| 1. Tonic action |
Aqueous extract (40 ºC, 2 h, 2×) |
In vivo: blood samples from mice |
To evaluate the tonic action of guarana on normal mice and trained mice on and epinephrine-induced glycogenolytics |
Control: without treatment |
20, 100, and 500 mg kg-1
|
Aqueous extract with suppressive activity of exercise-induced hypoglycemia in mice, which confirms its traditional use as a tonic |
(Miura et al., 1998Miura, T., Tatara, M., Nakamura, K., Suzuki, I., 1998. Effect of guarana on exercise in normal and epinephrine-induced glycogenolytic mice. Biol. Pharm. Bull. 21, 646-648.) |
| 2. Controlling hot flushes |
It is not clear. The extract contained 7.97% caffeine and 1.47% tannins |
In vivo: women |
To assess whether guarana decreases the number and severity of hot flushes in women after diagnosis of breast cancer |
Placebo |
50 mg of dry extract use by mouth twice a day for 6 weeks |
There was a reduction in the number and severity of hot flushes |
(Oliveira et al., 2013Oliveira, S.S., Giglio, A.B., Lerner, T.G., Zanellato, R.M., Tiemi, L., Reifur, L., Santi, P.X., Giglio, A., 2013. Paullinia cupana for control of hot flashes in breast cancer patients: a pilot study. Einstein 11, 435-438.) |
| 3. Relaxation of corpora cavernosa (aphrodisiac effect) |
Association: Catuama®. Mixture of hydroalcoholic extracts of 4 plants: 5% guarana, 1% Zingiber officinalis (ginger), 5% Trichiliacatigua (catuaba), and 5% Ptychopetalum olacoides (muirapuama). Ethanol extracts (1:1) were also extracted for 7 days at 25 ºC for each plant. |
Ex vivo: isolated corpus cavernosum of rabbits |
To investigate the effects of Catuama® and its constituent plants isolated in the tissue of the corpora cavernosa of rabbits using a cascade bioassay |
Positive control: acetylcholine (0.6 nmol) or glyceryl trinitrate (1.3 nmol) |
Bolus injections of Catuama®: 1, 3 and 10 mg, and individual doses of guarana (0.5-5 mg), Z. officinalis (1-10 mg), P. olacoides (2-20 mg) and T. catigua (1-10 mg) |
Catuama® caused short-term and dose-dependent relaxation. Out of the 4 extracts tested individually, the guarana plant was the most effective, indicating that it is the main responsible factor for the effect of relaxation of the corpora cavernosa of rabbits, allegedly attributed to Catuama®
|
(Antunes et al., 2001Antunes, E., Gordo, W.M., de Oliveira, J.F., Teixeira, C.E., Hyslop, S., De Nucci, G., 2001. The relaxation of isolated rabbit corpus cavernosum by the herbal medicine Catuama and its constituents. Phytother. Res. 15, 416-421.) |
| 4. Weight loss and delay in gastric emptying |
Association: preparation of extracts of herbal drugs (YGD) (capsules), containing: 112 mg yerba mate, 95 mg guarana, and 36 mg of damiana, administered with 420 ml of apple juice |
In vivo: humans |
To determine delayed gastric emptying and weight loss over 10 and 45 days and weight maintenance over 12 months |
Placebo capsules (lactose) administered with 420 ml of apple juice |
3 capsules of YGD per day |
There was a significant delay in gastric emptying; it reduced the time of perception of gastric fullness and led to significant weight loss over 45 days, in overweight patients treated in a context of primary health care |
(Andersen and Fogh, 2001Andersen, T., Fogh, J., 2001. Weight loss and delayed gastric emptying following a South American herbal preparation in overweight patients. J. Hum. Nutr. Dietet. 14, 243-250.) |
| 5. Weight loss |
Association: commercial mixture Metabolife-356® containing Ma Huang and guarana as main active ingredients. Each tablet contained 12 mg ephedrine alkaloids and 40 mg caffeine |
In vivo: humans (25-55 years) with BMI ≥ 29 and ≤35 kg m-2
|
To examine, in overweight people, short-term safety and effectiveness in weight loss, of a herbal supplement that contains Ma Huang, guarana and other ingredients |
Placebo: a tablet identical in appearance, but without the mixture of plants |
2 tablets, 30 min before meals, 3 times per day for 2 months. Daily: 72 mg - ephedrine alkaloids; 240 mg - caffeine |
The study reported weight loss, fat loss, reduction of waist circumference and hip circumference and of triglyceride levels; there were adverse effects with potential risks (self-reported palpitations, increase of serum glucose and transient increases in systolic blood pressure) |
(Boozer et al., 2001Boozer, C.N., Nasser, J.A., Heymsfield, S.B., Wang, V., Chen, G., Solomon, J.L., 2001. An herbal supplement containing Ma Huang-guarana for weight loss: a randomized, double-blind trial. Int. J. Obes. 25, 316-324.) |
| 6. Weight loss |
Association: the 4 mixtures (capsules) contained varying doses of green tea (in which epigallocatechin-3-gallate (EGCG) represented 45% of the dry weight) and white tea (with a fixed dose of caffeine). They also contained unknown amounts of catechins |
In vivo: men (20-50 years) with BMI between 20 and 27 kg m-2
|
To compare the effect of the mixture of extracts of green tea and guarana (fixed dose of caffeine and variable doses of EGCG), within 24 h, on energy expenditure and fat oxidation. To determine if there is a dose-dependent effect of EGCG and, if so, what dose produces better effect without inducing significant cardio stimulation |
Placebo: cellulose |
3 capsules per day. Each capsule has a fixed dose of caffeine (200 mg) and variable amounts of EGCG (90, 200, 300, and 400 mg) |
The mixture EGCG and caffeine must be considered as a good complement to a weight loss program and has potential for the treatment of obesity. Some authors suggest that a dose of 90 mg of EGCG (3 times a day) represents the optimum concentration to produce an effect on nutrient oxidation |
(Bérubé-Parent et al., 2005Bérubé-Parent, S., Pelletier, C., Doré, J., Tremblay, A., 2005. Effects of encapsulated green tea and guarana extracts containing a mixture of epigallocatechin-3-gallate and caffeine on 24 h energy expenditure and fat oxidation in men. Br. J. Nutr. 94, 432-436.) |
| 7. Ergogenic effect and "fat-burning" effect |
Two extracts were tested:
A. Extract obtained by percolation into ethanol:water solvent (6.6:3.4 v/v), with 0.153 g g-1 of caffeine.
B. Extract decaffeinated by extraction with chloroform (tannins and catechins were not removed) |
In vivo: Wistar rats |
To evaluate the effect of supplementation with guarana (14 days) on aspects of lipid metabolism in rats with a sedentary lifestyle and trained rats |
Non-supplemented sedentary and trained rats |
0.130 and 0.325 g kg-1-dry extract per BW (body weight) |
Intake of guarana is able to induce alterations in lipid metabolism, because of the methylxanthine content of the extract |
(Lima et al., 2005Lima, W.P., Carnevali, J.L.C., Eder, R., Rosa, L.F.B.P.C., Bacchi, E.M., Seelaender, M.C.L., 2005. Lipid metabolism in trained rats: effect of guarana (Paullinia cupana Mart.) supplementation. Clin. Nutr. 24, 1019-1028.) |
| 8. Weight loss and change in body composition |
Association of 2 tablets
A. Tablets with extracts of asparagus, green tea, black tea, guarana, yerba mate and purple beans; B. extracts of purple pods, Garcinia cambogia and chromium in the form of yeast |
In vivo: humans (21-55 years, with BMI between 25.2 and 39.6 kg m-2) |
To evaluate the efficacy and safety of plant extracts for weight reduction and changes in body composition |
Placebo |
Two tablet per meal, at two main meals.
Tablet A, 1 h before a meal
Tablet B, half an hour after a meal |
Reduction of fat and increase in lean body mass. There were no significant differences in weight and BMI measurements |
(Opala et al., 2006Opala, T., Rzymski, P., Pischel, I., Wilczak, M., Wozniak, J., 2006. Efficacy of 12 weeks supplementation of a botanical extract-based weight loss formula on body weight, body composition and blood chemistry in healthy, overweight subjects-a randomised double-blind placebo-controlled clinical trial. Eur. J. Med. Res. 11, 343-350.) |
| 9. Ergogenic and "fat burning" effect |
Two extracts were tested:
A. Extract obtained by percolation in ethanol: water (6.6:3.4, v/v), with caffeine content of 0.153 g g-1 of extract.
B. Decaffeinated extract by extraction with chloroform (eliminated all the methylxantines; tannins and catechins were not removed) |
In vivo: male Wistar rats |
To evaluate the effect of guarana (14 days) supplementation on aspects of lipid metabolism in sedentary and trained rats |
Sedentary and trained rats not supplemented |
0.130 and 0.325 g kg-1 (dry extract per BW) |
The consumption of guarana is able to induce changes in lipid metabolism, but the predominant element seems to be the methylxanthine content of the extract |
(Lima et al., 2005Lima, W.P., Carnevali, J.L.C., Eder, R., Rosa, L.F.B.P.C., Bacchi, E.M., Seelaender, M.C.L., 2005. Lipid metabolism in trained rats: effect of guarana (Paullinia cupana Mart.) supplementation. Clin. Nutr. 24, 1019-1028.) |
| 10. Weight loss |
Association: Zotrim®, tablets containing extracts of yerba mate, guarana and damiana (YGD). Each tablet of YGD contains: guarana (95 mg); yerba mate (112 mg); damiana (35 mg), with a total of approximately 11.2 mg caffeine |
In vivo: humans |
To evaluate the effect of the administration of YGD on the decrease in weight, BMI, waist circumference, hunger and satiety, in a group of health professionals |
Placebo: lactose tablet |
2 tablets 15 min before meals for 1 week; then increasing to 3 tablets 15 min before meals for 5 weeks. Total: 6 weeks, 3 meals per day |
Significant reduction in self-reported weight, waist circumference and hip circumference. 22% of individuals had clinically significant weight loss |
(Ruxton et al., 2007Ruxton, C.H.S., Kirkwood, L., McMillan, B., John, D.S., Evans, C.E.L., 2007. Effectiveness of a herbal supplement (Zotrim™) for weight management. Brit. Food J. 109, 416-428.) |
| 11. Weight loss and antioxidant activity |
Association: extract powders of Salvia officinalis, Camellia sinensis, guarana, and two vitamins (thiamine and niacin) (STG). The amount of each component was not informed |
In vivo: Fischer rats-344 |
To test a new diet that provides nutritional support for speeding up metabolism and maintaining healthy weight and energy, as well as to evaluate the safety and efficacy of STG |
Control: Group 1 that received normal feed |
Group 2: 1× STG; Group 3: 7× STG; 1×: normal feed with 192 mg of STG per kg |
The administration of STG has not reduced weight gain drastically. However, it has helped to maintain healthy body weight as well as antioxidant capacity of vital target organs (liver, heart and kidneys) |
(Bulku et al., 2010Bulku, E., Zinkovsky, D., Patel, P., Javia, V., Lahoti, T., Khodos, I., Stohs, S.J., Ray, S.D., 2010. A novel dietary supplement containing multiple phytochemicals and vitamins elevates hepatorenal and cardiac antioxidant enzymes in the absence of significant serum chemistry and genomic changes. Oxid. Med. Cell. Longev. 3, 129-144.) |
| 12. Anti-adipogenic effect |
Guarana: 2.42% of flavonoids, 9.18% of total phenolics and 12.4% of caffeine |
In vitro: 3T3-L1 cell line |
To evaluate the effects of guarana on genes and miRNAs related to adipogenesis in 3T3L1 cells |
Control: without treatment |
50, 100, 150, 200 and 300 µg ml-1
|
The results showed that guarana modulates the expression of several genes and miRNAs associated with adipogenesis, as well as an increase of β-catenin nuclear translocation, which might contribute to adipogenesis inhibition. The effect of guarana on the reduction of triglycerides was dose dependent of 100-300 µg ml-1 (12%, 20%, 24% and 40%, respectively) |
(Lima et al., 2017Lima, N.D., Numata, E.D., Mesquita, L.M.D., Dias, P.H., Vilegas, W., Gambero, A., Ribeiro, M.L., 2017. Modulatory effects of guarana (Paullinia cupana) on adipogenesis. Nutrients 9, http://dx.doi.org/10.3390/nu9060635.
http://dx.doi.org/10.3390/nu9060635...
