The rhizome of giant taro (Alocasia macrorrhiza (L.) Schott), which is a highly adaptable wild plant, is a traditional Chinese herbal medicine. In the current study, the antiproliferative constituents of giant taro were investigated and six new (1-6) and four known piperidine alkaloids (7-10) were isolated from its rhizomes. Their chemical structures and absolute configurations were elucidated using various spectroscopic methods and the Mosher ester method. The isolated alkaloids were screened for the antiproliferative activity through MTT assay. The results indicated that piperidine alkaloids exerted potential antiproliferative activity against HepG2, AGS and MCF-7 tumor cells. Further researches showed that compounds 3-5 dose-dependently decreased the colony formation rate and induced the apoptosis of AGS cells, while compound 4 induced AGS cell death via the proapoptotic pathway. This study demonstrates that the piperidine alkaloids isolated from giant taro exhibit significant antitumor activity, which provides phytochemical evidence for further development and utilization.
Alkaloids/pharmacology* ; Alocasia/chemistry* ; Humans ; Piperidines/pharmacology* ; Plants ; Rhizome/chemistry*

OBJECTIVETo investigate the effect of plant growth regulators on the growth and quality of Angelica dahurica var. formosana.

METHODFive plant growth regulators: chlormequat chloride (CCC), Mepiquat chloride (PIX), Gibberellic acid (GA3), Paclobutrazol (PP333) and Maleic Hydrazide (MH) were sprayed in rosette stage, the effects of these plant growth regulators (PGRs) on the growth, yield and quality of A. dahurica var. formosanaw were observed. The biological traits were first measured and then imperatorin and isoimperatorin contents in roots were determined by HPLC.

RESULTLow concentration GA3 increased the yield while not influenced the premature bolting rate and the coumarin content.

CONCLUSIONSpraying of GA3 (30 mg x L(-1)) could guarantee the growth and development of A. dahurica var. formosana to have a higher yield and maintain the active ingredients content in the root as well.

Angelica ; drug effects ; growth & development ; Chlormequat ; pharmacology ; Gibberellins ; pharmacology ; Maleic Hydrazide ; pharmacology ; Piperidines ; pharmacology ; Plant Growth Regulators ; pharmacology ; Triazoles ; pharmacology

To explore novel antifatigue agents targeting with AMPA receptor, 10 compounds were synthesized and their structures were confirmed by 1H NMR, ESI-MS and elemental analysis. 1-BCP was treated as the leading compound. The antifatigue activities were evaluated by weight-loaded forced swimming test, and the AMPA receptor binding affinities were tested with radioligand receptor binding assays. The results unveiled that 5b appeared to possess potent antifatigue activities and high affinity with AMPA receptor, which deserved further studies.
Animals ; Benzamides ; chemistry ; pharmacology ; Dioxoles ; chemistry ; pharmacology ; Fatigue ; prevention & control ; Piperidines ; chemistry ; pharmacology ; Radioligand Assay ; Receptors, AMPA ; metabolism ; Swimming

Cardiac dysfunctions such as myocardial functional failure and ventricular arrhythmia have been largely attributed to intracellular Ca2+ overload. One of the mechanisms of intracellular Ca2+ overload involves a rapid influx of Ca2+ via Na(+)-Ca2+ exchange during the reperfusion which utilizes the accumulation of Na+ in myocytes during ischemic cardiac arrest. Possible sources of the intracellular Na+ accumulation include Na+ channel, Na(+)-H+ exchange, Na(+)-Ca2+ exchange, and Na+ background current. In this study, we studied the role of the Na+ background current in intracellular Na+ accumulation during the cardiac arrest by measuring the Na+ background current in guinea pig ventricular myocytes with whole cell clamp method and evaluating the effects of cardioprotective drugs on the Na+ background current. The results were as follows: (1) The Na+ background inward current at -40 mV membrane potential was larger at Ca2+ free solution than 1.8 mM Ca2+ solution. (2) The Na+ background current was not affected by verapamil. (3) 2 microM O-(N, N-hexamethylene)-amiloride (HMA) decreased the Na+ background current at negative membrane potential. (4) The new cardioprotective drug, R 56865, decreased the Na+ background current. These results suggest that the Na+ background current plays a role in increasing the intracellular Na+ activity during high K+ cardioplegia and the blocking effect of myoprotective drugs, such as R 56865, on the Na+ background current may contribute to myocardial protection after cardioplegia.
Amiloride/pharmacology ; Animal ; Guinea Pigs ; Heart/*drug effects ; Heart Arrest, Induced ; Myocardium/metabolism ; Piperidines/pharmacology ; Potassium/pharmacology ; Sodium/*metabolism ; Support, Non-U.S. Gov't ; Thiazoles/pharmacology ; Verapamil/pharmacology

