This paper investigates the laxative effect and acute toxicity of certain fractions of senna extracts in mice. The same tests were also carried out with several pure anthraquinone derivatives common in senna pods. The results show that the laxative and toxic components of senna pods and senna extracts can be separated. The most potent laxative components, sennosides A + B and Fraction V (relative potencies 1 and 0.9 respectively), have the lowest toxicity (relative intravenous toxicities 1 and less than 1). Fractions with very low laxative activity (rhein-8-glucoside and Fraction IV, relative potencies 0.56 and 0.05) have the highest acute toxicity (relative toxicities 10 and 32 respectively).

Pure sennoside B was administered to rats. On appearance of the first wet faeces, sennoside B and its metabolites were determined in different parts of the alimentary tract, in faeces and in the urine. The total recovery of unchanged sennoside B and its metabolites was determined by alkali fusion followed by colorimetry and high-pressure liquid chromatography (HPLC). Alkali fusion in 1 N sodium hydroxide solution formed red solutions with sennosides and sennoside derivatives. The molar absorbance of sennosides A and B, sennidin B monoglucoside, sennidins, rhein, danthron, dithranol, rhein-8-glucoside and rhein anthrone at wavelengths of 505–530 nm related approximately to the number of ionizable hydroxy groups in the molecule. Brown polymerized products were isolated from the senna drug. The colour intensity of these products was approximately the same by weight as that of the sennosides themselves, although sennidins could no longer be freed from these by acid hydrolysis. After administration of sennoside B, the average sum of unchanged glucoside and known metabolites in different parts of the gastrointestinal tract and faeces of rats was 61.6% according to HPLC and 92.8% according to the alkali fusion procedure. This difference is indicative of the presence of substances which are no longer identifiable as sennoside derivatives, either by HPLC or by other classical chromatographic methods. Sennosides seem to be partly present in the alimentary tract in polymerized or bound form. The alkali fusion method may be useful in connection with the isolation of as yet unknown metabolites of the sennosides in the gastrointestinal tract.

This paper investigates the effect of different storage conditions on the chemical stability, laxative effect and acute toxicity of sennoside solutions. The variables in storage conditions were pH, time and temperature (room temperature or 100 degrees). The chemical stability of sennosides in aqueous solutions was found to be pH-dependent, with the best stability at pH 6.5 (t90. = 8.4 months) and the poorest at pH 8.0 (t90. = 2.5 months). Two years of storage at room temperature did not reduce the laxative potency in mice, regardless of the pH. After 4.25 years of storage the potency declined in alkaline solutions only. The degradation products with laxative potencies are chemically unknown. The acute toxicity of sennoside solutions increased with time during storage, the acid solution being more toxic than either the neutral or alkaline ones.