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1.
Pharm Biol ; 61(1): 241-248, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36655319

RESUMO

CONTEXT: α-Mangosteen (α-MG) attenuates insulin resistance (IR). However, it is still unknown whether α-MG could alleviate hepatic manifestations in IR rats. OBJECTIVE: To investigate the effect of α-MG on alleviating hepatic manifestations in IR rats through AMP-activated protein kinase (AMPK) and sterol-regulatory element-binding protein-1 (SREBP-1) pathway. MATERIALS AND METHODS: IR was induced by exposing male Sprague-Dawley rats (180-200 g) to high-fat/high-glucose diet and low-dose injection of streptozotocin (HF/HG/STZ), then treated with α-MG at a dose of 100 or 200 mg/kg/day for 8 weeks. At the end of the study (11 weeks), serum and liver were harvested for biochemical analysis, and the activity of AMPK, SREBP-1c, acetyl-CoA carboxylase (ACC), tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, insulin receptor substrate (IRS)-1, Bax and liver histopathology were analyzed. RESULTS: α-MG at both doses significantly lowered ALT, AST, triglyceride, and cholesterol total by 16.5, 15.7, 38, and 36%, respectively. These beneficial effects of α-MG are associated with the downregulation of the IR-induced inflammation in the liver. Furthermore, α-MG, at both doses, activated AMPK by 24-29 times and reduced SREBP-1c by 44-50% as well as ACC expression by 19-31% similar to metformin. All treatment groups showed liver histopathology improvement regarding fat deposition in the liver. CONCLUSIONS: Based on the findings demonstrated, α-MG protected against HF/HG/STZ-induced hepatic manifestations of the IR rats, at least in part via the modulation of the AMPK/SREBP-1c/ACC pathway and it could be a potential drug candidate to prevent IR-induced hepatic manifestations.


Assuntos
Fígado Gorduroso , Garcinia mangostana , Resistência à Insulina , Ratos , Masculino , Animais , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/farmacologia , Garcinia mangostana/metabolismo , Estreptozocina/farmacologia , Proteínas Quinases Ativadas por AMP/metabolismo , Glucose/metabolismo , Ratos Sprague-Dawley , Fígado , Dieta Hiperlipídica/efeitos adversos
2.
Pharmacol Res ; 188: 106630, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36581166

RESUMO

Mangosteen (Garcinia mangostana L.), also known as the "queen of fruits", is a tropical fruit of the Clusiacea family. While native to Southeast Asian countries, such as Thailand, Indonesia, Malaysia, Myanmar, Sri Lanka, India, and the Philippines, the fruit has gained popularity in the United States due to its health-promoting attributes. In traditional medicine, mangosteen has been used to treat a variety of illnesses, ranging from dysentery to wound healing. Mangosteen has been shown to exhibit numerous biological and pharmacological activities, such as antioxidant, anti-inflammatory, antibacterial, antifungal, antimalarial, antidiabetic, and anticancer properties. Disease-preventative and therapeutic properties of mangosteen have been ascribed to secondary metabolites called xanthones, present in several parts of the tree, including the pericarp, fruit rind, peel, stem bark, root bark, and leaf. Of the 68 mangosteen xanthones identified so far, the most widely-studied are α-mangostin and γ-mangostin. Emerging studies have found that mangosteen constituents and phytochemicals exert encouraging antineoplastic effects against a myriad of human malignancies. While there are a growing number of individual research papers on the anticancer properties of mangosteen, a complete and critical evaluation of published experimental findings has not been accomplished. Accordingly, the objective of this work is to present an in-depth analysis of the cancer preventive and anticancer potential of mangosteen constituents, with a special emphasis on the associated cellular and molecular mechanisms. Moreover, the bioavailability, pharmacokinetics, and safety of mangosteen-derived agents together with current challenges and future research avenues are also discussed.


