The potential role of mangiferin in cancer treatment through its immunomodulatory, anti-angiogenic, apoptopic, and gene regulatory effects.

Mangiferin (1,3,6,7-tetrahydroxyxanthone-C2-ß-D-glucoside) is a natural bioactive xanthonoid that can be found in many plant species, among which the mango tree (Mangifera indica L), a plant widely used in the traditional medicinal, is one of its primary sources. The use of mangiferin for cancer treatment has attracted the attention of research groups around the World. Single administration of mangiferin or in combination with known anticancer chemicals has shown the potential benefits of this molecule in lung, brain, breast, cervix, and prostate cancers, and leukemia. Mangiferin mechanisms of action against cancer cells through in vitro, ex vivo, or in vivo models are discussed besides its antioxidant and anti-inflammatory properties. Nevertheless, pharmaceutical development and, therefore, clinical trials on cancer targets are still lacking. © 2016 BioFactors, 42(5):475-491, 2016.

Mango Polyphenols and Its Protective Effects on Diseases Associated to Oxidative Stress.

Biological effects of natural polyphenols from mango and their potential impact on human health have become of increasing interest. The occurrence of glycosilated molecules, such as mangiferin (C2-ß-D-glucopyranosyl-1,3,6,7-tetrahydroxyxanthone), main component of the mango polyphenolic fraction, and benzophenones, flavonoids (catechin and epicatechin), phenolic acids (benzoic and gallic), and a wide range of derivatives, provide a high chemical complexity. In this review, the potential impact of mango polyphenols and its protective effects on diseases associated to oxidative stress is discussed.

Introducción de resultados de la investigación-desarrollo en el sistema de salud cubano / Introduction of research and development results in the Cuban healthcare system

La aplicación práctica de los resultados derivados de la investigación-desarrollo al sistema de salud y el avance propio de la Ciencia y la Técnica ha impuesto un reto a los investigadores, trabajadores y ejecutivos de las políticas de salud. Se destaca la importancia del diseño del proyecto de investigación-desarrollo que permite a una organización establecer su estrategia para poder acceder finalmente a la práctica social en términos de productos, tecnologías y servicios para la salud. Cuatro generaciones de investigación-desarrollo se reconocen hasta la era actual, la cuarta generación, llamada Administración del Conocimiento, está insertada en aquellos países con mayor desarrollo económico y social. Los países menos desarrollados no pueden acceder a ella por la carencia de recursos financieros y humanos y al fenómeno de que la mayor parte del conocimiento presente en las tecnologías de salud avanzadas es de propiedad privada, debido a los derechos de propiedad intelectual, fundamentalmente en países con altos niveles de desarrollo como los EE.UU., Japón y Europa Occidental. Sin embargo, existe una posibilidad para estos países menos desarrollados cuando se consideran la segunda y tercera generaciones de investigación-desarrollo, donde el factor clave es el proyecto de investigación-desarrollo. El presente trabajo se enfoca hacia los conceptos y condiciones para el diseño de estos proyectos en salud, que incluye todos los factores necesarios para alcanzar el éxito de la introducción del resultado y, por tanto, el objetivo principal de toda investigación en salud: llegar a los pacientes y elevar la calidad de vida de las poblaciones

The implementation of the results from research and development in the health care system and the inherent advance of Science and Technique have challenged researchers, workers and managers of the health policies. It was underlined that the design of the research and development project is important for the organization to set its own strategy to definitely accede to social practice in terms of health products, technologies and services. Four generations of research and development are acknowledged up to the present where the fourth generation called Knowledge Management is inserted into those countries with higher economic and social development. The less developed countries can not have access to this last generation because of the lack of financial and human resources and of the fact that most of knowledge present in advanced health technologies is private property as a result of copyright, mainly in highly developed countries like Japan, USA and Western Europe. However, there is a chance for these less developed nations when taking the second and third generations of research and development into consideration since the key factor here is the research and development project as such. The present paper focused on the concepts and conditions for the design of health projects including all the necessary factors to be successful in implementing the results, and therefore, in accomplishing the main objective of every health research work, that is, to reach the patients and to increase the quality of life of the populations

Introducción de resultados de la investigación-desarrollo en el sistema de salud cubano / Introduction of research and development results in the Cuban healthcare system

