Rheinanthrone, a metabolite of sennoside A, triggers macrophage activation to decrease aquaporin-3 expression in the colon, causing the laxative effect of rhubarb extract

Kon, Risako; Ikarashi, Nobutomo; Nagoya, Chika; Takayama, Tomoko; Kusunoki, Yoshiki; Ishii, Makoto; Ueda, Harumi; Ochiai, Wataru; Machida, Yoshiaki; Sugita, Kazuyuki; Sugiyama, Kiyoshi

doi:10.1016/j.jep.2013.12.055

Cited by 90 publications

(82 citation statements)

References 37 publications

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“…Sennosides A and B play a central role in the motility of the alimentary tract as prodrugs that are converted to an active principle, rheinanthrone, by intestinal microbiota (Hardcastle and Wilkins, 1970;Dreessen et al, 1981). A recent study showed that sennoside A may exert a laxative effect by inhibiting water transfer from the intestinal tract to the vascular side via decreasing aquaporin-3 expression in the colon (Kon et al, 2014). Daiokanzoto is a representative Rhei rhizoma-based JHM that comprises two herbs (Rhei rhizoma and Glycyrrhizae radix).…”

Section: Clinical Application and Pharmacology Of Rhei-rhizoma-based mentioning

confidence: 99%

Constipation and Herbal Medicine

Iizuka¹

2016

Herbal Medicines

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Citation:Iizuka N and Hamamoto Y (2015) Constipation and herbal medicine.Front. Pharmacol. 6:73. doi: 10.3389/fphar.2015.00073 Constipation is characterized by a variety of bowel symptoms such as difficulty passing stool, hard stool, and a feeling of incomplete evacuation. The multifactorial causes of constipation limit the clinical efficacy of current conventional treatments that use a single drug that acts through only one pathway. To complement the shortcomings of the current Western medical model and provide a complete holistic approach, herbal medicines capable of targeting multiple organs and cellular sites may be used. In Japan, many herbs and herbal combinations have traditionally been used as foods and medicines. Currently, Japanese physicians use standardized herbal combinations that provide consistent and essential quality and quantity. This review highlights representative Japanese herbal medicines (JHMs), Rhei rhizoma-based JHMs including Daiokanzoto and Mashiningan, and Kenchuto-based JHMs including Keishikashakuyakuto and Daikenchuto, which coordinate the motility of the alimentary tract. This review provides a framework to better understand the clinical and pharmacological efficacies of JHMs on constipation according to the unique theory of Japanese traditional medicine, known as Kampo medicine. Constipation and herbal medicine

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Section: Clinical Application and Pharmacology Of Rhei-rhizoma-based mentioning

confidence: 99%

Constipation and Herbal Medicine

Iizuka¹

2016

Herbal Medicines

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“…Today, it is already officially listed in Chinese, European, and Japanese Pharmacopoeia [24–26]. Rhubarb has many pharmacological activities including purgation [27], antidiarrhoeal effect [28], anti-inflammation [28], and immunoregulation [29]. On the other hand, rhubarb contains lots of compounds, mainly including anthraquinones (anthraquinone derivatives), tannins, polysaccharides, and other substances.…”

Section: Introductionmentioning

confidence: 99%

Rhubarb Tannins Extract Inhibits the Expression of Aquaporins 2 and 3 in Magnesium Sulphate-Induced Diarrhoea Model

Zheng

Wang

et al. 2014

BioMed Research International

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Tannins, a group of major active components of Chinese rhubarb and widely distributed in nature, have a significant antidiarrhoeal activity. Aquaporins (AQPs) 2 and 3 play important roles in regulating water transfer during diarrhoea. The present study aims to determine the effect of the total tannins extract of rhubarb on aquaporins (AQPs) 2 and 3 in diarrhoea mice and HT-29 cells both induced by magnesium sulphate (MgSO4). Our results showed that rhubarb tannins extract (RTE) significantly decreased the faecal water content in colon and evaluation index of defecation of diarrhoea mice. Interestingly, RTE could markedly reduce the mRNA and protein expression levels of AQPs 2 and 3 in apical and lateral mucosal epithelial cells in the colons of diarrhoea mice and HT-29 cells both induced by MgSO4 in a dose-dependent manner. Furthermore, RTE suppressed the production of cyclic monophosphate- (cAMP-) dependent protein kinase A catalytic subunits α (PKA C-α) and phosphorylated cAMP response element-binding protein (p-CREB, Ser133) in MgSO4-induced HT-29 cells. Our data showed for the first time that RTE inhibit AQPs 2 and 3 expression in vivo and in vitro via downregulating PKA/p-CREB signal pathway, which accounts for the antidiarrhoeal effect of RTE.

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“…Clinically, anthraquinone derivatives present in various drugs of plant origin are used all over the world for constipation remedy (Müller-Lissner, 2013). The best characterized compounds are sennoside and its aglycone (rhein anthrone) found in senna leaves and senna pods (Matsumoto et al, 2012;Kon et al, 2014). After oral administration, sennoside is degraded only in the lower parts of the gastrointestinal tract, releasing its active metabolite rhein anthrone.…”

Section: Discussionmentioning

confidence: 99%

The Drug-Drug Effects of Rhein on the Pharmacokinetics and Pharmacodynamics of Clozapine in Rat Brain Extracellular Fluid by In Vivo Microdialysis

Hou

Lin

et al. 2015

J Pharmacol Exp Ther

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Clozapine, an atypical antipsychotic agent, is highly effective in treatment-resistant schizophrenia; however, its major side effect is constipation. Instead of laxatives, rhein is a pharmacologically active component found in Rheum palmatum L., a medicinal herbal remedy for constipation. The purpose of this study is to determine whether rhein impacts the pharmacokinetics (PK) and pharmacodynamics (PD) of clozapine in brain when used to relieve clozapine-induced constipation. Here, we have investigated not only the PK of clozapine in blood but also the effects of rhein on the PK of clozapine in blood and in brain extracellular fluid together with the PD effects on neurotransmitters in extracellular fluid. The concentrations of clozapine and norclozapine in biologic samples were measured by ultra-performance liquid chromatography-tandem mass spectrometry. The drug-drug effects of rhein on extracellular neurotransmitter efflux in the rat medial prefrontal cortex (mPFC) produced by clozapine were assayed by highperformance liquid chromatography-electrochemical detection. The results demonstrate that the clozapine PK was nonlinear. Pretreatment with rhein for 7 days increased the total blood concentration of clozapine, but significantly reduced the unbound clozapine concentrations in the mPFC by approximately 3-fold. Furthermore, 7 days of rhein pretreatment thoroughly abolished the efflux of dopamine and its metabolite (3,4-dihydroxyphenylacetic acid) and altered the profile of homovanillic acid, another metabolite of dopamine, in the mPFC. In conclusion, rhein was found to substantially decrease clozapine and norclozapine concentrations in the mPFC dialysate, and this is accompanied by lower concentrations in the neurotransmitters in the same biophase. These findings suggest that a detailed clinical study for drug-drug interactions is recommended.

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Rheinanthrone, a metabolite of sennoside A, triggers macrophage activation to decrease aquaporin-3 expression in the colon, causing the laxative effect of rhubarb extract

Cited by 90 publications

References 37 publications

Constipation and Herbal Medicine

Constipation and Herbal Medicine

Rhubarb Tannins Extract Inhibits the Expression of Aquaporins 2 and 3 in Magnesium Sulphate-Induced Diarrhoea Model

The Drug-Drug Effects of Rhein on the Pharmacokinetics and Pharmacodynamics of Clozapine in Rat Brain Extracellular Fluid by In Vivo Microdialysis

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