Corydalis hendersonii(CH) is a Tibetan folk medicine with the functions of clearing heat, detoxifying, cooling blood, checking diarrhea, and lowering blood pressure. It is often used to treat high altitude polycythemia, vasculitis, peptic ulcer, and diarrhea. Nine compounds were separated from the ethanol extract of CH by silica gel, ODS, Sephadex LH-20 chromatography and semi-preparative HPLC. Their structures were identified as hendersine H(1),hendersine I(2), dehydrocheilanthifoline(3), protopine(4), izmirine(5), 6,7-methylenedioxy-1(2H)-isoquinolinone(6), icariside D_2(7), ethyl 4-(β-D-glucopyranosyloxy)-3-methoxybenzoate(8), 3-hydroxy-4-methoxybenzoic acid(9), respectively, by the spectroscopic data analysis and comparison with those in the literature. Among them, compounds 1 and 2 are new isoquinoline alkaloids, and compounds 7-9 are reported the first time for Corydalis. The hypoglycemic model of H9c2 cardiomyocytes and the inflammatory model of H9c2 cardiomyocytes induced by conditional supernatant were employed to determine the activities of the above compounds. The results showed that 20 μmol·L~(-1) compound 1 had a protective effect on H9c2 cardiomyocytes and 10 μmol·L~(-1) compounds 4 and 5 inhibited H9c2 cardiomyocyte inflammation induced by conditional supernatant.
Humans ; Corydalis/chemistry* ; Alkaloids/chemistry* ; Inflammation ; Spectrum Analysis ; Isoquinolines/pharmacology*

The alkaloid ecteinascidin-743, isolated from the marine tunicate Ecteinascidia turbinata, binds to DNA and induces cytotoxic effects in several tumors. The drug is being codeveloped by Pharma Mar and Ortho Biotech. In May 2001 and October 2003, it was granted orphan drug status by the European Commission for soft tissue sarcoma and ovarian cancer, respectively. This paper reviews its research progress, including chemical synthesis, in vitro studies and mechanism of action, antitumor activity in vivo, toxicity, pharmacokinetics, and clinical studies.
Animals ; Antineoplastic Agents, Alkylating ; pharmacokinetics ; pharmacology ; toxicity ; Dioxoles ; pharmacokinetics ; pharmacology ; toxicity ; Humans ; Isoquinolines ; pharmacokinetics ; pharmacology ; toxicity ; Tetrahydroisoquinolines

Lotus( Nelumbo nucifera) is a traditional medicinal plant,and nowadays it is regarded both as medicine and food. It is widespread across China and rich in natural resources. Almost every part of N. nucifera could be used for medical or edible purpose,including seeds( Lianzi),black ripe fruits( Shilianzi),seed coats( Lianyi),green embryos of mature seed( Lianzixin),flowers( Lianhua),stamens( Lianxu),receptacles( Lianfang),leaves( Heye),leaf or flower stalks( Hegeng),leaf bases( Heyedi),rhizomes( Ou) and rhizome nodes( Oujie). Therefore,this plant is praised as a commercial crop with great economic values. Isoquinoline type alkaloids are the main chemical components of lotus. Smooth muscles usually exist in the digestive tract,respiratory tract and vascular,urinary,reproductive and other human systems. Dysfunction of smooth muscle contraction will induce many diseases including hypertension,asthma and gastrointestinal disorder,etc.,and most of current therapeutic strategies rely on relaxation of smooth muscle by drugs.Previous studies have shown that alkaloids of lotus have strong relaxation activity on smooth muscle. The present paper reviews phytochemistry and smooth muscle relaxation activity of 59 isoquinoline alkaloids from N. nucifera through accessing CNKI,PubMed and multiple databases for biomedical sciences.
Alkaloids/pharmacology* ; China ; Humans ; Isoquinolines/pharmacology* ; Muscle Relaxation ; Muscle, Smooth/drug effects* ; Nelumbo/chemistry* ; Phytochemicals/pharmacology* ; Plant Extracts

