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The diagnostic efficiency of radiation encephalopathy (RE) remains heterogeneous, and prediction of RE is difficult at the pre-symptomatic stage. We aimed to analyze the whole-brain resting-state functional connectivity density (FCD) of individuals with pre-symptomatic RE using multivariate pattern analysis (MVPA) and explore its prediction efficiency. Resting data from NPC patients with nasopharyngeal carcinoma (NPC; consisting of 20 pre-symptomatic RE subjects and 26 non-RE controls) were collected in this study. We used MVPA to classify pre-symptomatic RE subjects from non-RE controls based on FCD maps. Classifier performances were evaluated by accuracy, sensitivity, specificity, and area under the characteristic operator curve. Permutation tests and leave-one-out cross-validation were applied for assessing classifier performance. MVPA was able to differentiate pre-symptomatic RE subjects from non-RE controls using global FCD as a feature, with a total accuracy of 89.13%. The temporal lobe as well as regions involved in the visual processing system, the somatosensory system, and the default mode network (DMN) revealed robust discrimination during classification. Our findings suggest a good classification efficiency of global FCD for the individual prediction of RE at a pre-symptomatic stage. Moreover, the discriminating regions may contribute to the underlying mechanisms of sensory and cognitive disturbances in RE.

Thrombin is a potent platelet activator and a key mediator of blood coagulation, thereby playing a crucial role in cardiovascular disease. Recently, protease-activated receptor 4 (PAR4), one of thrombin receptors in human platelets, is emerging as a promising target for antiplatelet therapy. 3,5,2',4'-Tetramethoxystilbene (TMS), a resveratrol analog, have demonstrated promising effects on preventing atherosclerosis and hypertension, whereas its antiplatelet effect has never been investigated. Herein we show that TMS at concentrations of a few micromolar selectively inhibits PAR4-mediated human platelet aggregation, ATP secretion, integrin αIIbβ3 activation, and signaling pathways. In a whole-blood model of arterial flow, TMS also significantly reduced in vitro thrombus formation. Analysis of the structure-activity relationships of TMS and a panel of stilbene analogs reveal that full methylation of hydroxy groups of the stilbenes is the critical structural determinant for the anti-PAR4 activity. Our results suggest that fully methylated resveratrol analogs with anti-PAR4 activity are potential candidates for development of novel antiplatelet agents.

Microglia, resident innate immune cells in central nervous system, regulates neuroinflammation and is associated with a variety of neuropathologies. The present study investigated the antineuroinflammatory effects of hispidulin (HPD), a naturally flavone compound, in lipopolysaccharide- (LPS-) stimulated BV2 microglia cells. The expression levels of nitric oxide (NO), reactive oxygen species (ROS), and pro-inflammatory factors were determined by the Griess method, flow cytometry, and enzyme-linked immunosorbent assay (ELISA). Western blotting was used to measure various transcription factors such as Akt, nuclear factor-kappa B (NF-κB), and signal transducer and activator of transcription 3 (STAT3) activities. Our experimental results demonstrated that HPD increased cell viability and reduced apoptosis in LPS-treated BV2 microglia cells. Moreover, HPD significantly reduced the levels of NO, ROS, inducible nitric oxide synthase (iNOS), cyclooxygenase- (COX-) 2, tumor necrosis factor- (TNF-) α, interleukin- (IL-) 1β, IL-6, and prostaglandin E2 (PGE2) in a dose-dependent manner. Phosphorylation of NF-κB/IκB, Akt, and STAT3 proteins expression by HPD was suppressed in LPS-induced BV2 microglial cells. We concluded that HPD may inhibit neuroinflammatory responses by inhibiting NF-κB pathway activation and ROS formation. These results propose that HPD has potential as anti-inflammatory agents against microglia-mediated neuroinflammatory disorders.

