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In China, the endemic species Garcinia yunnanensis and native Garcinia xanthochymus are known as edible and medicinal plants. However, a systematic metabolomic and bioactivity evaluation of different plant parts from both species is lacking. In this study, comprehensive investigations of 11 plant parts of G. yunnanensis and 10 of G. xanthochymus employing UPLC-ESI-QTOF-MS E -based metabolomic analysis in conjunction with three bioactivity assays were undertaken. A customized chemotaxonomic-based in-house library containing 6456 compounds was constructed and coupled to the Progenesis QI informatic platform for metabolite annotations. From these two species, a total of 235 constituents were characterized using multiple criteria. Differences in metabolite profiles between the plant parts within each species were uncovered using multivariate analysis. Based on orthogonal partial least-squares discriminant analysis (OPLS-DA), 23 markers were identified as highly differential metabolites from G. xanthochymus and 20 from G. yunnanensis . Comparative assessment of the biological assays revealed the activity variations among different plant parts. The seeds of both species and G. yunnanensis latex exhibited excellent cytotoxic and antibacterial activities, while G. xanthochymus roots and G. yunnanensis arils showed strong anti-inflammatory effects. S -plot analysis identified 26 potential biomarkers for the observed activities, including the known cytotoxic agent cycloxanthochymol and the anti-inflammatory compound garcimultiflorone B, which likely explains some of the potent observed bioactivity.

Garcinia xanthochymus fruits are edible and also used in traditional medicine. Our previous work showed that the isolated natural products from G. xanthochymus fruits have displayed antioxidant activity and cytotoxicity in the colon cancer cells. In this study, we developed a strategy to correlate a zebrafish angiogenesis assay with ultra-performance liquid chromatography quadrupole time of flight mass spectrometry-based chemometric analysis to identify potential anti-angiogenic activity compounds from G. xanthochymus fruits. Primary bioactivity results showed that the methanolic extracts from aril and pericarp but not from seed have significant inhibitory effects on the growth of subintestinal vessels (SIVs) in zebrafish embryos. A total of 13 markers, including benzophenones and biflavonoids, were predicted by untargeted principal component analysis and orthogonal partial least squares discriminate analysis, which were tentatively identified as priority markers for the bioactivity related in aril and pericarp. Amentoflavone, a biflavonoid, has been found to significantly inhibit the growth of SIVs at 10 and 20 μM and downregulate the expressions of Angpt2 and Tie2 genes of zebrafish embryos. Furthermore, seven biflavonoids, volkensiflavone, fukugetin, fukugeside, GB 1a, GB 1a glucoside, GB 2a, and GB 2a glucoside, isolated from Garcinia species were evaluated for their structure-activity relationship using the zebrafish model. Only fukugetin, which was previously shown to be anticancer, was active in inhibiting the SIV growth. In this report, both amentoflavone and fukugetin, for the first time, displayed anti-angiogenic effects on zebrafish, thus demonstrating an effective and rapid strategy to identify natural products for anti-angiogenesis activity.

A number of Garcinia species accumulate benzophenone derivatives that may be useful for the treatment of breast cancer. The dereplication of new benzophenone derivatives from Garcinia species is challenging due to the occurrence of multiple isomers and the known compounds found in their extracts. In the current study, a strategy is described using the UPLC-QTOFMS(E) technique to identify tentatively the known and uncharacterized benzophenones of interest based upon the characteristic fragmentation ions. Several UPLC-QTOFMS peaks (a-ee) appeared to contain benzophenone derivatives, and 12 of these peaks contained compounds with MS ionization profiles not consistent with previously identified compounds from the seeds of Garcinia paucinervis, an endangered Chinese species. The targeted isolation of unidentified compounds of interest afforded five new benzophenones, paucinones E-I (1-5), which were determined by MS and NMR analysis and ECD spectroscopy. These compounds were evaluated for cytotoxicity against three breast cancer cell lines inclusive of MDA-MB-231, SKBR3, and MCF-7. These results indicate that the UPLC-QTOFMS(E)-guided isolation procedure is an efficient strategy for isolating new benzophenones from Garcinia species.

