altered by both treatments, GSP and caffeine, without loss of diversity. In the liver, the kidney, and the colon, we observed a decrease in the antioxidant enzymes activities in the GSP group with no increase in the expression of oxidative damage markers, although some enzymes were also regulated by caffeine. Taken together, these results suggested that GSP ameliorates redox parameters but negatively affected gut microbiota, partially via caffeine., (© 2018 John Wiley & Sons, Ltd.)

Guaraná (Paullinia cupana) is a typical product from Amazon biota that exerts antioxidant capacity due to the presence of phenolic compounds, such as catechin, epicatechin and proanthocyanidins. The objective of this study was to evaluate the potential inhibitory activity of guaraná extracts, after digestion in vitro, on carbohydrates-metabolism enzymes and to assess the bioacessibility of guaraná polyphenols. The guaraná samples before and after enzymatic digestion, were compared for total phenolic content and phenolic profile. Furthermore, we investigated the uptake of polyphenols from guarana, using Caco-2 cells, and the effect of digested guaraná on carbohydrate metabolism enzymes. The amount of total phenolic compounds extracted from guaraná decreased after digestion in vitro, and native phenolics were not identified after cell permeation. On the other hand, polyphenols from guaraná were able to inhibit α-glucosidase and α-amylase activities. In conclusion, guaraná can be considered as a dietary source with anti-hyperglycemic potential., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The small tree Allophylus africanus, widespread in the African continent, has long been considered valuable, as noted by the number of reports on their multiple medicinal uses. With this work, we aimed to extend the current, and so far restricted, knowledge on the chemical composition of the plant, particularly as source of flavonoids, as well as to assess its potential anti-inflammatory properties. The chemical characterization of the aqueous extract obtained from the leaves allowed the identification and quantitation of 30 flavones, predominantly apigenin derivatives, but also four luteolin derivatives, while the stem bark extract was solely characterized by apigenin di-C-glycosides and mono-C-glycosides-O-glycosylated. Strong inhibitory effects towards 5-lipoxygenase were observed with the aqueous extracts obtained from the leaves and stem bark, with IC 50 values of 41.28 and 107.77 μg mL -1 , respectively. Both extracts were also found to reduce NO levels in LPS-challenged RAW 264.7 macrophages, without noticeable cytotoxicity. The flavonoid profile of the plant is disclosed for the first time, allowing the identification of several molecules that may contribute to mitigate the inflammatory response. Jointly, with the current study the anti-inflammatory use of the leaves and stem bark is partially validated., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Guarana (Paullinia cupana) is habitually ingested by people in the Amazon region and is a key ingredient in various energy drinks consumed worldwide. Extension in longevity and low prevalence of chronic age-related diseases have been associated to habitual intake of guarana. Anti-aging potential of guarana was also demonstrated in Caenorhabditis elegans; however, the mechanisms involved in its effects are not clear. Herein, we investigated the putative pathways that regulate the effects of guarana ethanolic extract (GEE) on lifespan using C. elegans. The major known longevity pathways were analyzed through mutant worms and RT-qPCR assay (DAF-2, DAF-16, SKN-1, SIR-2.1, HSF-1). The possible involvement of purinergic signaling was also investigated. This study demonstrated that GEE acts through antioxidant activity, DAF-16, HSF-1, and SKN-1 pathways, and human adenosine receptor ortholog (ADOR-1) to extend lifespan. GEE also downregulated skn-1, daf-16, sir-2.1 and hsp-16.2 in 9-day-old C. elegans, which might reflect less need to activate these protective genes due to direct antioxidant effects. Our results contribute to the comprehension of guarana effects in vivo, which might be helpful to prevent or treat aging-associated disorders, and also suggest purinergic signaling as a plausible therapeutic target for longevity studies.