) |
| 13. Protection against gastric lesions |
Dried seed extract. There is no information about the method of extract preparation, neither about the quantification of the main components |
In vivo: rats and mice |
To analyze the effects of the guarana extract on gastric lesions induced by indomethacin and ethanol, gastric secretion and gastrointestinal transit and to compare them with the effects of pure caffeine |
Control: tap water |
Guarana extract 50 and 100 mg kg-1
Caffeine 20 and 30 mg kg-1
|
Guarana seems to offer far better therapeutic benefits than caffeine in gastrointestinal disorders |
(Campos et al., 2003Campos, A.R., Barros, A.I.S., Santos, F.A., Rao, V.S.N., 2003. Guarana (Paullinia cupana Mart.) offers protection against gastric lesions induced by ethanol and indomethacin in rats. Phytother. Res. 17, 1199-1202.) |
| 14. Hepatoprotective effect |
Guarana seed powder diluted in water (12.240 mg g-1 of caffeine, 6.733 mg g-1 of theobromine, 4.336 mg g-1 of total catechins and 16 mg g-1 of condensed tannins) |
In vivo: male Wistar rats |
To evaluate the hepatoprotective effect of guarana seed powder on CCl4-induced liver injury (carbon tetrachloride) in rats |
Hepatoprotective agent: silymarin (100 mg kg-1). CCl4 (1 ml kg-1, 50 percent CCl4 in olive oil) for induction of liver toxicity. Control: water |
100, 300, and 600 mg kg-1, daily for 14 days |
The results indicate that guarana has hepatoprotective activity in CCl4-induced liver injury in rats, preventing the break of strands of cellular DNA |
(Kober et al., 2016Kober, H., Tatsch, E., Torbitz, V.D., Cargnin, L.P., Sangoi, M.B., Bochi, G.V., da Silva, A.R.H., Barbisan, F., Ribeiro, E.E., da Cruz, I.B.M., Moresco, R.N., 2016. Genoprotective and hepatoprotective effects of guarana (Paullinia cupana Mart. var. sorbilis) on CCl4-induced liver damage in rats. Drug. Chem. Toxicol. 39, 48-52.) |
| 15. Antiallergic effect |
Hydroethanolic extract 30% (reflux for 2 h). The dry extract was dissolved in DMSO and diluted in saline or buffer |
In vivo: mice |
To investigate the effects of the hydroethanolic extract of guarana seeds (GSE) on the increase of IgE-stimulated vascular permeability and the effects on IgE-induced mast cell degranulation |
Control: saline |
0.1, 0.3, or 1.0 g kg-1
|
GSE administered orally inhibited the reaction of anti-dinitrophenol IgE-induced passive cutaneous anaphylaxis.
GSE also inhibited β-hexisosaminidase release in RBL-2H3 cells induced by IgE receptor-mediated pathways.
These results indicate that GSE had an inhibitory effect on the allergic reaction and may have therapeutic application in inflammatory allergic diseases |
(Jippo et al., 2009Jippo, T., Kobayashi, Y., Sato, H., Hattori, A., Takeuchi, H., Sugimoto, K., Shigekawa, M., 2009. Inhibitory effects of guarana seed extract on passive cutaneous anaphylaxis and mast cell degranulation. Biosci. Biotechnol. Biochem. 73, 2110-2112.) |
| 16. Immunomodulatory activity |
Crude extract (CE) of guarana was prepared using acetone:water (7:3, v/v). The CE was partitioned with ethyl acetate, and removed the organic solvent to yield the EAF. |
In vitro: splenocytes and cytokines |
To evaluate immunomodulatory activity of guarana seeds crude extract (CE) and ethyl-acetate fraction (EAF) |
Untreated cells and cells treated with methylprednisolone (100 µM) |
CE and EAF: 5, 10, 50, and 100 µg ml-1
|
All cytokines evaluated had their levels reduced after treatment, following dose-response model |
(Carvalho et al., 2016Carvalho, L.V.N., Cordeiro, M.F., Lins, T.U.L., Sampaio, M.C.P.D., Mello, G.S.V., Costa, V.C.M., Marques, L.L.M., Klein, T., Mello, J.C.P., Cavalcanti, I.M.F., Pitta, I.R., Pitta, M.G.R., Rêgo, M.J.B.M., 2016. Evaluation of antibacterial, antineoplastic, and immunomodulatory activity of Paullinia cupana seeds crude extract and ethyl-acetate fraction. Evid. Based Complement. Altern. Med., http://dx.doi.org/10.1155/2016/1203274.
http://dx.doi.org/10.1155/2016/1203274...
) |
| 17. Antagonist action |
Aqueous extract of P. cupana and 4 TLC-separated fractions |
In vitro: blood of humans and rabbits and In vivo: rabbits |
To evaluate the antagonist action of guarana extract in platelet aggregation induced by (adenosine diphosphate) or arachidonate, but not by collagen
|
Control: without treatment |
There are no reports of the concentrations used for the study, only the volume used for the in vitro and in vivo tests |
Extracts of guarana inhibit platelet aggregation in rabbits, after administration both intravenously and orally |
(Bydlowski et al., 1988Bydlowski, S.P., Yunker, R.L., Subbiah, M.T., 1988. A novel property of an aqueous guarana extract (Paullinia cupana): inhibition of platelet aggregation in vitro and in vivo. Braz. J. Med. Biol. Res. 21, 535-538.) |
| 18. Antagonist action |
Aqueous extract of P. cupana and 4 TLC-separated fractions |
In vitro: blood of rabbits |
To evaluate the effect of guarana extract on platelet aggregation by studying its effects on platelet synthesis of thromboxane in rabbits |
Control: no treatment |
100 mg ml-1
|
Guarana has an antiplatelet action and this may be partly due to reduced thromboxane synthesis. The authors suggest that one of the fractions containing mainly caffeine would be partly responsible for this action, as well as other compounds that may be present |
(Bydlowski et al., 1991Bydlowski, S.P., D'Amico, E.A., Chamone, D.A.F., 1991. An aqueous extract of guarana (Paullinia cupana) decreases platelet thromboxane synthesis. Braz. J. Med. Biol. Res. 24, 421-424.) |
| 19. Effect on blood vessels in the papillary dermis |
Dry guarana extract (ESG) added to self-emulsifying bases. There is no information about the method of extract preparation |
In vivo: Wistar rats (topical use) |
To study the effects of the emulsion with different concentrations of extract, mixed with two chemicals promoters of cutaneous permeation (oleic acid or isopropyl myristate), on the blood vessels in the papillary dermis of rats |
The control group did not receive formulation |
ESG 20% or 50% |
The rats were not good experimental models to study hypodermis.
DGE 20% did not cause significant changes in the papillary dermis of rats. DGE 50% increased cutaneous microcirculation, and the chemical promoters of absorption did not potentiate the effects |
(Chorilli et al., 2004Chorilli, M., Ribeiro, M.C.A.P., Pires-de-Campos, M.S.M., Leonardi, G.R., Polacow, M.L.O., 2004. Emulsion effect containing dry extract of guarana over the blood vessels of the papillary dermis of rats. Saúde Rev. 6, 7-12.) |
| 20. Cognitive effect and muscle strength |
Guarana powder added to a complex consisting of creatine, dispersed in 500 ml of water |
In vivo: humans |
To compare the effects of ingestion of creatine + guarana (G+CRE) supplement on muscle strength and cognitive performance |
Placebo: sugar-free, flavored carbonated water |
Complex consisting of: 1 g of creatine; 1.5 g guarana; 150 mg of taurine; 133 mg of caffeine; 120 mg l-glutamine; 106.7 mg of vitamin C; 100 mg l-arginine and 1.1 mg of vitamin B1. Ingested in two doses, 60 and 30 min before exercise |
The creatine + guarana supplement seems to have a beneficial effect on muscle strength and cognitive performance for decision-making. Thus, it may be interesting to improve the performance of athletes in sports with high cognitive constraints |
(Pomportes et al., 2015bPomportes, L., Davranche, K., Hays, A., Brisswalter, J., 2015. Effect of a creatine-guarana complex on muscular power and cognitive performance in high-level athletes. Sci. Sports 30, 188-195.) |
| 21. Cognitive and mood effects |
Berocca®boost, multivitamin and mineral salts with 222.2 mg guarana (40 mg caffeine per tablet) |
In vivo: humans |
To investigate the impact of Berocca® Boost consumed before exercise on cognitive performance and mood measured before and after exercise, and substrate metabolism |
Placebo |
The effervescent tablet for each group (supplement with and without guarana) was randomly distributed. It was dissolved in 250 ml of water |
The consumption of a complex of vitamins and minerals containing guarana before exercise can positively impact the performance of posterior memory and reduce effort during moderate intensity exercise in active men |
(Veasey et al., 2015Veasey, R.C., Haskell-Ramsay, C.F., Kennedy, D.O., Wishart, K., Maggini, S., Fuchs, C.J., Stevenson, E.J., 2015. The effects of supplementation with a vitamin and mineral complex with guarana prior to fasted exercise on affect, exertion, cognitive performance, and substrate metabolism: a randomized Controlled Trial. Nutrients 7, 6109-6127.) |
| 22. Improvement of overall performance of the body |
Suspension of guarana seed powder of P. cupana in water: Tween-80. The powder contained 2.1% caffeine and 16% tannins |
In vivo: Swiss mice and Wistar rats |
To evaluate the action of guarana on the overall performance of the body in vivo: physical performance (forced swimming), learning and memory (active and passive avoidance) and Lashley maze III and longevity tests. To compare the effects of anti-fatigue with ginseng |
Control suspension: water/Tween 80. Drug Reference: caffeine (0.1 mg ml-1) |
Guarana: 0.3 and 3.0 mg ml-1; Ginseng: 5 mg ml-1
|
The animals treated with 0.3 mg ml-1 of guarana showed improved physical performance. It was useful for maintenance of previously acquired memory |
(Espinola et al., 1997Espinola, E.B., Dias, R.F., Mattei, R., Carlini, E.A., 1997. Pharmacological activity of guaraná (Paullinia cupana Mart.) in laboratory animals. J. Ethnopharmacol. 55, 223-229.) |
| 23. Cognitive effect |
Guarana powder (capsules). The powder contained 2.1% caffeine and 16% tannins |
In vivo: humans (above 60 years) |
To evaluate the effects of long-term administration of guarana on cognition of normal elderly volunteers |
Placebo: brown sugar capsules.
