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

The recent progresses on chemical components and pharmacological activities of the genus Gentiana were summarized. The main chemical constituents of this genus are iridoids, xanthone and flavone. There were more than ninety iridoid compounds, one hundred xanthone compounds, and thirty four flavone compounds isolated up till now. And flavone compounds were obtained mainly from aerial part. The plants of this genus had broad bioactivities such as antifungal activity, anti-inflammatory activity and liver protective effect. These mentioned above would be helpful for further studies on the plants of the genus Gentiana.
Animals ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Flavones ; Flavonoids ; chemistry ; pharmacology ; Gentiana ; chemistry ; Humans ; Xanthones ; chemistry ; pharmacology

This study was aimed to explore the potential therapy of Gambogic acid (GA) combined with magnetic nanoparticle of Fe3O4 (Fe3O4-MNP) on leukemia. The proliferation of U937 cells and the cytotoxicity were evaluated by MTT assay. Cell apoptosis was observed and analyzed by microscopy and flow cytometry respectively. The expressions of gene and protein were detected by quantitative real-time polymerase chain reaction and Western blot respectively. The results showed that GA enhanced the cytotoxicity for U937 cells in dose- and time-dependent manners. The Fe3O4-MNP itself had not cytotoxicity, but could enhance the inhibitory effect of GA on proliferation of U937 cells. The apoptotic rate of U937 cells induced by combination of GA with Fe3O4-MNP was higher than that by GA alone. The typical apoptotic features of cells treated with GA and Fe3O4-MNP were observed. The expression levels of caspase-3 and bax after co-treatment of GA and Fe3O4-MNP were higher than that exposed to GA or Fe3O4-MNP alone, but the expressions of bcl-2, NF-kappaB and survivin were down-regulated. It is concluded that Fe3O4-MNP can promote GA-induced apoptosis in U937 cells, and the combination of GA with Fe3O4-MNP may be a safer and less toxic new therapy for leukemia.
Apoptosis ; drug effects ; Humans ; Iron Compounds ; administration & dosage ; pharmacology ; Magnetics ; Nanoparticles ; U937 Cells ; Xanthones ; pharmacology

OBJECTIVE: To explore the inhibitive effects of 1,3,8-trihydroxy-5-methoxyxanthone (TMX) on cytochrome P450s (CYP450s) in human liver microsomes. METHODS: Probe drugs were incubated with and without adding TMX to determine the changes of enzyme activities. The concentration ratio of metabolites to probe drugs was used to present enzyme activities. Concentrations of the probe drugs and their metabolites in the incubated mixture were detected by high performance liquid chromatography. RESULTS: The variations (mean, 95%CI) of the activities of CYP1A2, CYP2C9, CYP2C19, CYP2E1 and CYP3A4 were 2.95 x 10(-3) (2.03 x 10(-3), 3.88 x 10(-3)), 3.14 x 10(-2) (1.87 x 10(-2), 4.42 x 10(-2)), 2.27 x 10(-3) (-1.4 x 10(-2),1.81 x 10(-2)), 7.72 x 10(-2) (-0.83 x 10(-2), 0.2374), and -0.2548 (-2.9802, 2.4707), respectively. The activities of CYP1A2 and CYP2C9 were significantly reduced in the present of TMX. CONCLUSION TMX (10 micromol/L) has significant inhibitive effect on the activities of CYP1A2 and CYP2C9, but no significant inhibitive effect on the activities of CYP2C19, CYP2E1 and CYP3A4.
Cytochrome P-450 Enzyme System ; metabolism ; Humans ; Microsomes, Liver ; drug effects ; enzymology ; Xanthones ; pharmacology

Five compounds (tenuifoliside C, tenuifoliside D, telephiose A, telephiose C and polygalaxanthone III) from polygala tenuifolia wild were incubated together with CYP probe substrate in human liver microsomes to investigate the inhibitory effect towards CYP450 enzyme. Phenacetin (CYP1A2), coumarin (CYP2A6), paclitaxel (CYP2C8), diclofenac (CYP2C9), S-mepheriytoin (CYP2C19), dextromethorphan (CYP2D6), chlorzoxazone (CYP2E1), midazolam (CYP3A) were selected as the isoforfn specific substrate. And the formation of paracetamol, 7-hydroxycoumarin, 6alpha-hydroxy paclitaxel, 4'-hydroxydiclofenac, dextrorphan, 6-hydroxychlorzoxazone, 1'-hydroxymidazolam, 4'-hydroxymephenytoin were detected respectively to measure the effect towards CYP450 by high-pressure liquid chromatography (HPLC). The result shows that five compounds from polygala tenuifolia willd significantly inhibit chlorzoxazone 6-hydroxylation catalyzed by CYP2E1, while showed no effect towards CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A. And IC50 value was 38.73, 54.14, 61.77, 62.22, 50.56 micromol x L(-1), respectively.
Cytochrome P-450 Enzyme System ; metabolism ; Esters ; pharmacology ; Glycosides ; pharmacology ; Humans ; Microsomes, Liver ; drug effects ; enzymology ; Oligosaccharides ; pharmacology ; Polygala ; chemistry ; Xanthones ; pharmacology

OBJECTIVETo investigate the role of chloride channels in the apoptosis of poorly differentiated nasopharyngeal carcinoma CNE-2Z cells induced by gambogic acid (GA).

METHODSMTT assay was applied to detect the proliferation of CNE-2Z cells after GA treatment, and the cell apoptosis was detected by Hoechst 33342 staining. Whole-cell patch clamp technique was employed to record GA-activated Cl(-) currents in the cells.

