Study on visualization of metabolic process of L-stepholidine in living rats by PET/CT in vivo / 中草药

Objective: To exolpre the feasibility to transform the metabolic process of active constituents of Chinese herbal medicine in vivo into images by PET/CT and to make quantitative analysis. Methods: The l-stepholidine was used as study object, and chemical synthesis of 11C-L-SPD was performed in hot room. PET/CT scan was performed in different time, 5, 15, 30, 45, 60, and 90 min after injecting 11C-L-SPD by vail in rats, and the information of brain, heart, lung, liver, kidney, intestine, and bladder was transferred to the Workststion. The distribution volume ratios (DVR) of the above tissues were obtained. Results: 11C-L-SPD was keeping in a relative higher level in liver and kidney at 5 min. metabolism through the liver, kidney was the main eccrisis organ. The distribution of 11C-L-SPD in liver, kidney, intestine, and bladder was (1.37 ± 0.42)%, (1.10 ± 0.19)%, (0.89 ± 0.18)%, and (0.97 ± 0.111)% respectively at 5 min and was (0.65 ± 0.11)%, (0.54 ± 0.05)%, (5.49 ± 1.44)%, and (9.86 ± 1.88)% respectively at 90 min. Conclusion: PET/CT imaging could observe the distribution and metabolism of 11C-L-SPD dynamically and directly. It could be used in the research of other Chinese medicines.

Antagonism of l-stepholidine on ?-adrenoceptors / 中草药

Object To study the effect of l stepholidine (l SPD) on ? adrenoceptors Methods The affinity of l SPD to ? adrenoceptors was investigated by radioligand binding assay by means of competitive [ 3H] labelled Dihydro Aprenolol ([ 3H] DHA) specific binding The antagonism of l SPD on ? adrenoceptors was tested on pig coronary artery rings in vitro. Results [ 3H] DHA binding assay showed that l SPD specifically displayed binding affinity to ? adrenoceptors The Ki value was (5 75?0 56) ?mol/L; the logarithmic cumulative concentration response curves (LCCRC) of l[WT5,5”BZ] SPD for NA on the pig coronary artery rings showed that the position of curves shifted to the right and the crest depressed The values of pA 2 an pD′ 2 were 7 21?0 78 and 5 32?0 13 respectively As a control, propranolol (Pro) could shift the curves parallelly to the right and the pA 2 value of Pro was 9 19?0 17 Conclusion The results suggested that l SPD is a ? adrenoceptor antagonist and has affinities to more than one kind of receptor

Somnogenic effects of L-stepholidine in mice / 中国药理学通报

Aim To set up a highly effective and automatic mouse sleep-wake bioassay system,and evaluate the system through analysis of the somnogenic effects of L-stepholidine(SPD),targeting at dopamine D1/D2 receptors in mice.Methods The animals were housed in an insulated and soundproof recording chamber maintained at a constant temperature and humidity on an automatically controlled 12 h light/12 h dark cycle.The electroencephalogram and electromyogram were recorded continuously for 48 hours and analyzed by SleepSign software.Saline was administered ip to the mice at 21:00 on the first day,and SPD was given on the next day at the same hour.The vigilance state was analyzed based on the polygraphic recordings by the same software.Results The system has been demonstrated to be highly efficient and stable in recording and reliable in analyzing sleep-wake behavior in mice.With the aid of the sleep bioassay system,we found that SPD significantly increased the total time spent in sleep during dark period,and prolonged durations of non-rapid eye movement sleep episodes,with a concomitant reduction in amount and EEG power density of wakefulness.SPD rendered no effect on rapid eye movement sleep.Conclusion Through the reliable mouse sleep bioassay system,we found that SPD promotes non-rapid eye movement sleep but not rapid eye movement sleep in mice.

STUDY OF HYPOTENSIVE ACTION INDUCED BY l-STEPHO LIDINE / 中国药理学通报

Intravenous injection of l-stepholildine (SPD) 2.5, 10 and 40 mg/kg decreased blood pressure(BP ) by 30, 40 and 55% respectively in anesthetized dogs. SPD also decreased BP in anesthetized rats (0.5mg/kg iv, by 29% and 2-50 mg/kg injected into duodenum, by 17-36%) and rabbits (2.5 mg/kg iv, by 24%). It could inhibit the pressor reflexes induced by occluding carotid, stimulating vagus Or sciatic nerve. Furthermore, SPD 2.5 mg/kg injected into fourth cerebroventricle of dog decreased BP by 20%, and in pithed rats SPD 10-40 mg/kg iv depreased BP by 7-40%. These results indicate that both central and peripheral mechanisms are involved in the hypotens-ive action of SPD and the peripheral seems to be more important. As showed in previous papers the effect of SPD on ?-adrenoceptors may be one of the chief mechanisms of the hypotensive action induced by SPD.

THE EXPERIMENTAL ANTI-ARRHYTHMIC EFFECTS OF l-STEPHOLIDINE / 中国药理学通报

Intravenous injection of SPD 10 mg/kg could increase the tolerant dose of ouabain, and prevent the arrhythmias induced by acute myo-cardial ischemia in rats and that elicited by adrenaline-chloroform model in rabbits. SPD 60 mg/kg intraperitoneally could abolish the ventricular fibrillation produced by chloroform inhalation in mice. It inhibited the contractility, prolonged the functional refractory period and decreased the automaticity significantly of the isolated guinea pig papillary muscles, but no significant effect on excitability.