Drug reference: caffeine (12.5 mg) |
Two guarana capsules per day (500 mg each) for 5 months |
There were no cognitive differences in volunteers. The length of treatment may have been insufficient and the neuropsychological tests employed were not sensitive enough to test the expected changes |
(Galduróz and Carlini, 1996Galduróz, J.C.F., Carlini, E.A., 1996. The effects of long-term administration of guarana on the cognition of normal, elderly volunteers. São Paulo Med. J. 114, 1073-1078.) |
| 24. Improvement in cognitive performance |
Ethanolic dry guarana extract; Panax ginseng, and their combination. Both standardized. Ginseng: exhaustive percolation (40% Ethanol-60% water at temperatures <40 ºC), 4% ginsenolides. Guarana: exhaustive percolation (50% ethanol-50% water at temperatures <50 ºC), methylxanthines (11-13%) |
In vivo: humans |
To analyze the cognitive effects and mood in the treatment with guarana. To evaluate the potential for additive effects or synergistic effects after the common combination, available commercially, of guarana with Panax ginseng
|
Gelatin capsules: without plant extracts |
2 capsules per day: 75 mg of guarana (≈12% caffeine), 200 mg of ginseng, or a combination of them (75 mg 200 mg-1) |
Single doses of either one (guarana and ginseng), and a combination of both of them, improved cognitive performance in comparison with the placebo in young and healthy subjects |
(Kennedy et al., 2004Kennedy, D.O., Haskell, C.F., Wesnes, K.A., Scholey, A.B., 2004. Improved cognitive performance in human volunteers following administration of guarana (Paullinia cupana) extract: comparison and interaction with Panax ginseng. Pharmacol. Biochem. Behav. 79, 401-411.) |
| 25. Cognitive effects |
Lyophilized crude extract (EBPC) and the semipurified constituents (EPA and EPB). There is no information about the extraction methodology |
In vivo: Male Wistar rats |
To investigate the effects of chronic treatment of EBPC or EPA and EPB of guarana seeds in the cognitive behavior of rats |
Control, Caffeine (10.0 mg kg-1) or scopolamine (2.0 mg kg-1). Control: treated with NaCl 0.9% and 0.2% Tween 80) |
EBPC (30.0 or 60.0 mg kg-1) and EPA (2.0 or 4.0 mg kg-1), and EPB (2.0 or 4.0 mg kg-1) |
EPBC and EPA of guarana seed extracts were active by oral administration and showed significant nootropic effect. The chronic treatment showed the same increase in body weight and average life time, indicating low toxicity of the extracts |
(Otobone et al., 2005Otobone, F.J., Sanches, A.C., Nagae, R.L., Martins, J.V.C., Obici, S., Mello, J.C.P., Audi, E.A., 2005. Effect of crude extract and its semi purifies constituents from guarana seeds (Paullinia cupana var. sorbilis (Mart.)) Lucke on cognitive performance in morris water maze in rats. Braz. Arch. Biol. Technol. 48, 723-728.) |
| 26. Cognitive effect |
Standardized extract (Kennedy et al., 2004Kennedy, D.O., Haskell, C.F., Wesnes, K.A., Scholey, A.B., 2004. Improved cognitive performance in human volunteers following administration of guarana (Paullinia cupana) extract: comparison and interaction with Panax ginseng. Pharmacol. Biochem. Behav. 79, 401-411.) of guarana seeds (PC-102) (11-12% caffeine) |
In vivo: humans |
To assess the acute effects of dose-dependent behavior of guarana extract |
Placebo: without the guarana extract |
1 capsule per day which contains: 37.5 mg, 75 mg, 150 mg, or 300 mg of a guarana extract |
Guarana has improved the performance of secondary memory and increased the alert and mood ratings. The two lower doses produced more positive cognitive effects that the higher doses |
(Haskell et al., 2007Haskell, C.F., Kennedy, D.O., Wesnes, K.A., Milne, A.L., Scholey, A.B., 2007. A double-blind, placebo-controlled, multi-dose evaluation of the acute behavioural effects of guarana in humans. J. Psychopharmacol. 21, 65-70.) |
| 27. Cognitive performance, mood, and functional activation of the brain |
Used 2 commercially available supplements: (A) Berocca® boost, multivitamin and mineral salts with 222.2 mg guarana (40 mg caffeine per tablet); (B) Berocca® performance (no guarana in its composition and the highest levels of B complex vitamins and vitamin C) |
In vivo: humans |
To determine if Berocca® boost and Berocca® performance could differentially affect the mood and mental performance when compared with the placebo. To examine neural substrates using functional magnetic resonance imaging (fMRI) to determine such effects |
Placebo: 330 ml effervescent drink with similar color |
1 tablet per day for each group (supplement with and without guarana) |
fMRI revealed that both multivitamin treatments increased activation in areas associated with working memory and processing of attention, with the effect being greater in the group treated with the supplement containing guarana. Moreover, they showed an increase in cerebral activation in the groups treated with the supplements containing guarana or not |
(Scholey et al., 2013Scholey, A., Bauer, I., Neale, C., Savage, K., Camfield, D., White, D., Maggini, S., Pipingas, A., Stough, C., Hughes, M., 2013. Acute effects of different multivitamin mineral preparations with and without guarana on mood, cognitive performance and functional brain activation. Nutrients 5, 3589-3604.) |
| 28. Cognitive performance |
0.4 g guarana complex (GUA: 37.5 mg of guarana + 12.5 mg ginseng + 22.5 mg vitamins C, Isoxan Actiflash® Booster |
In vivo: humans |
To investigate the influence of serial mouth rinsing (MR) with nutritional supplements on cognitive control and time perception during a 40 min submaximal exercise |
Placebo |
Guarana complex 0.4 g 25 ml-1 (GUAc); caffeine 67 mg 25 ml-1 (CAF); carbohydrate 1.6 g 25 ml-1 (CHO) |
The results suggest that the serial administration of CHO, CAF and GUAc MR improves cognitive performance and decreases subjective perception of effort |
(Pomportes et al., 2017Pomportes, L., Brisswalter, J., Casini, L., Hays, A., Davranche, K., 2017. Cognitive performance enhancement induced by caffeine, carbohydrate and guarana mouth rinsing during submaximal exercise. Nutrients 9, http://dx.doi.org/10.3390/nu9060589.
http://dx.doi.org/10.3390/nu9060589...
) |
| 29. Cognitive effects |
Effervescent drink prepared from two commercially available supplements: (MV1) Berocca® boost, multivitamin and mineral salts with 222.2 mg guarana (40 mg caffeine per tablet); (MV2) Berocca® performance (no guarana in its composition and the highest levels of B complex vitamins and vitamin C) |
In vivo: humans |
To investigate the acute brain electrophysiological changes associated with multivitamin and mineral supplementation, with and without guaraná, using the steady-state visually evoked potential (SSVEP) |
Placebo |
Effervescent drink prepared with and without guarana, MV1 and MV2, respectively |
The authors suggest that single doses of multivitamin and mineral preparations, both with and without guaraná, influence functional brain activity in healthy younger adults. In contrast, multivitamin and mineral treatment with guaraná showed a tonic shift toward greater excitatory processes after a single treatment, consistent with the known actions of caffeine |
(White et al., 2017White, D.J., Camfield, D.A., Maggini, S., Pipingas, A., Silberstein, R., Stough, C., Scholey, A., 2017. The effect of a single dose of multivitamin and mineral combinations with and without guarana on functional brain activity during a continuous performance task. Nutr. Neurosci. 20, 8-22.) |
| 30. Cognitive function and oxidative stress |
Power guaraná containing caffeine (34.19 mg g-1), theobromine (0.14 mg g-1), catechin (3.76 mg g-1), epicatechin (4.05 mg g-1) |
In vivo: middle-aged male Wistar rats |
To investigate the effect of a commercial guarana extract (CGE) on cognitive function, oxidative stress, and brain homeostasis proteins related to cognitive injury and senescence |
Control group (saline): gavage of 1 ml of 0.9% saline/BW (kg)/day |
Guarana-treated group: gavage of 21 mg of guarana powder/BW (kg day-1); Caffeine-treated group: gavage of 0.84 mg of caffeine powder/BW (kg day-1)
|
The chronic supplementation with guarana extract was not effective against oxidative stress and did not provide any cognitive benefit during the 6 months aging of the Wistar rat model. The authors suggest that CGE intake does not improve cognitive development, but modifies the oxidative stress machinery and neurodegenerative-signaling pathway, inhibiting pro-survival pathway molecules in the hippocampus and striatum |
(Mingori et al., 2017Mingori, M.R., Heimfarth, L., Ferreira, C.F., Gomes, H.M., Moresco, K.S., Delgado, J., Roncato, S., Zeidan-Chulia, F., Gelain, D.P., Moreira, J.C.F., 2017. Effect of Paullinia cupana Mart. commercial extract during the aging of middle age Wistar rats: differential effects on the hippocampus and striatum. Neurochem. Res. 42, 2257-2273.) |
31. Cognitive effect
and heart rate variability |
Commercial mineral vitamin supplement containing guarana and ginseng, effervescent tablet Isoxan Actiflash®. Each tablet: 300 mg guarana and 100 mg ginseng. In addition to Natrol® commercial caffeine supplement: 100 mg caffeine |
In vivo: humans |
To valuate cognitive performance and heart rate variability after ingestion: commercial supplement with multi-vitamin-mineral preparation supplemented with 300 mg guarana; caffeine supplement or placebo supplement |
Placebo |
1 tablet per day for each group (supplement with guarana, with caffeine or placebo) |
The results suggest that the intake of a mineral multivitamin supplement containing added guarana improves decision-making performance and is accompanied by a regulation of the stable autonomic nervous system in the first hour |
(Pomportes et al., 2015aPomportes, L., Davranche, K., Brisswalter, I., Hays, A., Brisswalter, J., 2015. Heart rate variability and cognitive function following a multi-vitamin and mineral supplementation with added guarana (Paullinia cupana). Nutrients 7, 196-208.) |
| 32. Effects on cognition, anxiety and sleep |
Guarana powder (capsules). The powder contained 2.1% caffeine and 16% tannins |
In vivo: humans |
To verify the eventual acute effects of guarana on cognition, anxiety and sleep in normal volunteers |
Group 1: placebo; Group 2: caffeine (12.5 mg) |
2 capsules per day per (500 mg each) for three consecutive days |
The authors could not demonstrate any significant change in the researched effects with the treatment with guarana powder |
(Galduróz and Carlini, 1994Galduróz, J.C.F., Carlini, E.A., 1994. Acute effects of the Paullinia cupana, "guarana" on the cognition of normal volunteers. São Paulo Med. J. 112, 607-611.) |
| 33. Anxiolytic effects |
The extract was prepared (1 kg) by turbolysis (acetone:water) (7:3, v/v). 158 g lyophilized extract (EBPC) (patented process) was partitioned with ethyl acetate: EPA (ethyl acetate fraction) (44 g) and FAQ (aqueous fraction) (114 g) |
In vivo: male Wistar rats |
To investigate the effects of chronic administration of semipurified extract (EPA) of guarana in rats submitted to the elevated t maze model (ETM) of generalized anxiety disorder and panic disorder |
Positive control: paroxetine (3 mg kg-1); Negative Control: vehicle (0.9% NaCl; 2% Tween 80) |
EPA; 4, 8, or 16 mg kg-1.
