Tsung-Hsien Chou

Cytotoxic flavonoids from the leaves of Cryptocarya chinensis.

Bioassay-guided fractionation led to the isolation of six new tetrahydroflavanones, cryptochinones A-F (1-6), from the neutral CHCl(3) fraction of Cryptocarya chinensis leaves, together with 14 known compounds (7-20). The structures of these new compounds were determined through spectroscopic analyses, including 2D-NMR, MS, CD, and X-ray crystallographic analysis. Among the isolates, infectocaryone (7) showed cytotoxic activities with IC(50) values of 11.0 and 3.7 μM against NCI-H460 and SF-268 cell lines, respectively, and cryptocaryanone A (9) showed cytotoxic activities with IC(50) values of 5.1, 4.3, and 5.0 μM against MCF-7, NCI-H460, and SF-268 cell lines, respectively.

Phthalides from Pittosporum illicioides var. illicioides with Inhibitory Activity on Superoxide Generation and Elastase Release by Neutrophils

Six new phthalides, (S)-3-ethyl-7-hydroxy-6-methoxyphthalide (1), (S)-3-ethyl-7-hydroxy-5,6-dimethoxyphthalide (2), (S)-3-ethyl-5,6,7-trimethoxyphthalide (3), (R)-3-ethyl-7-hydroxy-6-methoxyphthalide (4), (Z)-3-ethylidene-7-hydroxy-6-methoxyphthalide (5), and (Z)-3-ethylidene-6,7-dimethoxyphthalide (6), have been isolated from the root of Pittosporum illicioides var. illicioides, together with seven known compounds. The structures of these new compounds were determined through spectroscopic and MS analyses. Compounds 1-4 exhibited inhibition (IC50<or=29.8 microM) of superoxide anion generation by human neutrophils in response to formyl-L-methionyl-L-leucyl-L-phenylalanine/cytochalasin B (fMLP/CB). Compounds 5 and 6 inhibited fMLP/CB-induced elastase release with IC50 values of 38.6+/-4.3 and 33.9+/-3.9 microM, respectively.

Cryptocaryone, a Natural Dihydrochalcone, Induces Apoptosis in Human Androgen Independent Prostate Cancer Cells by Death Receptor Clustering in Lipid Raft and Nonraft Compartments

PURPOSE Androgen refractory prostate cancer is a major clinical challenge. Treatment approaches to prostate cancer are based on various mechanisms that cause malignant cell apoptosis. Of these strategies the anticancer effect of triggering death receptors is well substantiated. MATERIALS AND METHODS Several pharmacological and biochemical assays were used to characterize the apoptotic signaling pathways of the natural dihydrochalcone cryptocaryone in prostate cancer cells. RESULTS Cryptocaryone induced antiproliferative and apoptotic effects in human androgen independent prostate cancer cells. It induced caspase-8 and 3 activation but did not change total protein levels of death receptors and their ligands. DR5 surface expression was moderately increased by cryptocaryone. Confocal immunofluorescence examination showed that cryptocaryone induced Fas clustering and the association of downstream signaling molecules, including FADD and procaspase-8. DR4 and DR5 aggregation was also induced by cryptocaryone. Data were confirmed by protein profile analysis of detergent resistant membranes showing that Fas, DR4, DR5, FADD and procaspase-8 levels were increased 1.3, 3.5, 4.1, 13.1 and 4.1-fold, respectively, in the lipid raft compartment. Cryptocaryone mediated clustering of death receptors and associated molecules was also detected in nonraft compartments. The distribution between lipid raft and nonraft compartments was validated by the cholesterol depleting agent methyl-beta-cyclodextrin. Cryptocaryone significantly potentiated FasL induced apoptosis in PC-3 cells. CONCLUSIONS We suggest that cryptocaryone has anticancer activity via the stimulation of death receptor and associated molecule clustering, leading to caspase-8 and 3 activation, and apoptosis in prostate cancer cells.

A new dihydroagarofuranoid sesquiterpene and antituberculosis constituents from the root of Microtropis japonica.