Sixteen compounds were extracted and purified from the leaves of Liriodendron tulipifera. These compounds include aporphines, oxoaporphine, coumarin, sesquiterpene lactone, benzenoids, cyclitol and steroids. (+)-Norstephalagine (2) (an aporphine) and scopoletin (8) (a coumarin) were isolated from Liriodendron tulipifera leaves from the first time. The identified compounds were screened for their antiradical scavenging, metal chelating and ferric reducing power activities. The results have showed that these compounds have antioxidative activity. The study has also examined the chemopreventive property of the isolated compounds against human melanoma cells A375. The results shown that (−)-anonaine (1), (−)-liridinine (3), (+)-lirinidine (6), lysicamine (7) and epitulipinolide diepoxide (9) significantly inhibited the proliferation of melanoma cells. These results revealed that these compounds have antioxidative activity and chemopreventive activity in skin melanoma cells.

Methadone (Mtd) is a widely used opioid drug associated with the side effect of hyperprolactinemia. The mechanism of how Mtd induces prolactin secretion remains unclear. The effects of Mtd and its two main metabolites (EDDP: (±)-2-ethyl-1,5-dimethyl-3,3-diphenylpyrrolinium percholarate and EMDP: 2-ethyl-5-methyl-3,3-dipnehyl-1-pyrroline) on ion currents were investigated in GH₃ pituitary tumor cells. Hyperpolarization-elicited K+ currents in GH₃ cells bathed in a high-K(+), Ca(2+)-free solution were studied to evaluate the effects of Mtd and other related compounds on the ether-a-go-go-related-gene (erg) K(+) current (I(K(erg))). Mtd suppressed the amplitude of I(K(erg)) in a concentration-dependent manner with an IC(50) value of 10.4 μM. With the aid of a minimal binding scheme, the inhibitory action of Mtd on I(K(erg)) was estimated with a dissociation constant of 8.2 μM. Mtd tended to increase the rate of I(K(erg)) deactivation in a voltage-dependent fashion. EDDP (10 μM) had no effect on I(K(erg)), while EMDP (10μM) slightly suppressed it. In GH₃ cells incubated with naloxone (30 μM), the Mtd-induced inhibition of I(K(erg)) remained unaltered. Under cell-attached voltage-clamp recordings, Mtd increased the frequency of spontaneous action currents with no change in current amplitude. Similarly, Mtd can suppress I(K(erg)) in differentiated NG108-15 cells; dynorphin A(1-13) did not reverse Mtd-induced inhibition of I(K(erg)). This study shows that Mtd has a depressant effect on I(K(erg)), and suggests its ability to affect membrane excitability and prolactin secretion. The cyclization of Mtd, in which EDDP and EMDP are formed, tends to be critical in removal of the Mtd binding to erg K+ channel.

Champacaine (1), (–)-anonaine (2), (–)-norushinsunine (3), (–)-ushinsunine (4), (–)-N-acetylanonaine (5), (–)-roemerine (6), (–)-asimilobine (7), (–)-anolobine (8), (–)-isocorydine (9), liriodenine (10), atherospermidine (11), O-methylmoschatoline (12), (+)-syringaresinol (13), N-trans-feruloyltyramine (14), 4-hydroxybenzaldehyde (15), vanillin (16), vanillic acid (17), syringic acid (18), 3,4-dimethoxybenzoic acid (19), coniferyl aldehyde (20), syringin (21), scopoletin (22), 4-acetonyl-3,5-dimethoxy-p-quinol (23), β-sitostenone (24), and stigmasta-4,22-dien-3-one (25) were isolated from the stems of Michelia champaca L. (Magnoliaceae). Among them, 1 is a new 4,5-dioxoaporphine compound. The structures of these compounds were characterized and identified by spectral analyses.

