Effects of Ganoderma lucidum and 'Essence of Chicken' on Physical Fatigue Recovery and Exercise Performance Improvement.

A fast-paced lifestyle, pressure from the environment and a heavy work load often cause extreme tiredness in modern life. Different kinds of nutritional supplements in the form of functional foods or traditional Chinese medicine, such as 'essence of chicken' and Ganoderma lucidum have been claimed to benefit physical performance and promote health. Previous studies have revealed that 'essence of chicken' or G. lucidum have a wide spectrum of biological activities. In this study, we combined these two ingredients together (designated as CEG) to evaluate their synergistic effects on physiological adaption on exercise fatigue and physical activities. The ICR strain mice were allocated as 0, 833, 1666, and 4165 mg/kg dose groups and administrated by oral gavage consecutively for 4 weeks. Physical activities including grip strength and aerobic endurance were evaluated. Various fatigue-associated biochemical variables such as lactate, BUN or CK were also evaluated. The levels of liver and muscle glycogen were measured as an indicator of energy storage at the end of the experiment. Safety assessments for supplementation were also evaluated. CEG supplementation significantly increased the endurance and grip strength and demonstrated beneficial effects on lactate production and clearance rate after an acute exercise challenge. The CEG supplementation significantly mitigated the BUN and CK indexes after extended exercise and elevated the glycogen content in the liver and muscle tissues. According to body composition, biochemical and histopathological data, daily administration of CEG for over 28 days (subacute toxicity) also demonstrated reasonable safety results for supplementation. Combined G. lucidum and 'essence of chicken' can significantly increase the exercise performance and improve fatigue recovery. It may also provide a viable alternative nutritional supplement for health promotion.

The application of post-translational modification oriented serum proteomics to assess experimental diabetes with complications.

Proteome analysis of serum from type 2 diabetics with complications may lead to the discovery of diagnostic or prognostic biomarkers. To circumvent the principal barrier of serum proteomics, our investigation aimed to evaluate whether a study of post-translational modification enriched serum proteins could be valuable for the discovery of biomarkers or metabolic pathways related to type 2 diabetes pathogenesis. Type 2 diabetes was induced from high-fat diet fed Sprague Dawley rats with streptozotocin injection. Once diabetic status was confirmed, serum samples from either fasted healthy or diabetic rats were pooled and profiled by two-dimensional difference gel electrophoresis or comparative 2D electrophoresis after protein enrichments using immobilized metal ion, concanavalin A, and lentil affinity chromatography, respectively. Differential expressed proteins were identified and the associated networks were established by an Ingenuity Pathway Analysis. As a result, induced rats became severe diabetic and accompanied by hyperlipidemia, fatty liver, and glomerular hypertrophy. There were 3 total, 14 phosphorylated and 23 glycosylated protein targets differentially expressed. Proteins could be linked to HNF4A, HNF1A, and NFκB transcriptional factors and antigen presentation, humoral immune response, and inflammatory response pathways. Predicted organ toxicity in kidney, heart, and liver matched with our histopathological results. In conclusion, post-translational modification based serum protein enrichment could be a valuable approach to enhance the resolution of serum proteomics without depleting potentially valuable abundant proteins. Our results also indicated the potential association of the hepatic secretome and hepatocyte nuclear factors in the pathogenesis of type 2 diabetes and its complications.

Neuroprotective and Antineuroinflammatory Effects of Hydroxyl-Functionalized Stilbenes and 2-Arylbenzo[b]furans.

The drugs currently used to treat Alzheimer's disease (AD) are limited in the benefits they confer, and no medication has been clearly proven to cure or delay the progression of AD. Most candidate AD drugs are meant to reduce the production, aggregation, and toxicity of amyloid ß (Aß) or to promote Aß clearance. Herein, we demonstrate the efficient synthesis of hydroxyl-functionalized stilbene and 2-arylbenzo[b]furan derivatives and report on the neuroprotective and anti-inflammatory effects of these phenolic compounds in vitro and in an animal model. Structure-activity relationships revealed that the presence of an acrylate group on 2-arylbenzo[b]furan confers neuroprotective and anti-inflammatory effects. Furthermore, compounds 11 and 37 in this study showed particular potential for development as disease-modifying anti-Alzheimer's drugs, based on their neuroprotective effects on neuron cells, their antineuroinflammatory effects on glial cells, and the ability to ameliorate nesting behavior in APP/PS1 mice. These results indicate that 2-arylbenzo[b]furans could be candidate compounds for the treatment of AD.

