Structural Characterization, Biological Effects, and Synthetic Studies on Xanthones from Mangosteen (Garcinia mangostana), a Popular Botanical Dietary Supplement

ArticleinMini-Reviews in Organic Chemistry 5(4):355-364 · November 2008with 142 Reads
Abstract
Mangosteen (Garcinia mangostana L., Clusiaceae) is a popular botanical dietary supplement in the United States, where it is used principally as an antioxidant. It is referred to as the "queen of fruits" in Thailand, a country of origin. The major secondary metabolites of mangosteen, the xanthones, exhibit a variety of biological activities including antibacterial, antifungal, antiinflammatory, antioxidant, antiplasmodial, cytotoxic, and potential cancer chemopreventive activities. Moreover, some of the xanthones from mangosteen have been found to influence specific enzyme activities, such as aromatase, HIV-1 protease, inhibitor κB kinase, quinone reductase, sphingomyelinase, topoisomerase and several protein kinases, and they also modulate histamine H(1) and 5-hydroxytryptamine(2A) receptor binding. Several synthetic procedures for active xanthones and their analogs have been conducted to obtain a better insight into structure-activity relationships for this compound class. This short review deals with progress made in the structural characterization of the chemical constituents of mangosteen, as well as the biological activity of pure constituents of this species and synthetic methods for the mangosteen xanthones.

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  • ... Nowadays, the use of natural antioxidants is becoming a public concern. [16][17][18][19][20] One of the functions of xanthone antioxidants is as a hepatoprotective agent. A damaged liver will release enzymes into the blood such as serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), gamma-glutamyl transpeptidase (γGT), and alkaline phosphatase (ALP). ...
    ... Xanthone also neutralizes free radicals, which will prevent further damage of β-cells in the islet of Langerhans. [20] 4. Conclusion Interestingly, this study has proved that the administration of gamma-mangostin was able to lower SGOT and SGPT levels and also ameliorate damaged hepatocytes in diabetic mice significantly, mainly on swollen, hydropic, and necrotic cells. IOP Conf. ...
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    The aim of this study was to investigate whether gamma-mangostin could reduce fasting blood glucose, cholesterol, SGOT, SGPT, and also ameliorate damaged hepatocytes in diabetic mice. In this study, we used male BALB/C mice. Mice were divided into two groups: normal control (KN) and streptozotocin-induced diabetic. Streptozotocin (STZ) induction was performed using multiple low doses of 30 mg/kg body weight injected for five consecutive days. The diabetic mice were separated into three subgroups: diabetic control (KD), diabetic mice treated with acarbose (KA), and diabetic mice treated with gamma-mangostin at either 0,5 mg/kg body weight (P1), 1 mg/kg body weight (P2), or 2 mg/kg body weight (P3). Before and after STZ injection, fasting blood glucose and cholesterol level would be observed. Fasting blood glucose and cholesterol level were also measured at the 1st, 7th, and 14th day of gamma-mangostin treatment. Treatment was given for 14 days. On the 15th day, SGOT and SGPT were measured using a Pentra C 200 Reader, while the liver was collected and processed onto the histological slides. Interestingly, we found that gamma-mangostin was able to reduce the fasting blood glucose, cholesterol, SGOT, SGPT, and ameliorate the damaged hepatocytes in significant diabetic mice. Therefore, we concluded that gamma-mangostin is a promising anti-diabetic agent due to its anti-hyperglycemic and antioxidant activities.
  • ... The edible flesh of the fruit is covered by a thick rind, or pericarp, which is highly bioactive. 14,15 The pericarp is highly resistant to infection and has anti- inflammatory and antioxidant properties that protect the flesh and seed and allow the plant to reproduce suc- cessfully. Mangosteen pericarp has been shown to reduce levels of pro-inflammatory cytokines such as interleukin-6 and tumor necrosis factor-a, suppress cyclooxygenase and nitric oxide synthase, and attenuate mitogen-acti- vated protein kinase (MAPK) levels in vitro. ...
    ... 14 Lastly, mangosteen pericarp has been shown to affect levels of neurotransmitters and their recept- ors, including acetylcholine, acetylcholine esterase, and 5-hydroxytryptamine 2A receptors, the latter a common target for some antipsychotics and antidepressants. 15,21 A recent study in a translational animal model of depres- sion (Flinders Sensitive Line rat) found marked antidepres- sant and pro-cognitive effects of mangosteen pericarp, as well as a reduction in hippocampal lipid peroxidation and correction of disordered regional brain monoamines. 22 As the constituents of mangosteen pericarp also reduce oxi- dative stress and inflammation and improve neurogenesis, it appears to be a viable agent for exploration as an adjunc- tive therapy for bipolar depression. ...