BACKGROUNDRecently, the combination of sevoflurane and remifentanil has been widely used in general anesthesia. In this study, we investigated the sevoflurane-remifentanil pharmacodynamic interactions at clinical concentrations using the observer's assessment of alertness/sedation (OAA/S) and the bispectral index (BIS) by response surface analysis.

METHODSTotally 65 American Society of Anesthesiologists (ASA) I patients age 20 to 50 years old were included in this study. Patients were randomly assigned to be anesthetized with different target end-tidal sevoflurane concentrations that ranged from 0.2% to 3.4% in increments of 0.2%. The end-tidal sevoflurane concentration was maintained constant throughout the study. Remifentanil was infused with a target controlled infusion (TCI) system at increasing step-wise concentrations from 1 ng/ml to 10 ng/ml. The values of OAA/S and BIS at different sevoflurane-remifentanil concentration combinations were measured. The pharmacodynamic interactions between sevoflurane and remifentanil were analyzed by a response surface method. The three-dimensional response surfaces were constructed with Minitab Software. Model parameters were estimated with NONMEM program.

RESULTSSevoflurane and remifentanil acted synergistically on OAA/S. Sevoflurane alone could produce OAA/S ≤ 1 at a minimal alveolar concentration (MAC) of 0.93%. When used in combination with remifentanil at 1, 3, 6, and 10 ng/ml, the corresponding sevoflurane MACs were reduced to 0.79%, 0.58%, 0.48%, and 0.38%, with reductions of 17.2%, 37.6%, 48.4%, and 62.0% from baseline, respectively. In patients administered remifentanil alone, the OAA/S score was ≥ 3 even when the remifentanil concentration reached 10 ng/ml. BIS was closely associated with the sevoflurane concentration and the remifentanil concentration did not noticeably influence the relationship between the sevoflurane concentration and BIS. A sevoflurane concentration of (1.04 ± 0.19)% to (1.81 ± 0.21)% could maintain a BIS between 60 and 40.

CONCLUSIONSThe response surface method can analyze the pharmacodynamic interactions between remifentanil and sevoflurane qualitatively and quantitatively. Within the range of our study (remifentanil ≤ 10 ng/ml, sevoflurane ≤ 3.4%), the two drugs produced synergistic effects on OAA/S but had no interactive effect on BIS. A guideline of BIS between 40 and 60 may cause excessive anesthesia when opioids are used to maintain anesthesia.

Adult ; Anesthesia ; methods ; Consciousness ; drug effects ; Female ; Humans ; Male ; Methyl Ethers ; pharmacokinetics ; pharmacology ; Middle Aged ; Piperidines ; pharmacokinetics ; pharmacology ; Young Adult

OBJECTIVETo observe the effects of remifentanil combined with naloxone on human sperm motility in vitro and to investigate its possible mechanism.

METHODSTwenty normal semen samples were collected, each divided into 13 aliquots, one as the control and the others treated in vitro with different concentrations of remifentanil or remifentanil + naloxone for 35 min. The percentage of progressive mobile sperm was assessed by computer-assisted sperm analysis at 5, 10, 15, 20 and 35 min.