Bioactive chemical constituents from the root bark of Morus australis.

Two new pyranoflavonoids, morustralins A (1) and B (2), a new natural benzene derivative, one benzenoid (Z)-1-hydroxy-4-(2-nitroethenyl)benzene (3), and thirty known compounds were isolated and characterized from the root bark of Morus australis. The structures of the new compounds were established from spectroscopic and spectrometric analyses. Ten isolates (1-10) were examined for inhibitory effects on adenosine diphosphate (ADP)-, arachidonic acid (AA)-, and platelet-aggregating factor (PAF)-induced platelet aggregation. Among the tested compounds, compound 3 displayed the most significant inhibition of ADP- and AA-induced platelet aggregation with IC50 values of 9.76±5.54 and 9.81±2.7µM, respectively. In addition, eight purified compounds (3-10) were examined for inhibition of nitric oxide (NO) production in RAW 264.7 cells and six compounds (3-8) displayed significant inhibitory effects with IC50 values ranging from 2.1±0.3 to 6.3±0.6µM.

Antioxidant and Anti-Inflammatory Phenolic Glycosides from Clematis tashiroi.

From the 95% EtOH extract of dried aerial parts of Clematis tashiroi, eight new and four known phenolic (caffeic acid, coumaric acid, ferrulic acid) glycosides were isolated and characterized. The structures of the new isolates (clematisides A-H) were elucidated by spectroscopic data interpretation as trans-4-O-(6-O-trans-caffeoyl-ß-D- glucopyranosyl)-9-O-ß-D-glucopyranosyl caffeic acid (1), trans-4-O-(6-O-trans-feruloyl-ß-D-glucopyranosyll)-9-O-ß-D-glucopyranosyl caffeic acid (2), trans-4-O-(6-O-trans-p-coumaroyl-ß-D-glucopyranosyl)-9-O-ß-D-glucopyranosyl caffeic acid (3), trans-4-O-(6-O-trans-caffeoyl-ß-D-glucopyranosyl)-9-O-ß-D-glucopyranosyl p-coumaric acid (4), trans-3-O-(6-O-trans-caffeoyl-ß-D-glucopyranosyl)-9-O-ß-D-glucopyranosyl caffeic acid (5), trans-3-O-(6-O-trans-p-coumaroyl-ß-D-glucopyranosyl)-9-O-ß-D-glucopyranosyl caffeic acid (6), 6-(3',4'-dihydroxystyryl)-2-pyrone-4-O-(6-O-trans-caffeoyl)-ß-D-glucopyranoside (7), and 6-(3',4'-dihydroxystyryl)-2-pyrone-4-O-{6-O-[4-O-(6-O-trans-caffeoyl)-ß-D-glucopyranosyl]-trans-caffeoyl}-ß-D-glucopyranoside (8), respectively. In a DPPH radical-scavenging test, compounds 1, 7, and 8 showed more potent antioxidant activity than that of the positive control, vitamin E. In addition, compound 7 also showed inhibitory activity in an antinitric oxide release assay.

Lignans from the aerial parts of Saururus chinensis: isolation, structural characterization, and their effects on platelet aggregation.

Five new diaryldimethylbutane lignans, saurulignans A-E (1-5), four new tetrahydrofuran lignans, saurufurins A-D (6-9), and one arylnaphthalene lignan, saurunarin (10), were isolated from Saururus chinensis, along with 18 known compounds. Lignan 5 showed significant inhibition of ADP-induced aggregation with an IC50 value of 9.8 µM and AA-induced aggregation with an IC50 value of 14.0 µM. Compound 19 showed significant activity to inhibit PAF-induced aggregation with an IC50 value of 9.1 µM. In addition, five isolated compounds could induce platelet aggregation. These results suggest that secondary metabolites in S. chinensis have bidirectional regulation on blood clotting and anticlotting effects.

4-Hydroxy-17-methylincisterol from Agaricus blazei Decreased Cytokine Production and Cell Proliferation in Human Peripheral Blood Mononuclear Cells via Inhibition of NF-AT and NF-κB Activation.