La aplicación práctica de los resultados derivados de la investigación-desarrollo al sistema de salud y el avance propio de la Ciencia y la Técnica ha impuesto un reto a los investigadores, trabajadores y ejecutivos de las políticas de salud. Se destaca la importancia del diseño del proyecto de investigación-desarrollo que permite a una organización establecer su estrategia para poder acceder finalmente a la práctica social en términos de productos, tecnologías y servicios para la salud. Cuatro generaciones de investigación-desarrollo se reconocen hasta la era actual, la cuarta generación, llamada Administración del Conocimiento, está insertada en aquellos países con mayor desarrollo económico y social. Los países menos desarrollados no pueden acceder a ella por la carencia de recursos financieros y humanos y al fenómeno de que la mayor parte del conocimiento presente en las tecnologías de salud avanzadas es de propiedad privada, debido a los derechos de propiedad intelectual, fundamentalmente en países con altos niveles de desarrollo como los EE.UU., Japón y Europa Occidental. Sin embargo, existe una posibilidad para estos países menos desarrollados cuando se consideran la segunda y tercera generaciones de investigación-desarrollo, donde el factor clave es el proyecto de investigación-desarrollo. El presente trabajo se enfoca hacia los conceptos y condiciones para el diseño de estos proyectos en salud, que incluye todos los factores necesarios para alcanzar el éxito de la introducción del resultado y, por tanto, el objetivo principal de toda investigación en salud: llegar a los pacientes y elevar la calidad de vida de las poblaciones(AU)

The implementation of the results from research and development in the health care system and the inherent advance of Science and Technique have challenged researchers, workers and managers of the health policies. It was underlined that the design of the research and development project is important for the organization to set its own strategy to definitely accede to social practice in terms of health products, technologies and services. Four generations of research and development are acknowledged up to the present where the fourth generation called Knowledge Management is inserted into those countries with higher economic and social development. The less developed countries can not have access to this last generation because of the lack of financial and human resources and of the fact that most of knowledge present in advanced health technologies is private property as a result of copyright, mainly in highly developed countries like Japan, USA and Western Europe. However, there is a chance for these less developed nations when taking the second and third generations of research and development into consideration since the key factor here is the research and development project as such. The present paper focused on the concepts and conditions for the design of health projects including all the necessary factors to be successful in implementing the results, and therefore, in accomplishing the main objective of every health research work, that is, to reach the patients and to increase the quality of life of the populations(AU)

Experiencias de la terapia antioxidante con Vimang en la atención primaria de salud en Cuba / Experience of antioxidant therapy with Vimang in primary health care in Cuba

La terapia antioxidante con Vimang en la atención primaria de salud constituye una posible alternativa para el tratamiento eficaz, adyuvante o no, de enfermedades relacionadas con el estrés oxidativo o componentes de dolor e inflamación. Se muestra los resultados de estudios clínicos con Vimang en la atención al adulto mayor, el tratamiento de la displasia de mamas, leve o moderada, y el tratamiento de dermatopatías, a partir de experiencias etnomédicas publicadas con anterioridad. En la atención al adulto mayor (n = 31, tabletas Vimang, 300 mg) mejoró, en ocho de nueve indicadores evaluados de la calidad de vida (Cuestionario de Salud SF-36), la autopercepción del estado de salud de los ancianos; el indicador más significativo fue el dolor corporal. En la terapia de la displasia de mamas (n = 100, tabletas Vimang, 300 mg) se demostró una eficacia mayor al 85 por ciento, con resultados similares o superiores a la vitamina E. En el tratamiento de enfermedades de la piel (n = 590, crema Vimang, 1,2 por ciento), se observó mejoría en 86,8 y 96,7 por ciento de los pacientes tratados por inflamación y dolor, respectivamente, y más del 90 por ciento fueron curados de forma total o parcial. Los resultados más relevantes se obtuvieron en la recuperación del color de la piel en melasma del embarazo y pitiriasis versicolor, (52 pacientes), procesos infecciosos (53 pacientes), micosis (169 pacientes). No se observaron reacciones adversas ni signos de toxicidad durante el tratamiento.

Antioxidant therapy with Vimang in primary health care is a possible alternative for the effective treatment, either adjuvant or not, of diseases related to oxidative stress, pain and inflammation. The results of clinical studies with Vimang on the elderly, breast dysplasia (mild or moderate) and skin diseases were shown taking into account previously reported ethnomedical experience. On elderly subjects (n=31 , 300mg Vimang tablets), the self perception of their health status improved in 8 of 9 evaluated parameters of life quality, being body pain the most significant (health questionnaire SF-36). In the treatment of breast dysplasia (n=100, 300mg Vimang tablets), the efficacy was over 85 percent, with similar or higher results than vitamin E. In treating skin diseases (n=590, 1.2 percent Vimang cream), 86.8 percent and 96.7 percent of patients treated because of inflammation and pain improved their condition whereas over 90 percent of patients completely or partially recovered. The most relevant results were seen in the recovery of skin pigmentation in pregnancy melasme and pitiriasis versicolor (52 patients), infectious processes (53 patients), and mycosis (169 patients). Neither adverse reactions nor toxic signs were observed in the treatment.

