Search

Nine neolignan derivatives (1-9) were characterized from the roots of Magnolia officinalis, and their structures were elucidated based on spectroscopic and physicochemical analyses. Among them, houpulins E (1) and M (9) possess novel homo- and trinor-neolignan skeletons. In addition, 15 known compounds (10-24) were identified by comparison of their spectroscopic and physical data with those reported in the literature. Some of the purified constituents were examined for anti-inflammatory activity and, among the tested compounds, houpulins G (3), I (5), J (6), and 2,2'-dihydroxy-3-methoxy-5,5'-di-(2-propenylbiphenyl) (19) significantly inhibited superoxide anion generation and elastase release with IC50 values ranging from 3.54 to 5.48 μM and 2.16 to 3.39 μM, respectively. Therefore, these neolignan derivatives have tremendous potential to be explored as anti-inflammatory agents.

6,7-Methylenedioxy (or 5-hydroxy-6-methoxy)-2-(substituted selenophenyl)quinolin-4-ones and their isosteric compounds were synthesized and evaluated for anticancer activity. Structure–activity relationships (SAR) of these compounds were established. Among all tested compounds, 6,7-methylenedioxy-2-(5-methylselenophen-2-yl)quinolin-4-one (4d) was found to be the most promising anticancer agent. In screening against NCI’s 60 human tumor cell line panel, 4d exhibited highly selective and potent inhibitory activity against MDA-MB-435 melanoma. Furthermore, the results of COMPARE analysis suggested that 4d is an antimitotic agent with a different mechanism of action from the conventional antimitotic agents, such as colchicine, vinca alkaloids and paclitaxel. Therefore, 4d was identified as a new lead compound that merits further optimization.

Three new compounds: Graviquinone (1), cis-3-hydroxy-5-pentadecylcyclohexanone (2), and methyl 5-ethoxy-2-hydroxycinnamate (3), and thirty-eight known compounds were isolated and identified from the leaves of Grevillea robusta. The structures of these compounds were determined by spectroscopic and chemical transformation methods. Graviquinone (1) showed the strongest cytotoxicity against MCF-7, NCI-H460, and SF-268 cell lines. Methyl 2,5-dihydroxycinnamate (4), graviphane (13), and dehydrograviphane (14) exhibited very potent DPPH scavenging activity compared with α-tocopherol. Methyl 2,5-dihydroxycinnamate (4) and bis-norstriatol (17) demonstrated strong inhibition of L-DOPA oxidation by mushroom tyrosinase compared with kojic acid.

A new ‘one-flask’ synthesis of 3,5-disubstituted 1,2,4-triazoles has successfully been developed to synthesize a series of 3,5-disubstituted 1,2,4-triazoles. The transformation involves the 1,3-dipolar cycloaddition reaction of hydrazonoyl hydrochlorides with oxime intermediates prepared from aldehydes with hydroxylamine hydrochloride in the presence of excess amount of triethylamine. In this ‘one-flask’ 1,3-dipolar reaction, hydrazonoyl hydrochlorides was concerned as the masked 1,3-dipole nitrilimine under basic condition. Furthermore, this newly developed methodology can be applied to various aldehyde substrates including aliphatic, cyclic aliphatic, aromatic, and heterocyclic aldehydes.

Novel heteroatom-incorporated antofine and cryptopleurine analogues were designed, synthesized, and tested against a panel of five cancer cell lines. Two new S-13-oxo analogues (11 and 16) exhibited potent cell growth inhibition in vitro (GI(50): 9 nM and 20 nM). Interestingly, both compounds displayed improved selectivity among different cancer cell lines, in contrast to the natural products antofine and cryptopleurine. Mechanism of action (MOA) studies suggested that R-antofine promotes dysregulation of DNA replication during early S phase, while no similar effects were observed for 11 and 15 on corresponding replication initiation complexes. Compound 11 also showed greatly reduced cytotoxicity against normal cells and moderate antitumor activity against HT-29 human colorectal adenocarcinoma xenograft in mice without overt toxicity.

Some chalcones exert potent anti-inflammatory activities. Mannich bases of heterocyclic chalcones inhibited nitric oxide (NO) production in lipopolysaccharide and interferon-γ stimulated RAW 264.7 macrophages. Also Formyl-Met-Leu-Phe and cytochalasin B induced superoxide anion generation ( O 2 · - ) and elastase release in human neutrophils. Mannich bases of heterocyclic chalcone analogs exhibited potent inhibitory effects on NO production with IC50 values ranges between 10.5 and 0.018 μM, O 2 · - generation (IC50 39.87–0.68 μM) and elastase release (IC50 39.74–0.95 μM). Compound 29 (IC50 0.055 μM) and 34 (IC50 0.018 μM) were showed excellent inhibition on NO production. On the other hand, compounds 2 and 8 showed potent inhibition on O 2 · - generation and elastase release. Therefore, these four compounds may be new leads for development of anti-inflammatory activities. The structure–activity relationships are also discussed.