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    Objective: Bipolar depression is characterized by neurobiological features including perturbed oxidative biology, reduction in antioxidant levels, and a concomitant rise in oxidative stress markers. Bipolar depression manifests systemic inflammation, mitochondrial dysfunction, and changes in brain growth factors. The depressive phase of the disorder is the most common and responds the least to conventional treatments. Garcinia mangostana Linn, commonly known as mangosteen, is a tropical fruit. The pericarp's properties may reduce oxidative stress and inflammation and improve neurogenesis, making mangosteen pericarp a promising add-on therapy for bipolar depression. Methods: Participants will receive 24 weeks of either 1,000 mg mangosteen pericarp or placebo per day, in addition to their usual treatment. The primary outcome is change in severity of mood symptoms, measured using the Montgomery-Åsberg Depression Rating Scale (MADRS), over the treatment phase. Secondary outcomes include global psychopathology, quality of life, functioning, substance use, cognition, safety, biological data, and cost-effectiveness. A follow-up interview will be conducted 4 weeks post-treatment. Conclusion: The findings of this study may have implications for improving treatment outcomes for those with bipolar disorder and may contribute to our understanding of the pathophysiology of bipolar depression. Clinical trial registration: Australian and New Zealand Clinical Trial Registry, ACTRN12616000028404.
  • ... The most abundant xanthones in the mangosteen fruits are α-mangostin and γmangostin, and among these α-mangostin is reported to have antioxidant, antiinflammatory, anticancer, and antimicrobial activities [62][63][64][65]. ...
    ... The minimum inhibitory concentration of α-mangostin was between 1.25-50 μg ml À1 for bacteria and 1-5 μg ml À1 for fungi, respectively. Various scientists [62,81] evaluated the effect of α-mangostin against Methicillinresistant Staphylococus aureus (MRSA) and results revealed that minimum inhibitory values ranging between 1.57-12.5 μg ml À1. Gopalakrishnan et al. [27] demonstrated the potentiality of α-mangostin against phytopathogenic fungi, Fusarium oxysporum vasinfectum, Alternaria tenuis, and Drechslera oryzae. ...
  • ... Xanthone, a biologically active polyphenolic compound, isolated from G. mangostana have been shown to be a potent antioxidant, anti-inflammatory, and antidiabetic activities [10]. About sixty-eight xanthones such as α-mangostin, β-mangostin, γ-mangostin, garcinone C, garcinone D, 8-Desoxygartanin, and mangostenone E have been identified in G. mangostana [11]. In human umbilical vein endothelial (ECV304) cell line, the methanolic fraction of G. mangostana exhibited cytoprotective effect by lowering H 2 O 2 -induce ECV304 cell damage. ...
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    Hyperglycemia is well-known for inducing cellular oxidative damage in type II diabetes (T2D) patients. This research addressed the cytoprotective and anti-genotoxic effects of xanthone derivatives from Garcinia mangostana against hydrogen peroxide (H2O2)-induced human peripheral blood mononuclear cell (PBMC) and blood leucocytes damage of the normal and T2D volunteers. The cytoprotective effects of an aqueous extract of xanthone (100 and 200 µg/mL) was assessed by cell viability and free radical scavenging activity using the trypan blue exclusion method on PBMC cells. Malondialdehyde (MDA) level and lactate dehydrogenase (LDH) activity were measured as cellular oxidative damage markers and estimated from culture medium of PBMCs of normal and T2D volunteers. The anti-genotoxicity was assessed as the protective effect of xanthone against H2O2-induce DNA damage of blood leucocytes of the normal volunteers following comet assay technique. Xanthone and Gallic acid (control) concentrations 100, 200 and 100 µg/mL significantly (P < 0.05) protected from H2O2 (20 mM)-induced oxidative damage of PBMCs. It was confirmed by increased cell viability and free radical scavenging activity coupled with the decreased MDA and LDH levels in cell culture medium compared to H2O2 (20 mM)-treated group. In H2O2 (40 mM)-induced blood leucocytes of normal volunteers, different concentration xanthone (50 - 500 µg/mL) significantly (P < 0.05) improved the anti-genotoxicity effect compared to negative/positive control group by lowering comet formation. Xanthone treatments on PBMCs and blood leucocytes of the normal and T2D volunteers could attenuate the H2O2-induced cellular oxidative damage and cell death via exhibiting antioxidant and free radical scavenging activities.
  • ... The isolated compound was suggested as flavonoid due to the TLC chromatogram after was sprayed with AlCl 3 solution. AlCl 3 formed complex with hydroxyl groups and neighboring ketone (C-4 in ring C and C-5 on ring A). 7 This result was supported by UV-Vis spectrum. 8 The UV spectrum formed two bands on λ 355 and 275 nm which can be deduced that the isolate was flavonoid. ...
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    Objective: This research was conducted to screen inhibition of HIV-1 reverse transcriptase activity of selected Indonesia medicinal plants and to isolate HIV-1 reverse transcriptase inhibitor from Erythrina variegata leaves. Method: Screening inhibition of HIV-1 RT activity of selected Indonesia medicinal plants and isolated compounds were performed using HIV-1 RT colorimetric assay. The isolation of HIV-1 reverse transcriptase inhibitor was conducted using chromatography technique. The isolated compound was determined based on the data of UV, IR spectrophotometry, MS, 1D and 2D NMR spectroscopy. Results: Beside that, in vitro study of the leaves methanolic extract exhibited inhibition against HIV-1 RT activity with percent inhibition of 97.64% at concentration of 5 mg/mL. Ethyl acetate fraction from the extract showed the strongest HIV-1 RT inbitory activity with IC50 of 429.28 μg/mL. Isolation the HIV-1 RT inhibitor from the fraction give compound 1. Conclusion: Erythrina variegata leave extract exhibited potent inhibition on HIV-1 RT activity. The isolated compound from the leaves was determined as apigenin-7-O-β-D-glucopyranoside and demonstrated HIV-1 RT inhibitory activity with the IC50 value of 100.59 μg/mL.