Assuntos
Garcinia mangostana , Xantonas , Humanos , Garcinia mangostana/química , Garcinia mangostana/metabolismo , Xantonas/farmacologia , Xantonas/uso terapêutico , Disponibilidade Biológica , Frutas/química , Extratos Vegetais/farmacologia
3.
Cell Biochem Biophys ; 80(4): 633-645, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36184717

RESUMO

The MDM2-p53 protein-protein interaction is a promising model for researchers to design, study, and discover new anticancer drugs. The design of therapeutically active compounds that can maintain or restore the binding of MDM2 to p53 has been found to limit the oncogenic activities of both. This led to the current development of a group of xanthone-core and cis-imidazoline analogs compounds, among which γ-Mangostin (GM), α-Mangostin (AM), and Nutlin exhibited their MDM2-p53 interaction inhibitory effects. Therefore, in this study, we seek to determine the mechanisms by which these compounds elicit MDM2-p53 interaction targeting. Unique to the binding of GM, AM, and Nutlin, from our findings, they share the same three active site residues Val76, Tyr50, and Gly41, which represent the top active side residues that contribute to high electrostatic energy. Consequently, the free binding energy contributed enormously to the binding of these compounds, which culminated in the high binding affinities of GM, AM, and Nutlin with high values. Furthermore, GM, AM, and Nutlin commonly interrupted the stable and compact conformation of MDM2 coupled with its active site, where Cα deviations were relatively high. We believe that our findings would assist in the design of more potent active anticancer drugs.


Assuntos
Antineoplásicos , Garcinia mangostana , Imidazolinas , Xantonas , Domínio Catalítico , Garcinia mangostana/metabolismo , Imidazóis/química , Imidazóis/metabolismo , Imidazóis/farmacologia , Simulação de Dinâmica Molecular , Piperazinas/farmacologia , Ligação Proteica , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Xantonas/farmacologia
4.
Pak J Biol Sci ; 25(9): 843-851, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36098087

RESUMO

<b>Background and Objective:</b> Ulcerative colitis (UC) is inflammation of the large intestine with ulceration but can also cause extraintestinal manifestations (EIM) by damaging surrounding organs such as the liver. <i>Garcinia mangostana</i> (GM) pericarp and α-mangostin (MGS) have been reported to have anti-inflammatory activity. This study evaluated the effects of GM pericarp extract and MGS on the expression of hepatic cytochrome P450 (CYP) enzymes as an EIM of UC. <b>Materials and Methods:</b> Male ICR mice were orally administered GM pericarp extract (40, 200 and 1000 mg/kg/day), MGS (30 mg/kg/day) or sulfasalazine (SUL) (100 mg/kg/day) daily for 7 days. On days 4-7, UC was induced by dextran sulfate sodium (DSS 40 kDa, 6 g/kg/day). Profiles of CYP mRNA expression were determined by RT/qPCR. Alkoxyresorufin <i>O</i>-dealkylation (including ethoxy-, methoxy-, pentoxy- and benzyloxy-resorufin), aniline hydroxylation and erythromycin <i>N</i>-demethylation CYP responsive activities were also examined. <b>Results:</b> The DSS-induced UC mice showed suppressed expression<i> </i>of <i>Cyp1a1</i>, <i>Cyp1a2</i>, <i>Cyp2b9/10</i>, <i>Cyp2e1</i>, <i>Cyp2c29</i>, <i>Cyp2d9</i>, <i>Cyp3a11</i> and <i>Cyp3a13</i> mRNAs. The GM pericarp extract and MGS restored expression of all investigated CYPs and their responsive enzyme activities in DSS-induced UC mice to levels comparable to the control and parallel to the effects of the anti-inflammatory control SUL. <b>Conclusion:</b> The GM is a promising therapy to restore UC-modified hepatic CYP profiles.


Assuntos
Colite Ulcerativa , Garcinia mangostana , Animais , Anti-Inflamatórios/farmacologia , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Sistema Enzimático do Citocromo P-450/efeitos adversos , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Sulfato de Dextrana/efeitos adversos , Garcinia mangostana/metabolismo , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , Extratos Vegetais/farmacologia , Xantonas
5.
J Pharm Biomed Anal ; 218: 114835, 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-35659659

RESUMO

Mangosteen (Garcinia mangostana L.), known as "the queen of fruits", is one of the most praised tropical fruit due to its delicious taste. In the last years, the use of mangosteen in functional products has been increasing, mainly in food beverages and nutraceutical formulations due to its biological activities related to the content of xanthones. The quantitative Nuclear Magnetic Resonance (qNMR) analysis, a rapid and accurate method used for simultaneous quantification of plant metabolites, was here employed to determine the amount of bioactive xanthones in the extracts of G. mangostana arils and shells obtained by using solvent of increasing polarity along with ''eco-friendly'' solvents like ethanol and ethanol-water. Furthermore, the content of xanthones was compared with that occurring in four selected commercial food supplements, among which tablets and capsules, and two fruit juices, based on mangosteen. Quantitative results highlighted a significant variability: the extracts of the shells displayed a higher amount of bioactive xanthones than those of the arils, in particular, of γ-mangostin and α-mangostin, while ß-mangostin, demethylcalabaxanthone, mangostanin, 8-deoxygartanin occurred in higher amounts in arils. A certain variability in the amount of biologically active xanthones (i.e. α-mangostin and γ-mangostin) could be observed in commercial food supplements.