Nelumbo nucifera Gaertn. cv. Rosa-plena is a perennial aquatic crop grown and consumed throughout Asia. All parts of N. nucifera have been used for various medicinal purposes in oriental medicine. In particular, the leaves are known for diuretic and astringent properties and are used to treat fever, sweating, and strangury, and as a styptic [1]. To further understand the chemotaxonomy of the Nelumbo species [1, 2], Nelumbo nucifera Gaertn. cv. Rosa-plena was chosen for phytochemical investigation. There is only one paper describing the constituents of this plant [3]. Previously, we have isolated seven aporphines, two oxoaporphines, one dioxoaporphine, one dehydroaporphine, two steroids, and two chlorophylls from this plant [3]. As part of our continuing investigation of the phytochemical and bioactive compounds of Nelumbo plants, seven flavonoids, quercetin [4], quercetin 3-O-D-glucopyranoside [5], quercetin 3-O-D-galactopyranoside [6], quercetin 3-O-Dglucopyranosyl-(1 6)-D-glucopyranoside [7], isorhamnetin [8], isorhamnetin 3-O-D-glucopyranoside [8], and isorhamnetin 3-O-D-galactopyranoside [8] were obtained by systematic extraction and isolation from the leaves of Nelumbo nucifera Gaertn. cv. Rosa-plena. All of these compounds were isolated for the first time from this source. The leaves of Nelumbo nucifera Gaertn. cv. Rosa-plena were collected from Tainan County, Taiwan, November 2008. Plant material was identified by Prof. Fu-Yuan Lu (Department of Forestry and Natural Resources College of Agriculture, National Chiayi University). A voucher specimen (Nelumbo nucifera Gaertn. cv. Rosa-plena) was deposited in the Department of Medical Laboratory Science and Biotechnology, School of Medical and Health Sciences, Fooyin University, Kaohsiung, Taiwan. The air-dried leaves of Nelumbo nucifera Gaertn. cv. Rosa-plena (1.5 kg) were extracted with MeOH (5 L 5) at room temperature, and a MeOH extract (108.7 g) was obtained upon concentration under reduced pressure. The MeOH extract, suspended in H2O (1 L), was partitioned with CHCl3 (3 L 4) to give fractions soluble in CHCl3 (57.23 g) and H2O (43.62 g). The CHCl3-soluble fraction was chromatographed over silica gel (1700 g, 70–230 mesh) using n-hexane–EtOAc– MeOH mixtures as eluents to produce six fractions. Part of fraction 5 (5.34 g) was subjected to silica gel chromatography by eluting with CH2Cl2–MeOH (40:1) and enriched with MeOH to furnish two fractions (5-1–5-2). Fraction 5-2 (1.67 g) was eluted with n-hexane–EtOAc mixtures to obtain isorhamnetin (2 mg). Part of fraction 6 (4.21 g) was subjected to silica gel chromatography by eluting with EtOAc–MeOH (20:1) and enriched with MeOH to furnish five further fractions (6-1–6-5). Fraction 6-1 (1.46 g) was subjected to silica gel chromatography by eluting with n-hexane–EtOAc (1:9) and enriched gradually with EtOAc to produce quercetin (5 mg). Fraction 6-2 (0.76 g) was subjected to silica gel chromatography by eluting with EtOAc–MeOH (30:1) and enriched gradually with MeOH to produce isorhamnetin 3-O-D-glucopyranoside (5 mg) and isorhamnetin 3-O-D-galactopyranoside (7 mg). Fraction 6-3 (1.51 g) was further purified on a silica gel column using EtOAc–MeOH mixtures to obtain quercetin 3-O-D-glucopyranoside (5 mg) and quercetin 3-O-D-galactopyranoside (4 mg). Fraction 6-4 (0.76 g) was eluted with EtOAc–MeOH (9:1) and repeatedly subjected to silica gel CC to give quercetin 3-O-D-glucopyranosyl-(1 6)-D-glucopyranoside (6 mg).

