OBJECTIVETo predict the absorption of corynanthine (COR), yohimbine (YOH), ajmalicine (AMC) and ajmaline (AML) as chemical constituents of some traditional Chinese medicines in human intestinal epithelial.

METHODBy using Caco-2 (the human colonic adenocarcinoma cell lines) cell monolayers as a human intestinal epithelial cell model, the permeability of COR, YOH, AMC and AML were studied from apical side (AP side) to basolateral side (BL side) or from BL side to AP side. The four alkaloids were measured by high performance liquid chromatography (HPLC) coupled with UV detector. Transport parameters and apty) and atenolol (a control substance of poor permeability). The relationship between P(app) and log D values of four alkaloids was investigated by using drugs ADMET predict software.

RESULTThe P(app) values of COR, YOH, AMC and AML were (1.863 +/- 0.055) x 10(-5), (1.540 +/- 0.082) x 10(-5), (2.522 +/- 0.246) x 10(-5) and (1.155 +/- 0.099) x 10(-5) cm x s(-1) from AP side to BL side, and (2.390 +/- 0.017) x 10(-5), (1.987 +/- 0.154) x 10(-5), (1.374 +/- 0.260) x 10(-5) and (2.418 +/- 0.124) x 10(-5) cm x s(-1) from BL side to AP side, respectively, which P(app) values were identical with that of propranolol [(2.23 +/- 0.10) x 10(-5) cm x s(-1) from AP to BL side]. The ratio of P(app B --> A)/P(app A -->B) of COR, YOH, AMC and AML were 1.28, 1.29, 0.54 and 2.09, respectively, which suggested that the efflux transport of AML was 2.09 times higher more than its influx transport.

CONCLUSIONCOR, YOH, AMC and AML can be transported and absorbed across the human Caco-2 cells monolayers, and they belong to completely absorbed compounds. AML may have been involved in efflux mechanism in Caco-2 cells monolayers model from the BL to AP side direction. The oil-water partition coefficient play key roles in the transport and absorption of the four alkaloids.

Ajmaline ; metabolism ; Caco-2 Cells ; Chromatography, High Pressure Liquid ; Epithelial Cells ; metabolism ; Humans ; Intestinal Mucosa ; cytology ; Molecular Structure ; Secologanin Tryptamine Alkaloids ; metabolism ; Yohimbine ; metabolism

The present study investigated the chemical constituents from Uncaria sessilifructus and their neuroprotective activities. The compounds were separated and purified from the 90% ethanol extract of U. sessilifructus by various chromatographic methods, including silica gel, Sephadex LH-20, and semi-preparative HPLC. Seven compounds were obtained, and their structures were identified as uncanidine J(1), uncanidine K(2), 17-O-ethylhirsutine(3), tetrahydroalstonine(4), akuammigine(5), hirsutine(6), and hirsuteine(7) by physicochemical properties and various spectral techniques, including UV, IR, MS, and NMR. Compounds 1 and 2 are two new compounds. Compound 3 is a new natural product, and compound 4 was isolated from U. sessilifructus for the first time. In addition, the isolated compounds were evaluated for their neuroprotective effects on oxygen and glucose deprivation/reoxygenation(OGD/R) injury in primary cortical neurons in rats. The results showed that compounds 1-7 had different degrees of protective effects on OGD/R injury. The EC_(50) values of compounds 2-4 were(0.17±0.03),(1.70±0.38), and(1.79±0.23) μmol·L~(-1), respectively.
Animals ; Biological Products ; Drugs, Chinese Herbal/pharmacology* ; Ethanol ; Glucose ; Indole Alkaloids ; Neuroprotective Agents/pharmacology* ; Oxygen ; Rats ; Secologanin Tryptamine Alkaloids ; Silica Gel ; Uncaria/chemistry*