Introduction: COMP-4 is a natural compound-based dietary supplement consisting of the combination of ginger, Paullinia cupana, muira puama and l-citrulline, which when given long-term has been shown in the aged rat to a) upregulate iNOS in the penile smooth muscle cells (SMC), b) reverse the corporal SMC apoptosis and fibrosis associated with corporal veno-occlusive dysfunction (CVOD), and c) improve resulting erectile function. To elucidate the mechanism of how COMP-4 and its individual components modulate the iNOS-cGMP pathway, an in vitro study was conducted using a rat corporal primary SMC culture to determine its effect on NOS, soluble guanylate cyclase (sGC), cGMP and the phosphodiesterase 5 enzyme (PDE5)., Materials and Methods: Primary SMC cultures using the explant technique were initiated by cutting small pieces of corporal tissue from 8 week old Sprague-Dawley rats. The SMC were grown in Dulbecco media with 20% fetal calf serum. The SMC were then incubated with or without COMP-4 (0.69 mg/ml) or its ingredients alone (ginger: 0.225 mg/ml; muira puama, Paullinia cupana and l-citrulline each at 0.9 mg/ml) for up to 24 h mRNA and protein were extracted and used for the determination of NOS, sGC and PDE5 content. cGMP content was determined by ELISA. L-NIL (4 μM) was used as an inhibitor of iNOS activity., Results: Compared to the control values, COMP-4 upregulated expression of cGMP by 85%, induced a 42 fold increase in sGC as well as a 15 fold increase in both iNOS protein and mRNA content while it decreased both PDE5 mRNA and protein content each by about 50%. L-NIL completely inhibited the effect of COMP-4 on cGMP production. When compared with each of the individual four components of COMP-4, it appears that COMP-4 itself had the most profound effect in modulating each one the specific steps within the iNOS-cGMP pathway., Conclusions: This in vitro study demonstrates that COMP-4 is capable of activating the endogenous cellular iNOS-cGMP pathway within the CSM cells, which is theorized to be responsible for reducing the fibrosis and apoptosis as well as the CVOD observed in the aging rat penis. Further studies will be necessary in order to determine whether supplementation of COMP-4 on a daily basis may be beneficial in halting or reversing this aging related erectile dysfunction in the clinical setting., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Paullinia cupana-containing preparations are being consumed worldwide for weight reduction. As obesity and epilepsy are common comorbidities and lamotrigine (LTG) is a broad-spectrum antiepileptic drug, it is likely to find epilepsy patients taking P. cupana and LTG simultaneously. Thus, this work aimed to investigate the potential interaction between P. cupana extract and LTG in rats. In a study, rats were orally co-administered with a single-dose of P. cupana extract (821 mg/kg) and LTG (10 mg/kg). In another study, rats were orally pre-treated for 14 days with P. cupana extract (821 mg/kg/day) receiving LTG (10 mg/kg, p.o.) on the 15th day. Rats of the respective control groups received the corresponding volume of the extract vehicle. LTG concentrations were determined at several post-dose time-points and submitted to a non-compartmental pharmacokinetic analysis. The co-administration of P. cupana and LTG induced a significant reduction of LTG C max and AUC 0-24 and prolonged the mean residence time. However, no significant effects were observed on LTG pharmacokinetics following a 14-day pre-treatment period with the extract. In this study changes in the body weight of rats and in some biochemical parameters were also evaluated. Overall, the results revealed a pharmacokinetic-based herb-drug interaction between P. cupana extract and LTG, mainly after their co-administration., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The aim of this study was to evaluate the effects of guarana on mitochondrial biogenesis in a high-fat diet (HFD)-fed mice. C57BL6J mice were divided in two groups: high-fat diet HFD and high-fat diet + guarana (HFD-GUA). Both groups received HFD and water ad libitum and the HFD-GUA group also received a daily gavage of guarana (1 g/kg weight). Body weight and food intake was measured weekly. Glycemic, triglyceride, and cholesterol levels were determined. VO₂ and energy expenditure (EE) were determined by indirect calorimetry. Gene expression was evaluated by real-time PCR and protein content by western blotting. The HFD-GUA group presented lower body weight, subcutaneous, retroperitoneal, visceral, and epididyimal adipose tissue depots, and glycemic and triglyceride levels, with no change in food intake and cholesterol levels. Furthermore, the HFD-GUA group presented an increase in VO₂ and basal energy expenditure (EE), as well as Pgc1 α, Creb1 , Ampka1 , Nrf1 , Nrf2 , and Sirt1 expression in the muscle and brown adipose tissue. In addition, the HFD-GUA group presented an increase in mtDNA (mitochondrial deoxyribonucleic acid) content in the muscle when compared to the HFD group. Thus, our data showed that guarana leads to an increase in energetic metabolism and stimulates mitochondrial biogenesis, contributing to control of weight gain, even when associated with high-fat diet., Competing Interests: The authors declare no conflict of interest.