Assuntos
Garcinia mangostana , Xantonas , Suplementos Nutricionais/análise , Etanol/análise , Frutas/química , Garcinia mangostana/química , Garcinia mangostana/metabolismo , Espectroscopia de Ressonância Magnética , Extratos Vegetais/química , Solventes/análise , Xantonas/análise
6.
Biomolecules ; 11(2)2021 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-33514017

RESUMO

The aim of the present study was to examine the protective effect of γ-mangostin, a component of the mangosteen shell, against oxidative damage to nerve cells induced by excessive glutamate, a known excitatory neurotransmitter. To investigate the effect of γ-mangostin on apoptosis, 5 mM of glutamate was used to induce apoptotic cell death in mouse hippocampal HT22 cells. In this study, γ-mangostin was found to exert a stronger protection than N-acetyl cysteine against glutamate-induced cell damage. γ-Mangostin showed prevented glutamate-induced apoptosis in HT22 cells by reducing the production of reactive oxygen species and stimulating the expression of heme oxygenase-1 protein. In addition, glutamate significantly induced the accumulation of intracellular calcium ions, whereas treatment with γ-mangostin markedly reduced it. Hoechst 33342 staining showed an improvement in glutamate-induced nuclear condensation following γ-mangostin treatment. Furthermore, the number of annexin V-positive cells was significantly reduced following treatment with γ-mangostin. Western blot analysis showed the inhibition of glutamate-induced mitogen-activated protein kinase phosphorylation by γ-mangostin. γ-mangostin also inhibited the regulation of the intrinsic mitochondrial apoptotic pathway. Thus, the results of this study suggest that γ-mangostin is an active ingredient of mangosteen and exerts neuroprotective activities in HT22 cells.


Assuntos
Acetilcisteína/metabolismo , Apoptose , Garcinia mangostana/metabolismo , Ácido Glutâmico/química , Ácido Glutâmico/metabolismo , Heme Oxigenase-1/metabolismo , Hipocampo/metabolismo , Proteínas de Membrana/metabolismo , Neurônios/metabolismo , Estresse Oxidativo , Espécies Reativas de Oxigênio , Xantonas/farmacologia , Animais , Cálcio/metabolismo , Morte Celular/efeitos dos fármacos , Sequestradores de Radicais Livres , MAP Quinase Quinase 4/metabolismo , Camundongos , Fármacos Neuroprotetores/farmacologia , Transdução de Sinais , Xantonas/isolamento & purificação , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
7.
J Dermatolog Treat ; 32(3): 297-301, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-31424962

RESUMO

BACKGROUND: Herbal extracts with fewer adverse effects can be an alternative to these drugs because they can target various molecular pathways of acne pathogenesis. OBJECTIVES: To evaluate the clinical efficacy of herbal extracts (mangosteen, Lithospermum officinale, Tribulus terrestris L., Houttuynia cordata Thunb) for the treatment of mild to moderate acne vulgaris. METHODS: Sixty patients were randomized in a 1:1 ratio to receive blinded treatment with herbal extracts or vehicle for 8 weeks. Inflammatory and non-inflammatory acne lesion counts, Investigator's Global Assessment, patient's satisfaction and safety profiles were assessed. We also performed skin biopsy at baseline and week 8 to confirm immunological changes with immunohistochemistry staining. RESULTS: By the end of the study period, both inflammatory and non-inflammatory acne lesion counts were significantly decreased in herbal extracts group (p< .05). In immunohistochemistry staining, expressions of IL-1α, IL-8, and keratin 16 were significantly decreased in herbal extracts group compared to vehicle group from baseline to week 8. There was no serious adverse events in both groups. CONCLUSIONS: This herbal extracts can be a new therapeutic option for patients with mild to moderate acne vulgaris who are reluctant to use drugs.