Agaricus blazei Murill is an edible and medicinal mushroom. In the previous study, we have proved that extracts of A. blazei inhibit human peripheral blood mononuclear cell (PBMC) proliferation activated with phytohemagglutinin (PHA). Currently, we purified 4-hydroxy-17-methylincisterol (4-HM; C21H33O3) from A. blazei investigated its regulatory effects on cytokine productions and cell proliferation of PBMC induced by PHA. The results indicated that 4-HM suppressed, in activated PBMC, the production and mRNA expression of interleukin-2 (IL-2), IL-4, tumor necrosis factor- α , and interferon- γ in a concentration-dependent manner. This inhibition was not related to cell viability. While 4-HM did not affect ERK phosphorylation and its downstream c-fos gene expression in PBMC induced by PHA, it decreased both NF-AT and NF- κ B activation. The upstream signaling of NF-AT and NF- κ B, intracellular calcium concentrations ([Ca(2+)]i), and protein kinase C theta (PKC θ ) activation in PHA-treated PBMC were reduced by 4-HM. The data demonstrated that the suppressant effects of 4-HM on cell proliferation in PBMC activated by PHA appeared to be mediated, at least in part, through inhibition of Ca(2+) mobilization and PKC θ activation, NF-AT and NF- κ B activation, and cytokine transcripts and productions of PBMC. We suggested that A. blazei contained a potential immunomodulator 4-HM.

3-methoxyapigenin modulates ß-catenin stability and inhibits Wnt/ß-catenin signaling in Jurkat leukemic cells.

AIMS: Aberrant activation of Wnt/ß-catenin signaling has been implicated in carcinogenesis. Identification of inhibitors of this pathway may help in cancer therapy. The purpose of this study is to investigate the inhibitory effect of 3-methoxyapigenin (3-MA) with ß-catenin/LEF reporter system. The anti-cancer mechanisms in Jurkat leukemic cells were also examined. MAIN METHODS: HEK 293-TOP/FOP reporter cells were used to determine the inhibitory effect of 3-MA on Wnt/ß-catenin pathway. We also used Jurkat-TOP reporter cells to confirm the inhibitory effect and the action mechanisms of 3-MA. Target genes and cell proliferation were analyzed by RT-PCR and (3)H-thymidine uptake assay. The effects of 3-MA on ß-catenin phosphorylation was determined by Western blotting and by in vitro kinase assays. ß-catenin translocation and its transactivation were verified by cellular fractionation and EMSA. KEY FINDINGS: 3-MA inhibited Wnt-3A-induced luciferase activity in the HEK 293-TOP/FOP reporter system. Western blotting analysis showed that phosphorylation sites in ß-catenin by glycogen synthase kinase-3ß (GSK-3ß) and casein kinase 2 (CK2) were inhibited by 3-MA in Jurkat. In parallel, in vitro kinase assays verified this effect. As a result, total ß-catenin turnover remained balanced by this dual inhibitory effect of 3-MA. Although the ß-catenin protein level remained unchanged, 3-MA did inhibit ß-catenin translocation. Finally, we found that the ß-catenin/LEF transcriptional activity, expression of c-myc and cyclin-D3, and cell proliferation were inhibited by 3-MA. SIGNIFICANCE: 3-MA modulates the turnover of ß-catenin and suppresses the Wnt/ß-catenin signaling pathway through inhibition of ß-catenin translocation. We suggested that 3-MA has potential as an anti-cancer drug.

Structure-activity relationships of chalcone analogs as potential inhibitors of ADP- and collagen-induced platelet aggregation.

In an effort to develop potent antiplatelet agents, 12 O-prenylated (2-13) and 10 O-allylated (14-23) chalcones were synthesized and screened for in vitro inhibitory effects on aggregation of washed rabbit platelets induced by ADP (20 µM) and collagen (10 µg/mL). In addition, the platelet aggregation activity of previously synthesized Mannich bases of heterocyclic chalcones (MBHC) (24-62) was evaluated. The preliminary structure-activity relationships suggested that the antiplatelet activity was governed to a great extent by the presence of a pyridyl ring-B and a hydroxy group at position C-3' in ring-A of the MBHC templates.

Pharmacological evaluation of insulin mimetic novel suppressors of PEPCK gene transcription from Paeoniae Rubra Radix.