SummaryAmong the nine ellagitannins, rugosin E was the most potent platelet aggregating agent with an EC50 of 1.5 ± 0.1 µM in rabbit platelets and 3.2 ±0.1 µM in human platelets. The aggregations caused by rugosin E and ADP were inhibited by EGTA, PGE1, mepacrine, sodium nitroprusside and neomycin, but not by indomethacin, verapamil, TMB-8, BN52021 and GR32191B. Rugosin E-induced thromboxane formation was suppressed by indomethacin, EGTA, PGE,, verapamil, mepacrine, TMB-8 and neomycin. ADP-scavenging agents, such as CP/CPK and apyrase inhibited concentration-dependently ADP (20 εM)-, but not rugosin E (5 εM)-induced platelet aggregation. In thrombin (0.1 U/ml)-treated and degranulated platelets, rugosin E and ADP still caused 63.5 ± 3.0% and 61.2 ± 3.5% of platelet aggregation, respectively. Selective ADP receptor antagonists, ATP and FSBA inhibited rugosin E- and ADP-induced platelet aggregations in a concentration-dependent manner. Both rugosin E and ADP did not induce platelet aggregation in ADP (1 mM)-desensitized platelets. In contrast to ADP, rugosin E did not decrease cAMP formation in washed rabbit platelets. Both rugosin E and ADP did not cause phosphoinositide breakdown in [3H]myo-inositol-labeled rabbit platelets. In fura-2/AM- load platelets, both rugosin E and ADP induced increase in intracellular calcium concentration and these responses were inhibited by ATP and PGEj. All these data suggest that rugosin E may be an ADP receptor agonist in rabbit platelets.

Investigation of the leaves' extract of Cinnamomum tenuifolium (Lauraceae) led to the isolation of one novel benzodioxocinone, 2,3-dihydro-6,6-dimethylbenzo-[b][1,5]dioxocin-4(6 H)-one (1). The structure was determined through in-depth spectroscopic and mass-spectrometric analyses. The antioxidant potential was evaluated using the following in vitro method: scavenging of 1,1-diphenyl-2-picrylhydrazyl radical. We also detected the anti-proliferative effect of 1 on human oral cancer cells and its IC(50) is 107.7 µM.

Ilex (Aquifoliaceae) species are found throughout China, and some are used extensively in traditional Chinese medicine. For example, I. rotunda is antipyretic and used for the treatment of the common cold, tonsillitis, and stomach and intestinal ulcers. I. pubescens is used for the treatment of coronary disease, myocardial infarction, dysentery, and erysipelas, and I. cornuta and I. latifolia are used for the treatment of headaches, toothaches, bloodshot eyes, and tinnitus [1]. Previous studies on the Ilex genus have resulted in the isolation of essential oils [2] triterpenes, triterpene glycosides [3–7], hemiterpene glycosides [8], and phenolic compounds [9, 10]. In the present study, 12 compounds were isolated from the leaves of I. cornuta. A MeOH extract of the I. cornuta leaves was concentrated to obtain a residue, which was partitioned between CH2Cl2 and H2O. The aqueous layer was extracted with n-BuOH, and then the n-BuOH layer was concentrated and analyzed by chromatography. As a result, 12 compounds, including eight flavonoids and four phenolic carboxylic acids, were isolated. The flavonoids were quercetin [11], quercetin 3-O-D-glucopyranoside [12], quercetin 3-O-D-galactopyranoside [13], quercetin 3-O-D-glucopyranosyl-(1 6)-D-glucopyranoside [14], isorhamnetin [15], isorhamnetin 3-O-Dglucopyranoside [15], isorhamnetin 3-O-D-galactopyranoside [15], and isorhamnetin 3-O-D-glucopyranosyl-(1 6)D-glucopyranoside [15]. The phenolic carboxylic acids were caffeic acid [16], p-hydroxybenzoic acid [17], protocatechuic acid [11], and vanillic acid [16]. This is the first report of the isolation of these compounds from this source. Leaves from I. cornuta Lindl. & Paxton were collected in Kaohsiung, Taiwan, in October 2006. Plant material was identified by Dr. Fu-Yuan Lu (Department of Forestry and Natural Resources, College of Agriculture, National Chiayi University, Chiayi City, Taiwan). A voucher specimen was deposited in the School of Medical and Health Sciences, Fooyin University, Kaohsiung, Taiwan. The air-dried leaves of I. cornuta (4.2 kg) were extracted with MeOH (5 10 L) at room temperature, and each MeOH fraction was concentrated under reduced pressure. The MeOH fractions were concentrated by evaporation and then partitioned to yield CH2Cl2 and aqueous extracts. The aqueous extracts were concentrated by evaporation and extracted with n-BuOH to give a n-BuOH layer and an aqueous layer. The n-BuOH layer (178.6 g) was subjected to silica gel chromatography (500 g, 70–230 mesh) with EtOAc–MeOH elution. Ten fractions were obtained. Part of fraction 2 (20.3 g) was subjected to silica gel chromatography with n-hexane–EtOAc (1:1, v/v). The volume fraction of EtOAc was gradually increased to yield five fractions (2-1–2-5). Fraction 2-2 (2.2 g) was further purified on a silica gel column using an n-hexane– CH2Cl2 mixture to obtain caffeic acid (7 mg), vanillic acid (3 mg), and p-hydroxybenzoic acid (5 mg). Fraction 2-4 (5.7 g) was further purified on a silica gel column with n-hexane–EtOAc elution to obtain isorhamnetin (12 mg). Part of fraction 3 (12.7 g) was subjected to silica gel chromatography with n-hexane–EtOAc (1:8, v/v). The volume fraction of EtOAc was gradually increased to yield quercetin (20 mg) and protocatechuic acid (34 mg). Part of fraction 4 (32.5 g) was subjected to silica gel chromatography with EtOAc–MeOH (20:1, v/v). The volume fraction of MeOH was gradually increased to yield isorhamnetin 3-O-D-glucopyranoside (67 mg) and isorhamnetin 3-O-D-galactopyranoside quercetin (42 mg). Part of fraction 5 (17.3 g) was subjected to silica gel chromatography with EtOAc–MeOH (20:1). The volume fraction of MeOH was gradually increased to obtain five further fractions (5-1–5-5). Fraction 5-3 (5.8 g) was further purified on a silica gel column with EtOAc–MeOH to obtain quercetin 3-O-D-glucopyranoside (78 mg) and quercetin 3-O-D-galactopyranoside (113 mg). Fraction 6-8 (22.7 g) was eluted with EtOAc–MeOH (8:1) and was repeatedly subjected to silica gel chromatography to give quercetin 3-O-D-glucopyranosyl-(1 6)-D-glucopyranoside (56 mg) and isorhamnetin 3-O-D-glucopyranosyl-(1 6)-D-glucopyranoside (24 mg).