Assuntos
Acne Vulgar/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Acne Vulgar/patologia , Administração Cutânea , Adulto , Método Duplo-Cego , Esquema de Medicação , Feminino , Garcinia mangostana/química , Garcinia mangostana/metabolismo , Humanos , Interleucina-1alfa/metabolismo , Lithospermum/química , Lithospermum/metabolismo , Masculino , Satisfação do Paciente , Extratos Vegetais/química , Índice de Gravidade de Doença , Pele/metabolismo , Pele/patologia , Resultado do Tratamento , Adulto Jovem
8.
Anal Chem ; 92(13): 8793-8801, 2020 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-32479074

RESUMO

Whether chemists or biologists, researchers dealing with metabolomics require tools to decipher complex mixtures. As a part of metabolomics and initially dedicated to identifying bioactive natural products, dereplication aims at reducing the usual time-consuming process of known compounds isolation. Mass spectrometry and nuclear magnetic resonance are the most commonly reported analytical tools during dereplication analysis. Though it has low sensitivity, 13C NMR has many advantages for such a study. Notably, it is nonspecific allowing simultaneous high-resolution analysis of any organic compounds including stereoisomers. Since NMR spectrometers nowadays provide useful data sets in a reasonable time frame, we have embarked upon writing software dedicated to 13C NMR dereplication. The present study describes the development of a freely distributed algorithm, namely MixONat and its ability to help researchers decipher complex mixtures. Based on Python 3.5, MixONat analyses a {1H}-13C NMR spectrum optionally combined with DEPT-135 and 90 data-to distinguish carbon types (i.e., CH3, CH2, CH, and C)-as well as a MW filtering. The software requires predicted or experimental carbon chemical shifts (δc) databases and displays results that can be refined based on user interactions. As a proof of concept, this 13C NMR dereplication strategy was evaluated on mixtures of increasing complexity and exhibiting pharmaceutical (poppy alkaloids), nutritional (rosemary extracts) or cosmetics (mangosteen peel extract) applications. Associated results were compared with other methods commonly used for dereplication. MixONat gave coherent results that rapidly oriented the user toward the correct structural types of secondary metabolites, allowing the user to distinguish between structurally close natural products, including stereoisomers.


Assuntos
Produtos Biológicos/química , Espectroscopia de Ressonância Magnética/métodos , Software , Algoritmos , Alcaloides/química , Isótopos de Carbono/química , Bases de Dados de Compostos Químicos , Garcinia mangostana/química , Garcinia mangostana/metabolismo , Papaver/química , Papaver/metabolismo , Extratos Vegetais/química , Rosmarinus/química , Rosmarinus/metabolismo
9.
Sci Rep ; 10(1): 322, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31941927

RESUMO

Prostatic hyperplasia, characterized by progressive hyperplasia of glandular and stromal tissues, is the most common proliferative abnormality of the prostate in aging men. A high-fat diet (HFD) usually is a major factor inducing oxidative stress, inflammation, and an abnormal state of the prostate. Mangosteen pericarp powder (MPP) has abundant xanthones which can be antioxidant, anti-inflammatory, and antiproliferative agents. Therefore, the purpose of this study was to research whether MPP supplementation can affect the progression of prostatic hyperplasia. Twenty-four male F344 rats were randomly divided into four groups, including a control group (C), prostatic hyperplasia-induced group (P), prostatic hyperplasia-induced with low-dose MPP group (PL), and induced with high-dose MPP group (PH). The P, PL, and PH groups were given weekly intraperitoneal injections of 3,2'-dimethyl-4-aminobiphenyl (DMAB) at 25 mg/kg body weight for 10 weeks, and simultaneously fed an HFD for 24 weeks. Our findings first demonstrated that MPP consumption significantly decreased the prostate weight, serum testosterone and dihydrotestosterone concentrations, protein expression of proliferating cell nuclear antigen, and malondialdehyde levels and ameliorated mitochondrial function in prostatic tissues. These results suggest that MPP supplementation could be used to attenuate the progression of prostatic hyperplasia.


Assuntos
Garcinia mangostana/química , Mitocôndrias/efeitos dos fármacos , Extratos Vegetais/farmacologia , Hiperplasia Prostática/patologia , Animais , Peso Corporal/efeitos dos fármacos , Dieta Hiperlipídica , Suplementos Nutricionais , Di-Hidrotestosterona/sangue , Modelos Animais de Doenças , Progressão da Doença , Garcinia mangostana/metabolismo , Masculino , Malondialdeído/metabolismo , Mitocôndrias/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/química , Antígeno Nuclear de Célula em Proliferação/metabolismo , Próstata/metabolismo , Próstata/patologia , Hiperplasia Prostática/metabolismo , Ratos , Ratos Endogâmicos F344 , Testosterona/sangue
10.
PLoS One ; 14(7): e0219976, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31323060

