Enhanced absorption and inhibited metabolism of emodin by 2, 3, 5, 4′-tetrahydroxystilbene-2-O-β-D-glucopyranoside: Possible mechanisms for Polygoni Multiflori Radix-induced liver injury

Yu, Qiong; Jiang, Li; Luo, Na; Fan, Ya-Xi; Ma, Jie; Li, Ping; Li, Huijun

doi:10.1016/s1875-5364(17)30067-5

Cited by 13 publications

(14 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It was found that the presence of TSG could significantly increase the C max and AUC values of emodin via inhibiting its metabolism [34,56]. Moreover, the in vitro study also confirmed that TSG could increase the absorption of emodin via inhibiting its MRP mediated transport in Caco-2 cells and UDP glycosyltransferase-(UGT) mediated glucuronidation in human liver microsomes in a dose-dependent manner [57]. In addition to the influence of TSG, it was reported that the co-occurring anthraquinones components, including aloe-emodin, rhein, chrysophanol, and physcion, may lead to a decrease in emodin AUC in the cerebral ischemia-reperfusion model rats [58].…”

Section: Effect Of Co-occurring Ingredients In Rpm On the Pharmacokinmentioning

confidence: 68%

“…Although both CYP1A2 and UGT1A8 were involved in the metabolism of emodin in rats, UGT mediated phase II metabolism is the dominant metabolic pathway of emodin. After consecutively treating with TSG (117 mg/kg) for 7 days, a decrease in the mRNA expression of Ugt1a8 in rat liver and intestine led to increased C max and AUC of emodin in rats [34], and the metabolism of emodin could be inhibited by TSG in the human liver microsome in a dose-dependent manner [57]. Moreover, the absorption of emodin could be increased in the Caco-2 cell in the presence of TSG.…”

Section: Correlations Between Pharmacokinetics Of Rpm and Its Inducedmentioning

confidence: 99%

See 1 more Smart Citation

Overview of Pharmacokinetics and Liver Toxicities of Radix Polygoni Multiflori

Yang

Zuo

2020

Toxins

View full text Add to dashboard Cite

Radix Polygoni Multiflori (RPM), a traditional Chinese medicine, has been used as a tonic and an anti-aging remedy for centuries. However, its safe and effective application in clinical practice could be hindered by its liver injury potential and lack of investigations on its hepatotoxicity mechanism. Our current review aims to provide a comprehensive overview and a critical assessment of the absorption, distribution, metabolism, excretion of RPM, and their relationships with its induced liver injury. Based on the well-reported intrinsic liver toxicity of emodin, one of the major components in RPM, it is concluded that its plasma and liver concentrations could attribute to RPM induced liver injury via metabolic enzymes alteration, hepatocyte apoptosis, bile acids homeostasis disruption, and inflammatory damage. Co-administered 2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucopyranoside in RPM and other drugs/herbs could further aggravate the hepatotoxicity of emodin via enhancing its absorption and inhibiting its metabolism. To ensure the safe clinical use of RPM, a better understanding of the toxicokinetics and effect of its co-occurring components or other co-administered drugs/herbs on the pharmacokinetics of emodin is warranted.

show abstract

Section: Effect Of Co-occurring Ingredients In Rpm On the Pharmacokinmentioning

confidence: 68%

Section: Correlations Between Pharmacokinetics Of Rpm and Its Inducedmentioning

confidence: 99%

Overview of Pharmacokinetics and Liver Toxicities of Radix Polygoni Multiflori

Yang

Zuo

2020

Toxins

View full text Add to dashboard Cite

show abstract

“… Di et al (2015) showed that piperine significantly improved the in vivo bioavailability of emodin and inhibited glucuronidation metabolism of emodin. Yu et al (2017) demonstrated that 2,3,5,4’-tetrahydroxystilbene-2-β- D -glucoside could enhance the emodin absorption in a Caco-2 cell culture model. Meanwhile, many studies have shown synergistic effects between emodin and other antineoplastic drugs ( Ko et al, 2010 ; Wang et al, 2010 ; Tan et al, 2011 ; Guo et al, 2013 ).…”