RESULTSCompared with the control group, remifentanil at 0.1, 1, 10 and 100 microg/L significantly decreased sperm motility at 5 and 10 min in a dose-dependent manner, with no significant difference at 15 and 30 min; sperm motility showed no significant difference on 5 -35 min exposure to naloxone at 0.004 -0.04 mg/L, nor on 5, 10, 15 and 20 min exposure at 0.4 -4 mg/L, but was significantly increased at 35 min. Compared with the corresponding concentrations of remifentanil alone, remifentanil + naloxone remarkably increased sperm motility at 0.1 + 0.004, 1 + 0.04, 10 + 0.4, and 100 + 4 mg/L at 5 and 10 min, with no obvious difference at 15 and 30 min.

CONCLUSIONThe onset and offset of the effect of remifentanil on sperm motility are rapid and its inhibitory effect can be antagonized by naloxone, which may be related with the micro-opioid receptor.

Adult ; Humans ; Male ; Naloxone ; administration & dosage ; pharmacology ; Piperidines ; administration & dosage ; pharmacology ; Sperm Motility ; drug effects ; Spermatozoa ; drug effects ; Young Adult

Apoptosis of dopaminergic neurons in the nigrostriatal projection plays a crucial role in the pathogenesis of Parkinson's disease (PD). Although the detailed mechanisms responsible for dopaminergic neuron loss are still under investigation, oxidative stress is identified as a major contributor for neuronal apoptosis. In the current study, we studied the effects of MPP(+), a substrate that mimics oxidative stress, on neuron-like PC12 cells and the underlying mechanisms. PC12 cells were cultured and treated by 100 μmol/L MPP(+) for 4, 8, 16, 24 and 48 h, respectively. For drug pretreatment, the PC12 cells were incubated with N-acetyl-l-cysteine (NAC, 5 mmol/L), an antioxidant, SP600125 (20 μmol/L) or PD98059 (100 μmol/L), two pharmacological inhibitors of JNK and ERK1/2, for 1 h before addition of MPP(+). Cell apoptosis was measured by flow cytometry. The mRNA expression of Cu(2+)/Zn(2+)-SOD, GSH-Px, Bcl-2 and Bax was detected by RT-PCR. The protein expression of p-ERK1/2 and p-JNK was determined by Western blotting. Our results showed that MPP(+) exposure could induce substantial PC12 cell apoptosis. The pretreatment of SP600125 or PD98059 could effectively reduce the apoptosis rate by reducing the ratio of Bax/Bcl-2 mRNA levels. MPP(+) exposure also induced high level of reactive oxygen species (ROS), marked by dramatic increase of Cu(2+)/Zn(2+)-SOD and GSH-Px mRNA levels. The elevated ROS was strongly associated with the activation of JNK and ERK1/2 signal pathways after MPP(+) exposure, since the pretreatment of NAC significantly reduced the upregulation of p-JNK and p-ERK1/2. Finally, the pretreatment of SP600125, but not PD98059, alleviated the increase of Cu(2+)/Zn(2+)-SOD and GSH-Px mRNAs induced by MPP(+), suggesting that the activation of the JNK signal pathway, but not the ERK1/2 signal pathway, could, in some degree, antagonize the generation of ROS induced by oxidative stress. In conclusion, our results suggest that JNK and ERK1/2 signal pathways, which are activated via ROS, play a crucial role in neuronal apoptosis induced by oxidative stress.
Animals ; Apoptosis ; drug effects ; Cell Line, Tumor ; PC12 Cells ; Piperidines ; pharmacology ; Pyrazoles ; pharmacology ; Rats ; Reactive Oxygen Species ; metabolism

OBJECTIVETo study the effect of plant growth regulator mepiquat chloride (DPC) on the growing development of plant and the content of active compounds in Scutellaria baicalensis.

METHODAfter spraying DPC during the seedling period, the length of taproot, fresh weight of root, diameter of taproot and the length of stem were measured. The contents of baicalin, baicalein and wogonin were determined by HPLC, respectively. Total flavonoids and scavenging DPPH were determined with ultraviolet spectrophotometry.