We produced a new chemical compound based on methylxanthines and polyphenols (CCMP) present in the chemical matrix of guaraná (Paullinia cupana), a seed extract with antioxidant properties. After supplementation with the standard extract of resveratrol, a well documented antioxidant found in other plant sources, we investigated whether this resveratrol-enriched compound could improve sperm viability and modulate differentially reactive oxygen species (ROS) and nitric oxide (NO) levels in thawed sperm. Sperm samples obtained from healthy young donors were treated with different concentrations of guaraná extract (0.1, 1, 5 or 10 mg/ml) and cells were frozen at -80°C for 24 h. In addition, the potential protective effects of guaraná treatment on sperm treated with pro-oxidant compound (200 µM hydrogen peroxide, H2O2) were assessed. Samples were also exposed to three concentrations of CCMP before being frozen in liquid nitrogen (-196°C) or in an ultrafreezer (-80°C) for 24 h, and both pre-freezing and post-thaw measurements of viability and oxidative stress were performed. Guaraná supplementation at 10 mg/ml significantly increased post-thaw viability and decreased oxidative metabolism of the sperm. Moreover, selected concentrations of CCMP improved viability and oxidative metabolism in sperm samples pre-freezing. Furthermore, CCMP showed cryoprotective activity by increasing viability and decreasing oxidative stress in post-thaw samples. In summary, these findings suggested that CCMP supplementation acts as a cryoprotectant to modulate ROS and NO levels in thawed sperm. CCMP could be used to enhance sperm quality and reproductive success.

Paullinia cupana, commonly known as guarana, is an Amazonian fruit whose seeds are used to produce the powdered guarana, which is rich in caffeine and consumed for its stimulating activity. The metabolic profile of guarana from the two largest producing regions was investigated using UPLC-MS combined with multivariate statistical analysis. The principal component analysis (PCA) showed significant differences between samples produced in the states of Bahia and Amazonas. The metabolites responsible for the differentiation were identified by orthogonal partial least squares discriminant analysis (OPLS-DA). Fourteen phenolic compounds were characterized in guarana powder samples, and catechin, epicatechin, B-type procyanidin dimer, A-type procyanidin trimer and A-type procyanidin dimer were the main compounds responsible for the geographical variation of the samples., (Copyright © 2017. Published by Elsevier Ltd.)

