Abstract
Although Polygoni Multiflori Radix (PMR) has been widely used as a tonic and an anti-aging
remedy for centuries, the extensively reported hepatotoxicity and potential kidney
toxicity hindered its safe use in clinical practice. To better understand its toxicokinetics,
the current study was proposed, aiming to evaluate the biodistributions of the major
PMR components including 2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucopyranoside (TSG), emodin, emodin-8-O-β-D-glucopyranoside (EMG) and physcion as well as their corresponding glucuronides
following bolus and multiple oral administrations of PMR to rats. Male Sprague-Dawley
rats received a bolus dose or 21 days of oral administrations of PMR concentrated
granules at 4.12 g/kg (equivalent to 20.6 g/kg raw material). Fifteen minutes after
bolus dose or the last dose on day 21, rats were sacrificed and the blood, liver,
and kidney were collected for the concentration determination of both parent form
and glucuronides of TSG, emodin, EMG, and physcion by HPLC-MS/MS. Among all the
tested analytes, TSG, EMG, EMG glucuronides in liver and TSG, EMG, as well as all
the glucuronides of these analytes in the kidney demonstrated the most significant
accumulation after multiple doses. Moreover, the levels of the parent analytes were
all significantly higher in liver and kidney in comparison to their plasma levels.
Strong tissue binding of all four analytes and accumulation of TSG, EMG, and EMG glucuronides
in the liver and TSG, EMG, as well as the glucuronides of all four analytes in the
kidney after multiple dosing of PMR were considered to be associated with its toxicity.
Key words
Polygoni Multiflori Radix -
Polygonum multiflorum Thunb. - 2,3,5,4′-tetrahydroxystilbene-2-
O-
β-D-glucopyranoside - emodin - emodin-8-
O-
β-D-glucopyranoside - physcion - liver and kidney distribution
