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The rare phytoecdysteroid canescensterone is a potent activator of both natural and engineered ecdysteroid receptor (EcR) gene-expression systems. This steroid also shows a remarkable selectivity towards non-lepidopteran compared with lepidopteran EcRs in gene-switch assays, a property that makes it a novel candidate lead compound for use in insecticide discovery and gene-switch design. Canescensterone possesses an unusual ecdysteroid structure, including a pyrrole-2-carboxylate group attached to C-24, a moiety not yet found in any other natural ecdysteroid. We have investigated the ambiguous stereochemistry at C-24 of this steroid by 1D and 2D solution NMR experiments, which resulted in the assignment of the 24R-configuration and determination of the side-chain conformation. The complete stereochemical assignment allowed the generation of docking models of canescensterone in both a lepidopteran EcR and a non-lepidopteran EcR, which helps to explain its selective biological activity.

The naturally occurring ecdysteroids 2-deoxy-20-hydroxyecdysone (2-D-20-ECD, 2-deoxycrustecdysone), 2-D-20-ECD 3-acetate (2-deoxyecdysterone 3-acetate), 2-D-20-ECD 22-acetate and 2-D-20-ECD 22-benzoate have been partially synthesized from 20-hydroxyecdysone. Moulting hormone activity of these ecdysteroids has been studied using the Musca bioassay.

ESI mass spectrometry was used to assess the binding of 13-substituted, 5-nitro-2-phenylindolyl- and 2-naphthalenyl-based berberine derivatives to inter- and intramolecular G-quadruplex DNA molecules. In contrast with the parent berberine, the compounds showed selectivity for quadruplex over duplex DNA and stabilised the quadruplex structure. They represent a new class of quadruplex DNA-selective ligands.

The structure of a new labdane diterpene, limonidilactone , from the leaves of Vitex limonifolia Wall. ( Verbenaceae ) has been established by spectroscopic methods and a single-crystal X-ray structure determination. Crystals are orthorhombic, P212121, a 19.373(10), b 10.871(7), c 8.207(3) Ǻ, Z 4. Diffractometer data were refined by full-matrix least-squares techniques to a residual of 0.043 for 1436 independent 'observed' reflections.

Stachysterone C was synthesized from 20-hydroxyecdysone (20-ECD). Sharpless asymmetric dihydroxylation of this rare ecdysteroid using osmium tetroxide and a chiral ligand afforded 24- epi -abutasterone, another rare ecdysteroid, and its C-24 epimer, abutasterone. High diastereomeric excess of the former ecdysteroid was obtained when the chiral ligands dihydroquinidine 1,4-phthalazinediyl diether and dihydroquinidine 2,5-diphenyl-4,6-pyrimidinediyl diether were employed. The two C-24 epimeric ecdysteroids exhibited similar moulting hormone activity in the Musca bioassay. However, they were significantly less active than 20-ECD.

20,26-Dihydroxyecdysone (20,26-ECD) isolated from Vitex canescens, V. glabrata and V. pinnata has been shown to exist as two C-25 epimers. Synthesis and separation of the two epimers were accomplished and they exhibited different degree of moulting hormone activity in the Musca assay.

In order to have compounds available for structure-activity relationship studies, the ecdysteroid 24- epi -pterosterone was synthesized from 20-hydroxyecdysone and pterosterone was obtained from Vitex glabrata stem bark. The former was approximately 7-fold less active than the latter in the Musca bioassay for moulting hormone activity.

Catalytic hydrogenation with Pd–C as a catalyst in the presence of sodium nitrite is a simple, convenient and high yielding stereoselective reduction of olefinic function of Δ 7 -6-ketosteroids to the corresponding dihydro analogues.

Three new labdane diterpenes, curcucomosins A-C (1-3), four known labdane diterpenes, 4-7, and a known diarylheptanoid, 8, were isolated from the aerial parts of Curcuma comosa. The structures of the new diterpenes were elucidated by spectroscopic data analysis. The fetal hemoglobin (Hb F) induction potency of the isolated compounds was examined using a K562 reporter cell line harboring the enhanced green fluorescence protein (EGFP) gene under the control of a (G)gamma-globin promoter. Compound 6, isocoronarin D, exhibited the highest Hb F induction effect of 1.6-fold at 20 microM.