Two new saponins, panajaponol (1) and pseudoginsenoside RT1 butyl ester (2), together with 35 known compounds (3-37), were isolated from the roots of Panax japonicus var. major. The structures of 1 and 2 were elucidated on the basis of spectroscopic analysis and chemical methods. Furthermore, a LC-MS/MS method was developed for confirming 2, 3, and 8 as natural compounds containing a butyl ester group. This method should be useful for distinguishing between minor natural and artifactual compounds in Panax species. Moreover, compounds 3, 6, 8, 9, 11, 13, and 15 exhibited strong inhibition of superoxide anion generation and elastase release by human neutrophils in response to formyl-l-methionyl-l-leucyl-l-phenylalanine/cytochalasin B (fMLP/CB), with IC(50) values ranging from 0.78 to 43.6 μM. In addition, 1 showed greater than 2- to 3-fold selective cytotoxic activity against KB and DU145 cancer cell lines.

A series of novel bichalcone analogs were synthesized and evaluated in lipopolysaccharide (LPS)-activated microglial cells as inhibitors of nitric oxide (NO) and for in vitro anticancer activity using a limited panel of four human cancer cell lines. All analogs inhibited NO production. Compounds 4 and 11 exhibited optimal activity with IC(50) values of 0.3 and 0.5 μM, respectively, and were at least 38-fold better than the positive control. A mechanism of action study showed that both compounds significantly blocked the nuclear translocation of NF-κB p65 and up-regulation of iNOS at 1.0 μM. Compound 4 and three other analogs (3, 20, and 23) exerted significant in vitro anticancer activity GI(50) values ranging from 0.70 to 13.10 μM. A mode of action study using HT-29 colon cancer cells showed that 23 acts by inducing apoptosis signaling.

In the present study, various 1-substituted and 1,3-disubstituted β-carboline derivatives were synthesized by a modified single-step Pictet-Spengler reaction. The compounds were examined for cytotoxicity and anti-inflammatory activity, as measured by the inhibition of prostaglandin E(2) (PGE(2)) production and nitric oxide (NO) production. While only two compounds (28 and 31) showed marginal cytotoxicity against four human cancer cell lines, most of the tested compounds exhibited potent inhibitory activity of both NO and PGE(2) production. Moreover, compounds 6 and 16 significantly reduced the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2), suggesting that β-carboline analogs can inhibit NO and PGE(2) production at the translational level. In addition, several of the β-carboline derivatives (1, 2, 4-8, 11, 13, 22, 25, 27, 31, and 41-43) displayed significant inhibitory activity of superoxide anion (O(2)(·-)) generation or elastase release compared to the reference compound, with 6 being the most potent. N-Formyl-L-methionyl-phenylalanine (FMLP)-induced phosphorylation of c-JunN-terminal kinase (JNK) and protein kinase B (AKT) were also inhibited by 6, suggesting that it suppresses human neutrophil functions by inhibiting the activation of JNK and AKT signaling pathways. Therefore, the synthetic 1-benzoyl-3-carboxy β-carboline analogs may have great potential to be developed as anti-inflammatory agents.

Twenty-four secondary metabolites, including 16 isoflavonoids, 7 astragalasides, and 1 benzoquinone, have been isolated from the roots of Astragalus membranaceus (Astragali radix). Among these isolated isoflavonoids, (-)-methylinissolin 3-O-β-d-(6'-acetyl)-glucoside (1), (-)-methylinissolin 3-O-β-d-{6'-[(E)-but-2-enoyl]}-glucoside (2), and calycosin 7-O-β-d-(6''-acetyl)-glucoside (3) have been identified as new compounds on the basis of spectroscopic analysis; (-)-methylinissolin 3-O-β-d-glucoside (4) was isolated from the natural products for the first time. The nitric oxide (NO) production inhibitory activity of the major compounds has been assessed in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. To identify A. membranaceus, a fingerprint method was developed by using a high-performance liquid chromatography-evaporative light scattering detector (HPLC-ELSD) method. Furthermore, characteristic peaks for the 11 major compounds in the chromatogram were unambiguously confirmed.

Melatonin (5-15 mg/kg) protects male animals against ischemic stroke. We explored the potential interactions and synergistic neuroprotection of melatonin and estrogen using a panel of lipid peroxidation and radical-scavenging assays, primary neuronal cultures subjected to oxygen-glucose deprivation (OGD), and lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Neuroprotective efficacy of melatonin was also evaluated in both reproductively active and ovariectomized female rats subjected to transient focal cerebral ischemia. Relative to melatonin or estradiol (E2) alone, a combination of the two agents exhibited robust, synergistic antioxidant and radical-scavenging actions (P

The chalcone basic skeleton is a unique template which is associated with widespread biological activities. In the present study, a series of novel bichalcones linked with a 1,4-dimethylenepiperazine moiety was prepared through Mannich reaction and Clasien-Schmidt condensation. The synthetic analogs 2-16 were subjected into the cytotoxicity examinations using a panel of 25 human tumor cell lines. Among the tested compounds, 3 and 4 which possessed the 3-pyridyl and phenyl groups as the substructure, respectively, displayed significant cytotoxicity against all the tumor cell lines. The results suggested that these bichalcones were potential to be the anticancer lead drugs.