Background The study evaluated phytochemical composition, antidiabetic, oral glucose tolerance test and in vitro antioxidant activities of hydromethanol extract of Paullinia pinnata root bark. Methods Cold maceration method was used in extract preparation and scavenging of 2,2-diphenyl-1-picrylhydrazyl radicals was used to evaluate antioxidant properties of the extract. Diabetes was induced with alloxan at the dose of 160 mg/kg. The antidiabetic activity of the extract was tested at doses of 50, 100 and 200 mg/kg, and glibenclamide was used as reference drug. Results Phytochemical analysis of the extract showed the presence of alkaloids, flavonoids, glycosides, tannins, saponins and terpenes/sterols. The extract produced a significant (p<0.05) time-dependent decrease in the fasting blood glucose (FBG) levels in the treated rats when compared with the distilled water treated rats, but did not produce dose-dependent effects. The extract 50, 100 and 200 mg/kg and glibenclamide (2 mg/kg) caused 83.62 %, 60.66 %, 47.77 % and 68.52 % reduction respectively in FBG at 6 h post-treatment while the distilled water (5 mL/kg) produced 8.12 % reduction in FBG at 6 h post treatment. The extract (50 mg/kg) and glibenclamide (2 mg/kg) produced a significant (p<0.05) oral glucose tolerance effect in both normoglycemic and diabetic rats. The extract produced concentration-dependent increase in antioxidant activity and had its optimum effect at 400 µg/mL concentration. Conclusions This study suggests that P. pinnata root bark has potent antidiabetic and antioxidant activities and also validates its use in folkloric medicine in the management of diabetes-related conditions.

The mammalian target of rapamycin (mTOR) and mitogen-activated protein kinases (MAPKs) pathways are frequently upregulated in cancer. Some authors have reported that some antioxidant molecules could be potential inhibitors of these pathways. Therefore, we investigated the in vitro antitumor effect of guaraná by inhibiting the AKT/mTOR/S6K and MAPKs pathways. Colorectal and breast cancer cell lineages, HT-29 and MCF-7 cells, respectively, were exposed to different guaraná concentrations (0.1, 1, 10, and 100 µg/mL) as well as its main bioactive molecule, caffeine, in proportional concentrations to those found in the extract. Western blot, clonogenic assay, and growth curve were performed. Moreover, we investigated the potential cytotoxic effect of guaraná in normal cells. The results revealed that guaraná and caffeine inhibited some MAPKs proteins (p-p38 and p-HSP27) in MCF-7 cells. However, they did not affect this pathway in HT-29 cells. Furthermore, guaraná inhibited mTORC1 (p-S6K) and mTORC2 (p-AKT) in MCF-7 cells, but only mTORC1 in HT-29 cells. Caffeine only inhibited the mTOR pathway in MCF-7 cells. Guaraná decreased the colony formation and cell growth in MCF-7 and HT-29 cells. Guaraná did not affect normal cells. In conclusion, guaraná could be an important agent in antitumor pharmacologic therapies by inhibiting the mTOR and MAPKs pathways.

Guarana ( Paullinia cupana ) is a plant originated in Brazil that presents a beneficial effect on body weight control and metabolic alterations. The aim of this study was to evaluate the effects of guarana on genes and miRNAs related to adipogenesis in 3T3L1 cells. The anti-adipogenic effect of guarana was evaluated by Oil Red-O staining. Gene and miRNA expression levels were determined by real time PCR. The Cebpα and β-catenin nuclear translocation were evaluated using immunocytochemistry. Our data indicated that the triglyceride-reducing effect of guarana was dose-dependent from 100 to 300 µg/mL (-12%, -20%, -24% and -40%, respectively, p < 0.0001). An up-regulation of the anti-adipogenic genes Wnt10b , Wnt3a , Wnt1 , Gata3 and Dlk1 and a down-regulation of pro-adipogenic genes Cebpα , Pparγ and Creb1 were also observed. Furthermore, guarana repressed mmu-miR-27b-3p, mmu-miR-34b-5p and mmu-miR-760-5p, that contributed for up-regulation of their molecular targets Wnt3a , Wnt1 and Wnt10b . Additionally, cells treated with guarana presented an increase on β-catenin nuclear translocation ( p < 0.0018). In summary, our data indicate that guarana has an anti-adipogenic potential due to its ability to modulate miRNAs and genes related to this process. Together our data demonstrate the important role of guarana as a putative therapeutic agent., Competing Interests: The authors declare no conflicts of interest.