Three new isomeric flavanones, fuscaflavanones A1 (1), A2 (2) and B (3), together with six known flavanones, lupinifolin (4), lonchocarpol A (5), a mixture of lonchocarpols C1 and C2 (6a, b), and a mixture of lonchocarpols D1 and D2 (7a, b), five pterocarpans, sandwicensin (8), phaseollidin (9), erythrabissin I (10), and a mixture of dolichins A and B (11a, b), one chalcone, isobavachalcone (12), and one isoflavone, wighteone (13), were isolated from the bark of Erythrina fusca LOUR. Their structures were elucidated on the basis of spectroscopic data. Some isolates were tested for antiplasmodial and cytotoxic activities and it was found that 5 and 9 exhibited moderate antiplasmodial activity against Plasmodium falciparum. For cytotoxicity, compounds 1, 4, 5, 9 and 12 showed moderate to weak activity against KB, BC and NCI-H187 cells, whereas 2 exhibited only weak activity against KB cells.

Seven labdane-type diterpenes, coronarin E, coronarin A, yunnancoronarin A, yunnancoronarin B, hedyforrestin B, villosin, and hedyforrestin C were isolated from the rhizome of Hedychium gardnerianum and evaluated for cytotoxic activity against human small cell lung cancer (NCI-H187) and non-cancerous Vero cells. The results showed that villosin exhibited potent cytotoxic activity with IC(50) of 0.40 microM, which was higher than that of the drug ellipticine (IC(50) 1.79 microM). Moreover, ellipticine was very toxic to Vero cells (IC(50) 7.47 microM) whereas the toxicity of villosin was undetectable at concentration lower than 166.42 microM. The results have indicated that the lactone ring is essential for high cytotoxic activity and that the presence of a hydroxyl group at the 6 or 7 position causes decrease in activity. The very high cytotoxicity against the NCI-H187 cells and the exceptionally high selectivity index (416) of villosin suggested that this compound may be used as a potential lead molecule for antitumor therapeutic development.

Chemical investigation of the stems of Erythrina fusca Lour. led to the isolation of three new pterocarpans, named fuscacarpans A–C (1−3), together with fourteen known compounds, sandwicensin (4), erythribyssin A (5), erythrabissin I (6), demethylmedicarpin (7), eryvarin D (8), erypoegin I (9), hydroxycristacarpone (10), orientanol A (11), scandenone (12), genistein (13), liquiritigenin (14), isoliquiritigenin (15), vestitone (16) and 3,7,4′-trihydroxyflavone (17). Structures 1−3 were elucidated by spectroscopic and chemical methods. The isolates were evaluated for antibacterial, antiplasmodial and cytotoxic activities.

One new dihydrochalcone, dihydromonospermoside (7), was isolated from the flowers of Butea monosperma together with three known chalcones, butein (2), monospermoside (4) and isoliquiritigenin (8), one flavone, 7,3',4'-trihydroxyflavone (6), four flavanones, (-)-butin (1a), (-)-butrin (3a), (+)-isomonospermoside (5b) and (-)-liquiritigenin (9a), and three isoflavones, formononetin (10), afrormosin (11) and formononetin-7-O-beta-D-glucopyranoside (12). The structure of the new compound was elucidated by spectroscopic techniques whereas those of the known compounds were identified by comparisons of spectroscopic and some physical data with those of reported compounds. The absolute configurations at the 2-position of the flavanones 1a, 3a, 5b and 9a were established to be 2S, 2S, 2R and 2S, respectively, by circular dichroism spectral measurements and were confirmed by comparison of the optical rotations with those of reported values and by enzymic hydrolysis of the glucosides to the corresponding aglycones. The isolated flavonoids exhibited varying antimycobacterial activity with the chalcone 2 being the most active compound (MIC 12.5 microg/ml).

Three new isomeric flavanones, fuscaflavanones A(1) (1), A(2) (2) and B (3), together with six known flavanones, lupinifolin (4), lonchocarpol A (5), a mixture of lonchocarpols C(1) and C(2) (6a, b), and a mixture of lonchocarpols D(1) and D(2) (7a, b), five pterocarpans, sandwicensin (8), phaseollidin (9), erythrabissin I (10), and a mixture of dolichins A and B (11a, b), one chalcone, isobavachalcone (12), and one isoflavone, wighteone (13), were isolated from the bark of Erythrina fusca LOUR. Their structures were elucidated on the basis of spectroscopic data. Some isolates were tested for antiplasmodial and cytotoxic activities and it was found that 5 and 9 exhibited moderate antiplasmodial activity against Plasmodium falciparum. For cytotoxicity, compounds 1, 4, 5, 9 and 12 showed moderate to weak activity against KB, BC and NCI-H187 cells, whereas 2 exhibited only weak activity against KB cells.