The bradycardiac and presor to intravenous and intraventricular methoxamine were examined in urethane-anesthetized rabbits 1) Intravenous methoxamine produced bradycardiac pressor responses. Atropine (2 mg/kg, i,v.) weakened but not abloished the bradycardiac effect. 2) The bradycardiac effect elicited by intravenous methoxamine was not affected by int-ravenous prazosin, rehimbiine, guanethidine and propranolol, butt was attenuated by intra venous chlorisondamine reserpine. 3) The pressor effect elioited by intravenous methoxamine was weakened by prazosin, but was scarcely affected, rather potentiated, by intraTenous yohimblne, guanethidine, chlorisondamine, propranolol and resperpine. 4) Intraventricular methoxamine produced pressor and bradycardiac responses. 5) The bradycardiac effect elicited by intraventricular methoxamine was net affected by intravenous atropine, prasosin and yohimbine. This was attenuated by intravenous guane- thidine, chlorisondamine, propranolol and reserpine, and by intraventricular atropine prazosin and propranolol, respectively. 6) The pressor effect elicited by intraventricular methoxamine was attenuated by intra- ventricular and intravenous prazosin. This was not affected by intravenous atropine, gua-nethidine, chlorisondamine, propranolol, reserpine and yohimbine, and by intraventricular atropine, prasosin and Propranolol, respectivelr. 7) From these results it was inferred that bradycardiac effect elicited by methoxamine was not an action through the mediation of aleph 1-adrenoceptors but was a result from non-specific actions on some brain receptors.
Atropine ; Brain ; Chlorisondamine ; Guanethidine ; Methoxamine* ; Negotiating ; Prazosin ; Propranolol ; Rabbits* ; Reserpine ; Yohimbine

OBJECTIVEUnder various drought conditions and nitrogen application, the content of vindoline, catharanthine, vincristine and vinblastine in the leaf of Catharanthus roseus were illustrated to improve the content of alkaloid theoretically.

METHODSix groups were set in the experiment, which included: CK (natural control), CN (natural control + nitrogen), LK (low drought), LN (low drought + nitrogen), HK (high drought), HN (high drought + nitrogen) to discuss the change characteristics of total nitrogen, the activity of alkaline POD and TDC, the content of four alkaloids under the different conditions were measured.

RESULTUnder LK condition, the activity of POD, TDC were enhanced. In the early stage of stress (0-21 d), vindoline, catharanthine, vincristine and vinblastine accumulated, and reduced in the later stage (28-35 d). For all groups, adding exogenous nitrogen could improve the total content of nitrogen, vindoline and vinblastine, meanwhile the activity of POD and TDC were enhanced as well. The LN, HN treatments were beneficial to accumulating catharanthine and vinblastine.

CONCLUSIONDrought stress or additional nitrogen have an influence on both of the activities of POD and TDC, and the four alkaloids were affected as well. Thereinto, the LN condition was the most effective treatment for accumulating the four alkaloids (vindoline, catharanthine, vincristine and vinblastine), which were regulated by improve nitrogen content and enzymatic activity.

Catharanthus ; metabolism ; Nitrogen ; metabolism ; Peroxidase ; metabolism ; Stress, Physiological ; Vinblastine ; analogs & derivatives ; metabolism ; Vinca Alkaloids ; metabolism ; Vincristine ; metabolism ; Water ; metabolism

No abstract available.
Digoxin* ; Reserpine* ; Tachycardia*

Taurine has a number of beneficial pharmacological actions in the brain such as anxiolytic and neuroprotective actions. We explored to test whether taurine could be transported to the central nervous system through the intranasal route. Following intranasal administration of taurine in mice, elevated plus maze test, activity cage test and rota rod test were carried out to verify taurine’s effect on anxiety. For the characterization of potential mechanism of taurine’s anti-anxiety action, mouse convulsion tests with strychnine, picrotoxin, yohimbine, and isoniazid were employed. A significant increase in the time spent in the open arms was observed when taurine was administered through the nasal route in the elevated plus maze test. In addition, vertical and horizontal activities of mice treated with taurine via intranasal route were considerably diminished. These results support the hypothesis that taurine can be transported to the brain through intranasal route, thereby inducing anti-anxiety activity. Taurine’s anti-anxiety action may be mediated by the strychnine-sensitive glycine receptor as evidenced by the inhibition of strychnine-induced convulsion.
Administration, Intranasal ; Animals ; Anxiety ; Arm ; Brain ; Central Nervous System ; Isoniazid ; Mice ; Picrotoxin ; Receptors, Glycine ; Seizures ; Strychnine ; Taurine ; Yohimbine

