Metabolomic approaches to explore chemodiversity in seeds of guaraná (Paullinia cupana) using UPLC-QTOF-MSE and NMR analysis.

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-MSE 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-MSE, 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.

[Effect of guarana on lipid metabolism in obese rats: a study based on lipidomics].

This study investigated the effect of guarana on plasma lipid metabolites in obese rats and analyzed its mechanism in the treatment of dyslipidemia in obesity. High-fat diet was used to establish obese rat models, and the therapeutic effect of guarana on obese rats was evaluated by measuring body weight, white fat, liver weight, and lipid content, as well as observing liver histomorphology. Lipid metabolites in plasma of rats in each group were detected by UHPLC-Q-TOF-MS lipidomics. The protein expressions of fatty acid synthase, acetyl-CoA carboxylase 1, triglyceride synthesis enzyme, carnitine palmitoyltransferase Ⅰ, and acetyl-coenzyme A acyltransferase 2 in rat liver were detected using Western blot. The results revealed that guarana significantly reduced body weight, white fat, and liver weight of obese rats due to high-fat diet, and alleviated dyslipidemia and liver steatosis. Lipidomics showed that some triglycerides and phospholipids were significantly elevated in the high-fat model group, and part of them was reduced after guarana treatment. Western blot found that guarana inhibited the expression of hepatic fatty acid and triglyceride synthesis-related proteins and increased the expression of fatty acid ß-oxidation-related proteins. Abnormalities in triglyceride and phospholipid metabolism are the main characteristics of plasma lipid metabolism in obese rats induced by high-fat diet. Guarana may regulate partial triglyceride and phospholipid metabolism by inhibiting hepatic fatty acid and triglyceride synthesis and increasing fatty acid ß-oxidation, thereby improving rat obesity and dyslipidemia.

Metabolism of guarana (Paullinia cupana Kunth var. sorbilis) plants and fruit production subjected to glyphosate doses.

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.

Paullinia cupana seed extract ameliorated methotrexate-induced testicular dysfunction through the regulation of antioxidants, inflammatory, apoptosis/anti-apoptosis, and steroidogenesis-associated genes.

Methotrexate (MXT) is a medication used for cancer and rheumatoid treatment with severe organs toxicity as a side effect. Paullinia cupana (Guarana) is a plant with pleiotropic functions used to overcome the side effects of some chemotherapeutic medications. Current study aimed to examine the possible protective effect of guarana against oxidative stress induced by a single dose of MTX in testis. Forty male mice were divided into 4 groups (8 weeks old; 30 g weight), 1st group is negative control. The 2nd group is positive intoxicated group, received a single dose of MTX intraperitoneally (IP; 20 mg/kg BW in saline) on day 7. The 3rd group received guarana seed extract orally (300 mg/kg BW daily) for 12 days. The protective group was given guarana seed extract orally for 1 week, then on day 7 injected with MTX, and continued with guarana for extra 5 days. Blood was taken for biochemical measurement (hormones, antioxidants, cytokines, and oxidative stress biomarkers). Testicular tissues were taken for gene quantification (qRT-PCR), testicular oxidative stress activity (malondialdehyde; MDA, and SOD) and comet assay (sperm DNA damage), and histopathological changes at the end of experimental design. MTX intoxication caused a decrease in testicular SOD, GSH, and catalase and an increase in serum and tissue levels of MDA. Biomarkers of oxidative stress were increased by MTX intoxication, and were ameliorated by guarana administration to MTX-intoxicated mice. Guarana prevented the increase in IL-1ß and IL-6 levels compared to mice intoxicated with MTX alone. MTX upregulated the expression of caspase-3 and downregulated Bcl-2 expression using qRT-PCR analysis. These negative impacts of MTX were protected by guarana pre-administration. MTX decreased reproductive hormones and altered spermogram parameters (sperm concentration and motility, and percentage of live and dead sperms). In addition, the mRNA expression of steroidogenesis-associated genes, such cytochrome P450 cholesterol side-chain cleavage enzyme (P450scc), and 17ß hydroxyl steroid dehydrogenase (17ß-HSD) was downregulated in the MTX-treated group, all were prevented by guarana administration. The sperm DNA damage revealed by a comet assay was increased in MTX group and was reversed to control levels by guarana supplementation. Finally, testis histology of MTX-group showed marked spermatocytes vacuolization and a decrease in spermatogenesis. Guarana administration abrogated histopathological changes reported in the Leydig cells and testicular tissues. In conclusion, guarana has the potential as a supplement medication to antagonize testicular oxidative stress induced by methotrexate.

Production of Lignocellulolytic Enzymes and Phenolic Compounds by Lentinus strigosus from the Amazon Using Solid-State Fermentation (SSF) of Guarana (Paullinia cupana) Residue.