Aim of the study To investigate the protective effect and possible mechanism of Curcuma comosa hexane extract on CCl4-induced liver injury in adult male mice. Materials and methods Hepatotoxicity was induced by an intraperitoneal injection of CCl4 and was evaluated after 24 h from the elevations of plasma alanine transaminase (ALT) and aspartate transaminase (AST) activities, and histological analysis of liver injuries. Hexane extract of Curcuma comosa was given at different time points from 1 to 72 h, prior to CCl4 administration and the protection from liver injury was assessed. Results CCl4-induced damage to liver cells was resulted in elevations of plasma ALT and AST activities. Pretreatment with Curcuma comosa hexane extract 24 h at a dose of 100, 250, and 500 mg/kg BW resulted in a dose-dependent prevention of the increases in plasma ALT and AST activities as well as time dependent. The protective effect of the extract at a dose of 500 mg/kg BW was seen at 12–24 h. Pretreatment of the extract completely prevented elevation of plasma ALT and AST activities, and centrilobular necrosis. The protective effect of Curcuma comosa was associated with restoration of hepatic glutathione content, and CYP2E1 catalytic activity, and its mRNA and protein levels as well as increase in activity of glutathione-S-transferase (GST). Conclusion Curcuma comosa has a potent protective property against CCl4-induced hepatic injuries via the activation of detoxifying mechanisms (GST) as well as reduction of the bioactive toxic metabolites. Therefore, Curcuma comosa may be beneficial for prevention of hepatotoxicity.

One new dihydrochalcone, dihydromonospermoside (7), was isolated from the flowers of Butea monosperma together with three known chalcones, butein (2), monospermoside (4) and isoliquiritigenin (8), one flavone, 7,3',4'-trihydroxyflavone (6), four flavanones, (-)-butin (1a), (-)-butrin (3a), (+)-isomonospermoside (5b) and (-)-liquiritigenin (9a), and three isoflavones, formononetin (10), afrormosin (11) and formononetin-7-O-beta-D-glucopyranoside (12). The structure of the new compound was elucidated by spectroscopic techniques whereas those of the known compounds were identified by comparisons of spectroscopic and some physical data with those of reported compounds. The absolute configurations at the 2-position of the flavanones 1a, 3a, 5b and 9a were established to be 2S, 2S, 2R and 2S, respectively, by circular dichroism spectral measurements and were confirmed by comparison of the optical rotations with those of reported values and by enzymic hydrolysis of the glucosides to the corresponding aglycones. The isolated flavonoids exhibited varying antimycobacterial activity with the chalcone 2 being the most active compound (MIC 12.5 microg/ml).

Background Diarylheptanoids isolated from Curcuma comosa Roxb. have been recently identified as phyto estrogens. However, the mechanism underlying their actions has not yet been identified. Objectives We characterized the estrogenic activity of three active naturally occurring diarylheptanoids both in vitro and in vivo. Methods We characterized mechanisms of estrogenic action of the diarylheptanoids (3S)-1,7-diphenyl-(6E)-6-hepten-3-ol (D1), 1,7-diphenyl-(6E)-6-hepten-3-one (D2), and (3R)-1,7-diphenyl-(4E,6E)-4,6-heptadien-3-ol (D3) by using a real-time polymerase chain reaction assay, a mammalian transfection model, and a uterotrophic assay in mice. Results All diarylheptanoids up-regulated estrogen-responsive genes in estrogen-responsive breast cancer cells (MCF-7). In HepG2 cells transfected with estrogen receptor (ER) β or different ERα functional receptor mutants and the Vit-ERE-TATA-Luc reporter gene, all diarylheptanoids induced transcription through a ligand-dependent human ERα-ERE–driven pathway, which was abolished with ICI 182,780 (ER antagonist), whereas only D2 was active with ERβ. An ERα mutant lacking the functional AF2 (activation function 2) region was not responsive to 17β-estradiol (E2) or to any of the diarylheptanoids, whereas ERα lacking the AF1 domain exhibited wild-type–like activity. D3 markedly increased uterine weight and proliferation of the uterine epithelium in ovariectomized mice, whereas D1 and D2 were inactive. D3, like E2, up-regulated lactoferrin (Ltf) gene expression. The responses to D3 in the uterus were inhibited by ICI 182,780. In addition, D3 stimulated both classical (Aqp5) and nonclassical (Cdkn1a) ER-mediated gene regulation. Conclusions The results suggest that the D3 diarylheptanoid is an agonist for ER both in vitro and in vivo, and its biological action is ERα selective, specifically requiring AF2 function, and involves direct binding via ER as well as ERE-independent gene regulation.