EPA has 34.95% caffeine and 17.53% tannins |
EPA is administered orally; produced a panicolytic effect in rats in the ETM test; and the serotonergic and dopaminergic neurotransmitter systems are involved in this effect. It is suggested that EPA can be a useful drug in the treatment of mood disorders |
(Roncon et al., 2011Roncon, C.M., De Almeida, C.B., Klein, T., Mello, J.C.P., Audi, E.A., 2011. Anxiolytic effects of a semipurified constituent of guarana seeds on rats in the elevated T-maze test. Planta Med. 77, 236-241.) |
| 34. Anxiolytic and panicolytic effect |
The aqueous fraction (FAQ) of guarana (Roncon et al., 2011Roncon, C.M., De Almeida, C.B., Klein, T., Mello, J.C.P., Audi, E.A., 2011. Anxiolytic effects of a semipurified constituent of guarana seeds on rats in the elevated T-maze test. Planta Med. 77, 236-241.) |
In vivo: male Wistar rats |
To evaluate the anxiolytic and panicolytic effect of FAQ in rats (ETM) and if the serotoninergic, dopaminergic and glutamatergic neurotransmitters
are involved in this effect |
Positive control: Paroxetine (3 mg kg-1)
Control: vehicle (0.9% NaCl, 2% Tween 80) |
FAQ 8 mg kg-1
|
The FAQ is effective orally, produces anxiolytic and panicolytic activity in rats in the ETM test. The serotoninergic, dopaminergic and glutamatergic neurotransmitters are involved in the anxiolytic effect and the serotoninergic and dopaminergic neurotransmitters, in the panicolytic effect |
(Rangel et al., 2013Rangel, M.P., Mello, J.C.P., Audi, E.A., 2013. Evaluation of neurotransmitters involved in the anxiolytic and panicolytic effect of the aqueous fraction of Paullinia cupana (guarana) in elevated T maze. Rev. Bras. Farmacogn. 23, 358-365.) |
| 35. Psychological well-being, anxiety and mood |
Commercial product containing guarana extract containing 2.5% (m/m) of caffeine |
In vivo: humans |
To evaluate the effects on psychological well-being (PWB), anxiety and mood of a commercially available guarana preparation used according to the labeled dosages and instructions |
Placebo (corn starch) |
Capsules (360 mg), 3 times a day for 5 consecutive days |
There were no significant differences between the placebo and guarana in any of the 6 areas of PWB on SAS (state anxiety scale) or in any of the 16 mood scales. Therefore, these results did not show any significant effects on psychological well-being, anxiety or mood |
(Silvestrini et al., 2013Silvestrini, G.I., Marino, F., Cosentino, M., 2013. Effects of a commercial product containing guarana on psychological well-being, anxiety and mood: a single-blind, placebo-controlled study in healthy subjects. J. Negat. Results Biomed. 12, http://dx.doi.org/10.1186/1477-5751-12-9.
http://dx.doi.org/10.1186/1477-5751-12-9...
) |
| 36. Antidepressant effect |
Catuama® (commercial formulation already cited) (Antunes et al., 2001Antunes, E., Gordo, W.M., de Oliveira, J.F., Teixeira, C.E., Hyslop, S., De Nucci, G., 2001. The relaxation of isolated rabbit corpus cavernosum by the herbal medicine Catuama and its constituents. Phytother. Res. 15, 416-421.). The dry extract contains 40.31% guarana, 28.23% T. catigua, 28.23% P. olcaloides and 3.26% Z. Officinallis
|
In vivo: mice and rats
In vitro: synapto-somal membrane |
To assess the possible antidepressant-like effects of this product by means of pharmacological and neurochemical in vivo and in vitro procedures |
Negative control for all tests: saline (10 ml kg-1 po); in vivo tests: positive control, imipramine (10 or 15 mg kg-1ip, 6 h),
d) In vitro: fluoxetine, cocaine, or desipramine (35, 3.4; 30 µg ml-1), respectively |
Forced swimming: (150 to 300 mg kg-1 po), 6 h or (200 mg kg-1) for 7 days. Tail suspension test: Catuama® (150-300 mg kg- po), 6 h.
Open field test: Catuama® (300 mg kg-). In vitro: Catuama® (10-1000 µg ml-1 or 200 mg kg-1po) once a day for 42 days |
The results show pharmacological and neurochemical evidence of the antidepressant activity of Catuama®. The product might be useful for the clinical management of moderate and mild depressive states, alone or in association with current antidepressant drugs |
(Campos et al., 2004Campos, M.M., Fernandes, E.S., Ferreira, J., Bortolanza, L.B., Santos, A.R., Calixto, J.B., 2004. Pharmacological and neurochemical evidence for antidepressant-like effects of the herbal product Catuama. Pharmacol. Biochem. Behav. 78, 757-764.) |
| 37. Antidepressant effect |
Guarana extract, there are no reports about the extraction. It is a "short communication" |
In vivo: mice |
To analyze the effects of the guarana extract compared with caffeine in the behavior of the mouse in forced swimming and open field tests |
Distilled water (vehicle): 10 ml kg-1
|
Guarana extract (25; 50 and 100 mg kg-1). Caffeine (10, 20, and 30 mg kg-1) |
The results suggest possible antidepressant effects |
(Campos et al., 2005Campos, A.R., Barros, A.I.S., Albuquerque, F.A.A., Leal, L.K.A.M., Rao, V.S.N., 2005. Acute effects of guarana (Paullinia cupana Mart.) on mouse behaviour in forced swimming and open field tests. Phytother. Res. 19, 441-443.) |
38. Anxiolytic, antidepressant and motor stimulant
effects |
EBPC, EPA, and EPB (Roncon et al., 2011Roncon, C.M., De Almeida, C.B., Klein, T., Mello, J.C.P., Audi, E.A., 2011. Anxiolytic effects of a semipurified constituent of guarana seeds on rats in the elevated T-maze test. Planta Med. 77, 236-241.) |
In vivo: Wistar rats |
To investigate the pharmacological properties of EBPC and their EPA and EPB fractions, after acute and chronic oral administration in rats |
Control: NaCl 0.9% 0.2% Tween 80
Imipramine HCl (20.0 mg kg-1, ip), caffeine (10.0 mg kg-1, ip) and diazepan (2.0 mg kg-1, ip) |
EBPC (3.0; 30.0; or 60.0 mg kg-1). EPA (2.0 or 4.0 mg kg-1). EPB (2.0 or 4.0 mg kg-1) once a day for 40 days |
Results suggest that the extract EBPC and the EPA statement produced an antidepressant effect after long-term administration |
(Otobone et al., 2007Otobone, F.J., Sanches, A.C.C., Magae, R.L., Martins, J.V.C., Sela, V.R., Mello, J.C.P., Audi, E.A., 2007. Effect off liophilized extracts from guarana seeds [Paullinia cupana var. sorbilis (Mart.) Ducke] on behavioral profiles in rats. Phytother. Res. 21, 531-535.) |
| 39. Change in chemotherapy-induced fatigue and depressive symptoms |
Capsules of guarana extract (there is no information about extract preparation) |
In vivo: patients |
To evaluate the effect of the guarana extract on chemotherapy-induced symptoms of fatigue and depression in patients with solid tumors |
Placebo tablet |
75 mg orally for 21 days |
Results suggest that, guarana was not effective in preventing chemotherapy-related symptoms of depression and fatigue |
(Miranda et al., 2008Miranda, V.C., Trufelli, D.C., Fêde, A.B.S., Martins, F.D., Saad, L.S., Oliveira, V., Trindade, T.Z.C., Riechelmann, R., Giglio, A.D., 2008. Guarana (Paullinia cupana) for chemotherapy-related fatigue. Einstein 6, 195-199.) |
| 40. Postradiation depression and fatigue |
Capsules of extract of guarana (there is no information about extract preparation) |
In vivo: patients |
Evaluate the effectiveness of guarana in the treatment of fatigue and depression post-radiation |
Placebo tablet |
75 mg orally on a daily basis |
Results suggest that have no statistically significant differences between guarana and placebo groups. No statistical decrease of post-radiation effects of fatigue and depression |
(Miranda et al., 2009Miranda, V.C., Trufelli, D.C., Santos, J., Campos, M.P., Nobuo, M., Miranda, M.C., Schlinder, F., Riechelmann, R., Giglio, A.D., 2009. Effectiveness of guarana (Paullinia cupana) for postradiation fatigue and depression: results of a pilot double-blind randomized study. J. Altern. Complement. Med. 15, 431-433.) |
| 41. Improvement of fatigue in patients with breast cancer |
Capsules of standardized dried guarana extract (50 mg). The guarana preparation had a pH of 4.83 (10% solution in water), water content of 3.9%, 1.7% tannins, and 6.46% caffeine |
In vivo: a patient with breast cancer |
To evaluate the efficacy of the guarana extract on the fatigue, sleep quality, anxiety, depression symptoms and menopause in a group of patients with breast cancer, submitted to chemotherapy |
Placebo: cellulose capsules identical to guarana capsules |
50 mg orally twice a day for 21 days |
Guarana has proved to be an alternative non-toxic, effective, low-cost for short-term treatment of fatigue in patients with breast cancer receiving chemotherapy systematically |
(Campos et al., 2011Campos, M.P.d.O., Riechelmann, R., Casa, L.B.A., Hassan, B.J., Casa, F.B.A., Giglio, A.D., 2011. Guarana (Paullinia cupana) improves fatigue in breast cancer patients undergoing systemic chemotherapy. J. Altern. Complement. Med. 17, 505-512.) |
| 42. Fatigue related to chemotherapy |
Extraction in ethanol 70%. Standardized dried extract (PC-18) (0.096% theobromine) |
In vivo: patients with solid tumors |
Evaluate the effectiveness of an extract of guarana in patients with different solid tumors treated with chemotherapy |
Placebo |
37.5 mg orally twice per day starting after 7 days of beginning of chemotherapy, for 3 weeks |
The extract of guarana can be effective for the treatment of chemotherapy-related fatigue in patients with a variety of solid tumors with acceptable toxicity |
(del Giglio et al., 2013del Giglio, A.B., Cubero, D.I.G., Lerner, T.G., Guariento, R.T., de Azevedo, R.G., Paiva, H., Goldman, C., Carelli, B., Cruz, F.M., Schindler, F., Pianowski, L., de Matos, L.L., del Giglio, A., 2013. Purified dry extract of Paullinia cupana (guarana) (PC-18) for chemotherapy-related fatigue in patients with solid tumors: an early discontinuation study. J. Diet. Suppl. 10, 325-334.) |
| 43. Alteration in radioactive marking and cell morphology |
The commercial guarana powder was diluted in a solution with 0.9% NaCl |
In vivo: Wistar rats
In vitro: Heparinized whole blood |
To evaluate the influence of the guarana on process of marking using technetium-99m (Tc-99m) |
NaCl 0.9% |
20.0, 30.0, 50.0, 100.0, and 200.0 µg ml-1 prepared in NaCl 0.9% solution. |
The results showed a significant reduction in the uptake of radioactivity for RBC because of the guarana. Moreover, the addition of the dug caused a change in the morphology of these cells |
(de Oliveira et al., 2002de Oliveira, J.F., Avila, A.S., Braga, A.C., de Oliveira, M.B., Boasquevisque, E.M., Jales, R.L., Cardoso, V.N., Bernardo-Filho, M., 2002. Effect of extract of medicinal plants on the labeling of blood elements with Technetium-99m and on the morphology of red blood cells: I - a study with Paullinia cupana. Fitoterapia 73, 305-312.) |
| 44. Alteration in radiopharmaceutical binding of blood components |
2 g guarana powder has been diluted with 10 ml 0.9% NaCl. After centrifugation and discard of the supernatant, a salt solution of guarana (200 mg ml-1) was obtained, which was used in all subsequent dilutions |
In vivo: Wistar rats In vitro: Red blood cells (RBC) |
To study the influence of commercial guarana extract on the binding of radiopharmaceutical technetium-99m-dimercaptosuccinic acid (99m Tc-DMSA) on blood constituents using 2 precipitating agents: trichloroacetic acid (TCA) and ammonium sulphate (AS) |
NaCl 0.9% |
200 mg ml-1 prepared in NaCl 0.9% solution |
Guarana has a relevant effect on the binding of 99mTc-DMSA with insoluble fractions of the proteins of blood cells. It is suggested that this extract can affect the sites of action of AS and TCA. The presence of different metabolites with redox properties because of the metabolism of the guarana extract, could be competing for the same binding sites of 99mTc-DMSA in plasma proteins, and cell proteins |
(Freitas et al., 2007Freitas, R.S., Moreno, S.R.F., Lima-Filho, G.L., Fonseca, A.S., Bernardo-Filho, M., 2007. Effect of a commercial extract of Paullinia cupana (guarana) on the binding of 99mTc-DMSA on blood constituents: an in vivo study. Appl. Radiat. Isot. 65, 528-533.) |
| 45. Anti-aging and antioxidant activity |
A. Aqueous extract of guarana seeds (GE): Caffeine = 102.8 mg g-1, theophylline = 2.3 mg g-1, theobromine = 1.0 mg g-1. B. Alkaloid extract of guarana obtained through standard alkaline dichloromethane extraction (AlkE) |
A. antioxidant activity. In vitro: DPPH and in vivo: C. elegans. B. Anti-aging. In vivo: C. elegans
|
To investigate the anti-aging and antioxidant activity of guarana using the model organism Caenorhabditis elegans
|
Control: without guarana |
Antioxidant activity: 100, 200, and 300 mg ml-1 of GE and AlkE. Anti-aging: 300 mg ml-1 GE. PolyQ40: 100, 200, and 300 mg ml-1 of GE. |
This study demonstrated substantial antioxidant in vivo and anti-aging activity of guarana in C. elegans. Aqueous extract of guarana can extend the lifespan and attenuate markers of aging, such as the age-related muscle function decline and polyQ40 aggregation. |
(Peixoto et al., 2017Peixoto, H., Roxo, M., Röhrig, T., Richling, E., Wang, X., Wink, M., 2017. Anti-aging and antioxidant potential of Paullinia cupana var. sorbilis: findings in Caenorhabditis elegans indicate a new utilization for roasted seeds of guarana. Medicines 4, http://dx.doi.org/10.3390/medicines4030061.