The paradox of natural products as pharmaceuticals. Experimental evidences of a mango stem bark extract.

Recent findings regarding basic, pre-clinical and clinical studies on a mango stem bark extract (MSBE) developed in Cuba (Vimang) on an industrial scale are summarized. Ethnomedical studies, extract reproducibility, biological effects and clinical evaluations in terms of patient quality of life are described as experimental evidences to support the statement that natural products, even being a mixture of compounds, could be as effective as "monoceuticals" for medical uses. Discussion about the use of "monoceuticals" versus "natureceuticals" in health care and medicine is based on effectiveness and availability, taking Vimang as an example of a natural product with supported scientific evidence to be used as antioxidant, analgesic, anti-inflammatory and immunomodulator.

Dual mechanism of mangiferin protection against iron-induced damage to 2-deoxyribose and ascorbate oxidation.

We studied mangiferin effects on the degradation of 2-deoxyribose induced by Fe(III)-EDTA/citrate plus ascorbate, in relation to ascorbate oxidation (measured at 265 nm). Results revealed that mangiferin was equally effective in preventing degradation of both 15 and 1.5 mM 2-deoxyribose. At a fixed Fe(III) concentration, increasing the concentration of ligands (either EDTA or citrate) caused a significant reduction in the protective effects of mangiferin. Interestingly, mangiferin strongly stimulated Fe(III)-EDTA ascorbate oxidation, but inhibited it when citrate was used as iron co-chelator. Mangiferin stimulated O2 consumption due to Fe(II) (formed by Fe(III) ascorbate reduction) autoxidation when the metal ligand was EDTA, but inhibited it when citrate was used. These results suggest that mangiferin removes iron from citrate, but not from EDTA, forming an iron-mangiferin complex that cannot induce ascorbate oxidation effectively, thus inhibiting iron-mediated oxyradical formation. Taken together, these results indicate that mangiferin works mainly by a mechanism different from the classical hydroxyl radical scavengers, keeping iron in its ferric form, by complexing Fe(III), or stimulating Fe(II) autoxidation.

Mangifera indica L. extract (Vimang) inhibits 2-deoxyribose damage induced by Fe (III) plus ascorbate.

Vimang is an aqueous extract of selected species of Mangifera indica L, used in Cuba as a nutritional antioxidant supplement. Many in vitro and in vivo models of oxidative stress have been used to elucidate the antioxidant mechanisms of this extract. To further characterize the mechanism of Vimang action, its effect on the degradation of 2-deoxyribose induced by Fe (III)-EDTA plus ascorbate or plus hypoxanthine/xanthine oxidase was studied. Vimang was shown to be a potent inhibitor of 2-deoxyribose degradation mediated by Fe (III)-EDTA plus ascorbate or superoxide (O2-). The results revealed that Vimang, at concentrations higher than 50 microM mangiferin equivalent, was equally effective in preventing degradation of both 15 mM and 1.5 mM 2-deoxyribose. At a fixed Fe (III) concentration, increasing the concentration of ligands (either EDTA or citrate) caused a significant reduction in the protective effects of Vimang. When ascorbate was replaced by O2- (formed by hypoxanthine and xanthine oxidase) the protective efficiency of Vimang was also inversely related to EDTA concentration. The results strongly indicate that Vimang does not block 2-deoxyribose degradation by simply trapping *OH radicals. Rather, Vimang seems to act as an antioxidant by complexing iron ions, rendering them inactive or poorly active in the Fenton reaction.

Mangifera indica L. (Vimang) protection against serum oxidative stress in elderly humans.

BACKGROUND: We searched for the protective effect of a natural extract from stem bark of Mangifera indica L. extract (Vimang) on age-related oxidative stress. METHODS: Healthy subjects were classified in two groups, elderly (>65 years) and young group (<26 years). The elderly group received a daily dose of 900 mg of extract (three coated Vimang tablets, 300 mg each, before meals) for 60 days. Serum concentration of lipid peroxides, serum peroxidation potential, extracellular superoxide dismutase activity (EC-SOD), glutathione status (GSH, GSSG, GSSG/GSH ratio)) and total antioxidant status (TAS) were determined before (both experimental groups) and 15, 30, and 60 days after treatment (only elderly group). We confirmed the existence of an age-associated oxidative stress in human serum as documented by an age-related increase in serum lipoperoxides and GSSG and a decrease in serum antioxidant capacity and EC-SOD activity. RESULTS: Vimang tablet supplementation increased EC-SOD activity (p <0.01) and serum TAS (p <0.01). It also decreased serum thiobarbituric reactive substances (p <0.01) and GSSG levels (p <0.05). We suggested that the antioxidant components of the extract could have been utilized by the cells (especially blood and endothelial cells), sparing the intra- and extracellular antioxidant system and increasing serum peroxil scavenging capacity, thus preventing age-associated increase in GSH oxidation and lipoperoxidation. CONCLUSIONS: Vimang tablets prevent age-associated oxidative stress in elderly humans, which could retard the onset of age-associated disease, improving the quality of life for elderly persons.