Betulinic acid, oleanolic acid and ursolic acid have been modified at the C-3 position to cinnamate-based esters and in vitro antimycobacterial activity against Mycobacterium tuberculosis H(37)Ra has been determined. The results indicated that modification of the parent structures of betulinic acid, oleanolic acid and ursolic acid to the p-coumarate and, in the case of the latter two triterpenes, the ferulate ester analogues resulted in high antimycobacterial activity. Structure-activity relationships within the lupane, oleanane and ursane analogues and between these triterpenes are discussed.

The solid phase synthesis of a library of aminoglycerol–diamine conjugate-based transfection agents having urea linkage between diverse length of diamines and various lengths of hydrophobic tails is described. These compounds were characterized and structure–activity relationships were determined for DNA binding and transfection ability when formulated as cationic liposomes. Cationic lipids with short spacer length and short hydrophobic tails bound to DNA and delivered DNA into HEK293 cells more efficient than those with longer ones. Transfection efficiency of some of the cationic liposomes was superior to that of the commercial transfection agents, EffecteneTM, DOTAP and DC-Chol. The lipids 6Ab and 6Bb did not require the helper lipid DOPE to produce high-efficiency transfection of human cells while displaying minimal cytotoxicity. This suggests that these newly described aminoglycerol-based lipids should be very promising in liposome-mediated gene delivery and illustrate the potential of solid phase synthesis method for non-viral vector discovery.

AIM: To determine the effect of tetrahydrocurcumin (THC) on tumor angiogenesis compared with curcumin (CUR) by using both in vitro and in vivo models of human hepatocellular carcinoma cell line (HepG2). METHODS: The 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide (MTT) assay was used for testing the anti-proliferating activities of CUR and THC. In male BALB/c nude mice, 2 × 106 human HepG2 cells were inoculated onto a dorsal skin-fold chamber. One day after HepG2 inoculation, the experimental groups were fed oral daily with CUR or THC (300 mg/kg or 3000 mg/kg). On d 7, 14 and 21, the tumor microvasculature was observed using fluorescence videomicroscopy and capillary vascularity (CV) was measured. RESULTS: Pathological angiogenic features including microvascular dilatation, tortuosity, and hyper-permeability were observed. CUR and THC could attenuate these pathologic features. In HepG2-groups, the CV were significantly increased on d 7 (52.43%), 14 (69.17%), and 21 (74.08%), as compared to controls (33.04%, P < 0.001). Treatment with CUR and THC resulted in significant decrease in the CV (P < 0.005 and P < 0.001, respectively). In particular, the anti-angiogenic effects of CUR and THC were dose-dependent manner. However, the beneficial effect of THC treatment than CUR was observed, in particular, from the 21 d CV (44.96% and 52.86%, P < 0.05). CONCLUSION: THC expressed its anti-angiogenesis without any cytotoxic activities to HepG2 cells even at the highest doses. It is suggested that anti-angiogenic properties of CUR and THC represent a common potential mechanism for their anti-cancer actions.

Betulinic acid, oleanolic acid and ursolic acid have been modified at the C-3 position to cinnamate-based esters and in vitro antimycobacterial activity against Mycobacterium tuberculosis H(37)Ra has been determined. The results indicated that modification of the parent structures of betulinic acid, oleanolic acid and ursolic acid to the p-coumarate and, in the case of the latter two triterpenes, the ferulate ester analogues resulted in high antimycobacterial activity. Structure-activity relationships within the lupane, oleanane and ursane analogues and between these triterpenes are discussed.

A GC–MS analysis of the sesquiterpenoid volatile leaf oils of Polyscias fruticosa (L.) Harms. from Thailand and Fiji has shown large quantitative as well as some qualitative differences between them. About 24 constituents have been tentatively identified, β-elemene, α-bergamotene, germacrene-D and (E)-gM-bisabolene being present in major proportions.