Five new benzenoids, benzocamphorins A–E ( 1 – 5 ), and 10 recently isolated triterpenoids, camphoratins A–J ( 16 – 25 ), together with 23 known compounds including seven benzenoids ( 6 – 12 ), three lignans ( 13 – 15 ), and 13 triterpenoids ( 26 – 38 ) were isolated from the fruiting body of Taiwanofungus camphoratus . Their structures were established by spectroscopic analysis. Selected compounds were examined for cytotoxic and anti-inflammatory activities. Compounds 9 and 21 showed moderate cytotoxicity against MCF-7 and Hep2 cell lines with ED 50 values of 3.4 and 3.0 μg/mL, respectively. Compounds 21 , 25 , 26 , 29 – 31 , 33 , and 36 demonstrated potent anti-inflammatory activity by inhibiting lipopolysaccharide (LPS)-induced nitric oxide (NO) production with IC 50 values of 2.5, 1.6, 3.6, 0.6, 4.1, 4.2, 2.5, and 1.5 μM, respectively, which were better than those of the nonspecific nitric oxide synthase (NOS) inhibitor N -nitro- l -arginine methyl ester ( l -NAME) (IC 50 : 25.8 μM). These results may substantiate the use of T. camphoratus in traditional Chinese medicine (TCM) for the treatment of inflammation and cancer-related diseases. The newly discovered compounds deserve further development as anti-inflammatory candidates.

Linderaggrine A (1) was characterized from the roots of Lindera aggregata and its chemical structure was established by the spectral analysis and chemical transformation. The chemical preparation of 1 and its isomer 2 provide unambiguous evidences for the structural determination of the naturally isolated compound. In addition, the inhibition of superoxide anion generation and elastase release by human neutrophils in response to FMLP/cytochalasin B of these synthetic products had been examined and among the tested compounds, linderaggrine A (1) displayed significant potential against the superoxide anion generation.

Ten new triterpenoids, camphoratins A–J (1–10), along with 12 known compounds were isolated from the fruiting body of Taiwanofungus camphoratus. Their structures were established by spectroscopic analysis and chemical methods. Compound 10 is the first example of a naturally occurring ergosteroid with an unusual cis-C/D ring junction. Compounds 2–6 and 11 showed moderate to potent cytotoxicity with EC50 values ranging from 0.3 to 3 μM against KB and KB-VIN human cancer cell lines. Compounds 6, 10, 11, 14–16, 18, and 21 exhibited anti-inflammatory NO-production inhibition activity with IC50 values of less than 5 μM, which was more potent than the nonspecific NOS inhibitor Nω-nitro-L-arginine methyl ester (L-NAME).

Phalaenopsis hybrids are economically one of the most important groups of orchids which are native to Asia with white, yellow and red flowers. In the present study, the major pigments of various Phalaenopsis hybrids with red colors were identified and the quantitative analyses of the crude extracts were accomplished. The compositions of flavones and anthocyanin were simultaneously detected at 375 and 530 nm with the aid of high performance liquid chromatography/ultraviolet detector (HPLC/UV). The major pigments and co-pigments characterized in different Phalaenopsis species were (3',7-di-O-sinapylglucosyl)-3-glucosyl cyanidin, apigenin 6-C-ribosido-7-O-glucoside, and saponarin. The differences between various Phalaenopsis hybrids were only in the contents of the pigments. In addition, the pigment constituents were also examined for their antioxidant properties using the scavenging of the α,α-diphenyl-β-picrylhydrazyl (DPPH) free radical assay and the antityrosinase activities. (3',7-di-O-sinapylglucosyl)-3-glucosyl cyanidin and saponarin exhibited moderate scavenging activity with the IC 50 values of 27.3 and 307.1 μM, respectively, and apigenin 6-C-ribosido-7-O-glucoside displayed significant antityrosinase activities with the IC 50 values of 41.6 μM.

Bioassay-guided fractionation of the CHCl(3) soluble portion of the roots of Panax japonicus C. A. Meyer var. major afforded an active fraction with inhibitory activity against baker's yeast alpha-glucosidase with an IC(50) value 1.02 mg/mL. Furthermore, the active fraction isolated contained three previously unreported polyacetylenes, designated panaxjapynes A-C, together with 11 other compounds, including four polyacetylenes, five phenolic compounds, a sesquiterpenoid, and a sterol glucoside. The structures of the compounds were elucidated by spectroscopic and chemical methods. Compared with the control acarbose (IC(50) 677.97 mu M), six compounds were shown to be more potent alpha-glucosidase inhibitors with IC(50) values in the range 22.21-217.68 mu M. Crown Copyright (C) 2010 Published by Elsevier Ltd. All rights reserved.

Bioassay-guided investigation of the anti-inflammatory principles from the stem and root barks of Citrus medica L. var. sarcodactylis SWINGLE has led to the isolation of a new coumarin, namely citrumedin-B (1) and thirty known compounds. The anti-inflammatory components were xanthyletin (2), nordentatin (3), atalantoflavon (4) and lonchocarpol A (5) which displayed potent nitric oxide (NO)-reducing activity in microglial cells. The structure of this new compound was completely elucidated using a combination of 2D NMR techniques (correlation spectroscopy (COSY), nuclear Overhauser effect spectroscopy (NOESY), heteronuclear multiple quantum coherence (HMQC) and heteronuclear multiple bond connectivity (HMBC)) and HR-electrospray ionization (ESI)-MS analyses. The known compounds were identified by comparison of their spectroscopic and physical data with those reported in the literature. These results can be inferred from the treatment of allergic response and inflammatory properties of Citrus medica L. var. sarcodactylis SWINGLE in traditional Chinese medicine.

