A Mango Leaf Extract (Zynamite®) Combined with Quercetin Has Exercise-Mimetic Properties in Human Skeletal Muscle.

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-CaMKIIδD (2-fold, p = 0.007) and Ser9-GSK3ß (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-CaMKIIδD (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.

Influence of a new botanical combination on quality of life in menopausal Spanish women: Results of a randomized, placebo-controlled pilot study.

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).

Central nervous system activities of extract Mangifera indica L.

ETHNOBOTANICAL RELEVANCE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Supplementation with a Mango Leaf Extract (Zynamite®) in Combination with Quercetin Attenuates Muscle Damage and Pain and Accelerates Recovery after Strenuous Damaging Exercise.

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 hours thereafter for 24 hours, 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 hours 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.

Uromastyx acanthinura as a natural treatment in a mouse model of type 2 diabetes / Uromastyx acanthinura como tratamiento natural en un modelo murino de diabetes tipo 2

Aims: Oral testimonies from North Africa attribute anti-diabetic effects to medicinal preparations of the lizard Uromastyx acanthinura (UA). No scientific evidence of such effects is currently available. The acute effects of oral administration of UA to C57Bl/6J mice with diet-induced diabetes were tested and, if effectiveness was shown, the effect of subchronic UA administration was assessed in the same model. Methods: Mice were fed a diet containing 60% fat for at least 12 weeks. To assess acute effects, different doses of UA or saline were orally administered with 2 g of glucose/kg during an oral glucose tolerance test (OGTT) on different days in a randomised crossover design. The most effective dose was then fed together with the high-fat diet for 90 days and compared to high-fat diet alone in a parallel design. Body weight (BW), food consumption, welfare, and external appearance were assessed weekly. HbA1c, OGTT, and intraperitoneal insulin tolerance tests (IPITT) were performed at baseline and after treatment. Severity of neuropathy was evaluated by cold allodynia response in the acetone test. Results: UA significantly decreased glucose levels as compared to saline 15 min after administration. After 90 days of treatment, no differences were seen in OGTT or HbA1c between the groups, while IPITT showed higher glucose levels in UA-treated animals. Although weight increase was similar in both groups, weight tended to be higher in the treated group, which had a significantly higher daily food consumption. Cold allodynia response improved in frequency and intensity in the UA group. Conclusions: Orally administered UA acutely decreased blood glucose in diabetic mice. Paradoxically, long-term administration of UA increased food consumption, weight, and insulin resistance. Improved nociceptive response suggested an effect on pain and/or neuropathy. Although additional studies are needed to elucidate the properties and potential applications of UA, our results highlight the value of ethnomedical approaches to African traditional medicine as starting point to evaluate new bioactive components (AU)

Objetivos: Testimonios orales Norteafricanos atribuyen efectos hipoglucemiantes a preparados medicinales del lagarto Uromastyx acanthinura (UA), para los que no existen evidencias científicas actualmente. El objetivo de este trabajo fue el de investigar los efectos agudos de UA administrado oralmente en ratones diabéticos C57Bl/6J inducidos por dieta grasa, y si se demostrase su efectividad evaluar el efecto de su administración subcrónica en el mismo modelo animal. Métodos: Fue administrada una dieta a los animales con un contenido graso del 60% durante al menos 12 semanas. Para evaluar los efectos agudos diferentes dosis de UA o suero salino fueron administrados conjuntamente con 2 g/kg de glucosa durante sobrecargas orales de glucosa (SOG), en diferentes días, siguiendo un diseño cruzado aleatorizado. La dosis más efectiva en esta fase fue entonces administrada mezclada en la dieta durante 90 días y comparada con dieta solo en un diseño paralelo. El peso corporal y el consumo de alimento fueron evaluados semanalmente. HbA1c, SOG, y test de tolerancia intraperitoneal a la insulina (TTIPI) fueron realizados al inicio y tras el tratamiento. La gravedad de la neuropatía fue determinada mediante la evaluación de la alodinia al frío. Resultados: El UA redujo significativamente las concentraciones de glucosa de manera aguda en comparación con el control a los 15 min tras su administración. Tras 90 días de tratamiento no se observaron diferencias en las SOG o HbA1c entre grupos, mientras que para los test de tolerancia intraperitoneal a la isulina valores más altos de glucosa fueron determinados en los animales tratados con UA. Aunque ambos grupos aumentaron su peso, este tendió a ser mayor en los tratados, que a su vez consumieron significativamente más comida por día. La respuesta a la alodinia al frío mejoró en frecuencia e intensidad en los tratados con UA. Conclusiones: El UA administrado oralmente redujo de manera aguda la glucosa en sangre en ratones con diabetes. Paradójicamente, su administración crónica aumentó el consumo de alimento, el peso y la resistencia a la insulina. La mejora en la respuesta nociceptiva sugiere un efecto en el dolor y/o la neuropatía. Aunque son necesarios más estudios para aclarar las propiedades y posibles aplicaciones de este producto, nuestros resultados subrayan el valor de los enfoques etnomédicos hacia la medicina tradicional africana como origen para la evaluación de nuevos compuestos bioactivos (AU)

Uromastyx acanthinura as a natural treatment in a mouse model of type 2 diabetes.

