Rind from Purple Mangosteen (Garcinia mangostana) Attenuates Diet-Induced Physiological and Metabolic Changes in Obese Rats.
ABSTRACT: The pulp of the purple mangosteen, Garcinia mangostana, is a popular tropical fruit but the rind containing xanthones such as ?-mangostin together with procyanidins and anthocyanidins is usually discarded as waste. However, this rind has been used in South-East Asia for diarrhoea, dysentery, skin infections and wounds. As xanthones have reported anti-inflammatory and antioxidant responses, this study has determined the bioactive compounds and evaluated the effects of G. mangostana rind on physiological, metabolic, liver and cardiovascular parameters in rats with diet-induced metabolic syndrome. Rats fed a diet with increased simple sugars and saturated fats developed obesity, hypertension, increased left ventricular stiffness, dyslipidaemia and fatty liver. Administration of G. mangostana rind as 5% of the food to rats with diet-induced metabolic syndrome gave a dose of 168 mg/kg/day ?-mangostin, 355 mg/kg/day procyanidins, 3.9 mg/kg/day anthocyanins and 11.8 mg/kg/day hydroxycitric acid for 8 weeks which reduced body weight and attenuated physiological and metabolic changes in rats including decreased abdominal fat deposition, decreased abdominal circumference and whole-body fat mass, improved liver structure and function and improved cardiovascular parameters such as systolic blood pressure, left ventricular stiffness and endothelial function. These responses were associated with decreased infiltration of inflammatory cells, decreased deposition of collagen in both heart and liver and decreased mean adipocyte size in retroperitoneal adipose tissues. We conclude that, in rats with diet-induced metabolic syndrome, chronic intake of G. mangostana rind decreased infiltration of inflammatory cells which decreased physiological, metabolic, liver and cardiovascular symptoms.
Project description:Uncontrolled regulation of cyclin dependent kinases (CDKs) has negative implications in many cancers and malignancies and has recently led to the approval of select CDK inhibitors. Herein we present data reporting that xanthones, a class of compounds isolated from the purple mangosteen (<i>Garcinia mangostana</i>) fruit, can inhibit CDK2/CyclinE1. We evaluated nine different xanthones, including α-mangostin, β-mangostin, γ-mangostin, gartanin, 8-desoxygartanin, garcinone C, garcinone D, 9-hydroxycalabaxanthone, and 3-isomangostin for toxicity in 22Rν1 (prostate cancer cells) and MDA-MB-231 (breast cancer cells). All compounds dose-dependently inhibited the viability of both cell lines. A cell free biochemical assay was performed to determine if selected phytochemicals inhibited CDK2/CyclinE1. γ-Mangostin and α-mangostin were the strongest inhibitors, respectively. The results suggest that the position of key functional groups including hydroxyl and isoprenyl groups contribute to the CDK2 inhibitory effect. Taken together, the evidence suggests that xanthones can directly target CDK2 providing a possible explanation for their therapeutic potential.
Project description:Metabolic syndrome is a cluster of disorders that increase the risk of cardiovascular disease and diabetes. This study has investigated the responses to rind of yellow mangosteen (Garcinia dulcis), usually discarded as waste, in a rat model of human metabolic syndrome. The rind contains higher concentrations of phytochemicals (such as garcinol, morelloflavone and citric acid) than the pulp. Male Wistar rats aged 8-9 weeks were fed either corn starch diet or high-carbohydrate, high-fat diet for 16 weeks, which were supplemented with 5% freeze-dried G. dulcis fruit rind powder during the last 8 weeks. We characterised metabolic, cardiovascular, liver and gut microbiota parameters. High-carbohydrate, high-fat diet-fed rats developed abdominal obesity, hypertension, increased left ventricular diastolic stiffness, decreased glucose tolerance, fatty liver and reduced Bacteroidia with increased Clostridia in the colonic microbiota. G. dulcis fruit rind powder attenuated these changes, improved cardiovascular and liver structure and function, and attenuated changes in colonic microbiota. G. dulcis fruit rind powder may be effective in metabolic syndrome by appetite suppression, inhibition of inflammatory processes and increased fat metabolism, possibly related to changes in the colonic microbiota. Hence, we propose the use of G. dulcis fruit rind as a functional food to ameliorate symptoms of metabolic syndrome.