Four natural pyranocoumarins clausenidin (1), nordentatin (2), clausarin (3), and xanthoxyletin (4) were isolated from the medicinal plant Clausena excavata. Recently, we found that 1 and 2 suppressed hepatitis B virus surface antigen in HepA2 cells, and in addition, 1-3 showed cytotoxic activity against four human cancer cell lines (A549, MCF7, KB, and KB-VIN). To explore the SAR of 1-4, 17 pyranocoumarin analogues (5-21) were designed and synthesized. Among these analogues, 5 and 10 were the most potent against hepatitis B virus with EC(50) values of 1.14 and 1.34microM, respectively. The most interesting result in the cytotoxicity assay was the significant activity of 1, 5, and 6 against the multi-drug resistant cell line, KB-VIN, without activity against the KB cell line. These data suggest that these three compounds could be useful hits for developing MDR-inverse drugs.

Activity-monitored fractionation of the CHCl3 solubles of the MeOH extract of the roots of Ficus septica using cytotoxicity assay led to the isolation of twenty phenanthroindolizidine alkaloids, including ten new ficuseptines E-N and ten known compounds. The cytotoxic effects of some of the isolates were tested on gastric adenocarcinoma (NUGC) and nasopharyngeal carcinoma (HONE-1) cell lines and the results demonstrated that, with the exception of dehydrotylophorine, all the tested compounds displayed pronounced cytotoxic activity with significant cell growth inhibitory effects. In addition, 13a R-antofine was found to be highly effective with ED(50) values of < 0.1 microg/mL against L-1210, P-388, A-549 and HCT-8 cell lines in another assay.

Chemical investigation on the whole plant of Houttuynia cordata has resulted in the isolation of two new compounds, named as houttuynoside A (1) and houttuynamide A (2), together with thirty-eight known compounds. The structures of 1 and 2 were elucidated on the basis of spectroscopic analysis. In the inhibitory effects on herpes simplex virus type 1 (HSV-1) assay, norcepharadione B (10) showed good inhibitory activity against the replication of HSV-1. In addition, the antioxidant and antityrosinase activities of some isolated compounds were also evaluated. Among these compounds, quercitrin (25) and quercetin-3-O-beta-D-galactopyranoside (26) showed excellent 2,2-diphenyl-1-picrylhydrazyl radical-scavenging property with IC50 values of 31 and 63 microM, respectively. Cepharadione B (9) exhibited strong tyrosinase inhibitory activity with an IC50 value of 170 microM.

*† Contributed equally to this work. Summary Geranyl diphosphate (GDP) is the precursor of monoterpenes, which are the major floral scent compounds in Phalaenopsis bellina. The cDNA of P. bellina GDP synthase (PbGDPS) was cloned, and its sequence corresponds to the second Asp-rich motif (SARM), but not to any aspartate-rich (Asp-rich) motif. The recombinant PbGDPS enzyme exhibits dual prenyltransferase activity, producing both GDP and farnesyl diphosphate (FDP), and a yeast two-hybrid assay and gel filtration revealed that PbGDPS was able to form a homodimer. Spatial and temporal expression analyses showed that the expression of PbGDPS was flower specific, and that maximal PbGDPS expression was concomitant with maximal emission of monoterpenes on day 5 post-anthesis. Homology modelling of PbGDPS indicated that the Glu-rich motif might provide a binding site for Mg 2+ and catalyze the formation of prenyl products in a similar way to SARM. Replacement of the key Glu residues with alanine totally abolished enzyme activity, whereas their mutation to Asp resulted in a mutant with two-thirds of the activity of the wild-type protein. Phylogenetic analysis indicated that plant GDPS proteins formed four clades: members of both GDPS-a and GDPS-b clades contain Asp-rich motifs, and function as homodimers. In contrast, proteins in the GDPS-c and GDPS-d clades do not contain Asp-rich motifs, but although members of the GDPS-c clade function as heterodimers, PbGDPS, which is more closely related to the GDPS-c clade proteins than to GDPS-a and GDPS-b proteins, and is currently the sole member of the GDPS-d clade, functions as a homodimer.

Due to their limited natural abundance and significant biochemical effects, we synthesized the alkaloids (±)-antofine (1a), (±)-deoxypergularinine (1b), and their dehydro congeners (2 and 3) starting from the corresponding phenanthrene-9-carboxaldehydes. We also evaluated their in vitro cytotoxic activity. Compounds 1a and 1b showed significant potency against various human tumor cell lines, including a drug-resistant variant, with EC50 values ranging from 0.16 to 16 ng/mL. Structure–activity correlations of these alkaloids and some of their synthetic intermediates were also ascertained. The non-planar structure between the two major moieties, phenanthrene and indolizidine, plays a crucial role in the cytotoxic activity of phenanthroindolizidines. Increasing the planarity and rigidity of the indolizidine moiety significantly reduced potency. A methoxy group at the 2-position (1a) was more favorable for cytotoxic activity than a hydrogen atom (1b).

The first total synthesis of polygalatenosides A ( 1 ) and B ( 2 ), originally isolated from the traditional Chinese medicine and reported as antidepressant agents, is described here. Glycosylation between thiogalactosyl donors 6 and 7 and 1-deoxyglucosyl acceptor 5 yielded the corresponding key intermediates 10 and 16 , respectively, with an α(1→2)-glycosidic linkage in moderate yields. In addition, d -configuration of the galactoside residue in 1 and 2 was confirmed in our studies.