  • ... Cancer treatments are aimed to treatment, prolong and improve patient quality of life. Garcinia mangostana Linn or commonly known as mangosteen is a plant from Guttiferae family and have been used traditionally for the treatment of skin infections and wound, amoebic dysentery and inflammation ( Chaverri et al. 2008;Chin & Kinghorn 2008). These plants contain xanthone-type compounds, flavonoids, triterpenoids, benzophenones, biphenyl compounds, pyrrole, benzofuran, tannins, and saponins ( Chaverri et al. 2008;Hutapea 1994). ...
  • ... γ-Mangostin, garcinone A, 1,5-dihydroxy-3-methoxy xanthone, garcinone B and garcinone C were present in the stem bark. Xanthones were especially noted for their potential antitumour and chemopreventive abilities along with other biological activities such as antibacterial, antifungal, antiviral, antioxidant and anti-inflammatory ( Chin and Kinghorn 2008;Peres et al. 2000). The benzophenones identified from the fruits were gambogenone, aristophenone A, garcinol and garciyunnanin A. Aristophenone A and garcinol were present in the leaves, while none of the benzophenones were detected in the stem bark of G. travancorica. ...
  • Article
    Objective: Acne is a chronic skin disease that involves four key pathogenic factors: excess sebum production, ductal epidermal hyperproliferation, Propionibacterium acnes (P. acnes) colonization, and skin inflammation. Mangostins are well-known for their anti-bacterial and anti-inflammatory effects, suggesting that mangostins may have therapeutic potential for acne. The present study aimed to explore the anti-acne effects of mangostins from the perspective of multiple pathogenic mechanisms of acne. Methods: The effects of α- and γ-mangostins on the growth of P. acnes and lipase activity were analyzed. Their effects on P. acnes-induced keratinocyte proliferation were examined by CCK-8. The expression of inflammatory genes and activation of NF-κB and MAPK signaling pathways were detected by quantitative real-time PCR and western blotting, respectively. Results: Alpha- and γ-mangostins not only inhibited the growth of P. acnes, but also reduced the proliferation of keratinocytes induced by heat-killed P. acnes. Furthermore, α- and γ-mangostins were able to suppress P. acnes-induced expression of pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6 in keratinocytes by inhibiting the activation of NF-κB and MAPK signaling pathways. Discussion and conclusions: Mangostins appeared to possess multiple anti-acne activities, including the inhibition of P. acnes growth, regulation of keratinocytes proliferation, and attenuation of skin inflammatory reaction. Hence, mangostins might be developed into a potential therapeutic agent for the treatment of acne.
  • Article
    There is abundant evidence for both disorganized redox balance and cognitive deficits in major depressive disorder (MDD). Garcinia mangostana Linn (GM) has anti-oxidant activity. We studied the antidepressant-like and pro-cognitive effects of raw GM rind in Flinders Sensitive Line (FSL) rats, a genetic model of depression, following acute and chronic treatment compared to a reference antidepressant, imipramine (IMI). The chemical composition of the GM extract was analysed for levels of α- and γ-mangostin. The acute dose-dependent effects of GM (50, 150 and 200 mg/kg po), IMI (20 mg/kg po) and vehicle were determined in the forced swim test (FST) in FSL rats, versus Flinders Resistant Line (FRL) control rats. Locomotor testing was conducted using the open field test (OFT). Using the most effective dose above coupled with behavioral testing in the FST and cognitive assessment in the novel object recognition test (nORT), a fixed dose 14-day treatment study of GM was performed and compared to IMI- (20 mg/kg/day) and vehicle-treated animals. Chronic treated animals were also assessed with respect to frontal cortex and hippocampal monoamine levels and accumulation of malondialdehyde. FSL rats showed significant cognitive deficits and depressive-like behavior, with disordered cortico-hippocampal 5-hydroxyindole acetic acid (5-HIAA) and noradrenaline (NA), as well as elevated hippocampal lipid peroxidation. Acute and chronic IMI treatment evoked pronounced antidepressant-like effects. Raw GM extract contained 117 mg/g and 11 mg/g α- and γ-mangostin, respectively, with acute GM demonstrating antidepressant-like effects at 50 mg/kg/day. Chronic GM (50 mg/kg/d) displayed significant antidepressant- and pro-cognitive effects, while demonstrating parity with IMI. Both behavioral and monoamine assessments suggest a more prominent serotonergic action for GM as opposed to a noradrenergic action for IMI, while both IMI and GM reversed hippocampal lipid peroxidation in FSL animals. Concluding, FSL rats present with cognitive deficits and depressive-like behaviors that are reversed by acute and chronic GM treatment, similar to that of IMI.