The chemical constituents from the stems and leaves of Cratoxylum cochinchinense were isolated and purified using silica gel, ODS gel, and Sephadex LH-20 gel column chromatography, as well as preparative HPLC. The chemical structures of all isolated compounds were identified on the basis of their physicochemical properties, spectroscopic analyses, and the comparison of their physicochemical and spectroscopic data with the reported data in literature. As a result, 21 compounds were isolated from the 90% ethanol extract of the stems and leaves of C. cochinchinense, which were identified as cratocochine(1), 1-hydroxy-3,7-dimethoxyxanthone(2), 1-hydroxy-5,6,7-trimethoxyxanthone(3), ferrxanthone(4), 3,6-dihydroxy-1,5-dimethoxyxanthone(5), 3,6-dihydroxy-1,7-dimethoxyxanthone(6), 1,2,5-trihydroxy-6,8-dimethoxyxanthone(7), securixanthone G(8), gentisein(9), 3,7-dihydroxy-1-methoxyxanthone(10), pancixanthone B(11), garcimangosxanthone A(12), pruniflorone L(13), 9-hydroxy alabaxanthone(14), cochinchinone A(15), luteolin(16), 3,5'-dimethoxy-4',7-epoxy-8,3'-neolignane-5,9,9'-triol(17), N-benzyl-9-oxo-10E,12E-octadecadienamide(18), 15-hydroxy-7,13E-labdadiene(19), stigmasta-4,22-dien-3-one(20), and stigmast-5-en-3β-ol(21). Among these isolates, compound 1 was a new xanthone, compounds 2-5, 7, 8, 12, and 16-21 were isolated from the Cratoxylum plant for the first time, and compounds 11 and 13 were obtained from C. cochinchinense for the first time. Furthermore, all isolated compounds 1-21 were appraised for their anti-rheumatoid arthritis activities by MTS method through measuring their anti-proliferative effect on synoviocytes in vitro. As a result, xanthones 1-15 displayed notable anti-rheumatoid arthritis activities, which showed inhibitory effects on the proliferation of MH7A synoviocytes with the IC_(50) values ranging from(8.98±0.12) to(228.68±0.32) μmol·L~(-1).
Synoviocytes ; Clusiaceae/chemistry* ; Xanthones/analysis* ; Plant Leaves/chemistry* ; Cell Proliferation ; Arthritis

Eight compounds were isolated from ethyl acetate fraction of 80% ethanol extract of the hulls of Garcinia mangostana by silica gel, Sephadex LH-20 column chromatography, as well as prep-HPLC methods. By HR-ESI-MS, MS, 1D and 2D NMR spectral analyses, the structures of the eight compounds were identified as 16-en mangostenone E(1), α-mangostin(2), 1,7-dihydroxy-2-(3-methy-lbut-2-enyl)-3-methoxyxanthone(3), cratoxyxanthone(4), 2,6-dimethoxy-para-benzoquinone(5), methyl orselinate(6), ficusol(7), and 4-(4-carboxy-2-methoxyphenoxy)-3,5-dimethoxybenzoic acid(8). Compound 1 was a new xanthone, and compound 4 was a xanthone dimer, compound 5 was a naphthoquinone. All compounds were isolated from this plant for the first time except compounds 2 and 3. Cytotoxic bioassay suggested that compounds 1, 2 and 4 possessed moderate cytotoxicity, suppressing HeLa cell line with IC_(50) va-lues of 24.3, 35.5 and 17.1 μmol·L~(-1), respectively. Compound 4 also could suppress K562 cells with an IC_(50) value of 39.8 μmol·L~(-1).
Humans ; Garcinia mangostana/chemistry* ; HeLa Cells ; Antineoplastic Agents ; Magnetic Resonance Spectroscopy ; Xanthones/pharmacology* ; Garcinia/chemistry* ; Plant Extracts/chemistry* ; Molecular Structure