http://dx.doi.org/10.3390/medicines40300...
) |
| 46. Antioxidant activity |
The standardized guarana powder had 8.80% of moisture, 1.51% ash, 2.10% caffeine and 16% of tannins. An ethanolic extract at 50% was prepared for the in vitro assay |
In vitro: Lipid peroxidation reaction |
To investigate the in vitro antioxidant activity of guarana powder by measuring spontaneous lipid peroxidation inhibition in rat brain homogenates |
Without guarana (water 0.1% tween 80) |
0.8 1.6, 3.3, and 6.6 mg ml-1 of final concentration mid-reaction |
Guarana exerted a clear antioxidant effect by inhibiting the process of spontaneous peroxidation, a fact that might be related to the high concentrations of tannins present in guarana and may suggest a possible adaptogen effect of the plant |
(Mattei et al., 1998Mattei, R., Dias, R.F., Espinola, E.B., Carlini, E.A., Barros, S.B.M., 1998. Guarana (Paullinia cupana): toxic behavioral effects in laboratory animals and antioxidant activity in vitro. J. Ethnopharmacol. 60, 111-116.) |
| 47. Antioxidant activity |
Ethanolic extract (dynamic solid-liquid extraction: 8 h at 8 atm, ambient temperature) |
In vitro: 3T3-L1 cells |
To evaluate the antioxidant activity of ethanolic guarana extract on 3T3-L1 cells after induced cellular damage by using ferric ammonium citrate |
Inducer: ferric ammonium citrate |
0.5, 1.0, and 2.0 mg ml-1
|
Lipid peroxidation reduction was 62.5%, using the guarana extract at 2 mg ml-1. This effect was dose-dependent |
(Basile et al., 2005Basile, A., Ferrara, L., Del Pezzo, M., Mele, G., Sorbo, S., Bassi, P., Montesano, D., 2005. Antibacterial and antioxidant activities of ethanol extract from Paullinia cupana Mart. J. Ethnopharmacol. 102, 32-36.) |
| 49. Antioxidant activity |
Aqueous extract (AqE); acetone-water EBPC (crude extract) and two subfractions: EPB and EPA |
In vitro: Phospho-molybdate complex (RAC) and DPPH |
To determine the antioxidant activity of different guarana extracts (AqE, EBPC, EPA, and EPB) by the RAC (relative antioxidant activity) and DPPH |
DPPH: DPPH + methanol (control). BHT + DPPH + methanol (blank); (CAR): ascorbic acid (standard) |
RAC: 0.3 ml of the sample for 3 ml of reagent
DPPH: 2.0 for 20.0 mg ml-1
|
The semipurified fraction (EPA) presented the highest content of polyphenols in total, reflecting the analysis for antioxidants, with a low IC50 and a higher RAC compared with the other extracts |
(Yamaguti-Sasaki et al., 2007Yamaguti-Sasaki, E., Ito, L.A., Canteli, V.C.D., Ushirobira, T.M.A., Ueda-Nakamura, T., Dias Filho, B.P., Nakamura, C.V., Mello, J.C.P., 2007. Antioxidant capacity and in vitro prevention of dental plaque formation by extracts and condensed tannins of Paullinia cupana. Molecules 12, 1950-1963.) |
| 50. Antioxidant activity |
The seeds were degreased with toluene:ethanol (2:1, v/v) in a Soxhlet extractor (48 h). The dried material was treated with methanol:water (4:1, v/v) under reflux. The residue was dried in an oven and used for extraction of polysaccharides. Sequence of extraction: DMSO, water, NaOH |
In vitro: DPPH |
To investigate the antioxidant activity of the methanolic extract and the peptic fraction of guarana seeds |
Butyl hydroxyanisol (BHA) and ascorbic acid as positive controls |
0.1, 0.5, 1.0, and 10.0 mg ml-1
|
The methanolic extract exhibited a strong ability to capture the DPPH radical (90.9% and 10 mg ml-1). In the same concentration, the polysaccharide showed an antioxidant activity of 68.4%. For a higher concentration, the methanolic extract and the polysaccharide exhibited effects of removal of similar hydroxyl radicals (70%) |
(Dalonso and Petkowicz, 2012Dalonso, N., Petkowicz, C.L.d.O., 2012. Guarana powder polysaccharides: characterisation and evaluation of the antioxidant activity of a pectic fraction. Food Chem. 134, 1804-1812.) |
| 51. Antioxidant activity |
Hydroalcoholic guarana extract (70:30) (300 mg ml-1). The lyophilized extract was diluted in distilled water and prepared at the concentration of 200 mg ml-1 Caffeine = 12.240 mg g-1, theobromine = 6.733 mg g-1 total catechins = 4.336 mg g-1, and condensed tannins = 22 mg g-1
|
In vitro: Samples of LDL, human serum and TRAP |
To investigate in vitro the potential effects of guarana on the oxidation of LDL, human serum and TRAP |
Control: without guarana |
0.05, 0.1, 0.5, 1, and 5 µg ml-1. TRAP: 0.01-10 µg ml-1
|
Guarana has shown a high antioxidant activity in vitro, especially at concentrations of 1 and 5 µg ml-1, shown by the suppression of conjugated dienes and TBARS production, tryptophan destruction and high TRAP activity |
(Portella et al., 2013Portella, R.L., Barcelos, R.P., Rosa, E.J.F., Ribeiros, E.E., Cruz, I.B.M., Suleiman, L., Soares, F.A.A., 2013. Guarana (Paullinia cupana Kunth) effects on LDL oxidation in elderly people: an in vitro and in vivo study. Lipids Health Dis. 12, 1-9.) |
| 52. Protective/antioxidant effect |
Hydroalcoholic guarana extract (70:30) (300 mg ml-1). The lyophilized extract was diluted in distilled water and prepared (200 mg ml-1). Caffeine (12.240 mg g-1), theobromine (6.733 mg g-1), total catechins (4.336 mg g-1) and condensed tannins (16 mg g-1) |
In vitro: culture of embryonic fibroblasts (NIH-3T3 cells) |
To investigate the protective potential of guarana on cytotoxicity caused by sodium nitroprusside (SNP), which releases cyanide and/or nitric oxide (NO) |
Negative control: cell culture without SNP and guarana. Positive control of toxicity: sample with 10 µM SNP |
0.5, 1, 5, 10, and 20 mg ml-1 (aqueous solution) |
Guarana has antioxidant effects on NO metabolism, mainly in situations where increases NO levels occur |
(Bittencourt et al., 2013Bittencourt, L.S., Machado, D.C., Machado, M.M., Dos Santos, G.F.F., Algarve, T.D., Marinowic, D.R., Ribeiro, E.E., Soares, F.A.A., Barbisan, F., Athayde, M.L., Cruz, I.B.M., 2013. The protective effects of guarana extract (Paullinia cupana) on fibroblast NIH-3T3 cells exposed to sodium nitroprusside. Food Chem. Toxicol. 53, 119-125.) |
| 53. Protective effect |
Guarana powder (Bittencourt et al., 2013Bittencourt, L.S., Machado, D.C., Machado, M.M., Dos Santos, G.F.F., Algarve, T.D., Marinowic, D.R., Ribeiro, E.E., Soares, F.A.A., Barbisan, F., Athayde, M.L., Cruz, I.B.M., 2013. The protective effects of guarana extract (Paullinia cupana) on fibroblast NIH-3T3 cells exposed to sodium nitroprusside. Food Chem. Toxicol. 53, 119-125.). Hydroalcoholic guarana extract (70:30). Caffeine = 12.240 mg g-1, theobromine = 6.733 mg g-1 total catechins = 4.336 mg g-1
|
In vitro: worm strains (Caenorhabditis elegans) |
To investigate whether guarana demonstrates protective effects against methylmercury-induced toxicity, as well as the mechanisms involved |
Control: without extract |
100, 500, and 1000 µg ml-1
|
The guarana extract GEE afforded a protective effect in skn-1 (ok2315) worms (exposed to methylmercury for 6 h), an effect likely modulated by upregulation of genes involved in metal transport, detoxification and antioxidant response |
(Arantes et al., 2016Arantes, L.P., Peres, T.V., Chen, P., Caito, S.W., Aschner, M., Soares, F.A.A., 2016. Guarana (Paullinia cupana Mart.) attenuates methylmercury-induced toxicity in Caenorhabditis elegans. Toxicol. Res. 5, 1629-1638.) |
| 54. Oxidative Stress |
Extra fine guarana powder. Phytochemical composition and nutrient composition of the powder, for example: total phenolic compounds 151.8 mg g-1; catechin 30.0 mg g-1; proanthocyanidin B1 3.72 mg g-1; caffeine 39.8 mg g-1, among others |
In vivo: overweight humans; Ex vivo: oxidation of LDL and total plasma antioxidant capacity |
To evaluate the effects of guarana on antioxidant markers and antioxidant activity of phase II enzymes in healthy overweight individuals with after individual and daily intakes |
Each participant acted as control after the 15th day of treatment interruption, for a further 15 days |
3 g of the powder diluted in 300 ml of water before intake, daily for 15 days before breakfast |
The treatment has reduced oxidative stress of clinically healthy overweight individuals, by means of the direct antioxidant action of absorbed catechins and growing regulation of antioxidant/detoxifying enzymes |
(Yonekura et al., 2016Yonekura, L., Martins, C.A., Sampaio, G.R., Monteiro, M.P., Cesar, L.A.M., Mioto, B.M., Mori, C.S., Mendes, T.M.N., Ribeiro, M.L., Arcari, D.P., Torres, E., 2016. Bioavailability of catechins from guarana (Paullinia cupana) and its effect on antioxidant enzymes and other oxidative stress markers in healthy human subjects. Food Funct. 7, 2970-2978.) |
| 55. Oxidative stress and metabolic disorders (effects on the oxidation of LDL) |
Hydroalcoholic guarana extract - alcohol and water (70:30) (300 mg ml-1). Caffeine = 12.240 mg g-1, theobromine = 6.733 mg g-1 total catechins = 4.336 mg g-1, and condensed tannins = 22 mg g-1. Extract obtained and lyophilized was diluted in distilled water (200 mg ml-1), infused by 7 min, and centrifuged |
In vivo: Human blood samples;
In vitro: samples of isolated LDL |
To investigate the potential effects of guarana in elderly people in the oxidation of serum |
Control: without guarana |
0.05, 0.1, 0.5, 1, and 5 µg ml-1; 2 groups: those who ingest guarana (at least 5 times per week) and those who had never ingested it |
Regular intake of guarana or its possible inclusion in the diet may produce certain health benefits and potential defense against oxidative stress and metabolic changes. A reduction of 27% in LDL oxidation |
