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.

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.

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.

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.

(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.

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.

(S)-armepavine inhibits human peripheral blood mononuclear cell activation by regulating Itk and PLCgamma activation in a PI-3K-dependent manner.

Chinese herbs are useful edible and medicinal plants for their immune modulatory functions. We have proven that (S)-armepavine (C19H23O3N; MW313) from Nelumbo nucifera inhibits the proliferation of human PBMCs activated with PHA and improves autoimmune diseases in MRL/MpJ-lpr/lpr mice. In the present study, the pharmacological activities of (S)-armepavine were evaluated in PHA-activated PBMCs. The results showed that (S)-armepavine suppressed PHA-induced PBMC proliferation and genes expression of IL-2 and IFN-gamma without direct cytotoxicity. Inhibition of NF-AT and NF-kappaB activation suggested phospholipase Cgamma (PLCgamma)-mediated Ca2+ mobilization and protein kinase C activation were blocked by (S)-armepavine. Phosphorylation of PLCgamma is regulated by lymphocyte-specific kinase (Lck), ZAP-70, and IL-2-inducible T cell kinase (Itk). We found (S)-armepavine inhibited PHA-induced phosphorylation of Itk and PLCgamma efficiently but did not influence Lck or ZAP-70 phosphorylation. In addition, ZAP-70-mediated pathways, such as the association of linker for activation of T cells with PLCgamma and activation of ERK, were also intact in the presence of (S)-armepavine. Finally, reduction of phosphoinositide 3,4,5-trisphosphate formation and Akt phosphorylation suggested that (S)-armepavine inhibited Itk, and PLCgamma phosphorylation might be a result of the influence of PI-3K activation. Addition of exogenous IL-2 or PMA/A23187 rescued PBMC proliferation in the presence of (S)-armepavine. Therefore, we concluded that (S)-armepavine inhibited PHA-induced cell proliferation and cytokine production in a major way by blocking membrane-proximal effectors such as Itk and PLCgamma in a PI-3K-dependent manner.

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.

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.

Alpha-bulnesene, a PAF inhibitor isolated from the essential oil of Pogostemon cablin.

Steam distilled essential oil from the aerial parts of Pogostemon cablin was analyzed by gas chromatography-mass spectrometry (GC-MS). Forty one compounds were identified of which alpha-guaiene (20.62%) and alpha-bulnesene (16.18%) were major constituents. Furthermore, fractionation of the essential oil from P. cablin guided by inhibitory activity against PAF-induced platelet aggregation led to the isolation of the sesquiterpene, alpha-bulnesene.

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.

Yatein from Chamaecyparis obtusa suppresses herpes simplex virus type 1 replication in HeLa cells by interruption the immediate-early gene expression.

Inhibitory effects of methanolic extracts from nine Chinese herbs on herpes simplex virus type 1 (HSV-1) replication were studied. By a bioassay-guided fractionation procedure, yatein (C(22)H(23)O(7); M.W.399) was isolated from Chamaecyparis obtusa; yatein significantly suppressed HSV-1 multiplication in HeLa cells without apparent cytotoxicity. To further localize the point in the HSV-1 replication cycle where arrest occurred, a set of key regulatory events leading to the viral multiplication was examined, including viral immediate-early (alpha) and late (gamma) gene expression and DNA replication. Results indicated that levels of glycoprotein B (gB) and gC mRNA expression in HeLa cells were impeded by yatein. Data from polymerase chain reaction showed that replication of HSV-1 DNA in HeLa cells was arrested by yatein. Furthermore, yatein decreased ICP0 and ICP4 gene expression in HeLa cells. Results of an electrophoretic mobility shift assay demonstrated that yatein interrupted the formation of alpha-trans-induction factor/C1/Oct-1/GARAT multiprotein complex. The mechanisms of antiviral action of yatein seem to be mediated, by inhibiting HSV-1 alpha gene expression, including expression of the ICP0 and ICP4 genes, and by arresting HSV-1 DNA synthesis and structural protein expression in HeLa cells. These results suggest that yatein is an antiviral agent against HSV-1 replication.

Inhibition of (S)-armepavine from Nelumbo nucifera on autoimmune disease of MRL/MpJ-lpr/lpr mice.

T cell immune responses play important roles in the pathogenesis of systemic lupus erythematosus (SLE). (S)-Armepavine (C19H23O3N; MW313) from Nelumbo nucifera suppresses T cells proliferation. To study its potential benefit on SLE, we examined effects of (S)-armepavine on MRL/MpJ-lpr/lpr mice, which have similar disease features to human SLE. MRL/MpJ-lpr/lpr mice were treated orally with (S)-armepavine for 6 weeks and their SLE characteristics were evaluated. The results revealed that (S)-armepavine prevented lymphadenopathy and elongated life span of MRL/MpJ-lpr/lpr mice. It seemed to be mediated by inhibition of splenocytes proliferation, suppression of interleukin-2 (IL-2), interleukin-4, interleukin-10, and interferon-gamma (IFN-gamma) gene expressions, reduction of glomerular hypercellularity and immune complexes deposition, and decrease of urinary protein and anti-double stranded DNA autoantibody production. Furthermore, the data demonstrated (S)-armepavine impaired IL-2 and IFN-gamma transcripts in human peripheral blood mononuclear cells. We suggest that (S)-armepavine may be an immunomodulator for the management of autoimmune diseases like SLE.