OBJECTIVE: To analyze the effects of mangiferin combined with bortezomib on the proliferation, invasion, apoptosis and autophagy of human Burkitt lymphoma Raji cells, as well as the expression of CXC chemokine receptors (CXCRs) family, and explore the molecular mechanism between them to provide scientific basis for basic research and clinical work of Burkitt lymphoma. METHODS: Raji cells were intervened with different concentrations of mangiferin and bortezomib alone or in combination, then cell proliferation was detected by CCK-8 assay, cell invasion ability was detected by Transwell chamber method, cell apoptosis was detected by Annexin V/PI double-staining flow cytometry, apoptosis, autophagy and Akt/mTOR pathway protein expression were detected by Western blot, and the expression changes of CXCR family was detected by real-time quantitative PCR (RT-qPCR). RESULTS: Different concentrations of mangiferin intervened Raji cells for different time could inhibit cell viability in a concentration- and time-dependent manner (r =-0.682, r =-0.836). When Raji cells were intervened by combination of mangiferin and bortezomib, compared with single drug group, the proliferation and invasion abilities were significantly decreased, while the apoptosis level was significantly increased (P <0.01). Mangiferin combined with bortezomib could significantly up-regulate the expression of pro-apoptotic protein Bax and down-regulate the expression of anti-apoptotic protein Bcl-2 after intervention in Raji cells. Caspase-3 was also hydrolyzed and activated, and then induced the apoptosis of Raji cells. Mangiferin combined with bortezomib could up-regulate the expression of LC3Ⅱ protein in Raji cells, and the ratio of LC3Ⅱ/LC3Ⅰ in cells was significantly up-regulated compared with single drug or control group (P <0.01). Mangiferin combined with bortezomib could significantly inhibit the phosphorylation levels of Akt and mTOR, inhibit the proliferation and invasion of Raji cells by inhibiting Akt/mTOR pathway, and induce cell autophagy and apoptosis. Mangiferin and bortezomib could down-regulate the expressions of CXCR4 and CXCR7 mRNA after single-agent intervention in Raji cells, and the down-regulations of CXCR4 and CXCR7 mRNA expression were more significant when the two drugs were combined (P <0.01). Mangiferin alone or combined with bortezomib had no significant effect on CXCR5 mRNA expression in Raji cells (P >0.05), while the combination of the two drugs could down-regulate the expression of CXCR3 (P <0.05). CONCLUSION Mangiferin combined with bortezomib can synergistically inhibit the proliferation and invasion of Raji cells, and induce autophagy and apoptosis. The mechanism may be related to the inhibition of Akt/mTOR signaling pathway, down-regulation of anti-apoptotic protein Bcl-2 and up-regulation of pro-apoptotic protein Bax, and the inhibition of the expression of CXCR family.
Humans ; Antineoplastic Agents/therapeutic use* ; Apoptosis/drug effects* ; Apoptosis Regulatory Proteins/immunology* ; Autophagy/immunology* ; bcl-2-Associated X Protein/immunology* ; Bortezomib/therapeutic use* ; Burkitt Lymphoma/immunology* ; Cell Line, Tumor ; Cell Proliferation/drug effects* ; Drug Therapy, Combination ; Proto-Oncogene Proteins c-akt ; Proto-Oncogene Proteins c-bcl-2 ; Receptors, CXCR/immunology* ; RNA, Messenger ; TOR Serine-Threonine Kinases ; Xanthones/therapeutic use*

Repeated silica gel column chromatography, reversed-phase C_(18) column chromatography, Sephadex LH-20 column chromatography, high performance liquid chromatography and semi-preparative medium pressure liquid chromatography were performed to separate and purify the chemical constituents of Hypericum lagarocladum. Spectroscopic methods such as mass spectrometry(MS) and nuclear magnetic resonance(NMR) combined with physicochemical properties were adopted in identifying the structure of the isolated compounds. Ten compounds were isolated from the ethyl acetate fraction of H. lagarocladum and identified as lagarxanthone A(1), 1,7-dihydroxyxanthone(2), 3,4,5-trihydroxyxanthone(3), 2,7-dihydroxy-1-methoxyxanthone(4), 1,3-dihydroxy-7-methoxyxanthone(5), 1,5-dihydroxy-8-methoxyxanthone(6), 3,4-dihydroxy-2-methoxyxanthone(7), 3,4-dihydroxy-5-methoxyxanthone(8), 2,3-dimethoxyxanthone(9), and 2,3,4-trimethoxyxanthone(10). Among them, compound 1 was a new compound, and compounds 2-10 were isolated from this plant for the first time. These ten compounds were tested for glucose uptake in L6 cells, and the results showed that all the compounds had no significant effect on glucose uptake.
Hypericum/chemistry* ; Xanthones ; Chromatography, High Pressure Liquid ; Magnetic Resonance Spectroscopy ; Glucose

Hypericum species are distributed widely in China, especially in the southwest. This genus is rich in species types in China, including 55 species and 8 subspecies. The main chemical constituents of Hypericum species are flavonoids, xanthones and polycyclic polyprenylated acylphloroglucinols(PPAPs). PPAPs are characterized by polycyclic and branched-chain substitutions in their structures, which make their structure types diverse. Moreover, they have been found to have antitumor, antiviral, antibacterial, anti-inflammatory and other biological activities. This research classified and summarized 344 polycyclic polyprenylated acylphloroglucinols from Hypericum plants in order to provide a scientific basis for further development and utilization of PPAPs from the genus.
Flavonoids ; Hypericum ; Molecular Structure ; Phloroglucinol/pharmacology* ; Xanthones