ETHNOPHARMACOLOGICAL RELEVANCE: Paeoniae Rubra Radix (root of Paeonia lactiflora) has been frequently employed in Traditional Chinese Medicine (TCM) as and anti-diabetic therapy to enhance blood circulation and dissipate stasis. AIM OF THE STUDY: Previously, we identified a novel hypoglycemic action of a crude extract from Paeoniae Rubra Radix, which also suppressed phosphoenolpyruvate carboxykinase (PEPCK) gene transcription. Therefore, the current investigation intended to elucidate potential active bio-constituents of this herb and mechanisms of action. MATERIALS AND METHODS: Glucocorticoid receptor (GR) nuclear localization, the PEPCK messenger (m)RNA level, pregnane X receptor (PXR) mRNA expression, cAMP-responsive element-binding protein (CREB) serine phosphorylation and DNA binding were evaluated in dexamethasone (Dex) and 8-bromo-cAMP (CA)-stimulated H4IIE cells, while efficacy of agents was assessed in a stable cell line containing a green fluorescent protein (GFP) reporter driven by the PEPCK promoter. HPLC profiling, colorimetric assays, and NMR analysis were employed for chemical characterization purpose. RESULTS: An extract of Paeoniae Rubra Radix lacking the insulin mimetic compound, 1,2,3,4,6-penta-O-galloyl-beta-d-glucose (PGG), and termed the non-PGG fraction (NPF), consisting of tannin polymers, suppressed PEPCK expression in the presence of an insulin receptor antagonist (HNMPA-AM(3)), suggesting the action of this fraction is independent of the insulin receptor. Furthermore, Dex-stimulated GR nuclear localization and transactivation were prevented by the NPF. Similarly, CA-stimulated CREB serine phosphorylation and DNA binding were also inhibited by the NPF in H4IIE cells. Hence NPF antagonizes both signaling pathways that induce PEPCK gene transcription. CONCLUSION: In conclusion, the current study proposes that the potent suppressive activity on PEPCK gene transcription observed with Paeoniae Rubra Radix extract, can be attributed to at least two distinct components, namely PGG and NPF.

Arctigenin from Arctium lappa inhibits interleukin-2 and interferon gene expression in primary human T lymphocytes.

BACKGROUND: Arctium lappa (Niubang), a Chinese herbal medicine, is used to treat tissue inflammation. This study investigates the effects of arctigenin (AC), isolated from A. lappa, on anti-CD3/CD28 Ab-stimulated cell proliferation and cytokine gene expression in primary human T lymphocytes. METHODS: Cell proliferation was determined with enzyme immunoassays and the tritiated thymidine uptake method. Cytokine production and gene expression were analyzed with reverse transcription-polymerase chain reaction. RESULTS: AC inhibited primary human T lymphocytes proliferation activated by anti-CD3/CD28 Ab. Cell viability test indicated that the inhibitory effects of AC on primary human T lymphocyte proliferation were not due to direct cytotoxicity. AC suppressed interleukin-2 (IL-2) and interferon-γ (IFN-γ) production in a concentration-dependent manner. Furthermore, AC decreased the IL-2 and IFN-γ gene expression in primary human T lymphocytes induced by anti-CD3/CD28 Ab. Reporter gene analyses revealed that AC decreased NF-AT-mediated reporter gene expression. CONCLUSION: AC inhibited T lymphocyte proliferation and decreased the gene expression of IL-2, IFN-γ and NF-AT.

Characterized polysaccharides from black soybean induce granulocyte colony-stimulated factor gene expression in a phosphoinositide 3-kinase-dependent manner.

Black soybean (Glycine max L. merr.) is an edible Chinese medicine for nourishment spleen. In the present study, effects of characterized polysaccharides from black soybean (PGM) on granulocyte colony-stimulated factor (G-CSF) production in human peripheral blood mononuclear cells (PBMC) were determined and their action mechanisms were examined. The results indicated that PGM concentration-dependently enhanced G-CSF production in PBMC through modulation of mRNA expression. Data from Western blotting showed that PGM significantly induced the extracellular signal-regulated protein kinase (ERK) activation in PBMC. The nuclear factor (NF)-κB activation in PBMC was increased with PGM by modulation of IκB degradation and PKC θ activation. The levels of G-CSF mRNA in PGM-treated PBMC could be reduced by ERK inhibitor U0126 and NF-κB inhibitor pyrrolidine dithiocarbamate, respectively. Furthermore, the data showed that PGM stimulated phosphoinositide 3-kinase (PI3K)-regulated Akt phosphorylation. The PI3K inhibitor, Ly294002, blocked ERK, NF-κB, and PKC θ activation and G-CSF mRNA expression in PBMC induced by PGM. Thus, we first proved that the enhancement mechanisms of PGM on G-CSF production, appeared to be mediated, at least in part, through activation of PI3K, ERK, PKC θ, and NF-κB signaling pathways in PBMC. We suggest that PGM from black soybean is a potential G-CSF stimulator.

