Prolonged or unusual exercise may cause exercise-induced muscle damage (EIMD). To test whether Zynamite^®, a mango leaf extract rich in the natural polyphenol mangiferin, administered in combination with quercetin facilitates recovery after EIMD, 24 women and 33 men were randomly assigned to two treatment groups matched by sex and 5 km running performance, and ran a 10 km race followed by 100 drop jumps to elicit EIMD. One hour before the competition, and every 8 h thereafter for 24 h, they ingested placebo (728 mg of maltodextrin) or 140 mg of Zynamite^® combined with 140 mg of quercetin (double-blind). Although competition times were similar, polyphenol supplementation attenuated the muscle pain felt after the competition (6.8 ± 1.5 and 5.7 ± 2.2 a.u., p = 0.035) and the loss of jumping performance (9.4 ± 11.5 and 3.9 ± 5.2%, p = 0.036; p = 0.034) and mechanical impulse (p = 0.038) 24 h later. The polyphenols attenuated the increase of serum myoglobin and alanine aminotransferase in men, but not in women (interaction p < 0.05). In conclusion, a single dose of 140 mg Zynamite^® combined with 140 mg of quercetin, administered one hour before competition, followed by three additional doses every eight hours, attenuates muscle pain and damage, and accelerates the recovery of muscle performance.

Leaves of Mangifera indica L. have folk-uses in tropical regions of the world as health teas, as a remedy for exhaustion and fatigue, as a vegetable, and as a medicine. Mangifera indica leaf extract (MLE) had previously been demonstrated to alter brain electrical activity in-vivo. The aim of the present series of studies was to investigate whether mangiferin, a major compound in leaves and in MLE, is responsible for the neurocognitive activity of MLE, and if the CNS activities of MLE have translational potential. MLE, tradename Zynamite, is produced by Nektium Pharma, Spain. Isolated mangiferin was tested in-vitro in radioligand binding and enzyme inhibition studies against 106 CNS targets. Changes in the electroencephalograms (EEG's) of MLE and mangiferin were recorded in-vivo from four brain regions. Two double blind randomized placebo-controlled crossover clinical trials were conducted, each with 16 subjects. At 90 min and at 60 min respectively, after oral intake of 500 mg MLE, EEG recordings, psychometric tests, mood state, and tolerability were studied. Isolated mangiferin is a selective inhibitor of catechol-O-methyltransferase (COMT) with an IC50 of 1.1 μM, with no activity on the CNS targets of caffeine. Both mangiferin and MLE induce similar changes in long-term potentiation (LTP) in the hippocampus in-vitro, and induce a similar pattern of EEG changes in-vivo. In both translational clinical trials MLE was well tolerated, with no cardiovascular side-effects. In both studies MLE caused significant spectral changes in brain electrical activity in cortical regions during cognitive challenges, different to the attenuated spectral changes induced by caffeine. There were no significant changes in the psychometric tests other than reaction time for all groups. In the second study there was a trend to faster reaction time within group for MLE (p = 0.066) and the percentage improvement in reaction time for MLE compared to placebo was significant (p = 0.049). In the first study MLE improved all scores for Profile of Mood States (POMS), with the score for "fatigue" significantly improved (p = 0.015); in the second study the POMS score for "dejection" was improved in the caffeine group, p = 0.05. Mangiferin is a COMT inhibitor of moderate potency and is the major CNS-active compound in MLE. Both mangiferin and MLE increase hippocampal LTP in-vitro, and induce a similar pattern of changes in brain electrical activity in-vivo. While the translational clinical trials of MLE are limited by being single dose studies in a small number of subjects, they provide the first clinical evidence that the extract is well tolerated with no cardiovascular side-effects, can induce changes in brain electrical activity, may give a faster reaction time, and decrease fatigue. These CNS activities support the reported folk-uses use of mango leaf tea as a substitute for tea and as a traditional remedy for fatigue and exhaustion. Extract Mangifera indica L., Zynamite, has nootropic potential, and larger clinical studies are needed to realise this potential.

Background: This study was designed to evaluate the beneficial effects of a botanical extract combination containing soy isoflavone extract (100mg), Aframomum melegueta seed dry extract (50 mg), and Punica granatum skin dry extract (100mg) on health-related Quality of Life in healthy Spanish menopausal women with hot flashes, anxiety, and depressive symptoms using the validated Cervantes Scale. Methods and results: Fifty-seven outpatient women (45–65 years) with menstrual problems associated with climacteric syndrome were enrolled from April 2018 to April 2019 in the context of a prospective, placebo-controlled, double-blind study. Women were randomized to receive treatment with either the botanical combination (250 mg daily divided into two doses) or placebo for eight weeks. At the beginning and end of the study, health-related Quality of Life was assessed using the Cervantes Scale. Subjects treated with the botanical extract, compared to subjects in the placebo group, showed a significant improvement in the Global health-related Quality of Life score (38% [11.3–50.0]% vs. 18.8% [0–37.7]%; P = 0.04) on the Cervantes Scale and, specifically, in the menopause and health domain (13.6% [0–45.4]% vs. 40.7% [20.6–61.0]%; P = 0.05). By contrast, there were no significant changes in the psychic, sexuality, and couple relationship related domains of the Cervantes Scale. Patients who concluded the study did not report substantial side effects. Conclusion: Short-term intake of the botanical combination improved the Global Quality of Life of climateric women, according to the Cervantes Scale. Since this is a pilot trial, results should be analysed with caution. Trial registration: NCT04381026; ClinicalTrial.gov (retrospectively registered).

