Anthraquinone-containing compound in rhubarb prevents indole production via functional changes in gut microbiota
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ORIGINAL PAPER
Anthraquinone‑containing compound in rhubarb prevents indole production via functional changes in gut microbiota Kento Takayama1 · Shoji Maehara1 · Norihiko Tabuchi1 · Nobuyuki Okamura1 Received: 17 May 2020 / Accepted: 6 October 2020 © The Japanese Society of Pharmacognosy 2020
Abstract Indole is produced from dietary tryptophan by tryptophanase in intestinal bacteria, such as Escherichia coli. In the liver, indole is converted into indoxyl sulfate, a uremic toxin and risk factor for chronic kidney disease (CKD). Probiotics and prebiotics are currently used for suppressing CKD, but there are no drugs that directly suppress indole production. In this study, we developed an optimized HPLC method for analyzing indole production and evaluated the effect of diets and rhubarb on indole production via the changes of gut microbiota. In high-carbohydrate and high-fat diet-fed mice, the indole production was significantly higher than in high-fiber diet-fed mice. We further used the high-carbohydrate diet-fed mice as a model for examining the effect of rhubarb on indole production. The 20% methanol-eluted fraction of aqueous rhubarb extract significantly suppressed indole production, and the eluate constituent rhein 8-O-β-d-glucopyranoside (RG) contributed to this effect in a concentration-dependent manner. The effect of RG depended on the anthraquinone core substructure, i.e., the aglycone moiety (rhein) of RG, which appeared to inhibit the tryptophanase function in gut microbiota. Thus, in addition to earlier reports that rhubarb is an effective CKD treatment, our study demonstrated that the anthraquinone moiety in rhubarb prevents uremic toxin production via functional changes in gut microbiota, which suppresses CKD progression.
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11418-020-01459-w) contains supplementary material, which is available to authorized users. * Kento Takayama takayama@fukuyama‑u.ac.jp 1
Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, 1 Sanzo, Gakuen‑cho, Fukuyama, Hiroshima 729‑0292, Japan
13
Vol.:(0123456789)
Journal of Natural Medicines
Graphic abstract
Keywords Indole · Gut microbiota · Rhubarb · Rhein 8-O-β-d-glucopyranoside · Uremic toxin
Introduction In Japan, approximately 13.3 million patients suffer from chronic kidney disease (CKD), which is a state of chronically impaired renal function [1]. Moreover, CKD progression to end-stage kidney disease (ESKD), which requires hemodialysis, is considered to be associated with a further increase in the incidence and mortality of cardiovascular disease [1]. Hence, patients are burdened not only with the morbidity of ESKD requiring hemodialysis but also with large medical expenses, such as renal protection and drug costs for preventing the onset of cardiovascular disease. Therefore, the development of treatments to suppress CKD progression is an urgent medical need. In CKD management, therapies for exacerbating factors, including hypertension a
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