(S)-armepavine from Chinese medicine improves experimental autoimmune crescentic glomerulonephritis.

OBJECTIVE: Intra-renal T cells and macrophages play a key pathogenic role in the development and progression of glomerular crescents. We aimed to establish (S)-armepavine [(S)-ARM], a major bioactive compound of a Chinese medicinal plant, Nelumbo nucifera, as a potential therapeutic agent in the treatment of autoimmune crescentic glomerulonephritis (ACGN). METHODS: A mouse ACGN model associated with T-cell dysregulation, was used to evaluate the therapeutic effects of (S)-ARM on the rapidly progressive glomerular disorder. RESULTS: The results showed that (S)-ARM administered in the established phase of ACGN is capable of dramatically decreasing glomerular crescents in the kidney and improving proteinuria and renal dysfunction. These effects were associated with greatly inhibited infiltration of T cells/macrophages and suppressed nuclear factor (NF)-κB activation in the kidney, lowered serum levels of autoantibodies and both serum and intra-renal levels of pro-inflammatory cytokines, suppressed T/B-cell activation and T-cell proliferation of the spleen, reduced glomerular immune deposits and apoptosis in both the spleen and kidney in (S)-ARM-treated ACGN mice, compared with the vehicle-treated (disease control) group of ACGN mice. CONCLUSION: We demonstrated therapeutic effects of (S)-ARM on ACGN as a result of: (i) early systemic negative modulation of T/B cells; (ii) intra-renal regulation of combined NF-κB activation and mononuclear leucocytic infiltration, thereby preventing glomerular crescent formation; and (iii) protection from apoptosis in both the spleen and kidney.

Norcantharidin reduced cyclins and cytokines production in human peripheral blood mononuclear cells.

AIMS: To evaluate potential agents of therapeutic value in tissue inflammation, we studied norcantharidin (NCTD) and its derivatives for their effects on immune responses of human peripheral blood mononuclear cells (PBMC) in vitro. MAIN METHODS: PBMC proliferation was evaluated by tritiated thymidine uptake method. The production and gene expression of cytokines were determined with enzyme immunoassays (EIA) and reverse transcription-polymerase chain reaction (RT-PCR), respectively. KEY FINDINGS: Five derivatives from NCTD had no significant effect on cell proliferation in PBMC. NCTD inhibited PBMC proliferation induced by phytohemagglutinin (PHA) with a 50% inhibitory concentration (IC(50)) 42.1+/-2.3 microM. The inhibitory action of NCTD did not involve direct cytotoxicity. To localize the point in the PBMC proliferation where arrest occurred, a set of key regulatory events leading to the cell proliferation, including cell cycle progression, production and gene expression of interleukin-2 (IL-2), IL-4, IL-10, and interferon-gamma (IFN-gamma) and cyclins was examined. Data demonstrated NCTD arrested the cell cycle progression of activated PBMC from the G1 transition to the S phase. The cyclin D3, E, A, and B transcripts and protein production in PHA-treated PBMC was reduced by NCTD. Whereas NCTD exerted no effect on IL-4 and IFN-gamma production, it significantly alleviated the production and mRNA expression of IL-2 and IL-10 in activated PBMC. SIGNIFICANCE: The suppressant effects of NCTD on proliferation of PBMC activated by PHA therefore appear to be mediated, at least in part, through inhibition of cyclins and IL-2 production and arrest of cell cycle progression in the cells.

Astragalus membranaceus flavonoids (AMF) ameliorate chronic fatigue syndrome induced by food intake restriction plus forced swimming.

AIM OF THE STUDY: Alteration of immune function may be associated with chronic fatigue syndrome (CFS) and this study reveals the immunoregulatory effect of Astragalus membranaceus flavonoids (AMF). MATERIALS AND METHODS: CF rats were induced by food intake restriction plus forced swimming for 6 weeks. RESULTS: An atrophied spleen associated with a significantly decreased spleen/body weight ratio and a reduced spleen cells proliferation was found in CF rats when compared with home cage controls. AMF given orally at 20, 50 and 100 mg/kg body weight once a day consecutively for 6 weeks could recover the reduced cell proliferation. A switch to Th1-dominated immune regulation was observed in CF rats as the cultured splenocytes produced more interleukin-2 (IL-2) but less IL-4 when compared with controls. Supplementation with AMF could significantly counteract the aberrant cytokine production and rats received AMF exhibited higher endurance capacity to swim when compared with those without AMF administration. Checking the spectrum signals confirmed that the three major isoflavones contained in AMF were ononin, formononetin, and demethylhomopterocarpin. CONCLUSION: Alterations of immune function may be associated with CFS and the tonic effects of AMF against CF may be attributable to balance the abnormal cytokine level by isoflavones.