(Portella et al., 2013Portella, R.L., Barcelos, R.P., Rosa, E.J.F., Ribeiros, E.E., Cruz, I.B.M., Suleiman, L., Soares, F.A.A., 2013. Guarana (Paullinia cupana Kunth) effects on LDL oxidation in elderly people: an in vitro and in vivo study. Lipids Health Dis. 12, 1-9.) |
| 56. Effects on metabolic comorbidities |
Usually guarana power is mixed with water and sugar |
In vivo: humans |
To evaluate the association of metabolic disorders, anthropometry, oxidative metabolism and the habitual intake of guarana in the elderly |
Those who have never ingested guarana |
Variable: according to consumption before treatment, at least twice a week or more often |
The group that consumed guarana showed a lower prevalence of arterial hypertension, obesity and metabolic syndrome than the control group. A protective effect potential of guarana is suggested against metabolic disorders in the elderly |
(Krewer et al., 2011Krewer, C.C., Ribeiro, E.E., Ribeiro, E.A.M., Moresco, R.N., da Rocha, M.I.U.M., Montagner, G.F.F.S., Machado, M.M., Viegas, K., Brito, E., da Cruz, I.B.M., 2011. Habitual intake of guarana and metabolic morbidities: an epidemiological study of an elderly Amazonian population. Phytother. Res. 25, 1367-1374.) |
| 57. Hypercholestero-lemic and anti-inflammatory effects |
Guarana powder (Caffeine = 3.754 mg g-1; theobromine = 2.065 mg g-1, total catechins = 1.330 mg g-1; and condensed tannins = 6.747 mg g-1). |
In vivo: adult male Wistar rats |
To evaluate the effects of guarana on the metabolism of adenine nucleotides in lymphocytes and biochemical parameters of rats with induced hypercholesterolemia |
Saline |
Guarana powder 12.5, 25, or 50 mg kg-1 per day.
Caffeine 0.2 mg kg-1.
Oral administration for 30 days |
There was an increase in the hydrolysis of adenosine triphosphate in the lymphocytes of rats with hypercholesterolemia and treated with 25 or 50 mg kg-1 per day, when compared with the other groups. The cholesterolemic group treated with guarana (50 mg kg-1) showed a decrease in the activity of ecto-adenosine deaminase, in comparison with the groups with normal diet. Guarana has been able to reduce total cholesterol and LDL to basal levels in rats with hypercholesterolemia. High concentrations of guarana associated with a hypercholesterolemic diet probably contributed to the reduction of the inflammatory process |
(Ruchel et al., 2016Ruchel, J.B., Rezer, J.F.P., Thorstenberg, M.L., dos Santos, C.B., Cabral, F.L., Lopes, S.T.A., da Silva, C.B., Machado, A.K., da Cruz, I.B.M., Schetinger, M.R.C., Goncalves, J.F., Leal, D.B.R., 2016. Hypercholesterolemia and ecto-enzymes of purinergic system: effects of Paullinia cupana. Phytother. Res. 30, 49-57.) |
| 58. Hyperlipidemia and cognitive disorders |
Guarana powder (Caffeine = 3.754 mg g-1; theobromine = 2.065 mg g-1, total catechins = 1.330 mg g-1; and condensed tannins = 6.747 mg g-1). |
In vivo: adult male Wistar rats |
To determine the possible preventive effect of guarana powder on memory impairment and acetylcholinesterase (AChE) activity in the brain structures of rats with Poloxamer-407-induced hyperlipidemia |
Saline |
12.5, 25, and 50 mg kg-1, administered by oral gavage once a day for a period of 30 days.
Caffeine 0.2 mg kg-1; Sinvastatin human equivalent dose; To induce hyperlipidemia: 500 mg/kg of Poloxamer-407 |
Guarana powder was able to reduce the levels of total cholesterol and LDL in a manner similar to simvastatin and partially reduced the liver damage caused by hyperlipidemia. It also was able to prevent changes in the activity of AChE and improve memory impairment due to hyperlipidemia. The authors suggests these results may be due to the presence of methyxanthines in guarana, and it may be a source of promising phytochemicals that can be used as adjuvant therapy in the management of hyperlipidemia and cognitive disorders |
(Ruchel et al., 2017Ruchel, J.B., Braun, J.B.S., Adefegha, S.A., Manzoni, A.G., Abdalla, F.H., de Oliveira, J.S., Trelles, K., Signor, C., Lopes, S.T.A., da Silva, C.B., Castilhos, L.G., Rubin, M.A., Leal, D.B.R., 2017. Guarana (Paullinia cupana) ameliorates memory impairment and modulates acetylcholinesterase activity in Poloxamer-407-induced hyperlipidemia in rat brain. Physiol. Behav. 168, 11-19.) |
| 59. Cytoprotective/spermatogenic effect |
Guarana extract diluted in water at the time of administration |
In vivo: male Wistar rats |
To evaluate the potential effect of guarana in the prevention or attenuating of cadmium-induced damage in rats testis |
Water |
2 mg g-1, BW diluted on water, once a day for 56 days |
The guarana was effective in attenuating morphological changes in Leydig cells, as well reducing the inflammatory response. The animals treated only with guarana showed a significant increase in testosterone levels in plasma and in the proportions of volumetric seminiferous tubules, which are indicative of spermatogenic process stimulation |
(Leite et al., 2011Leite, R.P., Wada, R.S., Monteiro, J.C., Predes, F.S., Dolder, H., 2011. Protective effect of guarana (Paullinia cupana var. sorbilis) pre-treatment on cadmium-induced damages in adult Wistar testis. Biol. Trace Elem. Res. 141, 262-274.) |
| 60. Cytoprotective effect |
Commercial dry guarana seed powder (125 mg) has been diluted in DMSO (1 ml) for 24 h, centrifuged; supernatant was filtered |
In vitro: SH-SY5Y Cells |
To evaluate whether guarana could protect the dopaminergic human cell line SH-SY5Y against rotenone-induced cytotoxicity |
DMSO |
9.7-625.0 g ml-1 diluted in DMSO |
The guarana has significantly increased cell viability of SH-SY5Y cells treated with rotenone, in a dose-dependent manner |
(de Oliveira et al., 2011de Oliveira, D.M., Barreto, G., Galeano, P., Romero, J.I., Holubiec, M.I., Badorrey, M.S., Capani, F., Alvarez, L.D.G., 2011. Paullinia cupana Mart. var. sorbilis protects human dopaminergic neuroblastoma SH-SY5Y cell line against rotenone-induced cytotoxicity. Hum. Exp. Toxicol. 30, 1382-1391.) |
| 61. Cytoprotective effect |
Guarana extract diluted in water at the time of administration |
In vivo: male Wistar rats |
To evaluate if guarana is capable of reducing cadmium-induced morphological damage in rats testis |
Water |
2 mg g-1 BW, diluted on water, once a day for 56 days |
After exposure to cadmium, the animals supplemented with guarana showed a significant decrease in the proportion of damaged seminiferous tubules. Also, guarana supplementation has been effective in keeping the number of Leydig cells per testis in animals exposed to cadmium |
(Leite et al., 2013Leite, R.P., Predes, F.S., Monteiro, J.C., Freitas, K.M., Wada, R.S., Dolder, H., 2013. Advantage of guarana (Paullinia cupana Mart.) supplementation on cadmium-induced damages in testis of adult wistar rats. Toxicol. Pathol. 41, 73-79.) |
| 62. Anticholinesterase activity |
Ethanolic extract (exhaustive extraction) 1.5 mg ml-1
|
In vitro: liophilized anticholinesterase enzyme |
To evaluate extracts of various plants, including guarana, which could inhibit the activity of the enzyme acetylcholinesterase. The inhibitors of this enzyme showed greater efficiency in the clinical treatment in Alzheimer's Disease |
In microplates: blank (10% methanol in 50 mMTris buffer, HCl pH 8) |
1.5 mg ml-1
|
Guarana proved to be quite promising for the isolation and characterization of compounds that inhibit acetylcholinesterase, because its extract inhibited the enzyme by 65% |
(Trevisan and Macedo, 2003Trevisan, M.T.S., Macedo, F.V.V., 2003. Screening for acetylcholinesterase inhibitors from plants to treat Alzheimer's disease. Quim. Nova 26, 301-304.) |
| 63. Neuroprotective (prevents cell cytotoxicity) |
Guarana powder. Caffeine (34.19 mg g-1), theobromine (0.14 mg g-1), catechins (3.76 mg g-1) and epicatechin (4.05 mg g-1). A stock solution of guarana (10 mg ml-1) is prepared for subsequent dilution |
In vitro: neuronal cells (SH-SY5Y) |
To evaluate the potential effect of the guarana extract against aggregation β-amyloid 1-42, glycation of proteins, as well as cytotoxicity induced by methylglyoxal (MGO), glyoxal (GO), and acrolein (ACR) in SH-SY5Y cells |
Negative control: cells without treatment |
Guarana powder 10, 100, and 1000 µg ml-1 dissolved in a culture medium. Caffeine 40 µg ml-1 dissolved in a DMEM-F12 medium |
The guarana is capable of inhibiting albumin glycation mediated by glucose/fructose, MGO, and GO |
(Bittencourt et al., 2014Bittencourt, L.S., Zeidán-Chuliá, F., Yatsu, F.K.J., Schnorr, C.E., Moresco, K.S., Kolling, E.A., Gelain, D.P., Bassani, V.L., Moreira, J.C.F., 2014. Guarana (Paullinia cupana Mart.) prevents β-amyloid aggregation, generation of advanced glycation-end products (AGEs), and acrolein-induced cytotoxicity on human neuronal-like cells. Phytother. Res. 28, 1615-1624.) |
| 64. Protective effect against DNA damage |
Guarana powder diluted in water at the time of use:(total tannins: 13.0%, condensed tannins: 5.72%) |
In vivo: mice |
To investigate the cytotoxic/anti-genotoxic properties of guarana in rat hepatocytes injected with N-nitrosodiethylamine (NDE) |
Water |
Guarana powder 2.0 mg g-1 BW, for 16 days |
The treatment with guarana showed a reduction by 52.54% in comet image length of animals exposed to NDE. Guarana has a potential protective effect against NDE-induced DNA damage in rat liver |