Project description:This study investigated the in vivo and in vitro activity of ?-mangostin (?-MG), the most abundant xanthone in mangosteen pericarp, on HT-29 cell tumorigenicity, proliferation, and several markers of tumor cell activity, as well as the profile and amounts of xanthones in serum, tumor, liver, and feces.Balb/c nu/nu mice were fed either control diet or diet containing 900 mg ?-MG/kg. After 1 week of acclimation to diet, mice were injected subcutaneously with HT-29 cells and fed the same diets ad libitum for an additional 2 or 4 weeks. After 2 and 4 weeks, tumor mass and the concentrations of BcL-2 and ?-catenin in tumors of mice fed diet with ?-MG were significantly less than in mice fed control diet. Xanthones and their metabolites were identified in serum, tumor, liver, and feces. In vitro treatment of HT-29 cells with ?-MG also inhibited cell proliferation and decreased expression of BcL-2 and ?-catenin.Our data demonstrate that the anti-neoplastic effect of dietary ?-MG is associated with the presence of xanthones in the tumor tissue. Further investigation of the impact of beverages and food products containing xanthones on the prevention of colon cancer or as complementary therapy is merited.
Project description:Bacterial wilt caused by Ralstonia solanacearum is one of the most destructive bacterial diseases in agriculture. There is no effective control method, although chemical pesticides are used to prevent this disease, but they may lead to serious problems of environmental pollution. Natural products from plants can be rich and environmentally friendly sources for a broad spectrum biological control of bacteria. This study focuses on the pericarp of mangosteen (Garcinia mangostana) using bioactivity-guided analysis of different fractions and liquid chromatography-mass spectrometry combined with multivariate analysis to determine markers of active fractions. Six prenyl xanthones, including two new xanthones, garcimangosxanthones H and I, were isolated and identified by NMR and HRESIMS. The biomarker ?-mangostin displayed significant activity against the phytopathogen R. solanacearum with an IC50 of 34.7 ± 1.5 ?g/mL; ?-mangostin affected the bacterial morphology at a concentration of 16.0 ?g/mL as seen with a scanning electron microscope image, and it significantly repressed the virulence-associated genes HrpB, FihD, and PilT of R. solanacearum. ?-Mangostin also reduced the symptoms of bacterial wilt disease effectively that is caused by R. solanacearum in tomato and tobacco seedlings in vitro. These results suggested that the use of ?-mangostin from the mangosteen pericarp against R. solanacearum may be used as a natural bacteriostatic agent in agriculture.
Project description:This study investigated the chemical composition and antimicrobial activity of propolis collected from two stingless bee species Tetragonula laeviceps and Tetrigona melanoleuca (Hymenoptera: Apidae). Six xanthones, one triterpene and one lignane were isolated from Tetragonula laeviceps propolis. Triterpenes were the main constituents in T. melanoleuca propolis. The ethanol extract and isolated compounds from T. laeviceps propolis showed a higher antibacterial activity than those of T. melanoleuca propolis as the constituent ?-mangostin exhibited the strongest activity. Xanthones were found in propolis for the first time; Garcinia mangostana (Mangosteen) was the most probable plant source. In addition, this is the first report on the chemical composition and bioactivity of propolis from T. melanoleuca.
Project description:Bioassay-guided fractionation of an ethanol extract of the pericarps of Garcinia mangostana led to the isolation of two new prenylated xanthones, named 1,3,7-trihydroxy-2-(3-methyl-2-butenyl)-8-(3-hydroxy-3-methylbutyl)-xanthone (1) and 1,3,8-trihydroxy-2-(3-methyl-2-butenyl)-4-(3-hydroxy-3-methylbutanoyl)-xanthone (2), together with the five known compounds garcinones C (3) and D (4), gartanin (5), xanthone I (6), and ?-mangostin (7). Their structures were elucidated primarily based on MS and NMR data. Compounds 1-7 showed significant cytotoxic activities against various human cancer cell lines.
Project description:Low-grade chronic adipose tissue inflammation contributes to the onset and development of aging-related insulin resistance and type 2 diabetes. In the current study, ?-mangostin, a xanthone isolated from mangosteen (Garcinia mangostana), was identified to ameliorate lipopolysaccharides-induced acute adipose tissue inflammation in mice, by reducing the expression of pro-inflammatory cytokines and chemokines. In a cohort of young (3 months) and old (18-20 months) mice, ?-mangostin mitigated aging-associated adiposity, hyperlipidemia, and insulin resistance. Further study showed that ?-mangostin alleviated aging-related adipose tissue inflammation by reducing macrophage content and shifting pro-inflammatory macrophage polarization. Moreover, ?-mangostin protected the old mice against liver injury through suppressing the secretion of microRNA-155-5p from macrophages. The above results demonstrated that ?-mangostin represents a new scaffold to alleviate adipose tissue inflammation, which might be a novel candidate to treat aging-related metabolic disorders.