AIMS: Oral testimonies from North Africa attribute anti-diabetic effects to medicinal preparations of the lizard Uromastyx acanthinura (UA). No scientific evidence of such effects is currently available. The acute effects of oral administration of UA to C57Bl/6J mice with diet-induced diabetes were tested and, if effectiveness was shown, the effect of subchronic UA administration was assessed in the same model. METHODS: Mice were fed a diet containing 60% fat for at least 12 weeks. To assess acute effects, different doses of UA or saline were orally administered with 2g of glucose/kg during an oral glucose tolerance test (OGTT) on different days in a randomised crossover design. The most effective dose was then fed together with the high-fat diet for 90 days and compared to high-fat diet alone in a parallel design. Body weight (BW), food consumption, welfare, and external appearance were assessed weekly. HbA1c, OGTT, and intraperitoneal insulin tolerance tests (IPITT) were performed at baseline and after treatment. Severity of neuropathy was evaluated by cold allodynia response in the acetone test. RESULTS: UA significantly decreased glucose levels as compared to saline 15min after administration. After 90 days of treatment, no differences were seen in OGTT or HbA1c between the groups, while IPITT showed higher glucose levels in UA-treated animals. Although weight increase was similar in both groups, weight tended to be higher in the treated group, which had a significantly higher daily food consumption. Cold allodynia response improved in frequency and intensity in the UA group. CONCLUSIONS: Orally administered UA acutely decreased blood glucose in diabetic mice. Paradoxically, long-term administration of UA increased food consumption, weight, and insulin resistance. Improved nociceptive response suggested an effect on pain and/or neuropathy. Although additional studies are needed to elucidate the properties and potential applications of UA, our results highlight the value of ethnomedical approaches to African traditional medicine as starting point to evaluate new bioactive components.

Efecto de los ácidos grasos omega-3 en la evolución clínica, biomarcadores inflamatorios y el péptido natriurético cerebral de pacientes con cardiopatía isquémica / Effect of omega-3 acids on clinical evolution, plasma inflammatory biomarkers and B-type natriuretic peptide levels in patients with coronary heart disease

Background and objective: The consumption of fish has been associated with aminor risk of cardiovascular mortality. Patients and methods: Thirty-one patients with clinical and angiographic evidence of coronary illness and no data of heart failure were followed up. One gram per day of omega-3-acid ethyl esters was added to their usual cardiologic treatment. Demographic, clinical and analytical data (lipid, ESR, CRP, lipoprotein[a], fibrinogen, and BNP levels) were evaluated at the beginning and at 9 months. Results: Six patients had cardiologic events in the follow up although none presented acute coronary syndrome. Significant differences were seen in HDL cholesterol (mg/dL) (38,5[9,6] vs. 42,1 (11,0), p = 0,000), hemoglobin (g/dL) (13,2 [1,7] vs. 13,9 (1,7), p = 0,009) and pro-BNP (pg/dL) (745,5 [1,035,7] vs. 235,8 [194,0], p = 0,008) levels. No significant differences existed either in the inflammatory parameters or in total cholesterol, LDL cholesterol and triglycerides Conclusion: One gram day of omega-3-acid ethyl esters added to the usual cardiologic treatment in patients with coronary heart disease improves pro BNP levels of patients with preserved left ventricular function without modifying serum inflammatory parameters (AU)

