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Evaluation of genetic toxicity, acute and sub-chronic oral toxicity and systemic safety of Agrimonia pilosa and Rhus gall 50% ethanolic extract mixture (APRG64) in vitro and in vivo (rodent and non-rodent animal models)

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Abstract

Agrimonia pilosa (AP) and Rhus gall (RG) are traditional medicinal plants. The bioflavonoid composition standardized by HPLC analysis was named APRG64. Despite many studies reported to beneficial bioactivities of AP and RG, very limited range of toxicity tests have documented. So, we did experiment diversely on the toxicity tests of the substance APRG64. Genotoxicity (mammalian chromosomal aberration test, micronoucleus test) against APRG64, acute and sub-chronic toxicity test from rodent/non-rodent, and systemic safety pharmacology test were conducted. As a result of the test, genotoxicity against APRG64 was not observed. The NOAEL of rodents was confirmed as 2000 mg/kg/day and non-rodents was confirmed as 500 mg/kg/day. In addition, systemic safety pharmacological toxicity (effects on respiratory system, central nervous system, cardiovascular system) following administration of APRG64 was not observed. Finally, we accomplished ten potential toxicity tests and evaluated extensive safety of APRG64. Consequently, APRG64 may be a promising material for nutraceuticals and natural medicines.

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Abbreviations

AG:

Apigenin-7-O-β-glucuronide

AP:

Agrimonia Pilosa

APRG64:

AP and RG of each 50% ethanolic extracts mixed 64

CHO-K1:

Chinese hamster ovary

EG:

Ethyl gallate

FOB:

The functional observational battery

GA:

Gallic acid

HPLC:

High performance liquid chromatography

ICR:

CrljOriCD1

KCL/CRO:

Korea Conformity Laboratories

MBP:

The mean blood pressure

MFDS:

The Ministry of Food and Drug Safety

MMC:

Mitomycin C

MNPCE:

Micronucleated polychromatic erythrocytes

NCE:

Normochromatic erythrocytes

PCE:

Polychromatic erythrocytes

PGG:

Penta-galloyl glucose

RG:

Rhus javanica gall

SOPs:

Standard operation procedures

SPF:

Specific pathogenic free

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Acknowledgements

This research was supported by the Ministry of Trade, Industry & Energy (MOTIE), Korea Institute for Advancement of Technology (KIAT) through the Global collaborate R&D program and the MSIT (Ministry of Science and ICT), Korea, under the ICT Consilience Creative program (IITP-2019-2015-0-00742) supervised by the IITP (Institute for Information and Communications Technology Planning and Evaluation).

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  1. Jong-Hun Park and Jong-Sung Ra made equal contributions to this work (co-first author).

Authors and Affiliations

  1. College of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University, 1, Kangwondaehak-gil, Chuncheon-si, Gangwon-do, 24341, Republic of Korea

    Jong-Hun Park, Ho-Hyun Kwak & Heung-Myong Woo

  2. Department of Oriental Medicine Biotechnology, Kyung Hee University, 1732, Deogyong-daero, Giheung-gu, Yongin-si, Gyeonggi-do, 17104, Republic of Korea

    Jong-Sung Ra, Jeong Eun Kwon, Yang-Mi Her, Tae Hwan Choe, Yoon-Seo Lee, Hee Ju Suh, Seung-Yeon Shin, Dae Won Park & Se Chan Kang

  3. Research Institute, Genencell. Co. Ltd, 120, Heungdeokjungang-ro, Giheung-gu, Yongin-si, Gyeonggi-do, 16950, Republic of Korea

    Hyelin Jeon

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  1. Jong-Hun Park
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Correspondence to Se Chan Kang.

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Park, JH., Ra, JS., Kwon, J.E. et al. Evaluation of genetic toxicity, acute and sub-chronic oral toxicity and systemic safety of Agrimonia pilosa and Rhus gall 50% ethanolic extract mixture (APRG64) in vitro and in vivo (rodent and non-rodent animal models). Toxicol Res. 36, 367–406 (2020). https://doi.org/10.1007/s43188-020-00042-5

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