(Fukumasu et al., 2006aFukumasu, H., Avanzo, J.L., Heidor, R., Silva, T.C., Atroch, A., Moreno, F.S., Dagli, M.L.Z., 2006. Protective effects of guarana (Paullinia cupana Mart. var. sorbilis) against DEN-induced DNA damage on mouse liver. Food Chem. Toxicol. 44, 862-867.) |
| 65. Neuroprotective effect |
Guarana powder seeds. The administered solution was prepared on the day of use by dilution in water of guarana powder (12.240 mg g-1 caffeine, 6.733 mg g-1 theobromine, 4.336 mg g-1 total catechins, and 16 mg g-1 condensed tannins |
In vivo: male Wistar rats |
To evaluate the neuroprotective effects of guarana seed powder on DNA damage induced by CCl4 (carbon tetrachloride) in rats |
Normal control: water. CCl4 control: (1 ml kg-1, 50% in olive oil) to induce DNA damage. |
100, 300, and 600 mg kg-1, daily for a period of 14 days |
Guarana prevents CCl4-induced breakage of DNA strands in lesions in rats |
(Kober et al., 2016Kober, H., Tatsch, E., Torbitz, V.D., Cargnin, L.P., Sangoi, M.B., Bochi, G.V., da Silva, A.R.H., Barbisan, F., Ribeiro, E.E., da Cruz, I.B.M., Moresco, R.N., 2016. Genoprotective and hepatoprotective effects of guarana (Paullinia cupana Mart. var. sorbilis) on CCl4-induced liver damage in rats. Drug. Chem. Toxicol. 39, 48-52.) |
| 66. Chemopreventive effect |
Guarana powder (Fukumasu et al., 2006aFukumasu, H., Avanzo, J.L., Heidor, R., Silva, T.C., Atroch, A., Moreno, F.S., Dagli, M.L.Z., 2006. Protective effects of guarana (Paullinia cupana Mart. var. sorbilis) against DEN-induced DNA damage on mouse liver. Food Chem. Toxicol. 44, 862-867.) was mixed with commercial food powder with the same granulation |
In vivo: BALB/c female mice |
To check the effects of guarana on hepatocarcinogenesis in mice |
Control group: only commercial food |
0.1, 1.0, or 2.0 mg g-1 BW for 25 weeks |
The incidence and multiplicity of macroscopic lesions were reduced by the treatment with guarana. According to these results, guarana showed inhibitory effects on DEN-induced hepatocarcinogenesis in mice. P. cupana can act as a chemopreventive on carcinogenesis, reducing cellular expansion of preneoplastic cells. |
(Fukumasu et al., 2006bFukumasu, H., Silva, T.C.d., Avanzo, J.L., Lima, C.E.d., Mackwiak, I.I., Atroch, A., Spinosa, H.d.S., Moreno, F.S., Dagli, M.L.Z., 2006. Chemopreventive effects of Paullinia cupana Mart. var. sorbilis, the guarana, on mouse hepatocarcinogenesis. Cancer Lett. 233, 158-164.) |
| 67. Antineoplastic activity |
Crude extract (CE) of guarana was prepared using acetone:water (7:3, v/v). The CE was partitioned with ethyl acetate, and removed the organic solvent to yield the EAF |
In vitro: six human tumor cell lines |
To evaluate antineoplastic, activity of guarana seeds crude extract (CE) and ethyl-acetate fraction (EAF) |
Control groups were treated with the same amount of dimethyl sulfoxide (0.1%) |
CE and EAF: 10-200 µg ml-1
|
CE and EAF fractions presented IC50 values of 70.25 µg ml-1 and 61.18 µg ml-1 in HL-60 leukemia cell line, respectively |
(Carvalho et al., 2016Carvalho, L.V.N., Cordeiro, M.F., Lins, T.U.L., Sampaio, M.C.P.D., Mello, G.S.V., Costa, V.C.M., Marques, L.L.M., Klein, T., Mello, J.C.P., Cavalcanti, I.M.F., Pitta, I.R., Pitta, M.G.R., Rêgo, M.J.B.M., 2016. Evaluation of antibacterial, antineoplastic, and immunomodulatory activity of Paullinia cupana seeds crude extract and ethyl-acetate fraction. Evid. Based Complement. Altern. Med., http://dx.doi.org/10.1155/2016/1203274.
http://dx.doi.org/10.1155/2016/1203274...
) |
| 68. Anticancer effect |
Guarana powder diluted in water |
In vivo: female C57Bl/6 mice |
To evaluate the effect of growth inhibition of daily administration of guarana in the experimental model of metastasis of B16F10 melanoma cells |
Control: water |
2.0 mg g-1 BW diluted in water, daily until 21 days |
The treatment of guarana has decreased proliferation and increased apoptosis of tumor cells, thereby reducing the area of the tumor (68.6%) |
(Fukumasu et al., 2008Fukumasu, H., Avanzo, J.L., Nagamine, M.K., Barbuto, J.A., Rao, K.V., Dagli, M.L.Z., 2008. Paullinia cupana Mart var. sorbilis, guarana, reduces cell proliferation and increases apoptosis of B16/F10 melanoma lung metastases in mice Braz. J. Med. Biol. Res. 41, 305-310.) |
| 69. Anticancer effect |
Hydroethanolic extract of guarana (70:30) at 300 mg ml-1 (Bittencourt et al., 2013Bittencourt, L.S., Machado, D.C., Machado, M.M., Dos Santos, G.F.F., Algarve, T.D., Marinowic, D.R., Ribeiro, E.E., Soares, F.A.A., Barbisan, F., Athayde, M.L., Cruz, I.B.M., 2013. The protective effects of guarana extract (Paullinia cupana) on fibroblast NIH-3T3 cells exposed to sodium nitroprusside. Food Chem. Toxicol. 53, 119-125.): Caffeine (12.240 mg g-1), theobromine (6.733 mg g-1), total catechins (4.336 mg g-1) and condensed tannins (16 mg g-1). The in vitro tests were performed using lyophilized extract diluted directly in culture medium |
In vitro: human cancer colorectal HT-29 cell line |
To investigate effect of guarana and its metabolites (caffeine, theobromine and catechin) on HT-29 cytotoxicity and cell proliferation on colorectal cancer (CRC) and on oxaliplatin sensitivity. Also to evaluate the potential apoptosis induction by guarana with and without concomitant oxaliplatin exposure, considering late and early apoptotic HT-29 cells as well as by the differential modulation of genes related to apoptosis pathway. All protocols evaluated the cytotoxicity (24 h exposition) and anti-proliferative effect (72 h exposition) by MTT assay |
Cells untreated |
Concentrations of guarana extract (0, 5, 10, 30, 100, 300, and 1000 µg ml-1)with or without the LD50 oxaliplatin |
Cells exposed to guarana at a concentration of 100 µg ml-1 presented a similar cytotoxic effect as HT-29 cells treated with oxaliplatin and did not affect the sensitivity of the drug. Guarana was able to induce apoptosis and up-regulate the p53 and Bax/Bcl-2 genes. The result suggests that beverage foods rich in caffeine, other than coffee and teas, have an antitumor effect against CRC cancer. However, the chemical association caffeine-catechin is probably more plausible to explain the antitumor effect of these foods, such as guarana investigated here, rather than only caffeine |
(Cadona et al., 2016Cadona, F.C., Machado, A.K., Azzolin, V.F., Barbisan, F., Dornelles, E.B., Glanzner, W., Goncalves, P.B.D., Assmann, C.E., Ribeiro, E.E., da Cruz, I.B.M., 2016. Guarana caffeine-rich food increases oxaliplatin sensitivity of colorectal HT-29 cells by apoptosis pathway modulation. Anti-Cancer Agents Med. Chem. 16, 1055-1065.) |
| 70. Anticancer effect |
Guarana powder (Fukumasu et al., 2006aFukumasu, H., Avanzo, J.L., Heidor, R., Silva, T.C., Atroch, A., Moreno, F.S., Dagli, M.L.Z., 2006. Protective effects of guarana (Paullinia cupana Mart. var. sorbilis) against DEN-induced DNA damage on mouse liver. Food Chem. Toxicol. 44, 862-867.) diluted in ethanol |
In vivo: female BALB/c mice |
To report the antiproliferative effect of treatment with guarana in Ehrlich Ascitic Carcinoma (EAC) in mice |
Control: water |
100, 1000, and 2000 mg kg-1 BW for 28 days |
The treatment with guarana for 21 days increased survival of mice. The guarana acts directly on cells and the pre-treatment performed by the model proposed in this study is not necessary |
(Fukumasu et al., 2011Fukumasu, H., Latorre, A.O., Zaidan-Dagli, M.L., 2011. Paullinia cupana Mart. var. sorbilis, guarana, increases survival of Ehrlich ascites carcinoma (EAC) bearing mice by decreasing cyclin-D1 expression and inducing a G0/G1cell cycle arrest in EAC cells. Phytother. Res. 25, 11-16.) |
| 71. Antiproliferative effect |
Hydroethanolic extract of guarana (70:30). (Bittencourt et al., 2013Bittencourt, L.S., Machado, D.C., Machado, M.M., Dos Santos, G.F.F., Algarve, T.D., Marinowic, D.R., Ribeiro, E.E., Soares, F.A.A., Barbisan, F., Athayde, M.L., Cruz, I.B.M., 2013. The protective effects of guarana extract (Paullinia cupana) on fibroblast NIH-3T3 cells exposed to sodium nitroprusside. Food Chem. Toxicol. 53, 119-125.): Caffeine (12.240 mg g-1), theobromine (6.733 mg g-1), total catechins (4.336 mg g-1) and condensed tannins (16 mg g-1). The lyophilized extract was diluted in water (200 mg ml-1), boiled for 7 min, centrifuged, and filtered for later dilution in water |
In vitro: breast cancer cells MCF-7 |
To evaluate the effects of guarana in the response of breast cancer cells to 7 chemotherapy agents currently used in the treatment of breast cancer |
Untreated cells |
Guarana extract 1, 5, and 10 µg ml-1 diluted in distilled water and added to cell culture medium |
The main results showed an antiproliferative effect of guarana at concentrations of 5 and 10 µg ml-1, and a significant effect on chemotherapeutic drug action. Guarana improved the antiproliferative effect of chemotherapeutic agents, causing a decrease of >40% in cell growth after 72 h of exposure. The results suggest an interaction of guarana with chemotherapeutic drugs |
(Hertz et al., 2015Hertz, E., Cadoná, F.C., Machado, A.K., Azzolin, V., Holmrich, S., Assmann, C., Ledur, P., Ribeiro, E.E., Filho, O.C.d.S., Mânica-Cattani, M.F., Cruz, I.B.M.d., 2015. Effect of Paullinia cupana on MCF-7 breast cancer cell response to chemotherapeutic drugs. Mol. Clin. Oncol. 3, 37-43.) |
| 72. Proliferative effect (decrease in the process of senescence) |