Zynamite PX^®, a mango leaf extract combined with quercetin, enhances exercise performance by unknown molecular mechanisms. Twenty-five volunteers were assigned to a control (17 males) or supplementation group (8 males, receiving 140 mg of Zynamite^® + 140 mg quercetin/8 h for 2 days). Then, they performed incremental exercise to exhaustion (IE) followed by occlusion of the circulation in one leg for 60 s. Afterwards, the cuff was released, and a 30 s sprint was performed, followed by 90 s circulatory occlusion (same leg). Vastus lateralis muscle biopsies were obtained at baseline, 20 s after IE (occluded leg) and 10 s after Wingate (occluded leg), and bilaterally at 90 s and 30 min post exercise. Compared to the controls, the Zynamite PX^® group showed increased basal protein expression of Thr²⁸⁷-CaMKIIδ_D (2-fold, p = 0.007) and Ser⁹-GSK3β (1.3-fold, p = 0.005) and a non-significant increase of total NRF2 (1.7-fold, p = 0.099) and Ser⁴⁰-NRF2 (1.2-fold, p = 0.061). In the controls, there was upregulation with exercise and recovery of total NRF2, catalase, glutathione reductase, and Thr²⁸⁷-CaMKIIδ_D (1.2–2.9-fold, all p < 0.05), which was not observed in the Zynamite PX^® group. In conclusion, Zynamite PX^® elicits muscle signaling changes in resting skeletal muscle resembling those described for exercise training and partly abrogates the stress kinases responses to exercise as observed in trained muscles.

Mangiferin, a glucosyl xanthone, is a plant metabolite with promising nootropic and ergogenic properties. However, its poor and inconsistent systemic bioavailability limits its therapeutic potential. Additionally, the pharmacokinetics of mangiferin from mango leaf extract formulations remain uncharacterized in humans. This study validated a UHPLC-MS/MS method and conducted a human pharmacokinetic study approved by an ethics committee. The bioavailability of mangiferin and its monosodium salt was assessed from two standardized mango leaf extracts: MLE60, standardized to 60% mangiferin but practically insoluble in water, and MLES, the water-soluble monosodium salt form, also standardized to 60%. Twelve participants (six females) received oral doses of each extract in a crossover design with a 7-day washout period. Plasma analysis showed significantly higher AUC and C_max values with MLES than MLE60, while T_max and T_1/2 were similar. MLES demonstrated a 2.44-fold increase in AUC_0–24h compared to MLE60 (p = 0.0029 **), indicating improved bioavailability. This study highlights the salification method as a simple strategy to enhance mangiferin bioavailability, enabling broader applications in beverages and other products where solubility is a limitation.

Background/Objectives: A mango (Mangifera indica) leaf extract (Zynamite^®), rich in the polyphenol mangiferin, has been demonstrated to modulate brain activity, boost cognitive function, and reduce mental fatigue. Research evidence supports that improving the solubility of this extract could significantly enhance its efficacy as an active ingredient. This study examined the effects of a soluble version of Zynamite^®, Zynamite^® S (Zyn-S), on cognitive function and mood in young adults at low doses. Methods: A total of 119 university students were enrolled in the study. Participants were randomly assigned to receive either 100 mg, 150 mg, or placebo in a double-blind crossover design. Short- and long-term memory were evaluated using the Rey Auditory Verbal Learning Test (RAVLT), executive functions with the Trail Making Test (TMT), processing speed with the Digit Symbol Substitution Test (DSST), and selective attention with the Stroop Color and Word Test. Additionally, mood was assessed using the Spanish short version of the Profile of Mood States (POMS). All these assessments were conducted before taking the product and at 30 min, 3 h, and 5 h post-intake. Results: The results demonstrated that participants who received Zynamite^® S experienced significant improvements in reduced tension, depression, and confusion, suggesting an enhancement in mental clarity and overall emotional well-being. Both interventions also improved processing speed and cognitive flexibility. However, no significant differences were observed in short- and long-term verbal memory. Conclusions: In summary, these findings support Zynamite^® S as a natural nootropic capable of acutely improving key cognitive functions and emotional balance at low doses in young adults, with sustained efficacy for at least five hours.