Garcinia oblongifolia Champ. ex Benth. (Clusiaceae) is a well-known medicinal plant from southern China, with edible fruits. However, the phytochemistry and bioactivity of the different plant parts of G. oblongifolia have not been studied extensively. Comparative metabolic profiling and bioactivities of the leaf, branch, and fruit of G. oblongifolia were investigated. A total of 40 compounds such as biflavonoids, xanthones, and benzophenones were identified using UPLC-QTOF-MS and MS(E), including 15 compounds reported for the first time from this species. Heatmap analyses found that benzophenones, xanthones, and biflavonoids were predominately found in branches, with benzophenones present in relatively high concentrations in all three plant parts. Xanthones were found to have limited distribution in fruit while biflavonoids were present at only low levels in leaves. In addition, the cytotoxic (MCF-7 breast cancer cell line) and antioxidant (ABTS and DPPH chemical tests) activities of the crude extracts of G. oblongifolia indicate that the branch extract exhibits greater bioactivity than either the leaf or the fruit extracts. Orthogonal partial least squares discriminate analysis was used to find 12 marker compounds, mainly xanthones, from the branches, including well-known antioxidants and cytotoxic agents. These G. oblongifolia results revealed that the variation in metabolite profiles can be correlated to the differences in bioactivity of the three plant parts investigated. This UPLC-QTOF-MS strategy can be useful to identify bioactive constituents expressed differentially in the various plant parts of a single species., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Xanthochymol and garcinol, isoprenylated benzophenones purified from Garcinia xanthochymus fruits, showed multiple activities against Candida albicans biofilms. Both compounds effectively prevented emergence of fungal germ tubes and were also cytostatic, with MICs of 1 to 3 μM. The compounds therefore inhibited development of hyphae and subsequent biofilm maturation. Xanthochymol treatment of developing and mature biofilms induced cell death. In early biofilm development, killing had the characteristics of apoptosis, including externalization of phosphatidyl serine and DNA fragmentation, as evidenced by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) fluorescence. These activities resulted in failure of biofilm maturation and hyphal death in mature biofilms. In mature biofilms, xanthochymol and garcinol caused the death of biofilm hyphae, with 50% effective concentrations (EC50s) of 30 to 50 μM. Additionally, xanthochymol-mediated killing was complementary with fluconazole against mature biofilms, reducing the fluconazole EC50 from >1,024 μg/ml to 13 μg/ml. Therefore, xanthochymol has potential as an adjuvant for antifungal treatments as well as in studies of fungal apoptosis., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Species of Garcinia have been used to combat malaria in traditional African and Asian medicines, including Ayurveda. In the current study, we have identified antiplasmodial benzophenone and xanthone compounds from edible Garcinia species by testing for in vitro inhibitory activity against Plasmodium falciparum. Whole fruits of Garcinia xanthochymus, G. mangostana, G. spicata, and G. livingstonei were extracted and tested for antiplasmodial activity. Garcinia xanthochymus was subjected to bioactivity-guided fractionation to identify active partitions. Purified benzophenones (1-9) and xanthones (10-18) were then screened in the plasmodial lactate dehydrogenase assay and tested for cytotoxicity against mammalian (Vero) cells. The benzophenones guttiferone E (4), isoxanthochymol (5), and guttiferone H (6), isolated from G. xanthochymus, and the xanthones α-mangostin (15), β-mangostin (16), and 3-isomangostin (17), known from G. mangostana, showed antiplasmodial activity with IC50 values in the range of 4.71-11.40 µM. Artemisinin and chloroquine were used as positive controls and exhibited IC50 values in the range of 0.01-0.24 µM. The identification of antiplasmodial benzophenone and xanthone compounds from G. xanthochymus and G. mangostana provides evidence for the antiplasmodial activity of Garcinia species and warrants further investigation of these fruits as dietary sources of chemopreventive compounds., (Georg Thieme Verlag KG Stuttgart · New York.)