Purification of the cytotoxic fractions of the methanol extracts of Kalanchoe hybrida leads to three new compounds with the basic skeleton of α-pyrone ring-opening products of bufadienolides, namely, kalanhybrin A–C (1–3). Moreover, four bufadienolides (4–7) and eight other compounds were also characterized from the title plant. The isolated compounds (1–7) were evaluated for their cytotoxicity toward MCF-7, NCI-H460, and SF-268 tumor cell lines. Among them, compounds 4 and 6 displayed significant cytotoxicity toward MCF-7 and NCI-H460 tumor cell lines at the tested concentration. In addition, the biosynthetic pathway of these α-pyrone ring-opening derivatives was also proposed.

Background and purpose: Cinnamophilin, a thromboxane A2 receptor antagonist, has been identified as a prominent anti-arrhythmic agent in rat heart. This study aimed to determine its electromechanical and anti-arrhythmic effects in guinea-pig hearts. Experimental approach: Microelectrodes were used to study action potentials in ventricular papillary muscles. Fluo-3 fluorimetric ratio and whole-cell voltage-clamp techniques were used to record calcium transients and membrane currents in single ventricular myocytes, respectively. Intracardiac electrocardiograms were obtained and the anti-arrhythmic efficacy was determined from isolated perfused hearts. Key results: In papillary muscles, cinnamophilin decreased the maximal rate of upstroke (Vmax) and duration of action potential, and reduced the contractile force. In single ventricular myocytes, cinnamophilin reduced Ca2+ transient amplitude. Cinnamophilin decreased the L-type Ca2+ current (ICa,L)(IC50=7.5 μM) with use-dependency, induced a negative shift of the voltage-dependent inactivation and retarded recovery from inactivation. Cinnamophilin also decreased the Na+ current (INa) (IC50=2.7 μM) and to a lesser extent, the delayed outward (IK), inward rectifier (IK1), and ATP-sensitive (IK,ATP) K+ currents. In isolated perfused hearts, cinnamophilin prolonged the AV nodal conduction interval and Wenckebach cycle length and the refractory periods of the AV node, His-Purkinje system and ventricle, while shortening the ventricular repolarization time. Additionally, cinnamophilin reduced the occurrence of reperfusion-induced ventricular fibrillation. Conclusions and implications: These results suggest that the promising anti-arrhythmic effect and the changes in the electromechanical function induced by cinnamophilin in guinea-pig heart can be chiefly accounted for by inhibition of ICa,L and INa. British Journal of Pharmacology (2008) 153, 110–123; doi:10.1038/sj.bjp.0707541; published online 29 October 2007

Cytotoxicity-guided phytochemical investigation of a methanolic extract of Croton tonkinensis afforded two new kaurane diterpenoids (1, 2) and 10 known ent-kaurane-type diterpenoids (3- 12). The structures of 1 and 2 were based on analysis of spectroscopic and mass spectral data. Compounds 3- 12 were identified by comparison of their spectroscopic and physical data with those reported in the literature. Selected compounds from this plant were examined for cytotoxic and anti-inflammatory activities. Compounds 4 and 9 showed the highest cytotoxic activity against the tested tumor cell lines. Compounds 3, 4, 6, 8, 9, and 11 had IC 50 values less than 5 microM and were more potent than the nonspecific NOS inhibitor L-NAME in inhibiting LPS-induced NO production.

The methanolic extract of Piper lolot, having shown potent inhibitory activity on platelet aggregation induced by arachidonic acid (AA) and platelet activating factor (PAF), was subjected to activity-guided isolation to yield twelve new amide alkaloids, piperlotine A-L (1-12), along with twenty-nine known compounds. Their structures were elucidated on the basis of spectroscopic analysis. The isolated compounds were tested for their inhibitory activity on the rabbit platelet aggregation. The compounds piperlotine A (1), piperlotine C (3), piperlotine D (4), piperlotine E (5), 3-phenyl-1-(2,4,6-trihydroxyphenyl)propan-1-one (21), 3-(4-methoxyphenyl)-1-(2,4,6-trihydroxyphenyl)propan-1-one (22), 1-trans-cinnamoylpyrrolidine (24), sarmentine (26), pellitorine (27), methyl 3-phenylpropionate (32), and (10S)-10-hydroxypheophorbide a methyl ester (40) showed potent antiplatelet aggregation activity.

Phytochemical investigation of Physalis angulata was initiated following primary biological screening. Fractionation of CHCl3 and n-BuOH solubles of the MeOH extract from the whole plant was guided by in vitro cytotoxic activity assay using cultured HONE-1 and NUGC cells and led to the isolation of seven new withanolides, withangulatins B-H (1-7), and a new minor physalin, physalin W (8), along with 14 known compounds, including physaprun A, withaphysanolide, dihydrowithanolide E, physanolide A, withaphysalin A, and physalins B, D, F, G, I, J, T, U, and V. New compounds (1-8) were fully characterized by a combination of spectroscopic methods (1D and 2D NMR and MS) and the relative stereochemical assignments based on NOESY correlations and analysis of coupling constants. Biological evaluation of these compounds against a panel of human cancer cell lines showed broad cytotoxic activity. Withangulatin B (1) and physalins D (10) and F (11) displayed potent cytotoxic activity against a panel of human cancer cell lines with EC50 values ranging from 0.2 to 1.6 microg/mL. Structure-activity relationship analysis indicated that withanolides and physalins with 4beta-hydroxy-2-en-1-one and 5beta,6beta-epoxy moieties are potential cytotoxic agents.

