Aqueous extract of Forsythia viridissima fruits: Acute oral toxicity and genotoxicity studies
Authors: No Soo Kim
Jin-Mu Yi
Ok-Sun Bang
Chan-Sung Park
Su-Hwan Kim
Sarah Shin
Journal: Journal of Ethnopharmacology (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Acute oral toxicity; Ames; Chromosomal aberration; Forsythia viridissima; Micronucleus test.
Affiliations: Clinical Medicine Division, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon, 34054, Republic of Korea. Electronic address: ., Nonclinical Research Institute, Biotoxtech Co., Ltd., 53 Yeongudanji-ro, Cheongwon-gu, Cheongju-si, Cheungcheongbuk-do, 28115, Republic of Korea. Electronic address: .

Abstract:  Ethnopharmacological relevance: Forsythia viridissima fruit, one of Forsythiae Fructus (FF) is widely used in traditional medicine to treat diverse diseases-related clinical symptoms, including fever, pain, vomiting, nausea, and abscess. However, the safety of FF has not been fully assessed. Aim of the study: In this study, we evaluated the acute oral toxicity and genotoxic potential of an aqueous extract of Forsythia viridissima fruits (EFVF). Materials and methods: For an acute oral toxicity test, male and female SD rats (n = 5) orally received a single dose of 5000 mg/kg EFVF. The genotoxic potential of EFVF was evaluated with a battery of tests, including an in vitro bacterial reverse mutation test using five mutant strains of Salmonella typhimurium (TA100, TA1535, TA98, TA1537) and Escherichia coli (WP2 uvrA), an in vitro chromosomal aberration test using Chinese hamster lung (CHL/IU) cells, and an in vivo micronucleus test using bone marrow cells in male ICR mice that were orally administered EFVF. All tests were completed in compliance with Organization for Economic Cooperation and Development guidelines and/or regional regulatory standards for toxicity tests. Results: In the acute oral toxicity test, the animals did not show any significant mortality and body weight changes for 14 days following a single dose of EFVF at 5000 mg/kg. There was no evidence of genotoxicity of EFVF based on the results of the in vitro bacterial reverse mutation test (up to 5000 μg/plate), the in vivo micronucleus test (up to 5000 mg/kg), and the in vitro chromosomal aberration test (1100-2500 μg/mL). Conclusions: We found that EFVF is safe with regard to acute toxicity in rats as well as genotoxicity such as mutagenesis or clastogenesis under the present experimental conditions. These results might support the safety of EFVF as a potential therapeutic material for the traditional use or pharmaceutical development. 

Retracted: No

PubPeer comments:
 I have two questions about a reference to Qiao et al (2018):  Our results demonstrated that the quality of EFVF was consistent with that of our previous extract (Yi et al., 2019) and its constituents were stable for at least 2 weeks. However, it is suggested that new and potential approaches, such as presoaking in various organic solvents and maceration in extraction solvent, are required to extract of F. viridissima fruits for further systemic chemical study or bioassay-guided isolation, as shown in previous study (Qiao et al., 2018). - X.L. Qiao, C. Zhao, Q.J. Shao, M. Hassan **Structural Characterization of Corn Stover Lignin after Hydrogen Peroxide Presoaking Prior to Ammonia Fiber Expansion Pretreatment** Energy Fuels, 32r (2018), pp. 6022-6030, 10.1021 acs.energyfuels.8b00951 First, what does pre-treated corn stover have to do with extracting chemicals from *F. viridissima* fruits? Second, were the irrelevant reference and the sentence containing it added at the proof-reading correction stage, **after** the reviewers had accepted the manuscript? They do not seem to be present in an [archived copy of the pre-proof version] , where paragraph 3.1 finishes after the sentence  Our results demonstrated that the quality of EFVF was consistent with that of our previous extract (Yi et al., 2019) and its constituents were stable for at least 2 weeks. ,