RESULTAfter spraying DPC, fresh weight of S. baicalensis root was significant increased, and root diameter was also increased. The contents of baicalin and total flavonoids were significantly increased and baicalein and wogonin were decreased remarkably. Compared with controls, scavenging activity of ethanol extracts on DPPH free radical was no significant changed after spraying DPC.

CONCLUSIONPlant growth regulator DPC could regulate the growth on the ground and underground effectively, and could enhance the content of flavonoids compounds of S. baicalensis.

Chromatography, High Pressure Liquid ; Piperidines ; pharmacology ; Plant Growth Regulators ; pharmacology ; Scutellaria baicalensis ; chemistry ; drug effects ; growth & development

OBJECTIVETo investigate the expression of vascular cell adhesion molecule-1(VCAM-1) in lung slices from antigen -sensitized rats and the modulation by drugs.

METHODSIn isolated lung slices from ovalbumin(OVA)-sensitized rats, the relative expression of VCAM-1 was determined after drug treatment and OVA challenge.

RESULTThe expression of VCAM-1 was enhanced in the sensitized rat lungs,and OVA challenge did not further increase the expression. Glycocorticosteroid dexamethasone and leukotriene cysLT receptor antagonist ONO-1078 inhibited the expression,but tachykinin NK-1 receptor antagonist SR-140333 had no such effect.

CONCLUSIONVCAM-1 expression is enhanced in the sensitized rat lungs, and antigen challenge does not further up regulate the expression. Anti-inflammatory drugs have different effects on VCAM-1 expression. Dexamethasone and ONO-1078, but not SR-140333, can inhibit the expression.

Animals ; Chromones ; pharmacology ; Dexamethasone ; pharmacology ; Female ; In Vitro Techniques ; Lung ; chemistry ; Male ; Ovalbumin ; immunology ; Piperidines ; pharmacology ; Quinuclidines ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Vascular Cell Adhesion Molecule-1 ; analysis

AIMTo discover new regulators of potassium channel, an in vitro assay based on DiBAC4 (3) to determine the fluorescence was established for high throughput screening.

METHODSA cell-based 96-well format fluorescence assay using DiBAC4 (3) in cultured PC12 cells was described. Cells were loaded with 5 mumol.L-1 DiBAC4 (3) and incubated at 37 degrees C for 30 min before adding KCl or several known potassium channel regulators. The cellular DiBAC4 (3) fluorescence responce was then detected. The fluorescence changes can be used to evaluate membrane potential changes, which are determined mainly by potassium channels.

RESULTSExtracellular high K(+)-induced depolarization and several potassium channel blockers including 4-AP, TEA, E-4031, glibenclamide, quinidine and nifedipine all evoked increases in DiBAC4 (3) fluorescence response. The potassium channel opener, cromakalim, evoked decrease in DiBAC4 (3) fluorescence response. The fluorescence changes of 4-AP, TEA, glibenclamide, nifedipine and cromakalim were in a concentration-dependent manner. In 76 compounds screened by using the established DiBAC4 (3)-based assay, 9 compounds were found to change the fluorescence dose-dependently. Patch clamp technique is needed to further testify and screen their actions on potassium currents.

CONCLUSIONThe DiBAC4 (3)-based assay is easily operated, economical and repeatable. So, it can be performed by high throughput screening for potassium channel regulators.

4-Aminopyridine ; pharmacology ; Animals ; Barbiturates ; chemistry ; Calcium Channel Blockers ; pharmacology ; Cromakalim ; pharmacology ; Isoxazoles ; chemistry ; Membrane Potentials ; drug effects ; Nifedipine ; pharmacology ; PC12 Cells ; Patch-Clamp Techniques ; Piperidines ; pharmacology ; Potassium Channel Blockers ; pharmacology ; Potassium Channels ; drug effects ; Pyridines ; pharmacology ; Quinidine ; pharmacology ; Rats