Andrographolide acts through inhibition of ERK1/2 and Akt phosphorylation to suppress chemotactic migration.

We now evaluated the anti-inflammatory mechanisms of andrographolide on complement 5a (C5a)-induced macrophage recruitment in vitro. Andrographolide concentration dependently inhibited cell migration toward C5a with an IC50 of 5.6+/-0.7 microM. With relatively specific kinase inhibitors (PD98059, SB203580, SP600125, wortmannin and LY294002, respectively) the results showed that extracellular signal-regulated kinase1/2 (ERK1/2), p38 mitogen-activated protein kinase (p38 MAPK) and phosphatidylinositol-3-kinase (PI3K) were necessary for C5a-induced migration, whereas c-Jun N-terminal kinase (JNK) was nonessential. Andrographolide significantly attenuated C5a-stimulated phosphorylation of ERK1/2, and of its upstream activator, MAP kinase-ERK kinase (MEK1/2). C5a-activated ERK1/2 phosphorylation was 86+/-9% inhibited by 30 microM andrographolide. Under the same conditions, however, andrographolide failed to affect C5a-stimulated p38 MAPK and JNK phosphorylation. Andrographolide also strongly abolished C5a-stimulated Akt phosphorylation, a downstream target protein for PI3K. These results indicate that inhibition of cell migration by interfering with ERK1/2 and PI3K/Akt signal pathways may contribute to the anti-inflammatory activity of andrographolide.

C5a differentially stimulates the ERK1/2 and p38 MAPK phosphorylation through independent signaling pathways to induced chemotactic migration in RAW264.7 macrophages.

We elucidate the roles of various protein kinases involved in complement 5a (C5a)-induced cell migration. Results showed that extracellular signal-regulated kinase1/2 (ERK1/2), p38 mitogen-activated protein kinase (p38 MAPK) and phosphatidylinositol 3-kinase (P13K) were necessary for C5a-induced migration, whereas protein kinase C and c-Jun N-terminal kinase (JNK) were nonessential. C5a-induced migration was also suppresses by phospholipase C (PLC) inhibitor U73122 and pertussis toxin (PTX). We found that C5a-induced, time-dependent (1) ERK1/2 phosphorylation was markedly diminished by PTX, U73122, P13K inhibitors wortmannin and LY294002 and ERK1/2 inhibitor PD98059; (2) Akt phosphorylation was also attenuated by the above inhibitors except PD98059; (3) p38 MAPK phosphorylation was only affected by PTX. Furthermore, C5a also stimulated PLCbeta(2) membrane translocation in a time-dependent manner that occurred early prior to Akt phosphorylation and could be abolished only by PTX and U73122. These results suggest that C5a, through the activation of PTX-sensitive G protein, to differentially stimulate ERK1/2 and p38 MAPK phosphorylation and evoke cell migration. That is, ERK1/2 but not p38 MAPK phosphorylation is down stream of P13K/Akt and modulated by PLC. Additionally, beta(2) isoform may be one of the participates in C5a signal and acts more upstream of P13K/Akt.

The extracts from Nelumbo Nucifera suppress cell cycle progression, cytokine genes expression, and cell proliferation in human peripheral blood mononuclear cells.

In the hope of identifying agents of therapeutic value in tissue inflammation, we tested ethanolic extracts of six Chinese herbs for their effects on human peripheral blood mononuclear cells (PBMC) proliferation in vitro. The results indicated that the extracts from Nelumbo nucifera Gaertn, used in treatment of tissue inflammation in traditional Chinese medicine, inhibited PBMC proliferation activated with phytohemagglutinin (PHA). By a bioassay-guided fractionation procedure, NN-B-4 identified from N. nucifera ethanolic extracts significantly suppressed activated PBMC proliferation. The inhibitory action of NN-B-4 did not involve direct cytotoxicity. In an attempt to further 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) was examined. Cell cycle analysis indicated that NN-B-4 arrested the cell cycle progression of activated PBMC from the G1 transition to the S phase. The cyclin-dependent kinase (cdk) 4 mRNA expression in PBMC stimulated with PHA was reduced by NN-B-4. NN-B-4 suppressed, in activated PBMC, the production and mRNA expression of IL-2, IL-4, IL-10, and IFN-gamma in a dose-dependent fashion. The suppressant effects of NN-B-4 on proliferation of PBMC activated by PHA therefore appear to be mediated, at least in part, through inhibition of early transcripts of PBMC, especially those of important IL-2, IFN-gamma, and cdk4 and arrest of cell cycle progression in the cells.