OBJECTIVES: Chondrocyte apoptosis is an important process in the pathogenesis of osteoarthritis. Mangiferin exerts multiple pharmacological effects such as anti-inflammatory and anti-apoptosis. However, the role of mangiferin in chondrocyte apoptosis is not clear. In this study, we aimed to explore the role of mangiferin in IL-1β-induced chondrocyte apoptosis. METHODS: ATDC5 cells were randomly divided into a control group, a IL-1β group, a MFN-L group, a MFN-M group, a MFN-H group and a MFN+LY294002 group. Cells in the control group were treated with IL-1β (10 ng/mL) for 24 h; cells in the MFN-L group, the MFN-M group and the MFN-H group were pretreated with 5, 10 and 20 μmol/L mangiferin for 1 h respectively, and then they were treated with IL-1β (10 ng/mL) for 24 h; cells in the MFN+LY294002 group were treated with LY294002 (25 μmol/L) for 1 h, then mangiferin (20 μmol/L) and IL-1β (10 ng/mL) for 1 h and 24 h, respectively. Cell viability was detected by CCK-8 assay and cell apoptosis was measured by flow cytometry. Colorimetric assay was conducted to measure the caspase-3 activity. The protein levels of Bcl-2, Bax, and phosphoinositide 3-kinase (PI3K)/Akt signaling pathway related proteins were detected by Western blotting. RESULTS: Compared to the control group, cell viability was significantly decreased; cell apoptosis, caspase-3 activity and Bax protein expression were significantly increased; the protein levels of Bcl-2, p-PI3K, and p-Akt were significantly decreased in the IL-1β group (all CONCLUSIONS Mangiferin could attenuate IL-1β-induced apoptosis of the mice chondrocytes, which is mediated by the activation of PI3K/Akt signaling pathway.
Animals ; Apoptosis ; Chondrocytes ; Interleukin-1beta ; Mice ; Phosphatidylinositol 3-Kinases ; Proto-Oncogene Proteins c-akt ; Xanthones

To investigate the inhibitory effects of two xanthone compounds, 1-hydroxy-2,3,4,8-4 methoxy xanthone(here in after referred to as Fr15) and 1-hydroxy-2,3,4,6-4 methoxy xanthone(here in after referred to as Fr17), on the proliferation of hepatocellular carcinoma cells HepG2, and to further investigate their mechanism in combination with transcriptomics. Cell counting was used to detect the effects of two kinds of xanthone compounds Fr15 and Fr17(0, 0.03, 0.15, 0.3 mmoL·L~(-1)) on the proliferation of HepG2 cells; the effects of the two compounds Fr15 and Fr17 on HepG2 cell cycle were detected by flow cytometry; the changes of autophagosomes count in cells were observed under fluorescence microscope; the expression of autophagy marker proteins autophagy marker proteins SQSTM 1(p62) and microtubule associated protein 1 light chain 3 Ⅰ/Ⅱ(LC3 Ⅰ/Ⅱ) in the cells was detected by Western blot; the differentially expressed genes between the control group and the experimental group were analyzed by RNA-seq transcriptome sequencing; qRT-PCR was used to verify the differentially expressed genes in sequencing. The results showed that compounds Fr15 and Fr17 inhibited the proliferation of HepG2 cells with the increase of drug concentration and time. Flow cytometry showed that compounds Fr15 and Fr17 had little effect on HepG2 cell cycle. Fluorescence microscopy results showed that the number of autophagosomes in cells increased with the increase of drug concentration. Western blot showed that the expression of p62 protein was decreased and the expression of LC3-Ⅱ protein was significantly increased after drug addition. The results of RNA sequencing showed that 26 102 and 52 351 differentially expressed genes were obtained in Fr15 and Fr17 respectively. Analysis of KEGG showed that drug treatment had a great effect on autophagy pathway. qRT-PCR verified that 6 up-regulated genes were related to autophagy, and their trend was consis-tent with sequencing results, where all 6 genes showed an up-regulated trend. Two xanthone compounds Fr15 and Fr17 may inhibit proliferation of HepG2 cells by inducing autophagy.
Apoptosis ; Autophagy ; Cell Cycle ; Hep G2 Cells ; Xanthones