Project description:Among a series of xanthones identified from mangosteen, the fruit of Garcinia mangostana L. (Guttifereae), ?- and ?-mangostins are known to be major constituents exhibiting diverse biological activities. However, the effects of ?-mangostin on oxidative neurotoxicity and impaired memory are yet to be elucidated. In the present study, the protective effect of ?-mangostin on oxidative stress-induced neuronal cell death and its underlying action mechanism(s) were investigated and compared to that of ?-mangostin using primary cultured rat cortical cells. In addition, the effect of orally administered ?-mangostin on scopolamine-induced memory impairment was evaluated in mice. We found that ?-mangostin exhibited prominent protection against H2O2- or xanthine/xanthine oxidase-induced oxidative neuronal death and inhibited reactive oxygen species (ROS) generation triggered by these oxidative insults. In contrast, ?-mangostin had no effects on the oxidative neuronal damage or associated ROS production. We also found that ?-mangostin, not ?-mangostin, significantly inhibited H2O2-induced DNA fragmentation and activation of caspases 3 and 9, demonstrating its antiapoptotic action. In addition, only ?-mangostin was found to effectively inhibit lipid peroxidation and DPPH radical formation, while both mangostins inhibited ?-secretase activity. Furthermore, we observed that the oral administration of ?-mangostin at dosages of 10 and 30?mg/kg markedly improved scopolamine-induced memory impairment in mice. Collectively, these results provide both in vitro and in vivo evidences for the neuroprotective and memory enhancing effects of ?-mangostin. Multiple mechanisms underlying this neuroprotective action were suggested in this study. Based on our findings, ?-mangostin could serve as a potentially preferable candidate over ?-mangostin in combatting oxidative stress-associated neurodegenerative diseases including Alzheimer's disease.
Project description:The proposed health-promoting effects of the pericarp from mangosteen fruit have been attributed to a family of polyphenols referred to as xanthones. The purpose of this study was to determine the bioavailability of xanthones from 100% mangosteen juice in healthy adult participants (n = 10). Pericarp particles accounted for 1% of the mass and 99% of the xanthone concentration in the juice. The juice provided 5.3 ± 0.1 mmol/L total xanthones with ?-mangostin, garcinones (C, D, and E), ?-mangostin, gartanins, and other identified xanthones accounting for 58, 2, 6, 4, and 5%, respectively. Participants ingested 60 mL mangosteen juice with a high-fat breakfast. Free and conjugated (glucuronidated/sulfated) xanthones were detected in serum and urine. There was marked variation in the AUC (762-4030 nmol/L × h), maximum concentration (113 ± 107 nmol/L), and time to maximum concentration (3.7 ± 2.4 h) for ?-mangostin in sera during the 24-h collection. Similarly, xanthones in 24-h urine ranged from 0.9 to 11.1 ?mol and accounted for 2.0 ± 0.3% (range 0.3-3.4%) of the ingested dose. There were no significant differences between female and male participants in mean pharmacokinetic values of ?-mangostin in serum and urinary xanthones. Only 15.4 ± 0.7% of total xanthones in pericarp particles in the juice partitioned into mixed micelles during in vitro digestion. These results show that xanthones in mangosteen juice are absorbed when ingested along with a high-fat meal, although release of xanthones from pericarp particles during digestion may be limited.
Project description:We previously demonstrated that ?-mangostin, ?-mangostin, and 8-deoxygartanin have significant cytotoxic effects on human melanoma SK-MEL-28 cell line. The current study revealed the underlying mechanisms. ?-Mangostin (7.5? ?g/mL) activated caspase activity, with a 3-fold and 4-fold increased caspase 8 and 9 activity, respectively. The molecular mechanisms were investigated by qRT-PCR for mRNA related to cell cycle arrest in G1 phase (p21(WAF1) and cyclin D1), apoptosis (cytochrome C, Bcl-2, and Bax), and survival pathways (Akt1, NF?B, and I?B?). ?-Mangostin significantly upregulated mRNA expression of cytochrome C and p21(WAF1) and downregulated that of cyclin D1, Akt1, and NF?B. ?-Mangostin significantly downregulated mRNA expression of Akt1 and NF?B and upregulated p21(WAF1) and I?B?. 8-Deoxygartanin significantly upregulated the mRNA expression of p21(WAF1) and downregulated that of cyclin D1 and NF?B. The three xanthones significantly inhibited the mRNA expression of the BRAF V600E mutation. Moreover, ?-mangostin and ?-mangostin significantly downregulated Akt phosphorylation at Ser473. In conclusion, the three xanthones induced an inhibitory effect on SK-MEL-28 cells by modulating the molecular targets involved in the apoptotic pathways.