RESUMO

Translucent flash disorder (TFD) is one of the important physiological disorders in mangosteen (Garcinia mangostana L.). TFD has symptoms such as flesh arils that become firm and appear transparent similar to watercore in apple or pear. Information on the changes of gene expression in TFD-affected tissues remain limited, and investigations into the effects of different water regimes still need to be undertaken. Through an RNA sequencing approach using the Ion Proton, 183,274 contigs with length ranging from 173-13,035 bp were constructed by de novo assembly. Functional annotation was analyzed using various public databases such as non-redundant protein NCBI, SwissProt, and Gene Ontology, and KEGG pathway. Our studies compared different water regimes to incidence and differentially expressed genes of TFD-like physiological disorders. From the differentially expressed gene (DEG) between normal air and TFD-affected aril, we identified DEG-related TFD events, which 6228 DEGs in the control condition and 3327 DEGs in under water stress treatment condition remained, and confirmed these with RT-qPCR, including sucrose synthase (SUSY), endoglucanase (GUN), xyloglucan endotransglucosylase/hydrolase (XTH), and polygalacturonase (PG) showed statistically significant. In addition, transcription factors also indicated changes in MYB, NAC and WRKY between tissues and different water regimes.


Assuntos
Frutas/genética , Frutas/metabolismo , Garcinia mangostana/genética , Garcinia mangostana/metabolismo , Perfilação da Expressão Gênica , Transcriptoma , Água/metabolismo , Biologia Computacional/métodos , Regulação da Expressão Gênica de Plantas , Doenças das Plantas
11.
Metabolomics ; 15(5): 73, 2019 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-31054000

RESUMO

INTRODUCTION: Metabolomics is an important tool to support postharvest fruit development and ripening studies. Mangosteen (Garcinia mangostana L.) is a tropical fruit with high market value but has short shelf-life during postharvest handling. Several postharvest technologies have been applied to maintain mangosteen fruit quality during storage. However, there is no study to evaluate the metabolite changes that occur in different harvesting and ripening condition. Additionally, the effect of postharvest treatment using a metabolomics approach has never been studied in mangosteen. OBJECTIVES: The aims of this study were to evaluate the metabolic changes between different harvesting and ripening condition and to evaluate the effect of postharvest treatment in mangosteen. METHODS: Mangosteen ripening stage were collected with several different conditions ("natural on-tree", "random on-tree" and "off-tree"). The metabolite changes were investigated for each ripening condition. Additionally, mangosteen fruit was harvested in stage 2 and was treated with several different treatments (storage at low temperature (LT; 12.3 ± 1.4 °C) and stress inducer treatment (methyl jasmonate and salicylic acid) in comparison with control treatment (normal temperature storage) and the metabolite changes were monitored over the course of 10 days after treatment. The metabolome data obtained from gas chromatography coupled with mass spectrometry were analyzed by multivariate analysis, including hierarchical clustering analysis, principal component analysis, and partial to latent squares analysis. RESULTS: "On-tree" ripening condition showed the progression of ripening process in accordance with the accumulation of some aroma precursor metabolites in the flesh part and pectin breakdown in the peel part. Interestingly, similar trend was found in the "off-tree" ripening condition although the progression of ripening process observed through color changes occurred much faster compared to "on-tree" ripening. Additionally, low-temperature treatment is shown as the most effective treatment to prolong mangosteen shelf-life among all postharvest treatments tested in this study compared to control treatment. After postharvest treatment, a total of 71 and 65 metabolites were annotated in peel and flesh part of mangosteen, respectively. Several contributed metabolites (xylose, galactose, galacturonic acid, glucuronate, glycine, and rhamnose) were decreased after treatment in the peel part. However, low-temperature treatment did not show any significant differences compared to a room temperature treatment in the flesh part. CONCLUSIONS: Our findings clearly indicate that there is a similar trend of metabolic changes between on-tree and off-tree ripening conditions. Additionally, postharvest treatment directly or indirectly influences many metabolic processes (cell-wall degrading process, sweet-acidic taste quality) during postharvest treatment.