Protoapigenone, a natural derivative of the flavonoid apigenin, has been shown to exhibit potent antitumor activity in vitro and in vivo; the precise mechanism of action, however, is not fully elucidated. In this study, we investigated and compared the mechanisms by which protoapigenone and apigenin caused cell death in the human breast cancer MDA-MB-231 cells. Flow cytometry analysis revealed that protoapigenone induced apoptosis with 10-fold greater potency than apigenin. Cancer cells treated with protoapigenone resulted in persistent activation of mitogen-activated protein kinase (MAPK) ERK, JNK, and p38, hyperphosphorylation of Bcl-2 and Bcl-xL, and loss of mitochondrial membrane potential (MMP). The MAPK inhibitors effectively prevented the loss of MMP and apoptosis induced by protoapigenone. Treatment of cells with protoapigenone led to increased levels of reactive oxygen species (ROS) and decreased levels of intracellular glutathione. The thiol-antioxidant N-acetylcysteine abolished protoapigenone-induced MAPK activation, mitochondrial dysfunction, and apoptosis. These results suggest that the induction of oxidative stress preceding the activation of MAPK is required to initiate the mitochondria-mediated apoptosis induced by protoapigenone. Additionally, protoapigenone-induced JNK activation was linked to thiol modification of glutathione S-transferase π (GSTpi), which impeded GSTpi inhibition of JNK. In contrast to protoapigenone, apigenin-induced apoptosis was neither dependent on ROS nor on MAPK. Structure-activity relationship studies suggested that the thiol reacting effect of protoapigenone might be associated with an α, β-unsaturated ketone moiety in the structure of ring B.