In vivo and in vitro anti-inflammatory activity of Mangifera indica L. extract (VIMANG).

A standard aqueous extract of Mangifera indica L., used in Cuba as an antioxidant under the brand name of VIMANG, was tested in vivo for its anti-inflammatory activity using commonly accepted assays. M. indica extract, administered topically (0.5-2 mg per ear), reduced ear edema induced by arachidonic acid (AA) and phorbol myristate acetate (PMA, ED50 = 1.1 mg per ear) in mice. In the PMA model, M. indica extract also reduced myeloperoxidase (MPO) activity. This extract p.o. administered also inhibited tumor necrosis factor alpha (TNFalpha) serum levels in both models of inflammation (AA, ED50 = 106.1 mg kg(-1) and PMA, ED50 = 58.2 mg kg(-1)). In vitro studies were performed using the macrophage cell line RAW264.7 stimulated with pro-inflammatory stimuli (LPS-IFNgamma or the calcium ionophore A23187) to determine PGE2 or LTB4 release, respectively. The extract inhibited the induction of PGE2 with IC50 = 64.1 microg ml(-1) and LTB4 IC50 = 22.9 microg ml(-1). M. indica extract also inhibited human synovial secretory phospholipase (PL)A2 with IC 50 = 0.7 microg ml(-1). These results represent an important contribution to the elucidation of the mechanism involved in the anti-inflammatory and anti-nociceptive effects reported by the standard M. indica extract VIMANG.

Protection against septic shock and suppression of tumor necrosis factor alpha and nitric oxide production on macrophages and microglia by a standard aqueous extract of Mangifera indica L. (VIMANG). Role of mangiferin isolated from the extract.

The present study illustrates the effects of a standard aqueous extract, used in Cuba under the brand name of VIMANG, from the stem bark of Mangifera indica L. on the production of tumor necrosis factor alpha (TNFalpha) and nitric oxide (NO) in in vivo and in vitro experiments. In vivo was determined by the action of the extract and its purified glucosylxanthone (mangiferin) on TNFalpha in a murine model of endotoxic shock using Balb/c mice pre-treated with lipopolysaccharide (LPS) 0.125 mg kg(-1), i.p. In vitro, M. indica extract and mangiferin were tested on TNFalpha and NO production in activated macrophages (RAW264.7 cell line) and microglia (N9 cell line) stimulated with LPS (10ng ml(-1)) and interferon gamma (IFNgamma, 2U ml(-1)). M. indica extract reduced dose-dependently TNFalpha production in the serum (ED50 = 64.5 mg kg(-1)) and the TNFalpha mRNA expression in the lungs and livers of mice. Mangiferin also inhibited systemic TNFalpha at 20 mg kg(-1). In RAW264.7, the extract inhibited TNFalpha (IC50 = 94.1 microg ml(-1)) and NO (IC50 = 64.4 microg ml(-1)). In microglia the inhibitions of the extract were IC50 = 76.0 microg ml(-1) (TNFalpha) and 84.0 microg ml(-1) (NO). These findings suggest that the anti-inflammatory response observed during treatment with M. indica extract must be related with inhibition of TNFalpha and NO production. Mangiferin, a main component in the extract, is involved in these effects. The TNFalpha and NO inhibitions by M. indica extract and mangiferin on endotoxic shock and microglia are reported here for the first time.