In order to improve the indirect ELISA for detection of PGE(2), a modified direct ELISA technique was developed to measure PGE(2) in cell culture supernatants. An evaluation of three types of coating buffer showed that PGE(2) was adsorbed efficiently to the solid phase using the gelatin phosphate buffer. The sensitivity of the assay was increased by employing polyclonal rabbit anti-PGE(2) antibody dilution of 1/100 and 1% skimmed milk as a blocking solution, with the detection limit of 7.8-500 ng/well. The within-run and between-run coefficients of variation (CV) ranges were 3.2-3.7% and 3.4-3.8%, respectively. A linear standard curve was observed over the range of 0.078-5 microg/mL with a coefficient of determination (r(2)) of 0.99. Our results indicated that the developed direct ELISA was sensitive and suitable for a quick determination of PGE(2) levels from cell culture supernatants.

Investigation of the chemical constituents of the root bark of Artocarpus rigidus BLUME subsp. rigidus has led to the isolation of six, structurally diverse phenolic compounds. These included two new compounds with modified skeletons, the flavonoid 7-demethylartonol E (1) and the chromone artorigidusin (2), together with four known phenolic compounds, the xanthone artonol B (3), the flavonoid artonin F (4), the flavonoid cycloartobiloxanthone (5), and the xanthone artoindonesianin C (6). Compounds 1, 4, and 5 exhibited antiplasmodial activity against Plasmodium falciparum. All compounds showed antimycobacterial activity against Mycobacterium tuberculosis, with 4 being the most active compound (MIC 6.25 microg/ml). Compounds 5 and 6 were active against KB cells, whereas 2, 5, and 6 showed varying toxicity to BC cells. Compounds 1-3, 5, and 6 were active in the NCI-H187 cytotoxicity assay, with 3 being the most active compound (IC(50) 1.26 microg/ml).

Three new prenylated xanthones, mangostenones C (1), D (2), and E (3), together with 16 known xanthones 4-19, were isolated from the young fruit (7-week maturity stage) of Garcinia mangostana. The structural elucidation of the new compounds was mainly established on the basis of 1D and 2D NMR and HR-MS spectroscopic analysis. Compound 1 showed cytotoxic properties against three human cancer cell lines, epidermoid carcinoma of the mouth (KB), breast cancer (BC-1), and small cell lung cancer (NCI-H187), with IC50 values of 2.8, 3.53, and 3.72 microg/ml, respectively. Among the isolates, alpha-mangostin (12), the major metabolite, exhibited the most potent effects against the BC-1 cells with an IC50 value of 0.92 microg/ml, an activity greater than that of the standard drug ellipticine (IC50 = 1.46 microg/ml). Compound 12 also showed the highest activity against KB cells, while gartanin (10) displayed the strongest activity against the NCI-H187 cells at the respective IC50 values of 2.08 microg/ml and 1.08 microg/ml.

A library of hydroxycinnamic acid amides (HCAAs) and analogues were synthesized using solid-phase synthesis technique. These compounds were screened for antibacterial against methicillin-resistant Staphylococcus aureus (MRSA) (11 strains) and vancomycin-resistant S. aureus (VRSA) (4 strains). Dihydrocaffeoyl analogues showed activity against VRSA which were better than the reference drugs, vancomycin and oxacillin. These compounds also exhibited antibacterial activity against MRSA, which were more potent than oxacillin.

The present study examined the underlying mechanism by which 4-hydroxyacetophenone (4-HA), a bioactive compound found in several medicinal herbs, exerts its potent stimulatory effects on hepatic bile secretion.Bile flow, and biliary excretion of 4-HA, its metabolites, and inorganic electrolytes was examined in both normal Wistar rats and in TR(-) Wistar rats that have a congenital defect in the multidrug resistance-associated protein-2, Mrp2/Abcc2. The effects of 4-HA were also examined in animals treated with buthionine sulfoximine to decrease hepatic glutathione (GSH) levels.In normal rats, 4-HA dramatically increased bile flow rate, whereas it failed to exert a choleretic effect in TR(-) rats. This choleresis was not explained by increased biliary output of Na(+), K(+), Cl(-) or HCO(3) (-), or by increased biliary GSH excretion. Depletion of hepatic GSH with buthionine sulfoximine had no effect on the 4-HA-induced choleresis. HPLC analysis revealed that a single major compound was present in bile, namely.4-hydroxyacetophenone-4-O-beta-glucuronide, and that the parent compound was not detected in bile. Biliary excretion of the glucuronide was directly correlated with the increases in bile flow. In contrast to normal rats, this 4-HA metabolite was not present in bile of TR(-) rats.These results demonstrate that the major biliary metabolite of 4-HA in rats is the 4-O-beta-glucuronide, a compound that is secreted into bile at high concentrations, and may thus account in large part for the choleretic effects of 4-HA. Transport of this metabolite across the canalicular membrane into bile requires expression of the Mrp2 transport protein.