Hyperlipidemia is a risk factor for the development of cognitive dysfunction and atherosclerosis. Natural compounds have recently received special attention in relation to the treatment of disease due to their low cost and wide margin of safety. Thus, the aim of this study was to determine the possible preventive effect of guarana powder (Paullinia cupana) on memory impairment and acetylcholinesterase (AChE) activity in the brain structures of rats with Poloxamer-407-induced hyperlipidemia. Adult male Wistar rats were pretreated with guarana (12.5, 25 and 50mg/kg/day) and caffeine (0.2mg/kg/day) by gavage for a period of 30days. Simvastatin (0.04mg/kg) was administered as a comparative standard. Acute hyperlipidemia was induced with intraperitoneal injections of 500mg/kg of Poloxamer-407. Memory tests and evaluations of anxiety were performed. The cortex, cerebellum, hippocampus, hypothalamus and striatum were separated to assess acetylcholinesterase activity. Our results revealed that guarana powder was able to reduce the levels of TC and LDL-C in a manner similar to simvastatin. Guarana powder also partially reduced the liver damage caused by hyperlipidemia. Guarana was able to prevent changes in the activity of AChE and improve memory impairment due to hyperlipidemia. Guarana powder may therefore be a source of promising phytochemicals that can be used as adjuvant therapy in the management of hyperlipidemia and cognitive disorders., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Approximately 70% of the Brazilian production of guaraná (Paullinia cupana) seeds is absorbed by the beverage industries. Guaraná has several pharmacological properties: energy stimulant, antimicrobial, chemoprophylactic, antigenotoxic, antidepressive, anxiolytic, and anti-amnesic effects. Supercritical carbon dioxide extraction of bioactive compounds from guaraná seeds was carried out and optimized by an orthogonal array design (OA9(3(4))). The factors/levels studied were: modifier(s) (ethanol and/or methanol), extraction time (20, 40, and 60min), temperature (40, 50, and 60°C), and pressure (100, 200, and 300bar). The statistical design was repeated with increasing proportions of modifiers. The percentage of modifier used was proportional to the amount of polar compounds extracted. The best conditions for the supercritical extraction, based on the content of polyphenols, epicatechin/catechin quantification, yield and operating cost, proved to be: 40% ethanol:methanol during 40min, under 40°C, and 100bar. The temperature had a significant effect on the total phenolic content., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

This work aims the study of decomposition kinetics of guarana seed residue using thermogravimetric analyzer under synthetic air atmosphere applying heating rates of 5, 10, and 15°C/min, from room temperature to 900°C. Three thermal decomposition stages were identified: dehydration (25.1-160°C), oxidative pyrolysis (240-370°C), and combustion (350-650°C). The activation energies, reaction model, and pre-exponential factor were determined through four isoconversional methods, master plots, and linearization of the conversion rate equation, respectively. A scheme of two-consecutive reactions was applied validating the kinetic parameters of first-order reaction and two-dimensional diffusion models for the oxidative pyrolysis stage (149.57kJ/mol, 6.97×10(10)1/s) and for combustion stage (77.98kJ/mol, 98.611/s), respectively. The comparison between theoretical and experimental conversion and conversion rate showed good agreement with average deviation lower than 2%, indicating that these results could be used for modeling of guarana seed residue., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Paullinia pinnata is a medicinal plant traditionally used in West Africa against a wide range of diseases including soil-transmitted helminthiases. In this study, a hydroethanolic root extract was investigated for its phytochemical composition and in vitro activity against the free-living nematode Caenorhabditis elegans as well as the larval stages of the parasitic helminths Ancylostoma caninum, Haemonchus contortus, Toxocara cati, and Trichuris vulpis.LC-MS analysis of the ethanol-water (1 : 1) extract revealed epicatechin and different A-type linked oligomeric and polymeric procyanidins as the predominant compounds.Within an in vitro mortality assay, the extract showed a lethal activity against T. cati (LC50 of 112 µg/mL), T. vulpis (LC50 of 17 µg/mL), and C. elegans (LC50 2.5 of mg/mL), but not against A. caninum. Additionally, effects on egg hatching and larval migration of H. contortus were investigated, but no inhibitory activity was observed.Overall, these findings rationalize the traditional use of the root extract from P. pinnata as an anthelmintic remedy and provide insight into the phytochemical composition of the extract., (Georg Thieme Verlag KG Stuttgart · New York.)

