Abstract

Acer tegmentosum Maxim., commonly known as Manchurian stripe maple, is a deciduous tree belonging to the family of Aceraceae and has been traditionally used in folk medicine for its remedial effects in liver diseases and traumatic bleedings. With a growing body of experimental evidence for its pharmacological efficacies, such as neuroprotective, hepatoprotective, antioxidant, and anti-inflammatory activities, A. tegmentosum has gradually gained popularity as a health supplement and functional food. However, the large part of essential toxicity information still remained lacking despite the possibility of mutagenic potentials as previously suggested, posing safety concerns for human consumption. In this study, we evaluated 90-day repeated oral toxicity of A. tegmentosum Maxim. water extract (ATWE) in SD rats with acute toxicity assessment in beagle dogs, and reevaluated genotoxicity using a combination of in vitro and in vivo assays. During the oral study period, ATWE did not cause toxicity-related clinical signs and mortality in rodents without adverse effects observed in the analysis of hematology, serum biochemistry, and histopathology, establishing >5,000 mg/kg BW as the NOAEL. In addition, doses up to 5,000 mg/kg BW did not cause acute toxicity in beagle dogs. When assessed for genotoxicity using bacterial reverse mutation, chromosome aberration, and micronucleus formation, ATWE showed lack of mutagenicity and clastogenicity. These results demonstrated that AWTE was safe in the present preclinical study for systemic toxicity and genotoxicity at the tested doses, providing a guideline for safe use in humans.

Highlights

  • The family of Aceraceae, known as the maple family, is a group of deciduous trees and shrubs which contains 156 species (Cambelbeke, 2020)

  • Salidroside is a representative pharmacological effector in A. tegmentosum, so we selected it as the reference compound and quantified to confirm the validity of A. tegmentosum Maxim. water extract (ATWE) as a test substance for the toxicity study

  • The levels of salidroside measured in ATWE were 74.3 ± 0.8 mg/g, indicating that the test substance contained sufficient quantity which showed pharmacological effectiveness in other studies (Hwang et al, 2013; Nugroho et al, 2015; Lee et al, 2017a; Park et al, 2019)

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Summary

Introduction

The family of Aceraceae, known as the maple family, is a group of deciduous trees and shrubs which contains 156 species (Cambelbeke, 2020). Is commonly known as Manchurian stripe maple, and extracts of its parts, including the boughs and twigs, have been a popular ingredient in traditional medicine based on its empirical effects to treat various diseases such as liver diseases and traumatic bleeding. Recent studies reported that extracts from A. tegmentosum possessed various therapeutic effects in in vitro and in vivo model systems, including hepatoprotection (Park et al, 2019), alleviation of alcohol-induced liver injury and steatosis (Lee Y. et al, 2017), antioxidant and anti-inflammation (Kim et al, 2012), suppression of atopic dermatitis Fraxin Scopoletin (-)-Catechin (-)-Epicatechin (-)-Epicatechin gallate (-)-Epicatechin-3-O-gallate (+)-Catechin (+)-Catechin-3-O-(3,4-dihydroxybenzoyl) 3,7,3′,4′-Tetramethyl-quercetin 5,3′-Dihydroxy-3,7,4′-trimethoxy flavone 6-Carboxy-(-)-catechin methyl ester 6-Hydroxy-quercetin-3-O-galactose Avicularin Dihydromyricetin Erigeside B Feniculin Gallocatechin Hyperin Kaempferol-3-rhamnoside Morin-3-O-α-L-lyxoside Myricitrin Quercetin Quercetin 3-O-β-glucopyranoside Quercetin-3-O-[β-D-xylopyranosyl-(1→2)-β-glucopyranoside] Quercetin-3-O-β-arabinopyranoside Quercitrin.

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