Three known diarylheptanoids, 1,7-diphenyl-5-hydroxy-(1E)-1-heptene, 5-hydroxy-7-(4-hydroxyphenyl)-1-phenyl-(1E)-1-heptene and 7-(3,4-dihydroxyphenyl)-5-hydroxy-1-phenyl-(1E)-1-heptene, were isolated from the ethyl acetate extract of Curcuma comosa rhizomes. A phloracetophenone glucoside, 4,6- dihydroxy -2-O-(β- d -glucopyranosyl)acetophenone , was isolated from the ethyl acetate and n-butanol extracts. This compound exhibited choleretic activity in rats.

Seven pterocarpans, erybraedin B (1), erybraedin A (2), phaseollin (3), erythrabyssin II (4), erystagallin A (5), erythrabissin-1 (6) and erycristagallin (7), two flavanones, 5-hydroxysophoranone (8) and glabrol (9), and one isoflavone, erysubin F (10), were isolated from the stems of Erythrina subumbrans (Leguminosae). Their structures were identified by means of spectroscopy. This is the first report of the isolation of the non-alkaloidal compounds from Erythrina subumbrans and the observed dehydration of 6a-hydroxypterocarpans 5 and 6 in CDCl(3) to the corresponding pterocarpenes 11 and 12, respectively. Compounds 8 and 9 were isolated for the first time from the genus Erythrina. Compounds 2 and 4 exhibited the highest degree of activity against Streptococcus strains with an MIC range of 0.78-1.56 microg/ml, whereas compound 7 exhibited the highest degree of activity against Staphylococcus strains, including drug-resistant strains (MRSA and VRSA), with an MIC range of 0.39-1.56 microg/ml. Interestingly, compounds 2, 4, 5 and 7 were more active against several strains of Streptococcus and Staphylococcus than the standard antibiotics vancomycin and oxacillin. Compound 7 showed the highest level of activity against all VRSA strains tested, with an MIC range of 0.39-1.56 microg/ml, which were resistant to both antibiotics. These compounds may prove to be potent phytochemical agents for antibacterial activity, especially against the MRSA and VRSA strains.

The effects of the choleretic and cholesterol lowering compound, 2,4,6-trihydroxyacetophenone (THA) and its analog, 2,6-dihydroxyacetophenone (DHA), on ileal bile acid absorption were investigated in rats. THA inhibited taurocholate (TC) uptake into ileal brush-border membrane vesicles (BBMV), showing a maximum inhibition of 50%, whereas DHA completely inhibited TC uptake into ileal BBMV. THA exhibited competitive inhibition with a Ki of 9.88 mM, while DHA showed non-competitive inhibition with a Ki of 7.65 mM. Both total and ouabain-sensitive basolateral membrane (BLM) Na+-K+-ATPase activities, which are essential for maintenance of the Na+-gradient for bile acid transport, were inhibited by THA and DHA in a dose-dependent manner. The inhibition of BLM ATPase was uncompetitive with a Ki of 10.1 and 5.0 mM for THA and DHA, respectively. Administration of THA or DHA (400 micromol/kg) twice a day, to hypercholesterolemic rats for 3 weeks caused similar and marked reductions in plasma cholesterol to 60% of the cholesterol-fed controls. The data suggest that the inhibitory actions of THA and DHA on two essential components of ileal bile acid recycling to liver could, in part, contribute to the cholesterol lowering effect of the hydroxyacetophenone compounds. These effects on decreasing bile acid recycling, in combination with their potent choleretic effect, accelerating biliary excretion of bile acids, are responsible for the effective cholesterol lowering capacities of these compounds.

From the flowers of Chromolaena odorata (Eupatorium odoratum) four flavanones, isosakuranetin (5,7-dihydroxy-4'-methoxyflavanone) (1), persicogenin (5,3'-dihydroxy-7,4'-dimethoxyflavanone) (2), 5,6,7,4'-tetramethoxyflavanone (3) and 4'-hydroxy-5,6,7-trimethoxyflavanone (4), two chalcones, 2'-hydroxy-4,4',5',6'-tetramethoxychalcone (5) and 4,2'-dihydroxy-4',5',6'-trimethoxychalcone (6), and two flavones, acacetin (5,7-dihydroxy-4'-methoxyflavone) (7) and luteolin (5,7,3',4'-tetrahydroxyflavone) (8) were isolated and identified. Compound 1 exhibited moderate antimycobacterial activity against Mycobacterium tuberculosis with the MIC value of 174.8 microM, whereas compounds 4, 7, and 8 exhibited weak activity with the MIC values of 606.0, 704.2 and 699.3 microM respectively. Compound 7 showed moderate cytotoxicity against human small cell lung cancer (NCI-H187) cells with the MIC value of 24.6 microM, whereas compound 8 exhibited moderate toxicity against NCI-H187 cells and week toxicity against human breast cancer (BC) cells with the MIC values of 19.2 and 38.4 microM respectively.