Uso etnomédico de la corteza de Mangifera indica L. en Cuba / Ethnomedical use of the bark of Mangifera indica L. in Cuba

El objetivo del presente trabajo fue valorar el efecto del extracto acuoso de la corteza de Mangifera indica L., recomendado a más de 2 000 pacientes con diferentes enfermedades y atendidos en una consulta de fitoterapia de La Habana. Se escogió una muestra de 412 pacientes que tenían, entre 6 y 18 meses de tratamiento que cumplían los requisitos necesarios para dar respuesta al objetivo planteado. La actividad de este extracto natural fue evaluada por entrevistas al paciente, el criterio del médico de cabecera y los resultados de los exámenes realizados en instituciones del Sistema Nacional de Salud. La entidad tratada con mayor frecuencia fue el cáncer, donde un alto porcentaje de pacientes mostró una mejoría de la calidad de vida, se observaron buenos resultados en la diabetes mellitus, hiperplasia prostática, asma bronquial, psoriasis, lupus eritematoso y dermatitis. Este informe es la primera publicación acerca del uso etnomédico de este extracto en Cuba

Uso etnomédico de la corteza de Mangifera indica L. en Cuba / Ethnomedical use of the bark of Mangifera indica L. in Cuba

El objetivo del presente trabajo fue valorar el efecto del extracto acuoso de la corteza de Mangifera indica L., recomendado a más de 2 000 pacientes con diferentes enfermedades y atendidos en una consulta de fitoterapia de La Habana. Se escogió una muestra de 412 pacientes que tenían, entre 6 y 18 meses de tratamiento que cumplían los requisitos necesarios para dar respuesta al objetivo planteado. La actividad de este extracto natural fue evaluada por entrevistas al paciente, el criterio del médico de cabecera y los resultados de los exámenes realizados en instituciones del Sistema Nacional de Salud. La entidad tratada con mayor frecuencia fue el cáncer, donde un alto porcentaje de pacientes mostró una mejoría de la calidad de vida, se observaron buenos resultados en la diabetes mellitus, hiperplasia prostática, asma bronquial, psoriasis, lupus eritematoso y dermatitis. Este informe es la primera publicación acerca del uso etnomédico de este extracto en Cuba(AU)

Protective effect of Mangifera indica L. extract (Vimang) on the injury associated with hepatic ischaemia reperfusion.

The effect of Mangifera indica L. extract (Vimang) on treatment of injury associated with hepatic ischaemia/reperfusion was tested. Vimang protects from the oxidative damage induced by oxygen-based free radicals as shown in several in vitro test systems conducted. The ability of Vimang to reduce liver damage was investigated in rats undergoing right-lobe blood fl ow occlusion for 45 min followed by 45 min of reperfusion. The ischaemia/reperfusion model leads to an increase of transaminase (ALT and AST), membrane lipid peroxidation, tissue neutrophil in filtration, DNA fragmentation, loss of protein -SH groups, cytosolic Ca2+ overload and a decrease of catalase activity. Oral administration of Vimang (50, 110 and 250 mg/kg, b.w.) 7 days before reperfusion, reduced transaminase levels and DNA fragmentation in a dose dependent manner (p < 0.05). Vimang also restored the cytosolic Ca2+ levels and inhibited polymorphonuclear migration at a dose of 250 mg/kg b.w., improved the oxidation of total and non protein sulfhydryl groups and prevented modification in catalase activity, uric acid and lipid peroxidation markers (p < 0.05). These data suggest that Vimang could be a useful new natural drug for preventing oxidative damage during hepatic injury associated with free radical generation.

Isolation and quantitative analysis of phenolic antioxidants, free sugars, and polyols from mango (Mangifera indica L.) stem bark aqueous decoction used in Cuba as a nutritional supplement.

An aqueous decoction of mango (Mangifera indica L.) stem bark has been developed in Cuba on an industrial scale to be used as a nutritional supplement, cosmetic, and phytomedicine. Previously we reported its antioxidant activity, and we concluded that the product could be useful to prevent the production of reactive oxygen species and oxidative tissue damage in vivo. A phytochemical investigation of mango stem bark extract has led to the isolation of seven phenolic constituents: gallic acid, 3,4-dihydroxy benzoic acid, gallic acid methyl ester, gallic acid propyl ester, mangiferin, (+)-catechin, (-)-epicatechin, and benzoic acid and benzoic acid propyl ester. All structures were elucidated by ES-MS and NMR spectroscopic methods. Quantitative analysis of the compounds has been performed by HPLC, and mangiferin was found to be the predominant component. Total polyphenols were assayed also by the Folin-Ciocalteu method. The free sugars and polyols content was also determined by GC-MS.

VIMANG: nueva línea de productos naturales / VIMANG: new field of natural products

Revelaciones acerca de un novedoso producto, cuyas propiedades terapéuticas cubren un amplio espectro de enfermedades, mientras sus aplicaciones tienden a incrementarse

VIMANG : nueva línea de productos naturales / VIMANG : new field of natural products

Revelaciones acerca de un novedoso producto, cuyas propiedades terapéuticas cubren un amplio espectro de enfermedades, mientras sus aplicaciones tienden a incrementarse (AU)