rescinnamine and syrosingopine

It is difficult to understand the entire effect of a natural product because such products generally have multiple effects. We propose a strategy to understand these effects effectively by decomposing them with a profile data analysis method we developed. A transcriptome profile data set was obtained from a public database and analyzed. Considering their high similarity in structure and transcriptome profile, we focused on rescinnamine and syrosingopine. Decomposed effects predicted clear differences between the compounds. Two of the decomposed effects, SREBF1 activation and HDAC inhibition, were investigated experimentally because the relationship between these effects and the compounds had not yet been reported. Analyses in vitro validated these effects, and their strength was consistent with predicted scores. Moreover, the number of outliers in decomposed effects per compound was higher in natural products than in drugs in the data set, which is consistent with the nature of the effects of natural products.

Topics: Biological Products; Data Analysis; Databases, Factual; Reserpine; Transcriptome

Topics: Alkaloids; Antihypertensive Agents; Blood Pressure; Blood Pressure Determination; Chlorothiazide; Guanethidine; Hexamethonium; Humans; Hydrochlorothiazide; Hypotension; Pressure; Rauwolfia; Reserpine

Gastric haemorrhage was produced regularly in mice within 6 hours of the subcutaneous injection of a large dose (2 to 10 mg./kg.) of reserpine or of deserpidine. Rescinnamine, syrosingopine (SU-3118), and tetrabenazine (Ro 1-9569) were less active. Gastric haemorrhage was also produced within 6 hours when 5-hydroxytryptamine (10 mg./kg.) was injected every half-hour. Neither reserpine nor 5-hydroxytryptamine produced gastric haemorrhage in mice which had been vagotomized by tying the oesophagus at the cardio-oesophageal junction or which had been pre-treated with iproniazid. Amphetamine was less effective than iproniazid in preventing gastric haemorrhage after reserpine, and the following drugs were ineffective: cocaine, methyl phenidate (Ritalin), amarin, caffeine, nikethamide, lysergic acid diethylamide and its 2-bromo derivative (BOL148). Gastric haemorrhage was not observed in mice which had been given substantial doses of atropine or of hexamethonium before reserpine. The incidence of haemorrhage was substantially reduced by treatment with an antacid mixture. It is concluded that reserpine-like drugs cause gastric haemorrhage by a mechanism which has an important central component and which involves the liberation of 5-hydroxytryptamine.

Topics: Amphetamine; Animals; Anti-Ulcer Agents; Atropine; Cocaine; Hemorrhage; Iproniazid; Lysergic Acid Diethylamide; Mice; Reserpine; Serotonin; Stomach; Stomach Diseases