The effects of acute cooling/rewarming on cardiac K(+) currents and membrane potential were investigated. Membrane potential and current were assessed with whole-cell patch-clamp technique in current- and voltage-clamp modes. When the temperature of bath solution was decreased from 25 °C; to 4 °C, the transient outward current (I(to)) was completely abolished, the sustained outward K(+) current (I(ss)) at +60 mV and the inward rectifier K(+) current (I(K1)) at -120 mV were depressed by (48.5±14.1)% and (35.7±18.2)%, respectively, and the membrane potential became more positive. After the temperature of bath solution was raised from 4 °C; to 36 °C;, the membrane potential exhibited a transient hyperpolarization and then was maintained at a stable level. In some myocytes (36 out of 58), activation of the ATP-sensitive K(+) (K(ATP)) channels after rewarming was observed. The rewarming-induced change in the membrane potential was inhibited by the Na(+)/K(+)-ATPase inhibitor ouabain (100 μmol/L), and the rewarming-elicited activation of K(ATP) channels was inhibited by the protein kinase A inhibitor H-89 (100 μmol/L). Moreover, decrease of the temperature from 25 °C; to 4 °C; did not induce any significant change in cell volume when the cell membrane potential was clamped at 0 mV. However, significant cell shrinkage with spots was observed soon after rewarming-induced activation of K(ATP) channels. These data demonstrate that acute cooling/rewarming has a profound influence on the membrane potential and K(+) currents of ventricular myocytes, and suggest that activation of K(ATP) channels may play a role in cardiac cooling/rewarming injury.
Animals ; Cold Temperature ; Isoquinolines ; pharmacology ; KATP Channels ; metabolism ; Membrane Potentials ; Myocytes, Cardiac ; physiology ; Patch-Clamp Techniques ; Rats ; Rewarming ; Sulfonamides ; pharmacology

OBJECTIVETo study the pharmacodynamics of vecuronium,atracurium, mivacurium and rocuronium in patients with end-stage renal failure.

METHODSForty-six patients with end-stage renal failure scheduled for renal transplantation and 53 patients with normal renal function were given either vecuronium, atracurium, mivacurium or rocuronium. The neuromuscular effects were monitored by the evoked response of the adductor pollicis to train-of-four stimulation of the ulnar nerve.

RESULTSOnset of vecuronium, atracurium and mivacurium occurred faster or tended to be faster in patients with end-stage renal failure, but there was no significant difference in onset by rocuronium between the control patients and renal failure patients. Furthermore, the no-response period, duration of action and recovery of atracurium did not differ between the two groups. There was no significant difference in duration of action or recovery of mivacurium between the two groups, whereas its no-response period was significantly prolonged in the patients with end-stage renal failure. There was no difference in no-response period or duration of action after the initial dose of vecuronium or rocuronium between the two groups. However, no-response period and duration of effect by vecuronium and rocuronium were prolonged with increasing incremental doses in patients with end-stage renal failure.

CONCLUSIONSAll four muscle relaxants could be safely used in patients with end-stage renal failure. Onset of the relaxants were, in some cases, accelerated and no-response period of mivacurium was prolonged in patients with end-stage renal failure undergoing dialysis therapy. End-stage renal failure prolonged the no-response period and duration of action of vecuronium and rocuronium after repeated incremental doses, but did not alter those attributed to atracurium.

Adult ; Androstanols ; pharmacology ; Anesthesia, General ; Atracurium ; pharmacology ; Female ; Humans ; Isoquinolines ; pharmacology ; Kidney Transplantation ; Male ; Middle Aged ; Neuromuscular Blocking Agents ; pharmacology ; Succinylcholine ; pharmacology ; Time Factors ; Vecuronium Bromide ; pharmacology

Abstract: Our previous work revealed berberine can significantly enhance the susceptibility of fluconazole against fluconazole-resistant Candida albicans, which suggested that berberine has synergistic antifungal activity with fluconazole. Preliminary SAR of berberine needs to be studied for the possibility of investigating its target and SAR, improving its drug-likeness, and exploring new scaffold. In this work, 13-substitutited benzyl berberine derivatives and N-benzyl isoquinoline analogues were synthesized and characterized by 1H NMR and MS. Their synergetic activity with fluconazole against fluconazole-resistant Candida albicans was evaluated in vitro. The 13-substitutited benzyl berberine derivatives 1a-1e exhibited comparable activity to berberine, which suggested that the introduction of functional groups to C-13 can maintain its activity. The N-benzyl isoquinolines, which were designed as analogues of berberine with its D ring opened, exhibited lower activity than berberine. However, compound 2b, 2c, and 4b showed moderate activity, which indicated that berberine may be deconstructed to new scaffold with synergistic antifungal activity with fluconazole. The results of our research may be helpful to the SAR studies on its other biological activities.
Antifungal Agents ; pharmacology ; Berberine ; pharmacology ; Candida albicans ; drug effects ; Drug Resistance, Fungal ; Drug Synergism ; Fluconazole ; pharmacology ; Isoquinolines ; pharmacology ; Microbial Sensitivity Tests

A series of nitrogen-containing benzoheterocyclic derivatives were synthesized and tested for their antipsychotic activities. Their structures were confirmed by 1H NMR and HR-MS. Preliminary in vitro pharmacological trials showed that most of the target compounds have high affinity with D2 and 5-HT(2A) receptors. Among the tested compounds, 20 exhibited the highest affinity and D2 partial agonist activity. In vivo studies showed 20 has potent antipsychotic activities on apomorphine mice model, which is a chance to find a better precursor of D2 partial agonist for further optimization.
Animals ; Antipsychotic Agents ; chemical synthesis ; pharmacology ; Dopamine Agonists ; chemical synthesis ; pharmacology ; Drug Design ; Isoquinolines ; chemical synthesis ; pharmacology ; Mice ; Receptors, Dopamine D2 ; Structure-Activity Relationship

OBJECTIVETo identify the differentially expressed proteins in the liver of Oncomelania snails induced by Eomecon chinanthe sanguinarine.