Efficacy of orally administered Lobelia chinensis extracts on herpes simplex virus type 1 infection in BALB/c mice.

By a plaque reduction assay, methanolic extracts from Lobelia chinensis (LC) significantly blocked herpes simplex virus type 1 (HSV-1) replication in HeLa cells without apparent cytotoxicity. The 50% inhibitory concentration (IC(50)) of LC on HSV-1 replication is 139.2 microg/ml. To elucidate LC anti-HSV-1 activity in vivo, BALB/c mice were injected subcutaneously with HSV-1 (2.5 x 10(6)PFU/50 microl), treated orally thrice a day with acyclovir (60 mg/kg/dose) or LC (20 and 50 mg/kg/dose) for 7 days, and inspected daily for signs of disease. Data from the scoring system indicated that animals infected with HSV-1, developed progressive zoster lesions starting 2 days postinfection (p.i.) and appeared the most serious syndromes at 4-5 days p.i. In marked contrast to the results with control mice, treatment with acyclovir or 50 mg/kg/dose LC resulted in a sustained protective effect. The HSV-1 titers and DNA levels in ground skin samples were significantly reduced by LC. No toxic effect of LC on liver and kidney functions was apparent. These results indicated that LC was a potent inhibitor of the in vitro and in vivo replication of HSV-1.

Triterpenoid saponins from the fruits and galls of Sapindus mukorossi.

Six saponins, sapinmusaponin K (1) [hederagenin-3-O-(3-O-acetyl-alpha-L-arabinopyranosyl)-(1-->3)-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranoside], sapinmusaponin L (2) [hederagenin-3-O-(4-O-acetyl-alpha-L-arabinopyranosyl)-(1-->3)-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabino-pyranoside], sapinmusaponin M (3) [hederagenin-3-O-(2,3-O-diacetyl-beta-D-xylopyranosyl)-(1-->3)-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranoside], sapinmusaponin N (4) [hederagenin-3-O-(2,4-O-diacetyl-beta-D-xylopyranosyl)-(1-->3)-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranoside], sapinmusaponin O (5) [3,7,20(S)-trihydroxydammar-24-ene-3-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranoside], and sapinmusaponin P (6) [3,7,20(R)-trihydroxydammar-24-ene-3-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-d-glucopyranoside], along with seven known saponins (7-13), were isolated from fruits and the galls of Sapindus mukorossi. Their structures were elucidated by 1D and 2D NMR spectroscopic techniques and acid hydrolysis. Biological evaluation indicated that saponins 1-4 and 7-13 showed moderate cytotoxicity against several human tumor cell lines.

Selective COX-2 inhibitors. Part 2: synthesis and biological evaluation of 4-benzylideneamino- and 4-phenyliminomethyl-benzenesulfonamides.

Two series of 4-benzylideneamino- and 4-phenyliminomethyl-benzenesulfonamide derivatives were designed and synthesized for the evaluation as selective cyclooxygenase-2 (COX-2) inhibitors in a cellular assay using human whole blood (HWB). Extensive structure-activity relationships (SAR) were studied within these series. Several compounds were found to be novel and selective COX-2 inhibitors. Among them, the most potent and selective was 4-(3-carboxy-4-hydroxy-benzylideneamino)benzenesulfonamide (20, LA2135), (IC(50)'s for COX-1: 85.13 microM; COX-2: 0.74 microM; SI: 114.5), being more active COX-2 selective than celecoxib.

Isolation and identification of antiplatelet aggregatory principles from the leaves of Piper lolot.

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.

Anti-platelet aggregation triterpene saponins from the galls of Sapindus mukorossi.

Bioassay-directed fractionation of an ethanolic extract of the galls of Sapindus mukorossi has resulted in the isolation of two new tirucallane-type triterpenoid saponins, sapinmusaponins Q (1) and R (2), along with three known oleanane-type triterpenoid saponins (3-5). Their structures were elucidated on the basis of spectroscopic analysis and chemical hydrolysis. Biological evaluation showed that both sapinmusaponins Q and R demonstrated more potent anti-platelet aggregation activity than aspirin.