Mangosteen for malignancy prevention and intervention: Current evidence, molecular mechanisms, and future perspectives.

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.

Garcinia mangostana and α-Mangostin Revive Ulcerative Colitis-Modified Hepatic Cytochrome P450 Profiles in Mice.

<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.

Garcinia mangostana L. fruits and derived food supplements: Identification and quantitative determination of bioactive xanthones by NMR analysis.

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.

Clinical efficacy of herbal extracts in treatment of mild to moderate acne vulgaris: an 8-week, double-blinded, randomized, controlled trial.

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.

MixONat, a Software for the Dereplication of Mixtures Based on 13C NMR Spectroscopy.

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.

Mangosteen pericarp components alleviate progression of prostatic hyperplasia and mitochondrial dysfunction in rats.

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.

Antioxidant-Enhancing Property of the Polar Fraction of Mangosteen Pericarp Extract and Evaluation of Its Safety in Humans.

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.

Posibles efectos beneficiosos para la salud del fruto de mangostán / Health benefits of mangosteen fruit

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)

Cardioprotective effect of alpha-mangostin, a xanthone derivative from mangosteen on tissue defense system against isoproterenol-induced myocardial infarction in rats.

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.