A synthetic bichalcone analog, (E)-1-(3-((4-(4-acetylphenyl)piperazin-1-yl)methyl)-4-hydroxy-5-methoxyphenyl)-3-(pyridin-3-yl)prop-2-en-1-one (TSWU-BR23), has been shown to induce apoptosis in human colon cancer HT-29 cells involving the induction of CD95 and FAS-associated protein death domain (FADD), but its precise mechanism of action has not been fully elucidated. Using cell-surface biotinylation and sucrose density-gradient-based membrane flotation techniques, we showed that the disruption of TSWU-BR23-induced lipid raft localization of CD95/FADD by cholesterol-depleting agent (methyl-β-cyclodextrin) was reversed by cholesterol replenishment. Blockade of p53 expression by short-hairpin RNA (shRNA) suppressed oligomeric Bcl-2-associated x protein (BAX)/Bcl-2 antagonist killer 1 (BAK)-mediated mitochondrial apoptosis but did not inhibit lipid raft localization of CD95/FADD and pro-caspase-8 cleavage induced by TSWU-BR23. Co-expression of p53 shRNA and dominant-negative mutant of FADD completely inhibited TSWU-BR32-induced mitochondrial apoptotic cell death. Collectively, these data demonstrate that TSWU-BR23 leads to HT-29 cell apoptosis by inducing p53-mediated mitochondrial oligomerization of BAX/BAK and the localization of CD95/FADD with lipid rafts at the cell surface.

The p85α subunit of phosphatidylinositol 3-kinase (PI3K) acts as a key regulator of cell proliferation and motility, which mediates signals that confer chemoresistance to many human cancer cells. Using small interfering RNAs against matrix metalloproteinase-2 (MMP-2) and the MMP-2 promoter-driven luciferase assay, we showed that the new synthetic bichalcone analog TSWU-CD4 inhibits the invasion of human cancer cells by down-regulating MMP-2 expression. Treatment with TSWU-CD4 inhibited MMP-2 expression and cell invasion, which were restored by ectopic wild type (wt) p85α or a constitutively active form of MAPK kinase 3 (CA MKK3), CA MKK6, or CA p38α mitogen-activated protein kinase (MAPK). The attenuated formation of lipid raft-associated phospho (p)-p85α-GTP-Rac1 complexes, protein kinase B (Akt) Ser 473 phosphorylation, and cell invasion by TSWU-CD4 was reversed by overexpression of wt p85α or the p85α Brc-homology (BH) domain. The ectopic expression of CA Rac1

Total synthesis of viscolin, an anti-inflammatory 1,3-diphenylpropane isolated from Viscum coloratum, employing the Wittig reaction is reported. Key steps in the synthesis of viscolin depend on the selection of protecting groups to maintain the para hydroxyl group that is the most critical chemical structure influencing the biological activity of viscolin and the utilization of microwave-assisted Wittig olefination reaction. Anti-inflammatory potency of the synthetic viscolin, its precursor product 16, and its analogue 17, through their effects on reactive oxygen species (ROS), nitric oxide (NO), and pro-inflammatory cytokine production in leukocytes and microglial cells were evaluated. Excellent inhibition of ROS and NO production in inflammatory cells could confer the synthetic viscolin to be a potent anti-inflammatory agent for the treatment of oxidative stress-induced diseases.

[Structure: see text] Three new compounds, kalanchosides A-C (1-3), as well as five known compounds, were isolated from the aerial parts of Kalanchoe gracilis. The compound structures were determined by spectroscopic methods. All eight isolated compounds showed significant cytotoxic activity against a panel of human tumor cell lines, with potency reaching the nanomolar range. However, only bryophyllin B (8) inhibited HIV replication in H9 lymphocyte cells.

[(125)I]RTI-55-membrane binding assay-guided fractionation and separation of a water-soluble extract of the roots of Polygala tenuifolia gave five new oligosaccharide derivatives, polygalatenosides A-E (1-5). The structures of these new oligosaccharides were established on the basis of spectroscopic evidence. Polygalatenosides A and B (1 and 2) showed significant inhibitory activity, with IC(50) values of 30.0 and 6.04 microM, respectively, in this membrane binding assay and acted as norepinephrine reuptake inhibitors through blocking norepinephrine transport.

[reaction: see text] A novel withasteroid, physanolide A (1), with an unprecedented skeleton containing a seven-membered ring, and two new physalins, physalins U (2) and V (3), were isolated from Physalis angulata. The structures were elucidated from spectroscopic analysis, and plausible biosynthetic pathways were postulated. Physalins B (4), D (5), and F (6) showed strong cytotoxicity against multiple tumor cell lines, including KB, A431, HCT-8, PC-3, and ZR751, with EC(50) values less than 4 microg/mL.

Four new C 18 dibenzocyclooctadiene lignans, kadsuphilins A (1) and B (3), 6-epi-gomisin (2), and 1-demethylkadsuphilin A (4), along with eight known related metabolites, were isolated from an EtOAc fraction of an alcoholic extract of the aerial parts of Kadsura philippinensis growing in Taiwan. The structures of 1-4 were elucidated on the basis of spectroscopic analyses, including 2D NMR (HMQC, HMBC, and NOESY) experiments, and by comparison of their spectroscopic data with those of related metabolites. The configurations of the biphenyl and cyclooctadiene moieties were deduced from circular dichroism (CD) and NOESY NMR spectra, respectively. Some of the compounds showed radical-scavenging activity in a DPPH-HPLC method.