METHODSSanguinarine was extracted and purified from the dry powder of Eomecon chinanthe. Oncomelania snails were immersed in 5 mg/L sanguinarine (50 Oncomelania snails per 500 ml) or pure water for 36 h (25°C) and the livers were isolated from live snails. Total liver proteins were extracted and separated by two-dimensional gel electrophoresis. Electrophoretogram was analyzed by Image Master 2D 5.0 software. The differentially expressed proteins between sanguinarine group and pure water group were selected and analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and tandem mass spectrometry sequencing of tryptic peptides.

RESULTSIn terms of protein spots, 433 ± 14 and 385 ± 12 were observed in sanguinarine group and in water group respectively. The eleven identified differentially expressed proteins included tropomyosin, hypothetical protein XP_533132, actin 87E, keratin 6A, beta-tubulin, mitochondrial inner membrane protein isoform 4, keratin 2, allatostatin precursor, ENSANGP00000020184, actin-3 and ENSANGP00000013943. Among them, hypothetical protein XP_533132 and ENSANGP00000013943 were down-regulated and the other nine proteins were up-regulated in sanguinarine group.

CONCLUSIONSanguinarine could alter the expression of proteins in livers of Oncomelania snails.

Animals ; Benzophenanthridines ; pharmacology ; Electrophoresis, Gel, Two-Dimensional ; Isoquinolines ; pharmacology ; Liver ; drug effects ; metabolism ; Proteomics ; Snails ; drug effects ; metabolism ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

OBJECTIVETo investigate the influence of isoliensinine (IL) on CYP3A enzyme activity.

METHODSA mixture metabolic system of liver microsome enzymes in vitro was developed. A HPLC method to test the metabolic activity of CYP3A was established with testosterone as a probe. The activities of CYP3A enzymes were measured with different IL concentrations and incubation time with testosterone.

RESULTSIn mixture metabolic system of liver microsome enzymes, the best incubation concentration of testosterone was 200 μmol/L, the best incubation time was 210 min, in this condition the IC₅₀ of IL for CYP3A inhibition was >1 000 μmol/L.

CONCLUSIONNo significant interaction between IL and CYP3A is detected, which indicates that IL might be used with CYP 3A enzyme substrates.

Animals ; Cytochrome P-450 CYP3A ; metabolism ; In Vitro Techniques ; Isoquinolines ; pharmacology ; Male ; Microsomes, Liver ; drug effects ; enzymology ; Rats ; Rats, Sprague-Dawley ; Testosterone ; pharmacology

The aim of the present study was to investigate the effects of cyclic adenosine monophosphate (cAMP) on rat gastric antral circular smooth muscle function. Forskolin, a direct activator of adenylyl cyclase (AC), was used to observe the influences of cAMP. Multi-channel physiological recorder was used to record spontaneous contraction activity of gastric antral circular muscle from Wistar rats. And ELISA method was used to detect the change of cAMP production in perfusate. The results showed that forskolin concentration-dependently suppressed the amplitude and frequency of the spontaneous contraction of the gastric antral muscle, and lowered the baseline of contraction movement significantly. Forskolin concentration-dependently increased the production of cAMP in the perfusate, which showed a significant negative correlation with the contraction amplitude of gastric antral ring muscle. The inhibitory effect of forskolin on spontaneous contraction activity of rat gastric antral circular muscle could be blocked by cAMP-dependent protein kinase (PKA) inhibitor H-89. These results suggest forskolin increases cAMP production and then activates PKA pathway, resulting in the inhibition of the spontaneous contraction activity of rat gastric antral circular smooth muscle.
Adenylyl Cyclases ; metabolism ; Animals ; Colforsin ; pharmacology ; Cyclic AMP ; pharmacology ; Cyclic AMP-Dependent Protein Kinases ; metabolism ; Isoquinolines ; pharmacology ; Muscle, Smooth ; drug effects ; Pyloric Antrum ; drug effects ; Rats ; Rats, Wistar ; Sulfonamides ; pharmacology