Guarana powder (Bittencourt et al., 2013Bittencourt, L.S., Machado, D.C., Machado, M.M., Dos Santos, G.F.F., Algarve, T.D., Marinowic, D.R., Ribeiro, E.E., Soares, F.A.A., Barbisan, F., Athayde, M.L., Cruz, I.B.M., 2013. The protective effects of guarana extract (Paullinia cupana) on fibroblast NIH-3T3 cells exposed to sodium nitroprusside. Food Chem. Toxicol. 53, 119-125.). Hydroethanolic guarana extract (70:30) at 300 mg ml-1
|
In vitro: senescent adipocyte-mesenchymal cells (ASCs) |
To investigate whether supplementation with guarana in culture medium with SMA cells can help decrease the process of senescence, as well as reduce the potential damage caused by oxidative stress |
Untreated senescent cells |
Guarana extract 1, 5, 10, and 20 mg ml-1
|
In senescent cells exposed to guarana at 5 mg g-1 concentration increased cellular proliferation occurred compared to untreated senescent cells. The results suggest that supplementation of guarana could reverse the processes of early senescence in ASCs. These results have potential for application in regenerative medicine |
(Machado et al., 2015Machado, A.K., Canodá, F.C., Azzolin, V.F., Dornelles, E.B., Barbisan, F., Ribeiro, E.E., Mânica-Cattani, M.F., Duarte, M.M.M.F., Saldanha, J.R.P., Cruz, I.B.M., 2015. Guarana (Paullinia cupana) improves the proliferation and oxidative metabolim of senescent adipocyte stem cells derived from human lipoaspirates. Food Res. Int. 67, 426-433.) |
| 73. Herb-drug interaction |
Guarana extract containing 12% caffeine obtained commercially. There are no reports on extract preparation |
In vitro: male Wistar rats |
To investigate if a commercial standardized (certified) extract of guarana seeds may influence the pharmacokinetics of amiodarone in rats following their simultaneous oral co-administration and after a 14-day guarana pre-treatment period |
Control: Vehicle 0.5% aqueous solution of carboxymethyl cellulose |
A. Single dose of Guarana (821 mg kg-1) and amiodarone (50 mg kg-1) diluted on vehicle;
B. 14 days with Guarana (821 mg kg-1 per day) and amiodarone (50 mg kg-1) only on 15th day diluted on vehicle |
The decrease in plasma concentrations of amiodarone was also accomplished by a significant reduction in the tissue concentrations of amiodarone and MDEA (a metabolite of amiodarone), particularly in the heart. It is suggested that the guarana extract should not be ingested with amiodarone |
(Rodrigues et al., 2012Rodrigues, M., Alves, G., Lourenco, N., Falcao, A., 2012. Herb-drug interaction of Paullinia cupana (guarana) seed extract on the pharmacokinetics of amiodarone in rats. Evid. Based Complement. Alternat. Med., http://dx.doi.org/10.1155/2012/428560.
http://dx.doi.org/10.1155/2012/428560...
) |
| 74. Against oral diseases |
Extraction of guarana, acetone/water (70:30, v/v), obtaining the EBPC (patent). EBPC was partitioned with ethyl acetate, which resulted in aqueous and ethyl acetate fractions |
In vitro: buccal epithelial cells |
To evaluate the effect of guarana on cell surface hydrophobicity (CSH), biofilm formation and adhesion of C. albicans to polystirene, composite resins, and buccal epithelial cells (BEC) |
Positive control: chlorhexidine gluconate 2%; negative control: phosphate buffered saline |
Aqueous fraction from guarana extract 10 mg ml-1
|
The guarana extract showed no antifungal activity, nor reduced adhesion of C. albicans to the surface of nanoparticle composites. However, it reduced adhesion of C. albicans to BEC and to polystyrene. These results indicate that this extract has potential for use in the prevention of oral diseases |
(Matsuura et al., 2015Matsuura, E., Godoy, J.S.R., Bonfim-Mendonça, P.S., Mello, J.C.P., Svidzinski, T.I.E., Gasparetto, A., Maciel, S.M., 2015. In vitro effect of Paullinia cupana (guarana) on hydrophobicity, biofilm formation, and adhesion of Candida albicans to polystyrene, composites, and buccal epithelial cells. Arch. Oral Biol. 60, 471-478.) |
| 75. Control of dental plaque bacteria |
Aqueous guarana extract produced by turbolization. Total tannins: 5.78% |
In vivo: humans |
To test guarana extracts in different concentrations and in the form of mouth wash in the activity against dental plaque bacteria |
Positive control: chlorhexidine-gluconate 0.12% |
Mouthwashes with 10 ml of guarana extract at 5 and 7% for 1 min for 4 times per day |
The guarana extracts in the concentrations in use were efficient in comparison to the positive control |
(Barbosa and Mello, 2004Barbosa, G.D.A., Mello, J.C.P., 2004. Clinical evaluation of the guarana extract on the dental plaque control. Rev. Paul. Odontol. 26, 28-30.) |
| 76. Prevention of dental plaque bacteria |
AqE, EBPC, EPA, and EPB |
In vitro: Adhesion test and MIC |
To analyze, on a preliminary basis, the antibacterial potential of different guarana extracts of (AqE, EBPC, EPA and EPB) against Streptococcus mutans
|
Negative control: without treatment; positive control: chlorhexidine-gluconate 1.2 µg ml-1
|
Extracts with a final tannins concentration of 750 µg ml-1: AqE 4.64 mg ml-1; EBPC 2.41 mg ml-1; EPA 2.50 mg ml-1; and EPB 4.39 mg ml-1
|
EBPC gave the best result; even with a lower concentration, it showed the best action on the adherence of S. mutans, with 79.69% inhibition. It is suggested that this extract can be used for the prevention of dental plaque bacteria |
(Yamaguti-Sasaki et al., 2007Yamaguti-Sasaki, E., Ito, L.A., Canteli, V.C.D., Ushirobira, T.M.A., Ueda-Nakamura, T., Dias Filho, B.P., Nakamura, C.V., Mello, J.C.P., 2007. Antioxidant capacity and in vitro prevention of dental plaque formation by extracts and condensed tannins of Paullinia cupana. Molecules 12, 1950-1963.) |
| 77. Antimicrobial activity |
Ethanolic extract (dynamic solid-liquid extraction: 8 h at 8 atm, ambient temperature), evaporation of the solvent to a dry material |
In vitro: MIC |
To evaluate the antibacterial activity of the guarana extract against Gram-positive and Gram-negative bacteria |
Control cultures containing only buffer. Positive control: standard antibiotics |
Guarana extracts 16-128 µg ml-1
|
Pseudomonas aeruginosa (27853) (MIC = 16 µg ml-1), Proteus mirabilis (7002) (MIC = 32 µg ml-1), Proteus vulgaris (12454) (MIC = 32 µg ml-1), and Escherichia coli (11229) (MIC = 32 µg ml-1) were the most inhibited |
(Basile et al., 2005Basile, A., Ferrara, L., Del Pezzo, M., Mele, G., Sorbo, S., Bassi, P., Montesano, D., 2005. Antibacterial and antioxidant activities of ethanol extract from Paullinia cupana Mart. J. Ethnopharmacol. 102, 32-36.) |
| 78. Antimicrobial activity |
EBPC, FAQ, EPA, and subfractions of EPA, and isolated compounds |
In vitro: MIC |
To evaluate the antibacterial activity of extracts and isolated compounds of guarana against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa
|
Positive control: standard antibiotics |
All tested substances at 2 mg ml-1
|
Even in concentrations above 1000 µg ml-1, the guarana extract showed no activity against these organisms: Staphylococcus aureus (25923), Bacillus subtilis (6623), Escherichia coli (25922) and Pseudomonas aeruginosa (15442) |
(Antonelli-Ushirobira et al., 2007Antonelli-Ushirobira, T.M., Yamaguti, E., Uemura, L.M., Nakamura, C.V., Dias Filho, B.P., Mello, J.C.P., 2007. Chemical and microbiological study of extract from seeds of guarana (Paullinia cupana var. sorbilis). Lat. Am. J. Pharm. 26, 5-9.) |
| 79. Antimicrobial activity |
The different extracts were prepared with these solvents: distilled water, methanol, 35% acetone and 60% ethanol at room (TR) and at boiling (TB) temperature of solvent. The main substances of the extract were quantified |
In vitro: antimicro-bial activity |
Investigate the antimicrobial activity of extracts of guarana against three food-borne fungi: Aspergillus niger, Trichoderma viride and Penicilliumcyclopium, and three health-damaging bacteria: Escherichia coli, Pseudomonas fluorescens and Bacillus cereus by the agar well diffusion and broth dilution assay |
Control: ethanol at 96% |
0.2 g ml-1 at 96% ethanol |
The guarana extracts have significant activity against the growth of deteriorating bacteria that cause food poisoning, such as E. coli, B. cereus, P. fluorescens and deteriorating fungi, such as A. niger, T. viride and P. cyclopium. Ethanolic extracts showed greater antimicrobial activity than aqueous extracts |
(Majhenic et al., 2007Majhenic, L., Skerget, M., Knez, Z., 2007. Antioxidant and antimicrobial activity of guarana seed extracts. Food Chem. 104, 1258-1268.) |
| 80. Antimicrobial activity |
Crude extract (CE) of guarana was prepared using acetone:water (7:3, v/v). The CE was partitioned with ethyl acetate and removed the organic solvent to yield the EAF |
In vitro: MIC and MBC |
To evaluate antibacterial activity of guarana seeds crude extract (CE) and ethyl-acetate fraction (EAF) |
Without extract |
CE and EAF: 0.5-250 µg ml-1
|
CE and EAF fractions showed a bacteriostatic activity (MIC = 250 µg ml-1). However they do not show bactericidal activity (MBC > 250) |
(Carvalho et al., 2016Carvalho, L.V.N., Cordeiro, M.F., Lins, T.U.L., Sampaio, M.C.P.D., Mello, G.S.V., Costa, V.C.M., Marques, L.L.M., Klein, T., Mello, J.C.P., Cavalcanti, I.M.F., Pitta, I.R., Pitta, M.G.R., Rêgo, M.J.B.M., 2016. Evaluation of antibacterial, antineoplastic, and immunomodulatory activity of Paullinia cupana seeds crude extract and ethyl-acetate fraction. Evid. Based Complement. Altern. Med., http://dx.doi.org/10.1155/2016/1203274.
http://dx.doi.org/10.1155/2016/1203274...
) |