In this study, an attempt was made to elucidate the effects of thymol, a monocyclic phenolic compound, on Ca2+ mobilization and ion currents in pituitary GH3 cells with the aid of fura-2 fluorimetry and the whole-cell voltage-clamp technique. Thymol increased intracellular Ca2+ concentrations ([Ca2+]i) in GH3 cells loaded with Ca2+-sensitive dye fura-2. Removing extracellular Ca2+ reduced the thymol-induced [Ca2+]i rise. In Ca2+ -free solution, thymol-evoked [Ca2+]i rise was unchanged by depleting the Ca2+ store with thapsigargin (1 microM), while the thapsigargin-induced [Ca2+]i rise was reduced by pretreatment with thymol. These results imply that the Ca2+ stores depleted by thymol comprise thapsigargin-sensitive and thapsigargin-insensitive pools. In addition, after depletion of the internal Ca2+ store with 100 microM thymol in Ca2+ -free solution, a subsequent application of Ca2+ greatly induced a [Ca2+]i increase. The results indicate that, similar to thapsigargin, 100 microM thymol may activate the capacitative calcium entry (CCE) channel. However, thymol (100 microM) had a slight depressant action in L-type calcium current (I(CaL)). The stimulatory actions of thymol on Ca2+ signaling may partly be responsible for the underlying cellular mechanisms through which it affects neuroendocrine functions.

1. The effects of the thromboxane A2 (TxA2)-mimetic, U-46619, on the proliferation of vascular smooth muscle cells (VSMCs) were examined in a clonal smooth muscle cell line, A10, which was derived from foetal rat aorta. 2. [3H]-U-46619 bound to A10 cells of passages 18-20 (p18-20) with two classes of sites. The high affinity site showed a Bmax of 3.0 +/- 1.8 fmol mg-1 protein with a KD value 1.0 +/- 0.1 nM, while the low affinity site showed a Bmax of 43.0 +/- 6.0 fmol mg-1 protein and KD value of 129.0 +/- 7.9 nM. However, [3H]-U-46619 bound to A10 cells from passages 28-30 (p28-30) at a single class of site with a Bmax 111.0 +/- 9.0 fmol mg-1 protein and a KD value of 175.4 +/- 22.0 nM. 3. Cinnamophilin and SQ29548 inhibited specific [3H]-U-46619 binding to p18-20 A10 cells in a concentration-dependent manner with Ki values of 390.0 +/- 3.2 and 4.6 +/- 1.0 nM, respectively at a high affinity site, and 2.6 +/- 0.2 microM and 310.0 +/- 6.4 nM, respectively at the low affinity site. 4. U-46619 produced isometric contractions of rat aorta in a concentration-dependent manner with an EC50 7.0 +/- 1.2 nM. Cinnamophilin and SQ29548 antagonized U-46619-induced aortic contractions with pA2 values 6.3 +/- 0.1 and 8.2 +/- 0.2, respectively. 5. U-46619 increased [3H]-thymidine incorporation into DNA of p18-20 and p28-30 A10 cells in aconcentration-dependent manner with EC50 values 362.7 +/- 27.0 and 302.5 +/- 20.1 nm, respectively. The U-46619-induced increase of [3H]-thymidine incorporation into DNA of p28 -30 AO0 cells was potentiatedby PDGF (1 ng ml-1) and FCS (1%) and was inhibited by cinnamophilin (10 microM) and SQ29548 (1 microM)with estimated pKB values 5.4 +/- 1.2 and 6.3 +/- 0.9, respectively.6. Cell cycle analysis revealed that U-46619-increased cell cycle progression was primarily due to a rapidtransition from the DNA synthetic (S) to the G2/mitotic (M) phase. Moreover, U-46619 also increasedprotein synthesis and cell numbers in VSMC. All these effects of U-46619 were inhibited bycinnamophilin and SQ29548.7. U-46619 caused phosphoinositide breakdown and increased the intracellular Ca2+ concentration inVSMC, effects which were blocked by cinnamophilin and SQ29548.8 These data indicate there are two U-46619 binding sites in AlO VSMC. The high affinity site is correlated to U-46619-induced vasoconstriction while the low affinity site is correlated to U-46619-mediated VSMC proliferation. These data also reveal that U-46619 stimulates the cell cycle progression in VSMC primarily through a rapid transition from S to G2/M. Since cinnamophilin inhibits TPreceptor-mediated VSMC proliferation, it may thus hold promising potential for the prevention of atherosclerosis or vascular diseases.