RESULTSGA inhibited the cell proliferation in a time- and concentration-dependent manner with an IC(50) of 3.1 µmol/L for a 48-h treatment. The apoptosis-inducing effect of 8 µmol/L GA was attenuated by the chloride channel blocker NPPB (100 µmol/L) and tamoxifen (20 µmol/L). GA induced an outward-rectified Cl(-) current in the cells, which was significantly inhibited by NPPB.

CONCLUSIONGA suppresses cell proliferation and induces apoptosis by activating Cl(-) channels in CNE-2Z cells, suggesting the important role of Cl(-) channels in GA-induced apoptosis.

Apoptosis ; drug effects ; Cell Line, Tumor ; Chloride Channels ; drug effects ; physiology ; Humans ; Nasopharyngeal Neoplasms ; pathology ; Patch-Clamp Techniques ; Xanthones ; pharmacology

This study was aimed to investigate the effects and the mechanism of mangiferin on chronic myeloid leukemia cell lines K562 cells in vitro. The antiproliferation effects of mangiferin on K562 leukemia cells were tested by tetrazolium salt (MTT) method; the apoptosis induced by mangiferin on K562 cell line was explored by means of cell morphology, DNA gel electrophoresis and flow cytometry. The changes in bcr/abl gene expression was detected by using reverse transcriptase (RT)-PCR. The results showed that five different concentrations of mangiferin (25 - 200 micromol/L) dose-dependently and time-dependently inhibited the proliferation of K562 cells, and induced apoptosis in K562 cell line. RT-PCR revealed that bcr/abl gene expression was down-regulated when K562 cells had been treated with different concentrations of mangiferin. In conclusion, mangiferin remarkably inhibits the proliferation of K562 leukemia cells in vitro, and induces apoptosis in K562 cell line probably through down-regulation of bcr/abl gene expression.
Apoptosis ; drug effects ; Cell Proliferation ; drug effects ; DNA Fragmentation ; drug effects ; Flow Cytometry ; Genes, abl ; Humans ; K562 Cells ; Xanthones ; pharmacology

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

Mangosteen (Garcinia mangostana Linn.) is a well-known tropical tree indigenous to Southeast Asia. Its fruit's pericarp abounds with a class of isoprenylated xanthones which are referred as mangostins. Numerous in vitro and in vivo studies have shown that mangostins and their derivatives possess diverse pharmacological activities, such as antibacterial, antifungal, antimalarial, anticarcinogenic, antiatherogenic activities as well as neuroprotective properties in Alzheimer's disease (AD). This review article provides a comprehensive review of the pharmacological activities of mangostins and their derivatives to reveal their promising utilities in the treatment of certain important diseases, mainly focusing on the discussions of the underlying molecular targets/pathways, modes of action, and relevant structure-activity relationships (SARs). Meanwhile, the pharmacokinetics (PK) profile and recent toxicological studies of mangostins are also described for further druggability exploration in the future.
Animals ; Anti-Infective Agents ; pharmacology ; Anticarcinogenic Agents ; pharmacology ; Antineoplastic Agents, Phytogenic ; pharmacology ; Antioxidants ; pharmacology ; Cardiovascular Agents ; pharmacology ; Fruit ; chemistry ; Garcinia mangostana ; chemistry ; Humans ; Neuroprotective Agents ; pharmacology ; Phytotherapy ; Plant Extracts ; pharmacology ; Protective Agents ; pharmacology ; Xanthones ; pharmacology

To observe the protective effect of alpha-mangostin (α-MG) on focal segmental glomurular sclerosis (FSGS) induced by adriamycin.
 Methods: Adriamycin nephropathy (AN) model was induced by adriamycin (10 mg/kg) via a tail vein. Then the mice were treated with α-MG (12.5 mg/kg) or normal salin once daily for 6 weeks. At the end of 6 weeks, the mice were sacrificed, and the kidneys and blood samples were collected. Histopathology of the kidneys were analyzed under the optical microscope. The serum levels of biochemical indicators, such as serum creatinine (SCr), blood urea nitrogen (BUN) and cholesterol were determined. The levels of superoxide anion, malondialdehyde (MDA), and glutathione (GSH), the activity of superoxide dismutase (SOD) and catalase (CAT) in kidney tissues were determined. Serum levels of IL-1β, IL-18, IL-10 and adiponectin were determined. The levels of TGF-β1, collagen I (Col I), α-SMA, silent information regulator 1 (Sirt1) and the nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) in kidney tissues were determined using immunohistochemical staining, Western blot, and RT-PCR.
 Results: The levels of SCr, proteinuria, urine protein to creatinine ratio and serum cholesterol were attenuated in AN mice after α-MG treatment, while creatinine clearance rate and serum albumin were upregulated (P<0.05). α-MG treatment alleviated the glomerular and interstitial fibrosis, downregulated the expression of fibrosis markers, such as Col I and α-SMA (P<0.05). α-MG treatment reduced the production of superoxide anion, the levels of MDA and GSH, and increased the activity of CAT and SOD (P<0.05). α-MG treatment inhibitd the generation of pro-inflammatory cytokines, such as IL-1β and IL-18 and promoted the production of anti-inflammatory cytokines, such as the IL-10 and adiponectin (P<0.05); α-MG treatment promoted the expression of Sirt1, inhibitd the expression of NLRP3 in kidney tissues (P<0.05).
 Conclusion: α-MG could attenuates FSGS of mice induced by adriamycin ameliorate and improve renal function. α-MG exerts its anti-inflammatory and anti-oxidative effects by up-regulation the expression of Sirt1 and suppression of NLRP3.
Animals ; Disease Models, Animal ; Doxorubicin ; Glomerulosclerosis, Focal Segmental ; chemically induced ; Kidney ; drug effects ; Mice ; Mice, Inbred NOD ; Protein Kinase Inhibitors ; pharmacology ; therapeutic use ; Xanthones ; pharmacology ; therapeutic use