AUTHOR=Langeder Julia , Koch Mirijam , Schmietendorf Hannes , Tahir Ammar , Grienke Ulrike , Rollinger Judith M. , Schmidtke Michaela 

TITLE=Correlation of bioactive marker compounds of an orally applied Morus alba root bark extract with toxicity and efficacy in BALB/c mice

JOURNAL=Frontiers in Pharmacology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1193118

DOI=10.3389/fphar.2023.1193118

ISSN=1663-9812

ABSTRACT=<p><bold>Introduction:</bold> In traditional Chinese medicine, the root bark of <italic>Morus alba</italic> L. is used to treat respiratory infections. Recently, anti-inflammatory and multiple anti-infective activities (against influenza viruses, corona virus 2, <italic>S. aureus</italic>, and <italic>S. pneumoniae</italic>) were shown <italic>in vitro</italic> for a standardized root bark extract from <italic>M</italic>. <italic>alba</italic> (MA60). Sanggenons C and D were identified as major active constituents of MA60. The aim of the present preclinical study was to evaluate, whether these findings are transferable to an <italic>in vivo</italic> setting.</p><p><bold>Methods:</bold> MA60 was orally administered to female BALB/c mice to determine 1) the maximum tolerated dose (MTD) in an acute toxicity study and 2) its anti-influenza virus and anti-inflammatory effects in an efficacy study. A further aim was to evaluate whether there is a correlation between the obtained results and the amount of sanggenons C and D in serum and tissues. For the quantitation of the marker compounds sanggenons C and D in serum and tissue samples an UPLC-ESI-MS method was developed and validated.</p><p><bold>Results:</bold> In our study setting, the MTD was reached at 100 mg/kg. In the efficacy study, the treatment effects were moderate. Dose-dependent quantities of sanggenon C in serum and sanggenon D in liver samples were detected. Only very low concentrations of sanggenons C and D were determined in lung samples and none of these compounds was found in spleen samples. There was no compound accumulation when MA60 was administered repeatedly.</p><p><bold>Discussion:</bold> The herein determined low serum concentration after oral application once daily encourages the use of an alternative application route like intravenous, inhalation or intranasal administration and/or multiple dosing in further trials. The established method for the quantitation of the marker sanggenon compounds in tissue samples serves as a basis to determine pharmacokinetic parameters such as their bioavailability in future studies.</p>