In this study, an attempt was made to elucidate the effects of thymol, a monocyclic phenolic compound, on Ca2+ mobilization and ion currents in pituitary GH3 cells with the aid of fura-2 fluorimetry and the whole-cell voltage-clamp technique. Thymol increased intracellular Ca2+ concentrations ([Ca2+]i) in GH3 cells loaded with Ca2+-sensitive dye fura-2. Removing extracellular Ca2+ reduced the thymol-induced [Ca2+]i rise. In Ca2+-free solution, thymol-evoked [Ca2+]i rise was unchanged by depleting the Ca2+ store with thapsigargin (1 μM), while the thapsigargin-induced [Ca2+]i rise was reduced by pretreatment with thymol. These results imply that the Ca2+ stores depleted by thymol comprise thapsigargin-sensitive and thapsigargin-insensitive pools. In addition, after depletion of the internal Ca2+ store with 100 μM thymol in Ca2+-free solution, a subsequent application of Ca2+ greatly induced a [Ca2+]i increase. The results indicate that, similar to thapsigargin, 100 μM thymol may activate the capacitative calcium entry (CCE) channel. However, thymol (100 μM) had a slight depressant action in L-type calcium current ( ICaL). The stimulatory actions of thymol on Ca2+ signaling may partly be responsible for the underlying cellular mechanisms through which it affects neuroendocrine functions.

1 The effects of dicentrine on haemodynamic, plasma lipid, lipoprotein level and vascular reactivity were investigated in Wistar-Kyoto (WKY) and spontaneously hypertensive (SH) rats, fed a high fat-high cholesterol diet. 2 In high fat-high cholesterol (HF-HC) diet fed WKY and SH rats, oral administration of dicentrine (5 and 10 mg kg−1, twice a day) for 4 weeks caused significant reductions in total plasma cholesterol (CE) by reducing the low density lipoprotein (LDL) fraction, and reductions in total plasma triglyceride (TG) by reducing the very low density lipoprotein (VLDL) fraction. 3 Dicentrine therapy was associated with increased high density lipoprotein (HDL)-cholesterol levels; thus the ratio of total plasma cholesterol to HDL-cholesterol was improved. 4 In HF-HC diet fed conscious WKY and SH rats, oral administration of dicentrine (5 and 10 mg kg−1, twice a day) also evoked dose-related decreases in mean arterial pressure (MAP) which were of greater magnitude in SH rats. Neither dose of dicentrine caused a significant change in heart rate (HR). 5 The aortic arches from SH rats fed the HF-HC diet for 8 weeks were significantly more affected by the atherosclerotic lesions than the abdominal aortae and renal arteries of WKY and SH rats. Oral administration of dicentrine (5 and 10 mg kg−1) for 4 weeks did not diminish the atherosclerotic lesion areas in WKY and SH rats. 6 In aortae of the hyperlipidaemic rats, significantly attenuated EC50 values and augmented maximal responses for phenylephrine-induced contraction were obtained. Endothelium-dependent relaxation to acetylcholine was abolished, while endothelium-independent relaxation to nitroprusside was well preserved. Dicentrine therapy caused significantly augmented EC50 values and attenuated maximal responses for phenylephrine-induced contraction in hyperlipidaemic rats. However, dicentrine neither prevented the impaired relaxation to acetylcholine, nor affected the relaxation to nitroprusside during atherosclerosis progression. 7 It is concluded that dicentrine decreases MAP, plasma CE, LDL-CE, plasma TG, VLDL-TG, vascular hyperreactivity to phenylephrine and increases HDL-CE levels. Dicentrine may thus hold potential for the reduction of two of the major risk factors, hypertension and hyperlipidaemia, for cardiovascular disease.