Jozef Lemli

The metabolism of sennosides A and B by the intestinal microflora: in vitro and in vivo studies on the rat and the mouse.

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Three methylated flavones from Thymus vulgaris

Abstract Three highly oxygenated flavones were isolated from leaves of Thymus vulgaris . Their structures were determined by spectroscopic methods as 5, 6, 4′-trihydroxy- 7, 8, 3′-trimethoxyflavone (thymonin), 5, 4′-dihydroxy-6, 7, 3′-trimethoxyflavone (cirsilineol) and 5, 4′-dihydroxy-6, 7, 8, 3′-tetramethoxyflavone. These flavones are reported for the first time in the genus Thymus .

Metabolism of Sennosides – An Overview

The metabolism of sennosides is discussed in view of the results obtained during the last years. Rhein anthrone is to be considered as the ultimate active form produced by microorganisms in the colon. Several contributions of this senna symposium bring complementary information of utmost interest.

Metabolism of 14C-rhein and 14C-rhein anthrone in rats

The two radioactive compounds were administered intracaecally to rats, and the recovery rates amounted to 89.9% for 14C-rhein and to 97.4% for 14C-rhein anthrone after 5 days. All organs and tissues showed for both compounds a significant clearance of radioactivity with exception of the kidneys where high levels persisted even after 5 days. Different metabolites could be detected in urine as well as in faeces where also nonanthraquinone fractions could be found.

The effect of rhein and rhein anthrone on intestinal fluid transport and on large intestine transit in germ-free rats

The effect of rhein and rhein anthrone on the transit and the transport of water and electrolytes in the large intestine was investigated in germ-free rats. After intracaecal administration, neither of the two compounds was found to accelerate the transit of a colour marker through the large intestine. Both drugs reduced the net absorption of sodium and chloride in the colon and enhanced net potassium secretion. Net water absorption was decreased by rhein and even reversed into net secretion by rhein anthrone. Our results show that the secretagogue activity of the compounds is not sufficient to induce laxation in germ-free rats. Furthermore rhein and rhein anthrone had no laxative properties under our experimental conditions.

Influence of 1,8-dihydroxyanthraquinone and loperamide on the paracellular permeability across colonic mucosa

Administration of 1,8‐dihydroxyanthraquinone (DHA) markedly increases the permeability of guinea‐pig colonic mucosa. In 1 h 25% of the administered dose of99m Tc‐EDTA complex leaks through the mucosa. Orally administered loperamide blocks the99m Tc‐EDTA transfer after DHA administration. Loperamide injected in situ in the ligated colon segment shows the same blocking properties of the transfer rate of the complex. These findings suggest that the opposing action on fluid transport of the laxative DHA and the antidiarrhoeal loperamide could be due to these drugs affecting the permeability of the colonic mucosa. The minimal dose of loperamide, able to restore normal permeability, was as low as 0·01 mg kg−1.

Senna – an Old Drug in Modern Research

Senna was introduced in therapy in the 9th century by the Arabs. In the second half of the 19th century chemical investigation of the drug was undertaken, but only a century later the sennosides were isolated. Pharmacological research on senna started at the beginning of this century. During the last 25 years interest in the pharmacology of synthetic and natural laxatives steadily increased. Senna, containing only dianthrones as active substances, is still in the center of scientific research and merits this special attention.

Excretion and distribution of [14C]rhein and [14C]rhein anthrone in rat

Abstract— After single intracaecal administration of [14C]rhein (25 mg kg−1) and [14C]rhein anthrone (20 mg kg−1) to rats, the summated recovery rates of 14C after five days were in urine 37(±8.3)% and 2.8(±0.4)% and in faeces 53(±9.5)% and 95 (±10.1)%, respectively. The clearance of radioactivity from the organs and tissues was almost complete within three days, with the exception of the kidney which exhibited pronounced retention of radioactivity even after five days (<61% of 24 h values). Extracts of faeces from animals treated with [14C]rhein of [14C]rhein anthrone, revealed rhein as well as other radioactive substances, which chemically did not react as 1,8‐dihydroxyanthraquinones.

A rapid method for the estimation of prostaglandin E2 in intestinal tissues using fluorescence derivatization

A sensitive spectrofluorimetric method is described to determine small quantities of prostaglandin E2 in complex biological systems as intestinal tissues. The method is based on a solid phase extraction combined with a coupling with a fluorescent marker and measuring the derivatization product by fluorescence densitometry. After mixing the tissue with an ice-cold perchloric acid solution, adjusting the pH, centrifugation and filtration steps, the prostaglandins are retained on a solid phase extraction C18 disposable column. They are eluted with diethylether, derivatized with 4-bromomethyl-7-methoxy-coumarin using potassium carbonate as condensating agent and finally analysed using fluorescence densitometry on silica gel TLC plates. Applying this method, amounts down to 5 ng (per gram wet tissue) could be measured in intestinal tissues, the s.e.m. for replicated total analysis being less than 15%. The foregoing method is applied for the determination of PGE2 released in the intestinal wall under the influence of laxatives.

Combined manometric and radiological study of the changes in colonic motility induced by sennosides in rats.

Colonic motility changes induced by sennosides in rats were studied by an original method, which permits the simultaneous projection of manometric and fluoroscopic registrations on a single monitor. The results of this study allowed us to confirm the laxative effect of sennosides by inducing mass movements within 60-80 min after intracecal administration leading to a complete emptying of the whole colon. These mass movements were preceded by hypotonia of cecum and colon and impeded pellet formation.