Steady-state pharmacokinetics and tissue distribution of anthraquinones of Rhei Rhizoma in rats

Shia, Chi-Sheng; Tsai, Shu-Yao; Lin, Jer‐An; Li, Mingli; Ko, Miau-Hwa; Chao, Pei‐Dawn Lee; Huang, Yu‐Ching; Hou, Yu‐Chi

doi:10.1016/j.jep.2011.08.003

Cited by 48 publications

(34 citation statements)

References 24 publications

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“…Studies in rodents have shown that, following intravenous administration, the half-life of emodin is only 23 min (61). Emodin in the serum predominately exists as glucuronides/sulfates, whereas the free form is mainly found in organs such as the liver and kidneys (62). For emodin to be effectively developed into a clinical therapy, methods will need to be developed to improve its bioavailability.…”

Section: Discussionmentioning

confidence: 99%

Emodin Bidirectionally Modulates Macrophage Polarization and Epigenetically Regulates Macrophage Memory

Iwanowycz

Wang

Altomare

et al. 2016

Journal of Biological Chemistry

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Macrophages are pleiotropic cells capable of performing a broad spectrum of functions. Macrophage phenotypes are classified along a continuum between the extremes of proinflammatory M1 macrophages and anti-inflammatory M2 macrophages. The seemingly opposing functions of M1 and M2 macrophages must be tightly regulated for an effective and proper response to foreign molecules or damaged tissue. Excessive activation of either M1 or M2 macrophages contributes to the pathology of many diseases. Emodin is a Chinese herb-derived compound and has shown potential to inhibit inflammation in various settings. In this study, we tested the ability of emodin to modulate the macrophage response to both M1 and M2 stimuli. Primary mouse macrophages were stimulated with LPS/IFN␥ or IL4 with or without emodin, and the effects of emodin on gene transcription, cell signaling pathways, and histone modifications were examined by a variety of approaches, including microarray, quantitative real-time PCR, Western blotting, chromatin immunoprecipitation, and functional assays. We found that emodin bidirectionally tunes the induction of LPS/IFN␥-and IL4-responsive genes through inhibiting NFB/IRF5/STAT1 signaling and IRF4/STAT6 signaling, respectively. Thereby, emodin modulates macrophage phagocytosis, migration, and NO production. Furthermore, emodin inhibited the removal of H3K27 trimethylation (H3K27m3) marks and the addition of H3K27 acetylation (H3K27ac) marks on genes required for M1 or M2 polarization of macrophages. In conclusion, our data suggest that emodin is uniquely able to suppress the excessive response of macrophages to both M1 and M2 stimuli and therefore has the potential to restore macrophage homeostasis in various pathologies.

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Section: Discussionmentioning

confidence: 99%

Emodin Bidirectionally Modulates Macrophage Polarization and Epigenetically Regulates Macrophage Memory

Iwanowycz

Wang

Altomare

et al. 2016

Journal of Biological Chemistry

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“…The hypolipidemic mechanisms of rhubarb may also be associated with the increased expression of muscle PPAR␣ in rats fed a high-fat diet . Furthermore, anthraquinones can enter the bloodstream (Shia et al, 2011) and may exert systemic effects in vivo. The overadministration of rhubarb can cause adverse effects, including vomiting, headache, diarrhea, and abdominal pain.…”

Section: Semen Cassiae (Cassia Seed Jue Ming Zi )mentioning

confidence: 99%

Emerging approaches of traditional Chinese medicine formulas for the treatment of hyperlipidemia

Xie

Zhao

2012

Journal of Ethnopharmacology

117

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“…To the residue, an appropriate volume of water was added to afford a solution with a 10-fold serum concentration, which was divided into aliquots and stored at −80°C for later use. The procedures for the characterization of RPMs followed that of a previous study [2, 3]. Briefly, 100 μ L of serum sample were mixed with 50 μ L of sulfatase solution (containing 1000 units/mL of sulfatase and 35,600 units/mL of β -glucuronidase) and 50 μ L of ascorbic acid (100 mg/mL) and incubated at 37°C for 10 min under anaerobic condition.…”

Section: Methodsmentioning

confidence: 99%

“…The major constituents of RP include a variety of anthraquinones such as aloe-emodin, rhein, emodin, chrysophanol and physcion [2, 3], which have been reported to show various beneficial effects, including neuroprotective, antioxidant, anti-inflammatory, and anticancer activities [4–8]. Recent pharmacokinetic studies of RP have revealed that the anthraquinones were all predominantly present as glucuronides and sulfates in the blood [3, 8] and they are also putative substrates of multidrug resistance proteins (MRPs), namely, the anion transporters.…”

Section: Introductionmentioning

confidence: 99%

Acute and Chronic Administrations ofRheum palmatumReduced the Bioavailability of Phenytoin in Rats: A New Herb-Drug Interaction

Chi

Juang

Chui

et al. 2012

Evidence-Based Complementary and Alternative Medicine

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The rhizome of Rheum palmatum (RP) is a commonly used herb in clinical Chinese medicine. Phenytoin (PHT) is an antiepileptic with narrow therapeutic window. This study investigated the acute and chronic effects of RP on the pharmacokinetics of PHT in rat. Rats were orally administered with PHT (200 mg/kg) with and without RP decoction (single dose and seven doses of 2 g/kg) in a crossover design. The serum concentrations of PHT, PHT glucuronide (PHT-G), 4-hydroxyphenytoin (HPPH), and HPPH glucuronide (HPPH-G) were determined by HPLC method. Cell line models were used to identify the underlying mechanisms. The results showed that coadministration of single dose or multiple doses of RP significantly decreased the C max and AUC0-t as well as the K 10 of PHT, PHT-G, HPPH, and HPPH-G. Cell line studies revealed that RP significantly induced the P-gp-mediated efflux of PHT and inhibited the MRP-2-medicated transport of PHT and HPPH. In conclusion, acute and chronic coadministrations of RP markedly decreased the oral bioavailability of PHT via activation of P-gp, although the MRP-2-mediated excretion of PHT was inhibited. It is recommended that caution should be exercised during concurrent use of RP and PHT.

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Steady-state pharmacokinetics and tissue distribution of anthraquinones of Rhei Rhizoma in rats

Cited by 48 publications

References 24 publications

Emodin Bidirectionally Modulates Macrophage Polarization and Epigenetically Regulates Macrophage Memory

Emodin Bidirectionally Modulates Macrophage Polarization and Epigenetically Regulates Macrophage Memory

Emerging approaches of traditional Chinese medicine formulas for the treatment of hyperlipidemia

Acute and Chronic Administrations ofRheum palmatumReduced the Bioavailability of Phenytoin in Rats: A New Herb-Drug Interaction

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