Pharmacokinetics, Tissue Distribution, and Excretion Characteristics of a Radix Polygoni Multiflori Extract in Rats

Abstract

Although progress has been achieved in the pharmacological activity and toxicity of Radix Polygoni Multiflori (RPM), the chemical basis of its toxicity is still unclear. Here, we performed a multicompound pharmacokinetic analysis and investigated the tissue distribution and excretion characteristics of RPM components after oral administration in rats. The findings demonstrated that the active ingredients of the RPM extract were quickly absorbed after oral administration, with high exposure levels of emodin, 2,3,5,4′-teterahydroxystilbene-2-O-β-D-glucoside (TSG), citreorosein, torachrysone-8-O-glucoside (TG), emodin-8-O-β-D-glucoside (EG), and physcion-8-O-β-D-glucoside (PG). The tissue distributions of emodin, TSG, TG, EG, and PG were high in the liver and kidney. These components were the key contributors to the effectiveness and toxicity of RPM on the liver and kidney. Most of the active ingredients were mainly excreted through feces and bile, while a few were converted into other products in the body and excreted through urine and feces.

Idiosyncratic liver injury induced by bolus combination treatment with emodin and 2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucopyranoside in rats

“…Since trans -TSG was reported to be the dominant form in the PMR due to its higher stability than the cis -form ( Gao et al, 2016a ) and showed no hepatotoxicity in the LPS-mediated inflammatory stress model rats ( Meng et al, 2017 ; Zhang et al, 2020 ), cis or trans -TSG may not be the major reason behind the PMR-induced idiosyncratic liver injury. In addition, as demonstrated in previous studies ( Li et al, 2020 ; Li et al, 2021 ), the systemic or hepatic exposure of EMG was much lower than that of emodin despite its higher content (0.029–0.365% w/w) in PMR than that of emodin (0.0064–0.082% w/w) ( Zhang et al, 2018 ; Li et al, 2021 ; Cheng et al, 2022 ) and EMG could be hydrolysed to emodin via intestinal microflora ( Ullah et al, 2018 ), suggesting the higher potency of emodin than EMG in PMR-induced liver injury. Therefore, among the above-mentioned potential hepatotoxic components, emodin is considered to be the major component contributing to PMR-induced idiosyncratic liver injury.…”

Gender-Related Differences in Tissue Distribution, Excretion, and Metabolism Studies of Panaxadiol in Rats and Anti-inflammatory Study

“…By measuring the drug excretion rate, we can infer the means of drug elimination from the body. Therefore, the study of drug excretion is of great significance for drug design and clinical application . In the excretion study, the cumulative amounts and recovery cumulative excess after single intragastric administration of PD in rats are shown in Figure .…”

“…Therefore, the study of drug excretion is of great significance for drug design and clinical application. 28 In the excretion study, the cumulative amounts and recovery cumulative excess after single intragastric administration of PD in rats are shown in Figure 3. The peak of PD excretion in rats occurred 12−24 h after administration and then gradually decreased.…”

Measurement of Pharmacokinetics and Tissue Distribution of Four Compounds from Nauclea officinalis in Rat Plasma and Tissues through HPLC-MS/MS

“…The peak concentration of chlorogenic acid in most tissues is much lower than in plasma and may be related to the absorption of the compound in the tissue. Drugs enter tissues that receive high blood flow first, followed by those that receive low blood flow [ 29 ]. Our study demonstrated that the four compounds are mainly distributed in organs with relatively large blood flows, such as the liver and kidneys.…”