BACKGROUND: Ischemic preconditioning(IP) is known to be effective in the protection of myocardial necrosis, arrhythmia, and the restoration of the myocardial function in the ischemia-reperfusion state of the heart. However the exact mechanism is not clearly understood. The purpose of this study was to elucidate the trigger mechanism of IP on the restoration of the myocardial function after ischemia-reperfusion. MATERIAL AND METHOD: By connecting a Langendorff perfusion apparatus with an isolated heart of a rat, the normal temperature of the heart was maintained. The experiment was conducted in seven groups, which were divided according to the preconditioning stimuli and blockage methods: Group I(n=10) was a group without IP, Group II(n=10) a group of three-minute IP, Group III(n=10) a group of PEIP, Group IV(n=10) a group of clonidine IP, Group V(n=10) a group of IP after reserpine, Group VI(n=10) a group of PE & prazosin IP, and Group VII(n=10) a group of clonidine & yohimbine IP. Hemodynamic parameters of DP, LVEDP, +/-dP/dT and the changes of perfusion in the coronary artery were evaluated. RESULT: Developed pressure and +dP/dT changed per unit time. After 20 minutes of reperfusion, those of Group II and III were 63.1+/-3.7%, 64.8+/-4.6% and 64.5+/-4.6%, 63.8+/-4.4%, which improved more significantly than those of Group I(P<0.05). However, there were no significant differences between the Groups V and VI, and Group I. CONCLUSION: The Brief ischemic preconditioning and pharmacological preconditioning using alpha-receptor sympathomimetics have protecting effects on the restoration of myocardial function after reperfusion. And the protecting effect of preconditioning seems to be related to sympathetic neurotransmitters and to the selective action of the alpha1-adrenergic receptor.
Animals ; Arrhythmias, Cardiac ; Clonidine ; Coronary Vessels ; Heart ; Hemodynamics ; Ischemic Preconditioning ; Ischemic Preconditioning, Myocardial* ; Necrosis ; Neurotransmitter Agents ; Perfusion ; Prazosin ; Rats* ; Reperfusion ; Reserpine ; Sympathomimetics ; Yohimbine

OBJECTIVETo investigate the clinical efficacy of bleomycin, cyclophosphamide, vindesine, Ara-C and dexamethasone(BACOD) for treatment of patients with relapsed/refractory diffuse large B cell lymphoma.

METHODSA total of 56 patients with relapsed/refractory diffuse large B cell lymphoma were divided into control group and treatment group. The control group were received the conventional BACOD treatment, and the treatment group received continuous venoclysis with BACOD. Clinical efficacy was observed and compared.

RESULTSIn control group, 6 patients achieved CR, 9 patients achieved PR, and their overall remission rate was 53.6%. In treatment group, 10 patients achieved CR, 12 patients achieved PR, and their overall remission rate was 78.6%. The overall remission rate of treatment group was significantly higher than that of control group (χ2=3.903, P<0.05). The incidence rates of nausea and vomiting, thrombocytopenia, abnormal liver function, fever and granulocytopenia were not significant difference (P>0.05) between the two groups.

CONCLUSIONThe clinical efficacy of cyclophosphamide, vindesine and dexamethasone for treatment of patients with relapsed/refractory/diffuse large B cell lymphoma has been confirmed to be satisfactory, suggesting that the continuous venoclysis with BACOD can be apptied to the in clinical treatment.

Antineoplastic Combined Chemotherapy Protocols ; Bleomycin ; Cyclophosphamide ; Cytarabine ; Dexamethasone ; Doxorubicin ; Humans ; Lymphoma, Large B-Cell, Diffuse ; Recurrence ; Treatment Outcome ; Vincristine ; Vindesine

No abstract available.
Vincristine*

OBJECTIVETo study tissue culture of Vinca minor and determine the content of vincamine.

METHODLeaf blades, stalks, root segment of V. minor were used as explants to study the effect of 2, 4-D,6-BA,NAA on its callus induction and vincamine contents in the orthogonal design experiment. In the peak period of callus formation, vincamine content in callus of V. minor and sterile plants was determined by HPLC. The experimental data was statistically analyzed.

RESULTThe content of 6-BA and NAA had no significant effect on its callus induction. But the content of 2, 4-D had significant effect on its callus induction. Within 20,40,60 d, the content of vincamine in sterile plant was (0.015 +/- 0.003)%, (0.097 +/- 0.001)% , (0.113 +/- 0.06)%, respectively. In the peak period of callus formation, vincamine content in callus of leaf blades, stalks, root segment was (0.024 +/- 0.0025)%, (0.016 +/- 0.0015)%, (0.010 +/- 0.0015)%, respectively. To 30 days of subculture, vincamine content in callus of leaf blades, stalks, root segment was (0.041 +/- 0.002)%, (0.019 +/- 0001)%, (0.016 +/- 0.002)%, respectively.

CONCLUSIONThe optimal hormone combination for callus initiation was MS +2, 4-D 1.0 mg x L(-1) +6-BA 0.5 mg x L(-1) + NAA 0.5 mg x L(-1). In different growth periods, vincamine content in sterile plants is significantly different. From different explants in callus vincamine content is different, in which leaves callus is significantly higher than that of stems, roots produced callus organization.

Culture Techniques ; methods ; Linear Models ; Plant Infertility ; Vinca ; chemistry ; growth & development ; physiology ; Vincamine ; analysis