The Amazon rainforest has a rich biodiversity, and studies of Basidiomycete fungi that have biomolecules of biotechnological interest are relevant. The use of lignocellulosic biomass in biotechnological processes proposes an alternative use, and also adds value to the material when employed in the bioconversion of agro-industrial waste. In this context, this study evaluate the production of lignocellulolytic enzymes (carboxymethylcellulases (CMCase), xylanase, pectinase, laccase) as well as phenolic compounds and proteases by solid-state fermentation (SSF) using the fungus Lentinus strigosus isolated from Amazon. The guarana (Paullinia cupana) residue was characterized using scanning electron microscopy (SEM), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR). SSF was carried out with 60% humidification of the residue, at 30 °C, for 10 days. The lignocellulosic biomass presented fragmented structures with irregular shapes and porosities, and was mainly constituted by cellulose (19.16%), hemicellulose (32.83%), and lignin (6.06%). During the SSF, significant values of CMCase (0.84 U/g) on the 8th day, xylanase (1.00 U/g) on the 7th day, pectinase (2.19 U/g) on the 6th day, laccase (176.23 U/mL) on the 5th day, phenolic compounds (10.27 µg/mL) on the 1st day, soluble proteins (0.08 mg/mL) on the 5th day, and protease (8.30 U/mL) on the 6th day were observed. In general, the agro-industrial residue used provided promising results as a viable alternative for use as a substrate in biotechnological processes.

TNF-α inhibition, antioxidant effects and chemical analysis of extracts and fraction from Brazilian guaraná seed powder.

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 IC50 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 IC50 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.

Safety of Guarana Seed as a Dietary Ingredient: A Review.

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.

Guarana (Paullinia cupana) Extract Protects Caenorhabditis elegans Models for Alzheimer Disease and Huntington Disease through Activation of Antioxidant and Protein Degradation Pathways.

Guarana (Paullinia cupana) is largely consumed in Brazil in high energy drinks and dietary supplements because of its stimulant activity on the central nervous system. Although previous studies have indicated that guarana has some protective effects in Parkinson's (PD), Alzheimer's (AD), and Huntington's (HD) disease models, the underlying mechanisms are unknown. Here, we investigated the protective effects of guarana hydroalcoholic extract (GHE) in Caenorhabditis elegans models of HD and AD. GHE reduced polyglutamine (polyQ) protein aggregation in the muscle and also reduced polyQ-mediated neuronal death in ASH sensory neurons and delayed ß-amyloid-induced paralysis in a caffeine-independent manner. Moreover, GHE's protective effects were not mediated by caloric restriction, antimicrobial effects, or development and reproduction impairment. Inactivation of the transcription factors SKN-1 and DAF-16 by RNAi partially blocked the protective effects of GHE treatment in the AD model. We show that the protective effect of GHE is associated with antioxidant activity and modulation of proteostasis, since it increased the lifespan and proteasome activity, reduced intracellular ROS and the accumulation of autophagosomes, and increased the expression of SOD-3 and HSP-16.2. Our findings suggest that GHE has therapeutic potential in combating age-related diseases associated with protein misfolding and accumulation.

Broad distribution of TPI-GAPDH fusion proteins among eukaryotes: evidence for glycolytic reactions in the mitochondrion?

Glycolysis is a central metabolic pathway in eukaryotic and prokaryotic cells. In eukaryotes, the textbook view is that glycolysis occurs in the cytosol. However, fusion proteins comprised of two glycolytic enzymes, triosephosphate isomerase (TPI) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), were found in members of the stramenopiles (diatoms and oomycetes) and shown to possess amino-terminal mitochondrial targeting signals. Here we show that mitochondrial TPI-GAPDH fusion protein genes are widely spread across the known diversity of stramenopiles, including non-photosynthetic species (Bicosoeca sp. and Blastocystis hominis). We also show that TPI-GAPDH fusion genes exist in three cercozoan taxa (Paulinella chromatophora, Thaumatomastix sp. and Mataza hastifera) and an apusozoan protist, Thecamonas trahens. Interestingly, subcellular localization predictions for other glycolytic enzymes in stramenopiles and a cercozoan show that a significant fraction of the glycolytic enzymes in these species have mitochondrial-targeted isoforms. These results suggest that part of the glycolytic pathway occurs inside mitochondria in these organisms, broadening our knowledge of the diversity of mitochondrial metabolism of protists.

Guarana (Paullinia cupana var. sorbilis), an anciently consumed stimulant from the Amazon rain forest: the seeded-fruit transcriptome.

Guarana (Paullinia cupana var. sorbilis) is a plant native to the central Amazon basin. Roasted seed extracts have been used as medicinal beverages since pre-Colombian times, due to their reputation as stimulants, aphrodisiacs, tonics, as well as protectors of the gastrointestinal tract. Guarana plants are commercially cultivated exclusively in Brazil to supply the national carbonated soft-drink industry and natural product stores around the world. In this report, we describe and discuss the annotation of 15,387 ESTs from guarana seeded-fruits, highlighting sequences from the flavonoid and purine alkaloid pathways, and those related to biotic stress avoidance. This is the largest set of sequences registered for the Sapindaceae family.