FOLLOWUS
1.College of Pharmacy, Zhejiang Chinese Medical University, Hangzhou (310053), China
2.Department of Plastic and Aesthetic Center, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou (310003), China
3.School of Biological and Chemical Engineering, Zhejiang University of Science and Technology, Hangzhou (310058), China
4.Center for Disease Control and Prevention of Zhejiang Province, Hangzhou (310051), China
5.Zhejiang Institute of Orthopedics and Traumatology, the First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou (310006), China
6.Department of Pediatrics, the First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou (310006), China
Dr. LI Lan, E-mail: lilan99@zcmu.edu.cn
Published:2023-04,
Published Online:27 January 2022,
Accepted:25 August 2020
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WANG Rong-rong, LI Ting, ZHANG Lei, et al. Acute Developmental Toxicity of
WANG Rong-rong, LI Ting, ZHANG Lei, et al. Acute Developmental Toxicity of
Objective:
2
To evaluate toxicity of raw extract of
Panax notoginseng
(rPN) and decocted extract of PN (dPN) by a toxicological assay using zebrafish larvae
and explore the mechanism by RNA sequencing assay.
Methods:
2
Zebrafish larvae was used to evaluate acute toxicity of PN in two forms: rPN and dPN. Three doses (0.5
1.5
and 5.0 μg/mL) of dPN were used to treat zebrafishes for evaluating the developmental toxicity. Behavior abnormalities
body weight
body length and number of vertebral roots were used as specific phenotypic endpoints. RNA sequencing (RNA-seq) assay was applied to clarify the mechanism of acute toxicity
followed by real time PCR (qPCR) for verification. High performance liquid chromatography analysis was performed to determine the chemoprofile of this herb.
Results:
2
The acute toxicity result showed that rPN exerted higher acute toxicity than dPN in inducing death of larval zebrafishes (
P
<
0.01). After daily oral intake for 21 days
dPN at doses of 0.5
1.5 and 5.0 μg/mL decreased the body weight
body length
and vertebral number of larval zebrafishes
indicating developmental toxicity of dPN. No other adverse outcome was observed during the experimental period. RNA-seq data revealed 38 genes differentially expressed in dPN-treated zebrafishes
of which carboxypeptidase A1 (cpa1) and opioid growth factor receptor-like 2 (ogfrl2) were identified as functional genes in regulating body development of zebrafishes. qPCR data showed that dPN significantly down-regulated the mRNA expressions of cpa1 and ogfrl2 (both
P
<
0.01)
verifying cpa1 and ogfrl2 as target genes for dPN.
Conclusion:
2
This report uncovers the developmental toxicity of dPN
suggesting potential risk of its clinical application in children.
Panax notoginsengzebrafish larvaedevelopmental toxicityRNA sequencing
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