Fundamento y objetivo: El consumo de pescado se ha asociado a un menor riesgo de mortalidad cardiovascular. Pacientes y método: Se siguió a un total de 31 pacientes con evidencia clínica y angiográfica de enfermedad coronaria sin datos de insuficiencia cardiaca. Se añadió al tratamiento habitual un gramo al día de ésteres etílicos de ácidos grasos omega-3 al 90%. Se determinaron parámetros demográficos, clínicos y analíticos (lipidograma, velocidad de sedimentación globular [VSG], proteína C reactiva [PCR], fibrinógeno, lipoproteína [a] y propéptido natriurético cerebral [proBNP]) al inicio y a los 9 meses.Resultados: Seis pacientes presentaron eventos cardiológicos en el seguimiento, aunque ninguno presentó síndrome coronario agudo. De los parámetros analíticos estudiados existieron diferencias significativas, entre el inicio y el final del seguimiento, en las cifras de colesterol unido a lipoproteínas de alta densidad (colesterol HDL, media [DE] de 38,5 [9,6] frente a 42,1 [11,0] mg/dL, p=0,000), hemoglobina (media de 13,2 [1,7] frente a 13,9 [1,7] g/dL, p=0,009) y pro-BNP (media de 745,5 [1.035,7] frente a 235,8 [194,0] pg/dL, p=0,008). No existieron diferencias significativas en los parámetros inflamatorios ni en los valores de colesterol total, colesterol unido a lipoproteínas de baja densidad (colesterol LDL) ni triglicéridos.Conclusión: Un gramo al día de ácidos grasos omega-3 contribuye a una mejoría en los valores de pro-BNP en pacientes con cardiopatía isquémica y función ventricular izquierda global conservada, sin modificar los parámetros inflamatorios (AU)

[Effect of omega-3 acids on clinical evolution, plasma inflammatory biomarkers and B-type natriuretic peptide levels in patients with coronary heart disease]. / Efecto de los ácidos grasos omega-3 en la evolución clínica, biomarcadores inflamatorios y el péptido natriurético cerebral de pacientes con cardiopatía isquémica.

BACKGROUND AND OBJECTIVE: The consumption of fish has been associated with a minor risk of cardiovascular mortality. PATIENTS AND METHODS: Thirty-one patients with clinical and angiographic evidence of coronary illness and no data of heart failure were followed up. One gram per day of omega-3-acid ethyl esters was added to their usual cardiologic treatment. Demographic, clinical and analytical data (lipid, ESR, CRP, lipoprotein[a], fibrinogen, and BNP levels) were evaluated at the beginning and at 9 months. RESULTS: Six patients had cardiologic events in the follow up although none presented acute coronary syndrome. Significant differences were seen in HDL cholesterol (mg/dL) (38,5[9,6] vs. 42,1 (11,0), p=0,000), hemoglobin (g/dL) (13,2 [1,7] vs. 13,9 (1,7), p=0,009) and pro-BNP (pg/dL) (745,5 [1,035,7] vs. 235,8 [194,0], p=0,008) levels. No significant differences existed either in the inflammatory parameters or in total cholesterol, LDL cholesterol and triglycerides. CONCLUSION: One gram day of omega-3-acid ethyl esters added to the usual cardiologic treatment in patients with coronary heart disease improves pro BNP levels of patients with preserved left ventricular function without modifying serum inflammatory parameters.

HDL cholesterol levels in children with mild hypercholesterolemia: effect of consuming skim milk enriched with olive oil and modulation by the TAQ 1B polymorphism in the CETP gene.

BACKGROUND: This study aimed to examine the changes in serum lipids in children with mild hypercholesterolemia after the use of skim milk or olive-oil-enriched skim milk in their diet and the modulation of lipid levels by the Taq 1B polymorphism in the cholesteryl-ester transfer protein gene. METHODS: Thirty-six prepubertal children with mild hypercholesterolemia were randomly assigned in a crossover design into 2 groups of 16 and 20 individuals. Both groups received, in sequential inverse order, the 2 types of milk for 2 periods of 6 weeks. RESULTS: Carriers of at least 1 B2 allele had an adjusted basal HDL cholesterol level significantly higher than children with the B1B1 genotype (1.291 mmol/l, 95% CI: 1.184-1.397, vs. 1.082 mmol/l, 95% CI: 0.931-1.233; p = 0.027). In contrast, there were no significant differences in the adjusted basal levels of apolipoprotein A-I (B2 carriers: 1.292 g/l, 95% CI: 1.218-1.367; B1B1 genotype: 1.215 g/l, 95% CI: 1.109-1.320; p = 0.223). The intake of olive-oil-enriched skim milk caused significant increases in HDL cholesterol and apolipoprotein A-I, both in B2 (0.089 mmol/l, 95% CI: 0.032-0.146, p = 0.005; 0.55 g/l, 95% CI: 0.012-0.098; p = 0.018) and in B1B1 carriers (0.179 mmol/l, 95% CI: 0.096-0.262; p < 0.001; and 0.095 g/l, 95% CI: 0.032-0.157; p = 0.003). This increase in HDL cholesterol was significantly higher in the B1B1 group (p = 0.049). CONCLUSION: The consumption of skim milk enriched with olive oil increases the HDL cholesterol and apolipoprotein A-I levels in children with hypercholesterolemia, this effect being more intense in carriers of the B1B1 genotype.