Assuntos
Frutas/metabolismo , Garcinia mangostana/metabolismo , Metabolômica , Garcinia mangostana/química
12.
J Biosci Bioeng ; 125(2): 238-244, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28970109

RESUMO

Metabolomics is an emerging research field based on exhaustive metabolite profiling that have been proven useful to facilitate the study of postharvest fruit development and ripening. Specifically, tracking changes to the metabolome as fruit ripens should provide important clues for understanding ripening mechanisms and identify bio-markers to improve post-harvest technology of fruits. This study conducted a time-course metabolome analysis in mangosteen, an economically important tropical fruit valued for its flavor. Mangosteen is a climacteric fruit that requires an important plant hormone ethylene to regulate ripening processes and rate. We first categorized mangosteen samples in different ripening stages based on color changes, an established indicator of ripening. Using gas chromatography/mass spectrometry, small hydrophilic metabolites were profiled from non-ripened to fully ripened (ripening stages 0-6). These metabolites were then correlated with color changes to verify their involvement mangosteen ripening. Our results suggest that the increase of 2-aminoisobutyric acid, psicose, and several amino acids (phenylalanine, valine, isoleucine, serine, and tyrosine) showed a correlation with the progression of mangosteen ripening. This is the first report of the application of non-targeted metabolomics in mangosteen.


Assuntos
Frutas/crescimento & desenvolvimento , Frutas/metabolismo , Garcinia mangostana/metabolismo , Metabolômica , Aminoácidos/metabolismo , Ácidos Aminoisobutíricos/metabolismo , Etilenos/metabolismo , Frutose/metabolismo , Cromatografia Gasosa-Espectrometria de Massas , Metaboloma , Reguladores de Crescimento de Plantas/metabolismo
13.
Oxid Med Cell Longev ; 2016: 1293036, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27703599

RESUMO

Crude extract from the pericarp of the mangosteen (mangosteen extract [ME]) has exhibited several medicinal properties in both animal models and human cell lines. Interestingly, the cytotoxic activities were always observed in nonpolar fraction of the extract whereas the potent antioxidant was often found in polar fraction. Although it has been demonstrated that the polar fraction of ME exhibited the antioxidant activity, the safety of the polar fraction of ME has never been thoroughly investigated in humans. In this study, we investigated the safety of oral administration of the polar fraction of ME in 11 healthy Thai volunteers. During a 24-week period of the study, only minor and tolerable side effects were reported; no serious side effects were documented. Blood chemistry studies also showed no liver damage or kidney dysfunction in all subjects. We also demonstrated antioxidant property of the polar fraction of ME both in vitro and in vivo. Interestingly, oral administration of the polar fraction of ME enhanced the antioxidant capability of red blood cells and decreased oxidative damage to proteins within red blood cells and whole blood.


Assuntos
Antioxidantes/administração & dosagem , Garcinia mangostana/química , Extratos Vegetais/administração & dosagem , Administração Oral , Adulto , Alanina Transaminase/metabolismo , Antioxidantes/efeitos adversos , Antioxidantes/química , Aspartato Aminotransferases/metabolismo , Cromatografia em Camada Fina , Tontura/etiologia , Eritrócitos/citologia , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Exantema/etiologia , Feminino , Garcinia mangostana/metabolismo , Humanos , Fígado/enzimologia , Masculino , Pessoa de Meia-Idade , Náusea/etiologia , Fosforilação Oxidativa , Extratos Vegetais/efeitos adversos , Extratos Vegetais/química , Espécies Reativas de Oxigênio/metabolismo , Adulto Jovem
14.
Biosci Biotechnol Biochem ; 77(5): 984-7, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23649258

RESUMO

Xanthone compounds in mangosteen (Garcinia mangostana Linn.) fruit have been reported to have biological activities including antioxidative and anti-inflammatory effects, and the major xanthone compounds in mangosteen are α-mangostin and γ-mangostin. The objectives of this research were to quantify and qualify the major xanthones in each part of the mangosteen fruit with and without yellow gum from the point of view of effective utilization of agricultural product. Quantitative evaluation revealed that yellow gum had extremely high amounts of α-mangostin and γ-mangostin (382.2 and 144.9 mg/g on a wet basis, respectively) followed by pericarp and aril. In mangosteen fruit with yellow gum inside, xanthones seemed to have shifted from the pericarp and to have concentrated in a gum on the surface of aril, and there was almost no difference between the amounts of α-mangostin and γ-mangostin in whole fruits with and without yellow gum. Pericarp and yellow gum showed much higher radical-scavenging activity and ferric reducing antioxidant potential than the aril.