OBJECTIVE: To investigate the effects of mangiferin on proliferation, apoptosis and cycle of FLT3-ITD mutation-positive acute myeloid leukemia cells and its mechanism. METHODS: The effects of different concentration of mangiferin on proliferation of MV4-11 cells were detected by CCK8 method. Apoptosis, cell cycle and FLT3 transmembrane protein expression were detected by flow cytometry. FLT3 mRNA expression was detected by real-time fluorescent quantitative polymerase chain reaction (PCR) . RESULTS: Mangiferin obviously inhibited MV4-11 proliferation in a concentration and time dependent manner (48 h，r=0.922；72 h，r=0.959；96 h，r=0.973). The ratio of G0/G1 phase in cell cycle increased with the enhancement of concentration of mangiferin in MV4-11 cells for 48 h, and the ratio of S phase decreased with enhasment of concentration. The increase of apoptosis was more obvious. The expression of FLT3 transmembrane protein significantly decreased after the actior of IC50 concentration of mangiferin in MV4-11 cells for 48 h. The results of qRT-PCR showed that the expression of FLT3 mRNA significantly decreased after treatment of MN4-11 cells with mangiferin (P＜0.05). CONCLUSION Mangiferin inhibits MV4-11 cell proliferation, arrests cell cycle progression and promotes apoptosis, which may be related with the inhibition of FLT3 activity by mangiferin and the subsequent signaling pathways involved in apoptosis and proliferation of cells.
Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Humans ; Leukemia, Myeloid, Acute ; Mutation ; Xanthones ; fms-Like Tyrosine Kinase 3

OBJECTIVE: Garcinia mangostana Linn., commonly known as mangosteen, is a tropical fruit with a thick pericarp rind containing bioactive compounds that may be beneficial as an adjunctive treatment for schizophrenia. The biological underpinnings of schizophrenia are believed to involve altered neurotransmission, inflammation, redox systems, mitochondrial dysfunction, and neurogenesis. Mangosteen pericarp contains xanthones which may target these biological pathways and improve symptoms; this is supported by preclinical evidence. Here we outline the protocol for a double-blind randomized placebo-controlled trial evaluating the efficacy of adjunctive mangosteen pericarp (1,000 mg/day), compared to placebo, in the treatment of schizophrenia. METHODS: We aim to recruit 150 participants across two sites (Geelong and Brisbane). Participants diagnosed with schizophrenia or schizoaffective disorder will be randomized to receive 24 weeks of either adjunctive 1,000 mg/day of mangosteen pericarp or matched placebo, in addition to their usual treatment. The primary outcome measure is mean change in the Positive and Negative Symptom Scale (total score) over the 24 weeks. Secondary outcomes include positive and negative symptoms, general psychopathology, clinical global severity and improvement, depressive symptoms, life satisfaction, functioning, participants reported overall improvement, substance use, cognition, safety and biological data. A 4-week post treatment interview at week 28 will explore post-discontinuations effects. RESULTS: Ethical and governance approvals were gained and the trial commenced. CONCLUSION: A positive finding in this study has the potential to provide a new adjunctive treatment option for people with schizophrenia and schizoaffective disorder. It may also lead to a greater understanding of the pathophysiology of the disorder.
Cognition ; Depression ; Fruit ; Garcinia mangostana ; Garcinia ; Inflammation ; Neurogenesis ; Outcome Assessment (Health Care) ; Oxidation-Reduction ; Oxidative Stress ; Psychopathology ; Psychotic Disorders ; Schizophrenia ; Synaptic Transmission ; Xanthones

The present study was undertaken to investigate the isolated compounds from the stem bark of Garcinia atroviridis as potential cholinesterase inhibitors and the ligand-enzyme interactions of selected bioactive compounds in silico. The in vitro cholinesterase results showed that quercetin (3) was the most active AChE inhibitor (12.65 ± 1.57 µg/ml) while garcinexanthone G (6) was the most active BChE inhibitor (18.86 ± 2.41 µg/ml). It is noteworthy to note that compound 6 was a selective inhibitor with the selectivity index of 11.82. Molecular insight from docking interaction further substantiate that orientation of compound 6 in the catalytic site which enhanced its binding affinity as compared to other xanthones. The nature of protein-ligand interactions of compound 6 is mainly hydrogen bonding, and the hydroxyl group of compound 6 at C-10 is vital in BChE inhibition activity. Therefore, compound 6 is a notable lead for further drug design and development of BChE selective inhibitor.
Butyrylcholinesterase ; Catalytic Domain ; Cholinesterase Inhibitors ; Cholinesterases ; Computer Simulation ; Drug Design ; Garcinia ; Hydrogen Bonding ; In Vitro Techniques ; Quercetin ; Xanthones