Previous studies indicate that extracts and purified components from Garcinia species inhibit the growth of human colon cancer cells. Garcinia benzophenones activate the expression of genes in the endoplasmic reticulum and cellular energy stress (mTOR) pathways. This study examines the growth inhibitory and synergistic effects of Garcinia benzophenones, alone or combined with chemopreventive agents, on human colon cancer cells. To find optimal combination treatments, HT29 colon cancer cells were treated with benzophenones alone, or combined with chemopreventive agents, and cell growth measured using the MTT assay. To reveal effects on signaling pathways, we assessed effects of the MEK inhibitor U0126 and the ER IP3 receptor antagonist heparin, as well as effects on the phosphorylation of 4E-BP-1 (mTOR pathway), using Western blot analysis. New and known benzophenones from Garcinia intermedia inhibited the growth of human colon cancer cells; an alcohol extract of Garcinia xanthochymus, as well as purified guttiferones (guttiferone E and xanthochymol), preferentially inhibited the growth of colon cancer versus nonmalignant intestinal epithelial cells. Guttiferone E exhibited synergy with the NSAID sulindac sulfide and xanthochymol, with the spice turmeric. Guttiferone A did not alter phosphorylation of 4E-BP-1, indicating that the mTORC1 pathway is not involved in its action. The effects of xanthochymol were enhanced by U0126, at low doses, and were blocked by heparin, indicating that the MEK pathway is involved, while the ER IP3 receptor is critical for its action. These studies indicate the potential of benzophenones, alone or combined with sulindac sulfide or turmeric, to prevent and treat colon cancer.

A series of 13 known compounds, including seven benzophenones [guttiferone A (1), guttiferone K (2), xanthochymol (3), guttiferone E (4), cycloxanthochymol (5), isoxanthochymol (6), and gambogenone (7)], five biflavonoids [amentoflavone (8), 3,8''-biapigenin (9), (+)-volkensiflavone (10), (+)-morelloflavone (11), and (+)-fukugiside (12)], and the xanthone derivative alloathyriol (13), were identified from the fruits of Garcinia livingstonei (Clusiaceae). This is the first time that compounds 2-7, 9, 12, and 13 have been reported in this species. The cytotoxicity of benzophenones 1 and 2 was assessed for their effect on HCT-116, HT-29, and SW-480 human colon cancer cell lines. Both compounds exhibited strong activity against HCT-116 and HT-29 cell lines with IC(50) values between 5 and 10 microM, and somewhat weaker activity with SW-480 cells (IC(50) values ranging from 18 to 25 microM).

A MeOH extract of Garcinia xanthochymus fruits was subjected to activity-guided fractionation, yielding two new benzophenones, guttiferone H (1) and gambogenone (2). Compound 1 contains a seven-membered ring attached to the bicyclo[3.3.1]nonane system at positions 7 and 8 and displayed cytotoxicity in the SW-480 colon cancer cell line (IC(50) = 12 microM). Compound 2 has a novel benzophenone bicyclo[3.3.2]decane system and displayed cytotoxicity in the SW-480 colon cancer cell line (IC(50) = 188 microM). Both 1 and 2 induced apoptosis in SW-480 colon cancer cells and displayed antioxidant activity in the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay (IC(50) = 64 and 38.7 microM, respectively). The structures of 1 and 2 were established by 1D and 2D NMR data analysis. Eleven known compounds, aristophenone A, alloathyriol, amentoflavone, 3,8' '-biapigenin, cycloxanthochymol, (+/-)-fukugetin, (+/-)-fukugiside, guttiferone E, isoxanthochymol, (+/-)-volkensiflavone, and xanthochymol, were also obtained. The 11 known compounds were also tested against SW-480 colon cancer cells and in the DPPH assay.

Abstract: Eight Garcinia species including seven edible fruits, Garcinia aristata, G. hombroniana, G. intermedia, G. livingstonei, the “superfruit”G. mangostana, G. spicata, and G. xanthochymus, and the wood of G. kola were analyzed using a validated high-performance liquid chromatography photo-diode array (HPLC-PDA) method. Three benzophenones, guttiferone A, guttiferone E, and xanthochymol, and four biflavonoids amentoflavone, fukugeside, fukugetin, and volkensiflavone were identified and quantified by HPLC-PDA with authentic standards to verify their identity. Garcinia intermedia (IC50 =60.1±27.3μg/mL) and G. mangostana (IC50 =64.3±11.3μg/mL) fruits demonstrated the highest antioxidant activity. The highest level of xanthochymol was found in G. spicata (70.50±1.10mg/g dry weight), while the highest quantity of guttiferone A was detected in G. intermedia (43.00±0.30mg/g dry weight), and thus was determined to be rich in total phenolic content. [Copyright &y& Elsevier]