Abstract

Senna and rhubarb are often used as routine laxatives, but there are differences in mechanism of action and potential side effects. Here, we studied metabolites of senna anthraquinones (SAQ), rhubarb anthraquinones (RAQ) and their chemical marker, sennoside A (SA), in a rat diarrhea model. In in vitro biotransformation experiments, SAQ, RAQ and SA were incubated with rat fecal flora solution and the metabolites produced were analyzed using HPLC. In in vivo studies, the same compounds were investigated for purgation induction, with measurement of histopathology and Aqps gene expression in six organs. The results indicated that SAQ and RAQ had similar principal constituents but could be degraded into different metabolites. A similar profile of Aqps down-regulation for all compounds was seen in the colon, suggesting a similar mechanism of action for purgation. However, in the kidneys and livers of the diarrhea-rats, down-regulation of Aqps was found in the RAQ-rats whereas up-regulation of Aqps was seen in the SAQ-rats. Furthermore, the RAQ-rats showed lower Aqp2 protein expression in the kidneys, whilst the SA-rats and SAQ-rats had higher Aqp2 protein expression in the kidneys. This may have implications for side effects of SAQ or RAQ in patients with chronic kidney or liver diseases.

Highlights

  • Constipation is a common gastrointestinal disorder that affects 16% of the adult population globally [1]

  • The anthraquinones belong to anthranoid glycosides, for which sennoside A is used as a chemical marker for quality control [4,5]

  • Different Metabolite Profiles Produced from Senna Anthraquinones (SAQ), Rhubarb Anthraquinones (RAQ) and sennoside A (SA)

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Summary

Introduction

Constipation is a common gastrointestinal disorder that affects 16% of the adult population globally [1]. Senna (Cassia angustifolia Vahl) and rhubarb (Rheum spp.) are widely used herbal laxatives, due to their rapid purgative actions and availability without prescription [2]. Senna and rhubarb are classified as stimulative laxatives, and known to have similar effective constituents, the anthraquinones [3]. The purgative action of sennoside A conversion to rheinanthrone in the intestine has previously been explained in terms of Na+/K+ transport, water and mucus secretion in the colon [8]. It is these complex metabolites that produce the laxative effects. The similarities and differences of action between anthraquinones require further elucidation

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