We assessed the effects of guaraná (Paullinia cupana) consumption on plasma catechins, erythrocyte antioxidant enzyme activity (superoxide dismutase, catalase and glutathione peroxidase) and biomarkers of oxidative stress (ex vivo LDL oxidation, plasma total antioxidant status and ORAC, and lymphocyte single cell gel electrophoresis) in healthy overweight subjects. Twelve participants completed a 15-day run-in period followed by a 15-day intervention with a daily intake of 3 g guaraná seed powder containing 90 mg (+)-catechin and 60 mg (-)-epicatechin. Blood samples were taken on the first and last day of the intervention period, fasting and 1 h post-dose. The administration of guaraná increased plasma ORAC, while reducing ex vivo LDL oxidation (only in the first study day) and hydrogen peroxide-induced DNA damage in lymphocytes, at 1 h post-dose. Plasma catechin (0.38 ± 0.12 and 0.44 ± 0.18 nmol mL(-1)), epicatechin (0.59 ± 0.18 and 0.64 ± 0.25 nmol mL(-1)) and their methylated metabolites were observed at 1 h post-dose but were almost negligible after overnight fasting. The activities of catalase (in both study days) and glutathione peroxidase (in the last intervention day) increased at 1 h post-dose. Furthermore, the activity of both enzymes remained higher than the basal levels in overnight-fasting individuals on the last intervention day, suggesting a prolonged effect of guaraná that continues even after plasma catechin clearance. In conclusion, guaraná catechins are bioavailable and contribute to reduce the oxidative stress of clinically healthy individuals, by direct antioxidant action of the absorbed phytochemicals and up-regulation of antioxidant/detoxifying enzymes.

Hypercholesterolemia is a metabolic disorder characterized by high levels of low-density lipoprotein and blood cholesterol, causing inflammatory lesion. Purinergic signaling modulates the inflammatory and immune responses through adenine nucleotides and nucleoside. Guaraná has hypocholesterolemic and antiinflammatory properties. Considering that there are few studies demonstrating the effects of guaraná powder on the metabolism of adenine nucleotides, we investigated its effects on the activity of ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase) and ecto-adenosine deaminase activity in lymphocytes of rats with diet-induced hypercholesterolemia. The rats were divided into hypercholesterolemic and normal diet groups. Each group was subdivided by treatment: saline, guaraná powder 12.5, 25, or 50 mg/kg/day and caffeine concentration equivalent to highest dose of guaraná, fed orally for 30 days. An increase in adenosine triphosphate hydrolysis was observed in the lymphocytes of rats with hypercholesterolemia and treated with 25 or 50 mg/kg/day when compared with the other groups. The hypercholesterolemic group treated with the highest concentration of guaraná powder showed decreased ecto-adenosine deaminase activity compared with the normal diet groups. Guaraná was able to reduce the total cholesterol and low-density lipoprotein cholesterol to basal levels in hypercholesterolemic rats. High concentrations of guaraná associated with a hypercholesterolemic diet are likely to have contributed to the reduction of the inflammatory process., (Copyright © 2015 John Wiley & Sons, Ltd.)

