Aquaporins Alteration Profiles Revealed Different Actions of Senna, Sennosides, and Sennoside A in Diarrhea-Rats

Abstract

Senna and its main components sennosides are well-known effective laxative drugs and are used in the treatment of intestinal constipation in the world. Their potential side effects have attracted more attention in clinics but have little scientific justification. In this study, senna extract (SE), sennosides (SS), and sennoside A (SA) were prepared and used to generate diarrhea rats. The diarrhea rats were investigated with behaviors, clinical signs, organ index, pathological examination, and gene expression on multiple aquaporins (Aqps) including Aqp1, Aqp2, Aqp3, Aqp4, Aqp5, Aqp6, Aqp7, Aqp8, Aqp9, and Aqp11. Using qRT-PCR, the Aqp expression profiles were constructed for six organs including colon, kidney, liver, spleen, lung, and stomach. The Aqp alteration profiles were characterized and was performed with Principle Component Analysis (PCA). The SE treatments on the rats resulted in a significant body weight loss (p < 0.001), significant increases (p < 0.001) on the kidney index (27.72%) and liver index (42.55%), and distinguished changes with up-regulation on Aqps expressions in the kidneys and livers. The SS treatments showed prominent laxative actions and down regulation on Aqps expression in the colons. The study results indicated that the SE had more influence/toxicity on the kidneys and livers. The SS showed more powerful actions on the colons. We suggest that the caution should be particularly exercised in the patients with kidney and liver diseases when chronic using senna-based products.

Multi-Class Determination of 64 Illicit Compounds in Dietary Supplements Using Liquid Chromatography–Tandem Mass Spectrometry

“…Cascara and senna extracts are well known effective laxative drugs and used in the treatment of intestinal constipation. Some side effects have been reported in the administration of senna extracts [ 27 ]. Icariin was detected in two samples (0.77–3.03 mg g −1 ).…”

Analysis of Synthetic Adulterants, Mean Weight and Labeling in Traditional Phytotherapic Products

“…The sample number 8 has senna in its composition, a powerful laxative due the presence of anthracene derivatives (anthraquinones) and senosides A and B. They have reactive structures to the chromatographic developers, discarding the possibility of adulteration of the sample 34 .…”

Identification of rhein as the metabolite responsible for toxicity of rhubarb anthraquinones

“…Compared to the NC-rats, the RA-rats showed significant increases of the colon (p=0.0001) and stomach index (p=0.0044), and had significant decreases of the testis index (p=0.0364). Our previous study demonstrated that oral administration with anthraquinones could result in change of expression of aquaporins (AQPs) in the rat tissues (Cao et al, 2018). AQPs are known to modulate water transport in intracellular and extracellular cells, so these changes in gene expression of AQPs may change water content of the tissues.…”

“…SA and anthraquinone derivatives are thought to be protected by a β-glucoside bond allowing them to reach the colon where they are degraded into complex metabolites by enzymes secreted from the intestinal microbiome (Matsumoto et al, 2012). It is these metabolites that actually produce the laxative functions through stimulating the intestinal wall innervation, modulating multiple aquaporin proteins, and increasing intestinal reflex peristalsis (Cao et al, 2018). Therefore, the cumulative toxicity of the metabolites might be unavoidable when the RA products are used chronically.…”