Assuntos
Antioxidantes/metabolismo , Antioxidantes/farmacologia , Frutas/anatomia & histologia , Frutas/metabolismo , Garcinia mangostana/metabolismo , Xantonas/metabolismo , Xantonas/farmacologia , Antioxidantes/isolamento & purificação , Xantonas/isolamento & purificação
15.
Aging Cell ; 12(4): 574-83, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23521895

RESUMO

The discovery that genetic mutations in several cellular pathways can increase lifespan has lent support to the notion that pharmacological inhibition of aging pathways can be used to extend lifespan and to slow the onset of age-related diseases. However, so far, only few compounds with such activities have been described. Here, we have conducted a chemical genetic screen for compounds that cause the extension of chronological lifespan of Schizosaccharomyces pombe. We have characterized eight natural products with such activities, which has allowed us to uncover so far unknown anti-aging pathways in S. pombe. The ionophores monensin and nigericin extended lifespan by affecting vacuolar acidification, and this effect depended on the presence of the vacuolar ATPase (V-ATPase) subunits Vma1 and Vma3. Furthermore, prostaglandin J2 displayed anti-aging properties due to the inhibition of mitochondrial fission, and its effect on longevity required the mitochondrial fission protein Dnm1 as well as the G-protein-coupled glucose receptor Git3. Also, two compounds that inhibit guanosine monophosphate (GMP) synthesis, mycophenolic acid (MPA) and acivicin, caused lifespan extension, indicating that an imbalance in guanine nucleotide levels impinges upon longevity. We furthermore have identified diindolylmethane (DIM), tschimganine, and the compound mixture mangosteen as inhibiting aging. Taken together, these results reveal unanticipated anti-aging activities for several phytochemicals and open up opportunities for the development of novel anti-aging therapies.


Assuntos
Guanosina Monofosfato/metabolismo , Dinâmica Mitocondrial/efeitos dos fármacos , Ácido Micofenólico/metabolismo , Schizosaccharomyces/fisiologia , Vacúolos/metabolismo , Dinaminas/genética , Dinaminas/metabolismo , Garcinia mangostana/metabolismo , Guanosina Monofosfato/genética , Hidroxibenzoatos/farmacologia , Indóis/farmacologia , Isoxazóis , Monensin/farmacologia , Ácido Micofenólico/farmacologia , Nigericina/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Schizosaccharomyces/efeitos dos fármacos , Schizosaccharomyces/genética , Proteínas de Schizosaccharomyces pombe/genética , Proteínas de Schizosaccharomyces pombe/metabolismo , Fatores de Tempo , ATPases Vacuolares Próton-Translocadoras/genética , ATPases Vacuolares Próton-Translocadoras/metabolismo
16.
Rev. fitoter ; 11(2): 119-129, dic. 2011. tab, ilus
Artigo em Espanhol | IBECS | ID: ibc-125878

RESUMO

El mangostán (Garcinia mangostana L.) es un árbol tropical, de origen asiático, perteneciente a la familia de las Gutíferas, cuyos frutos de color rojo a púrpura y pulpa blanquecina se emplean en alimentación por su agradable sabor aromático, ligeramente ácido. Se utiliza además en distintas medicinas tradicionales del sudeste asiático para el tratamiento de la diarrea, infecciones de la piel y heridas crónicas, disentería amebiana y algunos procesos inflamatorios. Sus principales componentes son de tipo fenólico, en concreto del grupo de las xantonas isopreniladas, como α -, β - y γ -mangostinas, garcinona E y otras. Se han estudiado sus propiedades anticancerosas, analgésicas y antiinflamatorias, antidepresivas, antimicrobianas, antifúngicas y antivirales. A pesar de los múltiples estudios publicados, son pocos los realizados en humanos por lo que al día de hoy es necesario ser prudentes a la hora de aconsejar este fruto para el tratamiento de enfermedades (AU)


The mangosteen (Garcinia mangostana L.) is a tropical, Asian tree that belongs to the Gutifferae family. Its red to purple fruits with white pulp are edible and have a pleasant aromatic, slightly acid flavour. Moreover they are used in different traditional medicines from Southeast Asia against diarrhoea, skin infections and chronic wounds, amoebic dysentery and some inflammatory processes. Their main constituents are polyphenols, especially isoprenylated xanthones, such as α -, β - and γ -mangostin, garcinone E, and others. Its anticancer, analgesic and anti-inflammatory, neuropsychiatric, antimicrobial, antifungal and antiviral properties have been studied. Despite multiple published studies, very few have been done on humans. Thus, nowadays it is necessary to be cautious when advising this fruit to treat diseases (AU)