A new dihydroagarofuran‐based sesquiterpene, 15‐acetoxyorbiculin A (1), was isolated from the root of Microtropis japonica, together with 13 known compounds. Their structures were determined through in‐depth spectroscopic and mass‐spectrometric analyses. Among the isolated compounds, celahin C (6) and salasol A (7) exhibited potent in vitro antituberculosis activity, both with an MIC value of 15.0 μg/ml against Mycobacterium tuberculosis H37Rv.

New flavanones from the leaves of Cryptocarya chinensis and their antituberculosis activity.

Four new flavanones, cryptoflavanones A–D (1–4, resp.), together with eight known compounds, were isolated from the leaves of Cryptocarya chinensis. The structures of these new compounds were determined by spectral analyses. Among the isolated compounds, pinocembrin (5) and cryptocaryone (6) exhibited antituberculosis activity against Mycobacterium tuberculosis H37Rv strain in vitro with MIC values of 3.5 and 25.0 μg/ml, respectively.

A New Ferulic Acid Ester, a New Ellagic Acid Derivative, and Other Constituents from Pachycentria formosana: Effects on Neutrophil Pro- Inflammatory Responses

A new ferulic acid ester derivative, tetracosane‐1,24‐diyl di[(Z)‐ferulate] (1), and a new ellagic acid derivative, 3,4 : 3′,4′‐bis(O,O‐methylene)ellagic acid (2), have been isolated from leaves and twigs of Pachycentria formosana, together with eight known compounds. Their structures were determined by in‐depth spectroscopic and mass‐spectrometric analyses. Among the isolated compounds, oleanolic acid (6), ursolic acid acetate (7), and 3‐epibetulinic acid (9) exhibited potent inhibition (IC50 values ≤21.8 μM) of O2⋅− generation by human neutrophils in response to N‐formyl‐L‐methionyl‐L‐leucyl‐L‐phenylalanine/cytochalasin B (fMLP/CB). In addition, oleanolic acid (6), 3‐O‐[(E)‐feruloyl]ursolic acid (8), 3‐epibetulinic acid (9), and lawsonic acid (10) also inhibited fMLP/CB‐induced elastase release with IC50 values ≤18.6 μM.

Cryptochinones from Cryptocarya chinensis act as farnesoid X receptor agonists.

Cryptochinones A-D are tetrahydroflavanones isolated from the leaves of Cryptocarya chinensis, an evergreen tree whose extracts are believed to have a variety of health benefits. The origin of their possible bioactivity is unclear. The farnesoid X receptor (FXR) is a member of nuclear receptor superfamily that has been widely targeted for developing treatments for chronic liver disease and for hyperglycemia. We studied whether cryptochinones A-D, which are structurally similar to known FXR ligands, may act at this target. Indeed, in mammalian one-hybrid and transient transfection reporter assays, cryptochinones A-D transactivated FXR to modulate promoter action including GAL4, SHP, CYP7A1, and PLTP promoters in dose-dependent manner, while they exhibited similar agonistic activity as chenodeoxycholic acid (CDCA), an endogenous FXR agonist. Through molecular modeling docking studies we evaluated their ability to bind to the FXR ligand binding pocket. Our results indicate that cryptochinones A-D can behave as FXR agonists.

Orthoquinone and Naphthalenone Derivatives from Berrya ammonilla and Their Anti-Inflammatory Activity

A new orthoquinone, berryammone A (1), and four new naphthalenone derivatives, berryammone B (2), berryammone C (3), 6-O-methylberryammone C (4), and 4-O-methylberryammone C (5), have been isolated from the stem of Berrya ammonilla, together with eleven known compounds (6-16). The structures of these new compounds were determined through spectroscopic and MS analyses. Among the isolates, compounds 1-3, 5, (+)-pinoresinol (6), and betulinic acid (12) exhibited inhibition (IC50 ≤ 4.41 µM) of superoxide anion generation by human neutrophils in response to formyl-L-methionyl-L-leucyl-L-phenylalanine/cytochalasin B (fMLP/CB). Compounds 1, 2, and 5 also inhibited fMLP/CB-induced elastase release with IC50 values ≤ 3.95 µM.