A new monoterpene ester, (+)-bornyl piperate was isolated from the underground roots of Piper aff. pedicellatum and its structure was elucidated on the basis of spectroscopic evidence and confirmed by X-ray analysis. The compound crystallizes in the triclinic space group P1 with a=7.3232(4) A, b=11.4705(7) A, c=23.2520(14) A, V=1943.6(2) A(3). This compound showed an antituberculosis activity against Mycobacterium tuberculosis (H(37)Ra strain) with the minimum inhibitor concentration (MIC) of 25 microg/ml.

Effects of elephant garlic (Allium ampeloprasum) volatile oil (GVO) and trichothecene (T-2) toxin were studied in Swiss albino mice. The animals were 1) topically applied GVO, 2) topically applied T-2 toxin, 3) topically applied GVO followed by T-2 toxin (GVO/T-2), and 4) T-2 toxin application followed by GVO (T-2/GVO) on the right footpad. All animals were observed by Langerhans cell enumeration and pathological changes of the footpad on days 1, 3, 5 and 7. The number of Langerhans cells in the GVO treated group (1,097 +/- 33/mm2 to 1,624 +/- 19/mm2) was not significantly different when compared with the corresponding control left footpad (1,143 +/- 33/mm2 to 1,674 +/- 21/mm2). Langerhans cells density in T-2 toxin treated group (629 +/- 29/mm2to 1,090 +/- 31/mm2) was reduced by 20-35% of the opposite control footpad (962 +/- 40/mm2 to 1,392 +/- 29/mm2). Furthermore, GVO/T-2 and T-2/GVO treated mice showed a decrease in Langerhans cell number than a single T-2 toxin treated group. While Langerhans cells in T-2 toxin, GVO/T-2 and T-2/GVO groups revealed a smaller cell size with shortening dendritic processes when compare to the normal control group. Histopathological findings of the footpad skin in T-2 toxin treated group revealed epidermal desquamation and necrosis with edema and inflammatory cells infiltration. While GVO/T-2 and T-2/GVO showed a similar sequence but a lesser severe degree. These findings suggested that GVO both in pre- and posttreatment could protect T-2 toxin induced epidermal damage in a mouse footpad.

Ten triterpenes (1-10) were isolated and identified from the twigs of Gardenia saxatilis (Rubiaceae) and were subjected to antiplasmodial evaluation against the parasite Plasmodium falciparum. The first six compounds, lupenone (1), lupeol (2), betulinic acid (3), oleanolic acid (4), ursolic acid (5), and winchic acid (27-O-feruloyloxybetulinic acid) (6) were inactive in the assay. The other four compounds, messagenic acid A (7) and messagenic acid B (8), the 27-O-p-(Z)- and 27-O-p-(E)-coumarate esters of betulinic acid, and a mixture of uncarinic acid E (27-O-p-(E)-coumaroyloxyoleanolic acid) (9) and 27-O-p-(E)-coumaroyloxyursolic acid (10) exhibited antiplasmodial activity, with the IC50 values of 1.5, 3.8 and 2.9 microg/ml, respectively. The results indicated that the p-coumarate moieties at the 27-position, both the cis and trans isomers, contributed to antiplasmodial activity. Introduction of a methoxyl group to the 3-position of the p-coumarate moiety to give a ferulate moiety resulted in loss of activity.

Eight amides, pellitorine (1), guineensine (2), brachystamide B (3), sarmentine (4), brachyamide B (5), 1-piperettyl pyrrolidine (6), 3',4',5'-trimethoxycinnamoyl pyrrolidine (7) and sarmentosine (8), two lignans, (+)-asarinin (9) and sesamin (10), and four other compounds, 1-(3,4-methylenedioxyphenyl)-1E-tetradecene (11), methyl piperate (12) and a mixture of beta-sitosterol (13) and stigmasterol (14), were isolated from the fruits of Piper sarmentosum (Piperaceae). This is the first reported isolation of compounds 2, 3, 5, 6, 7, 9, 10 and 12 from this plant species. Their structures were established from spectral data. These compounds were evaluated in antituberculosis and antiplasmodial tests. The results showed that compounds 4 and 6 exhibited both activities while compounds 1, 2, 5, 8 and 11 showed only antituberculosis activity. This is the first report of the antituberculosis and antiplasmodial activities for these compounds.