Section: Introductionmentioning

confidence: 94%

Interactions Between Emodin and Efflux Transporters on Rat Enterocyte by a Validated Ussing Chamber Technique

et al. 2018

View full text Add to dashboard Cite

Emodin, a major active anthraquinone, frequently interacts with other drugs. As changes of efflux transporters on intestine are one of the essential reasons why the drugs interact with each other, a validated Ussing chamber technique was established to detect the interactions between emodin and efflux transporters, including P-glycoprotein (P-gp), multidrug-resistant associated protein 2 (MRP2), and multidrug-resistant associated protein 3 (MRP3). Digoxin, pravastatin, and teniposide were selected as the test substrates of P-gp, MRP2, and MRP3. Verapamil, MK571, and benzbromarone were their special inhibitors. The results showed that verapamil, MK571, and benzbromarone could increase digoxin, pravastatin, and teniposide absorption, and decrease their Er values, respectively. Verapamil (220 μM) could significantly increase emodin absorption at 9.25 μM. In the presence of MK571 (186 μM), the Papp values of emodin from M-S were significantly increased and the efflux ratio decreased. With the treatment of emodin (185, 370, and 740 μM), digoxin absorption was significantly decreased while teniposide increased. These results indicated that emodin might be the substrate of P-gp and MRP2. Besides, it might be a P-gp inducer and MRP3 inhibitor on enterocyte, which are reported for the first time. These results will be helpful to explain the drug–drug interaction mechanisms between emodin and other drugs and provide basic data for clinical combination therapy.

show abstract

“…In alcohol-induced liver injury, the metabolism of aloe-emodin, chrysophanol, physcion, aurantio-obtusin, chrysoobtusin, emodin, obtusin and rhein increase. This may result from that alcohol induces P450 (e.g., CTP2E1, CYP3A and CYP1A) (Shao and Feng, 2015;Li P. et al, 2017). Furthermore, the metabolism of rhein decreases under acute liver injury because of the lower expression and activity of CYP450, especially in males (Zhang et al, 2015).…”

Section: Disordersmentioning

confidence: 99%

Pharmacokinetics of Anthraquinones from Medicinal Plants

Wang

et al. 2021

Front. Pharmacol.

View full text Add to dashboard Cite

Anthraquinones are bioactive natural products, some of which are active components in medicinal medicines, especially Chinese medicines. These compounds exert actions including purgation, anti-inflammation, immunoregulation, antihyperlipidemia, and anticancer effects. This study aimed to review the pharmacokinetics (PKs) of anthraquinones, which are importantly associated with their pharmacological and toxicological effects. Anthraquinones are absorbed mainly in intestines. The absorption rates of free anthraquinones are faster than those of their conjugated glycosides because of the higher liposolubility. A fluctuation in blood concentration and two absorption peaks of anthraquinones may result from the hepato-intestinal circulation, reabsorption, and transformation. Anthraquinones are widely distributed throughout the body, mainly in blood-flow rich organs and tissues, such as blood, intestines, stomach, liver, lung, kidney, and fat. The metabolic pathways of anthraquinones are hydrolysis, glycuronidation, sulfation, methylation/demethylation, hydroxylation/dehydroxylation, oxidation/reduction (hydrogenation), acetylation and esterification by intestinal flora and liver metabolic enzymes, among which hydrolysis, glycuronidation and sulfation are dominant. Of note, anthraquinones can be transformed into each other. The main excretion routes for anthraquinones are the kidney, recta, and gallbladder. Conclusion: Some anthraquinones and their glycosides, such as aloe-emodin, chrysophanol, emodin, physcion, rhein and sennosides, have attracted the most PK research interest due to their more biological activities and/or detectability. Anthraquinones are mainly absorbed in the intestines and are mostly distributed in blood flow-rich tissues and organs. Transformation into another anthraquinone may increase the blood concentration of the latter, leading to an increased pharmacological and/or toxicological effect. Drug-drug interactions influencing PK may provide insights into drug compatibility theory to enhance or reduce pharmacological/toxicological effects in Chinese medicine formulae and deserve deep investigation.

show abstract

Enhanced absorption and inhibited metabolism of emodin by 2, 3, 5, 4′-tetrahydroxystilbene-2-O-β-D-glucopyranoside: Possible mechanisms for Polygoni Multiflori Radix-induced liver injury

Cited by 13 publications

References 19 publications

Overview of Pharmacokinetics and Liver Toxicities of Radix Polygoni Multiflori

Overview of Pharmacokinetics and Liver Toxicities of Radix Polygoni Multiflori

Interactions Between Emodin and Efflux Transporters on Rat Enterocyte by a Validated Ussing Chamber Technique

Pharmacokinetics of Anthraquinones from Medicinal Plants

Contact Info

Product

Resources

About