Agrostis avenacea J. F. Gmel., Agrostis stolonifera L., Alopecurus pratensis L., and Deschampsia atropurpurea (Wahl.) Scheele were recently found at middle elevations of southern and central Taiwan, respectively. We present their descriptions, distribution map, and line-drawings.

A simple, sensitive and specific high-performance liquid chromatographic method has been developed for the first time to simultaneously determine the eight major biologically active ingredients, namely paeoniflorin, naringin, sennoside A, baicalin, baicalein, saikosaponin a, rhein and emodin of the Chinese herbal formula Da-Chai-Hu-Tang. The contents of these marker substances in Da-Chai-Hu-Tang extract could be easily determined within 85 min. The assay was reproducible and accurate with overall intra-day variations and accuracy of less than 2% and more than 97.9%, respectively. Results indicate that the developed HPLC assay can be successfully utilized as a quality control method for simultaneous determination of eight representative substances in Da-Chai-Hu-Tang.

Prostate cancer is the most prevalent type of cancer in the United States. The most common site of prostate cancer metastasis is bone. CXCL12 is preferentially expressed in bone and is targeted by prostate cancer cells, which over-express the receptor for CXCL12, CXCR4. In response to CXCL12 stimulation, Rac1, a GTPase, along with its effectors, regulates actin polymerization to form lamellipodia, which is a critical event for cell migration. Cortactin, an actin-binding protein, is recruited to the lamellipodia and is phosphorylated at tyrosine residues. The phosphorylated cortactin is also involved in cell migration. The inhibition of Rac1 activity using a dominant negative Rac1 impairs lamellipodial protrusion as well as cortactin translocation and cortactin phosphorylation. Denbinobin, a substance extracted from Dendrobium nobile, has anticancer effects in many cancer cell lines. Whether denbinobin can inhibit prostate cancer cell migration is not clear. Here, we report that denbinobin inhibited Rac1 activity. The inhibition of Rac1 activity prevented lamellipodial formation. Cortactin phosphorylation and translocation to the lamellipodia were also impaired, and PC3 cells were unable to migrate. These results indicate that denbinobin prevents CXCL12-induced PC3 cell migration by inhibiting Rac1 activity.

Nine new abietane diterpene alkaloids containing an oxazole ring, salviamines A-F (1-6) and isosalviamines C-E (7-9), together with 17 known abietane diterpenes, were isolated and characterized from the roots of Salvia yunnanensis. The structures of 1-9 were elucidated by interpretation of their spectroscopic data.

Acute neuroprotective effects of cinnamophilin (CINN; (8R, 8'S)-4, 4'-dihydroxy-3, 3'-dimethoxy-7-oxo-8, 8'-neolignan), a novel antioxidant and free radical scavenger, were studied in a mouse model of transient middle cerebral artery (MCA) occlusion. CINN was administered intraperitoneally either 15 min before (pretreatment) or 2 h after the onset of MCA occlusion (postischemic treatment). Relative to vehicle-treated controls, animals pretreated with CINN, at 20-80 mg/kg, had significant reductions in brain infarction by 33-46% and improvements in neurobehavioral outcome. Postischemic administration with CINN (80 mg/kg) also significantly reduced brain infarction by 43% and ameliorated neurobehavioral deficits. Additionally, CINN administration significantly attenuated in situ accumulation of superoxide anions (O2-) in the boundary zones of infarct at 4 h after reperfusion. Consequently, CINN-treated animals exhibited significantly decreased levels of oxidative damage, as assessed by immunopositive reactions for 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 4-hydroxynonenal (4-HNE), and the resultant inflammatory reactions at 24 h post-insult. It is concluded that CINN effectively reduced brain infarction and improved neurobehavioral outcome following a short-term recovery period after severe transient focal cerebral ischemia in mice. The finding of a decreased extent of reactive oxygen species and oxidative damage observed with CINN treatment highlights that its antioxidant and radical scavenging ability is contributory.

Twelve new compounds, vittarin-A (1), -B (2), -C (3), -D (4), -E (5), -F (6), 3-O-acetylniduloic acid (7), ethyl 3-O-acetylniduloate (8), methyl 4-O-coumaroylquinate (9), vittarilide-A (10), and -B (11), and vittariflavone (12), as well as 20 known compounds have been isolated from the whole plant of Vittaria anguste-elongata. The structures of these compounds were determined by spectroscopic and chemical transformation methods. 5,7-Dihydroxy-3',4',5'-trimethoxyflavone (18) displayed moderate cytotoxicity against human lung carcinoma and central nervous system carcinoma cell lines with inhibition of 89 and 61% at a concentration of 58 microM, respectively. Vittarilide-A (10) and -B (11) and ethyl 4-O-caffeoylquinate (14) exhibited moderate DPPH radical scavenging activity with IC50 values of 91, 290, and 234 microM, respectively.