Two new ecdysteroids, 24-epi-pinnatasterone (1) and scabrasterone (2), together with 11 known ecdysteroids, calonysterone, pterosterone, 24-epi-makisterone A, 20-hydroxyecdysone (3), polypodine B, ajugasterone C, pinnatasterone (4), 11alpha-hydroxyecdysone, 24-epi-abutasterone, 20,26-dihydroxyecdysone, and turkesterone (5), were isolated from the stem bark of Vitex scabra. This plant species contained a very high concentration (1.8%) of 3 and thus provided a good source of this parent ecdysteroid and related rare ecdysteroids. Compounds 1 and 2 exhibited very low moulting activity in the Musca bioassay. The low biological activity of these two ecdysteroids was in agreement with those of other 22-deoxyecdysteroids.

A novel piperine dimer, named chabamide, was isolated from stems of Piper chaba Hunter and its structure was elucidated on the basis of spectroscopic evidence. Chabamide showed antimalarial activity with an IC(50) value of 2.7 microg/ml and antituberculosis activity with the minimum inhibitory concentration (MIC) of 12.5 microg/ml.

A new ecdysteroid, zoanthusterone, has been isolated from a marine zoanthid, Zoanthus sp. Ten known ecdysteroids, ponasterone A, 20-hydroxyecdysone 2-acetate, viticosterone E, integristerone A 25-acetate, 2-deoxy-20-hydroxyecdysone, ecdysone, ajugasterone C, dacryhainansterone, inokosterone, and 20-hydroxyecdysone, have also been isolated. This is the first report of ecdysteroids in a Zoanthus species.

The plasma cholesterol-lowering effect and mechanism thereof of a choleretic phloracetophenone or 2,4,6-trihydroxyacetophenone (THA) were investigated in hypercholesterolemic male hamsters. Intragastric administration of THA (300-600 micromol/kg) twice a day for 7 days to these animals caused a dose- and time-dependent decrease in both plasma cholesterol and triglyceride levels. THA at a dose of 400 micromol/kg reduced the cholesterol and triglyceride levels in plasma to 52% and 25% of the level in corresponding cholesterol-fed controls, respectively, with decreases in both plasma very low density lipoprotein and low density lipoprotein cholesterol but not in high density lipoprotein cholesterol. THA did not significantly alter total hepatic cholesterol content but significantly increased the excretion of both bile acids and cholesterol into the intestinal lumen for elimination. Corresponding to the increase in bile acid excretion, THA caused a seven-fold increase in hepatic cholesterol 7alpha-hydroxylase activity. These results suggest that THA exerts its cholesterol lowering effect by increasing hepatic cholesterol 7alpha-hydroxylase activity which increases hepatic conversion of cholesterol to bile acid for disposal via biliary secretion. This compound may have a potential for future development as a therapeutic agent for lowering lipids in hypercholesterolemic patients.

A new iridoid, pedunculariside, together with the known iridoid agnuside were isolated from the butanol extract of Vitex peduncularis stem bark. Both pedunculariside and agnuside showed preferential inhibition of COX-2, with IC50 values of 0.15 +/- 0.21 mg/ml and 0.026 +/- 0.015 mg/ml respectively, while having only small inhibitory effects on COX-1. Both compounds did not exhibit cytotoxicity against vero cells.

A number of 22-O-alkyl ether and acyl ester derivatives have been prepared and their moulting activity determined, using the Musca assay. It was found that a free 22-hydroxyl group is not an essential structural requirement for an ecdysteroid to exhibit high moulting activity. The activity of a 22-O-substituted ecdysteroid may even be higher than that of the parent compound, providing that the substituent constitutes a functional group that can enhance biological activity. The moulting activity is not sensitive to steric factors at the 22-position. Ecdysteroid without a 22-hydroxyl group may exhibit high moulting activity if a functional group that can enhance activity is present at an appropriate position.

Highly oxygenated ecdysteroids, (24R)-11 alpha, 20,24-trihydroxyecdysone and 11 alpha,20,26-trihydroxyecdysone, have been isolated from the polar fraction of Vitex canescens root bark. The latter exists as two C-25 epimers which could be separated by reversed-phase HPLC.