Assuntos
Humanos , Masculino , Feminino , Garcinia mangostana , Garcinia mangostana/metabolismo , Anticarcinógenos/farmacologia , Anti-Inflamatórios/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/farmacocinética , Anti-Infecciosos/isolamento & purificação , Anti-Infecciosos/uso terapêutico , Plantas Medicinais/metabolismo , Fitoterapia/métodos , Fitoterapia/tendências , Fitoterapia , Frutas/química , Frutas/metabolismo
17.
Planta ; 229(6): 1323-34, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19306102

RESUMO

Mangosteen (Garcinia mangostana L.) fruit undergo rapid red colour development, both on the tree and after harvest, resulting in high anthocyanin production in the pericarp. Here, we report the isolation of three full-length mangosteen MYB transcription factors (GmMYB1, GmMYB7 and GmMYB10) and all the anthocyanin biosynthetic pathway genes (GmPal to GmUFGT). Phylogenetic analysis at the protein level of the R2R3-MYB transcription factor family showed GmMYB10 had a high degree of similarity with production of anthocyanin pigment1 in Arabidopsis and as well as sequences from other plant species related to the elevation of anthocyanin pigmentation. In transient transactivation assays, GmMYB10, co-expressed with AtbHLH2, strongly activated the GmDFR and AtDFR promoters. Transcripts of GmMYB10 and GmUFGT were highly abundant with onset of pigmentation and subsequently during red colouration. Our results suggest that GmMYB10 plays an important role in regulating anthocyanin biosynthesis both on the tree and after harvest, while GmUFGT may be a key biosynthetic gene in mangosteen pigmentation. The expression patterns of GmMYB10 and GmUFGT correlated with ethylene production that increased linearly until stage 5 (dark purple) and decreased thereafter. 1-Methycyclopropene (1-MCP) clearly delayed red colouration with resulting down-regulation of GmMYB10. These results suggest that the effect of ethylene on anthocyanin biosynthesis may be via the regulation of GmMYB10 expression.


Assuntos
Antocianinas/biossíntese , Frutas/metabolismo , Garcinia mangostana/metabolismo , Proteínas de Plantas/metabolismo , Fatores de Transcrição/metabolismo , Oxirredutases do Álcool/genética , Oxirredutases do Álcool/metabolismo , Antocianinas/metabolismo , Etilenos/metabolismo , Frutas/genética , Frutas/fisiologia , Garcinia mangostana/enzimologia , Garcinia mangostana/genética , Regulação da Expressão Gênica no Desenvolvimento , Regulação da Expressão Gênica de Plantas , Glucosiltransferases/genética , Glucosiltransferases/metabolismo , Luciferases/genética , Luciferases/metabolismo , Dados de Sequência Molecular , Oxigenases/genética , Oxigenases/metabolismo , Filogenia , Proteínas de Plantas/genética , Regiões Promotoras Genéticas/genética , Proteínas Proto-Oncogênicas c-myb/classificação , Proteínas Proto-Oncogênicas c-myb/genética , Proteínas Proto-Oncogênicas c-myb/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de DNA , Fatores de Tempo , Fatores de Transcrição/classificação , Fatores de Transcrição/genética , Transfecção
18.
J Biochem Mol Toxicol ; 21(6): 336-9, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17994576

RESUMO

Increased oxidative stress and antioxidant deficit have been suggested to play a major role in isoproterenol-induced myocardial infarction. The present study was designed to evaluate the effect of alpha-mangostin on the antioxidant defense system and lipid peroxidation against isoproterenol-induced myocardial infarction in rats. Induction of rats with ISO (150 mg/kg body weight, ip) for 2 days resulted in a marked elevation in lipid peroxidation, serum marker enzymes (LDH, CPK, GOT, and GPT) and a significant decrease in the activities of endogenous antioxidants (SOD, CAT, GPx, GST, and GSH). Pre-treatment with alpha-mangostin (200 mg/kg of body weight per day) orally for 6 days prior to the ISO administration and 2 days along with ISO administration significantly attenuated these changes when compared to the individual treatment groups. These findings indicate the protective effect of alpha-mangostin on lipid peroxidation and antioxidant tissue defense system during ISO-induced myocardial infarction in rats.


Assuntos
Cardiotônicos/uso terapêutico , Garcinia mangostana/metabolismo , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/imunologia , Xantonas/uso terapêutico , Animais , Antioxidantes/metabolismo , Biomarcadores/metabolismo , Isoproterenol , Peróxidos Lipídicos , Masculino , Infarto do Miocárdio/induzido quimicamente , Fitoterapia , Ratos , Ratos Wistar
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