Purpose: Anorexia is prevalent in cancer patients with advanced disease. In this pilot phase II, open label, nonrandomized trial, we evaluated the efficacy and safety of guarana (Paullinia cupana) in patients with cancer and weight loss., Methods: We included advanced cancer patients with decreased appetite and weight loss of more than 5% from their baseline. All of the patients received 50 mg of the crude dry extract of guarana twice a day for 4 weeks. The trial was designed in two phases (Simon model). We considered a positive response in the first phase to be at least 5% weight gain or a three-point improvement in the appetite scale in at least three of the first 18 evaluable patients., Results: Of the 34 eligible patients, 30 were included and 18 completed the protocol. Only one patient abandoned the protocol due to toxicity (grade II arthralgia). No grade 3 or 4 toxicities and no significant differences in nausea, weight loss, or quality of life (FACT-G) occurred. Only two of the 18 patients who completed the study had weight gain above 5% from their baseline, whereas six patients had at least a 3-point improvement in the visual appetite scale. The M.D. Anderson Symptom Inventory (MDASI) was used to evaluate several symptoms, and we observed a significant decrease in the lack of appetite (p = 0.02) and in somnolence (p = 0.0142)., Conclusion: We concluded that the weight stabilization and increased appetite that we observed in this study justify further studies of guarana in this patient population.

Ethnopharmacological Relevance: Snakebite envenomation causes 5000-10,000 mortalities and results in more than 5-15,000 amputations in sub-Saharan Africa alone every year. The inaccessibility of antiserum therapy is a vast problem, and only about 2.5% of the actual need for antiserum in Africa is covered. Numerous plants have shown in vitro inhibitory activity against one or more of the hydrolytic enzymes involved in snakebite-induced necrosis. However, a more thorough examination of the plant species in ex vivo and in vitro cell assay models is needed to test their ability to inhibit necrosis., Materials and Methods: Extracts which had previously shown in vitro inhibitory activity against necrosis enzymes, were tested in an ex vivo air-liquid-interface model, and a wound healing scratch assay as well as for their ability to permeate the skin barrier and inhibit venom induced cell death., Results: Of the 14 water extracts and 16 ethanol extracts tested at a concentration of 10 μg/mL, only the ethanol extracts of Tamarindus indica and Paullinia pinnata resulted in a small but significant increase in cell migration of around 10% compared to treatment with buffer after 24h treatment. The remaining extracts showed no effect, or they even delayed the cell migration compared to the treatment with buffer. After 48 h treatment, 10 of the tested extracts showed a decreased cell migration compared to no treatment. At a 100 μg/mL concentration all the extracts inhibited cell migration and five extracts killed some of the cells, while four extracts killed all the cells. Ten of the thirty extracts were tested in a Franz cell set-up but none of the extracts tested did permeate the skin barrier over a 48 h period, and will therefore be of very limited use topically in the initial treatment of snakebites in its present form. None of the extracts were able to directly interact with the enzyme to lower the cell toxicity of the venom. Two extracts, Dichrostachys cinerea and Grewia mollis, were tested in the ex vivo model, but none of them inhibited the tissue destruction caused by venom., Conclusion: On the basis of this study, topical treatment with plant extracts for snakebite-induced tissue necrosis cannot be recommended., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

The stimulant effect of energy drinks is primarily attributed to the caffeine they contain. Many energy drinks also contain other ingredients that might enhance the tonic effects of these caffeinated beverages. One of these additives is guarana. Guarana is a climbing plant native to the Amazon whose seeds contain approximately four times the amount of caffeine found in coffee beans. The mix of other natural chemicals contained in guarana seeds is thought to heighten the stimulant effects of guarana over caffeine alone. Yet, despite the growing use of guarana as an additive in energy drinks, and a burgeoning market for it as a nutritional supplement, the science examining guarana and how it affects other dietary ingredients is lacking. To appreciate the stimulant effects of guarana and other natural products, a straightforward model to investigate their physiological properties is needed. The planarian provides such a system. The locomotor activity and convulsive response of planarians with substance exposure has been shown to provide an excellent system to measure the effects of drug stimulation, addiction and withdrawal. To gauge the stimulant effects of guarana we studied how it altered the locomotor activity of the planarian species Dugesia tigrina. We report evidence that guarana seeds provide additional stimulation over caffeine alone, and document the changes to this stimulation in the context of both caffeine and glucose.