We have previously shown that melatonin reduces infarct volumes and enhances neurobehavioral and electrophysiological recoveries following transient middle cerebral artery (MCA) occlusion in rats. In the study, we examined whether melatonin would display neuroprotection against neuronal, axonal and oligodendrocyte pathology after 24 hr of reperfusion following 1 hr of MCA occlusion in mice. Melatonin (5 mg/kg) or vehicle was given intraperitoneally at the commencement of reperfusion. Neurological deficits were assessed 24 hr after ischemia. Gray matter damage was evaluated by quantitative histopathology. Axonal damage was determined with amyloid precursor protein and microtubule-associated protein tau-1 immunohistochemistry to identify postischemic disrupted axonal flow and oligodendrocyte pathology, respectively. Oxidative damage was assessed by 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 4-hydroxynonenal (4-HNE) immunohistochemistry. Relative to controls, melatonin-treated animals not only had a significantly reduced volume of gray matter infarction by 42% (P

Three new flavonoid derivatives, 6'''-O-acetyl amurensin (1), 6'''-O-acetyl phellamurin (3) and (2R)-phellodensin-F (5), together with thirty known compounds have been isolated from the leaves of Phellodendron japonicum MAXIM. Their structures were established by means of spectroscopic analysis, including extensive 2D NMR and Mass spectra. The known compounds were identified by comparison with published physical and spectral data. The isolated compounds were screened for their in vitro antioxidant activity through DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging assay. Compounds quercetin and phellodenin-A demonstrated significant radical scavenging activity.

Three new naturally occurring anthraquinones, ophiohayatone-A (1), -B (2), and -C (3), together with four known anthraquinones, were isolated from Ophiorrhiza hayatana OHWI (Rubiaceae). Structures of these new compounds were established by spectral methods.

We developed an analytical method using 1H nuclear magnetic resonance (NMR) spectrometry to resolve analytical problems with Ginkgo. After a simple hydrolysis step, an NMR analysis of the terpene trilactone H-12 signals and the flavonol aglycone H-2‘ (or H-2‘/6‘ for kaempferol) signals was performed. By comparing the solvent effects on the resolution of these signals, methanol-d4−benzene-d6 (65:35) was selected as the optimal 1H NMR solvent. The amounts of terpene lactones and flavonol aglycones in various commercial Ginkgo products and Ginkgo leaves were determined. This newly developed 1H NMR method enables the simultaneous analysis of terpene trilactones and flavonols and allows simple, rapid quantification of these compounds in pharmaceutical Ginkgo preparations. Keywords: 1H NMR; Ginkgo biloba; terpene trilactone; flavonol

A naturally occurring enynyl-benzenoid, Benzocamphorin H (1), from the edible fungus Taiwanofungus camphoratus (Antrodia camphorata) was characterized by the comprehensive spectral analysis. It displayed potent anti-inflammatory bioactivity and would be valuable for further biological studies. The present study is the first total synthesis of Benzocamphorin H and the developed strategy described a more efficient procedure that allowed large-scale production of Benzocamphorin H for the further research of biological activity both in vitro and in vivo.

A facile reversed‐phase HPLC method for simultaneous resolution and quantitative determination of 17 analogues of aristolochic acid (AA) and aristolactam (AL) under gradient elution, with solvent mixture of sodium acetate and acetonitrile, is described. The retention scale of analytes examined in this study is found to be dependent on the pH of mobile phase and highly relevant to the presence of functional groups on analytes as well, under the same chromatographic conditions. Analytes with high polarity (i.e., many functional groups) elutes early. Increasing the pH of mobile phase decreases the retention time of AA analogues, however, it increases that of AL analogues slightly. At higher pH (>5.0), the elution reversal between AA and AL is observed and believed to be from the ionization of carboxyl groups on aristolochic acid. Quantitative analysis of Chinese herbs such as Aristolochia heterophylla and Aristolochia fangchi has proven this method to be facile and reliable, which can be considered ...

Two new dihydroflavonols, phellodensin-A (1) and phellodensin-C (2); three new coumarins, phellodenol-A (3), phellodenol-B (4), and phellodenol-C (5); one new chlorophyll, phellophyll-a (6); and one new phenyllactate, (2R)-sodium 3-phenyllactate (7), in addition to 35 known compounds have been isolated from the leaves of Phellodendron amurense var. wilsonii. The structures of the new compounds were established based on 1D, 2D NMR and mass spectral analyses. The stereochemistry at the C-2, C-3, and C-2' ' positions of new dihydroflavonol 1 was determined by CD spectroscopy. The known compounds were identified by comparison with authentic samples. The antioxidant and antityrosinase activities were also described.

Eight tetrahydrofurofuran nucleus lignans: syringaresinol, epi-syringaresinol, lirioresinol-B dimethyl ether, xanthoxylol, phillygenin, fargesin, sesamin and asarinin are separated on a C 1 8 column in the reversed-phase mode. These lignans are plant products formed primarily by the carbon-carbon coupling of derivatives of cinnamyl alcohol units, in which the two units may be linked by an oxygen bridge to form a tetrahydrofurofuran nucleus and are found to be highly similar in structure. However, these lignans can be baseline resolved under gradient elution in less than 25 minutes. The resolution also can be optimized through altering the flow rate in an isocratic elution. This method is proven to be facile and reliable in routine quantitative analysis of ingredients such as asarinin and sesamin in traditional Chinese medicine Asarum sieboldii. The corresponding recoveries (%) were found to be 95.65 and 96.14, respectively.