IN VIVO ACUTE TOXICITY OF DETOXIFIED FUZI (LATERAL ROOT OF ACONITUM CARMICHAELI) AFTER A TRADITIONAL DETOXIFICATION PROCESS

Publication type:

Journal article

Metadata:

Autoren

Wan Sun
Bo Yan
Rongrong Wang
Fucun Liu
Zhengyan Hu
Li Zhou
Li Yan
Kang Zhou
Jiawei Huang
Peijian Tong
Letian Shan
Thomas Efferth

Autoren-URL

https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000443352500002&DestLinkType=FullRecord&DestApp=WOS_CPL

DOI

10.17179/excli2018-1607

Externe Identifier

Clarivate Analytics Document Solution ID: GS2DY
PubMed Identifier: 30564068

ISSN

1611-2156

Zeitschrift

EXCLI JOURNAL

Schlüsselwörter

acute toxicity
Aconitum carmichaeli
aconitine
zebrafish
UPLC-MS

Paginierung

889 - 899

Datum der Veröffentlichung

2018

Status

Published

Titel

IN VIVO ACUTE TOXICITY OF DETOXIFIED FUZI (LATERAL ROOT OF ACONITUM CARMICHAELI) AFTER A TRADITIONAL DETOXIFICATION PROCESS

Sub types

Article

Ausgabe der Zeitschrift

Data source: Web of Science (Lite)

Other metadata sources:

Abstract

Many herbs of traditional Chinese medicine (TCM) possess not only therapeutic efficacy, but also toxicity towards normal tissues. The herbal toxicities occasionally cause serious adverse events or even fatal poisoning due to the erroneous use of TCM herbs. Fuzi (lateral root of Aconitum carmichaeli) is such an herb with its toxic ingredient, aconites. Aconitine, mesaconitine, and hypaconitine are the main toxic components of Fuzi, which are hydrolyzed into non-toxic derivatives by water decoction. Therefore, long-time decoction was commonly applied as a traditional way to detoxify Fuzi before use. Nevertheless, recent clinical trials presorted on adverse events induced by long-time decocted Fuzi, putting some doubt on the safety of Fuzi after the traditional detoxification procedure. To thoroughly determine whether or not long-time decocted Fuzi was safe, we conducted in vivo acute toxicity assays using both rodent and zebrafish models and performed chemoprofile analyses using HPLC and UPLC-MS. The HPLC analysis showed that toxic aconitine components were hydrolyzed into benzoyl derivatives with increasing time of decoction. These aconitines were undetected by HPLC in Fuzi after 2 h-decoction (FZ-120), indicating seemingly non-toxicity of FZ-120. Unlike the non-decocted Fuzi (FZ-0) and 60 min-decocted Fuzi (FZ-60) with lethal toxicity, FZ-120 at 130 g/kg did not cause any deaths or side effects in mice regarding body weight and biochemical parameters. This seems to confirm safety of Fuzi after long-time decoction. However, histopathological observations revealed an abnormal liver phenotype and a significant decrease of the liver index following FZ-120 treatment, indicating a potential hepatoxicity of FZ-120. By using a zebrafish model, we observed that FZ-120 at a dose range from 288 to 896 μg/ml caused considerable adverse events including arrhythmia, liver degeneration, yolk sac absorption delay, length decrease, and swim bladder loss, which clearly speak for acute toxicity on cardiovascular, digestive, development, and respiratory systems. The dose range of FZ-120 was lower than that used for clinical application in human beings. Moreover, UPLC-MS revealed that FZ-120 still contained toxic aconitines that were not detectable by HPLC, which might explain its acute toxicity in zebrafish. We concluded that Fuzi is not sufficiently safe even after long-time decoction. The zebrafish model combined with UPLC-MS assay may represent an appropriate test system to unravel aconitine-related acute toxicity.

Addresses

The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, China.

Autoren

Wan Sun
Bo Yan
Rongrong Wang
Fucun Liu
Zhengyan Hu
Li Zhou
Li Yan
Kang Zhou
Jiawei Huang
Peijian Tong
Letian Shan
Thomas Efferth

DOI

10.17179/excli2018-1607

eISSN

1611-2156

Externe Identifier

PubMed Identifier: 30564068
PubMed Central ID: PMC6295630

Open access

true

ISSN

1611-2156

Zeitschrift

EXCLI journal

Sprache

eng

Medium

Electronic-eCollection

Online publication date

2018

Open access status

Open Access

Paginierung

889 - 899

Datum der Veröffentlichung

2018

Status

Published

Publisher licence

CC BY

Datum der Datenerfassung

2018

Titel

In vivo acute toxicity of detoxified Fuzi (lateral root of Aconitum carmichaeli) after a traditional detoxification process.

Sub types

research-article
Journal Article

Ausgabe der Zeitschrift

Files

https://europepmc.org/articles/PMC6295630?pdf=render

Data source: Europe PubMed Central

Abstract

Many herbs of traditional Chinese medicine (TCM) possess not only therapeutic efficacy, but also toxicity towards normal tissues. The herbal toxicities occasionally cause serious adverse events or even fatal poisoning due to the erroneous use of TCM herbs. Fuzi (lateral root of Aconitum carmichaeli) is such an herb with its toxic ingredient, aconites. Aconitine, mesaconitine, and hypaconitine are the main toxic components of Fuzi, which are hydrolyzed into non-toxic derivatives by water decoction. Therefore, long-time decoction was commonly applied as a traditional way to detoxify Fuzi before use. Nevertheless, recent clinical trials presorted on adverse events induced by long-time decocted Fuzi, putting some doubt on the safety of Fuzi after the traditional detoxification procedure. To thoroughly determine whether or not long-time decocted Fuzi was safe, we conducted in vivo acute toxicity assays using both rodent and zebrafish models and performed chemoprofile analyses using HPLC and UPLC-MS. The HPLC analysis showed that toxic aconitine components were hydrolyzed into benzoyl derivatives with increasing time of decoction. These aconitines were undetected by HPLC in Fuzi after 2 h-decoction (FZ-120), indicating seemingly non-toxicity of FZ-120. Unlike the non-decocted Fuzi (FZ-0) and 60 min-decocted Fuzi (FZ-60) with lethal toxicity, FZ-120 at 130 g/kg did not cause any deaths or side effects in mice regarding body weight and biochemical parameters. This seems to confirm safety of Fuzi after long-time decoction. However, histopathological observations revealed an abnormal liver phenotype and a significant decrease of the liver index following FZ-120 treatment, indicating a potential hepatoxicity of FZ-120. By using a zebrafish model, we observed that FZ-120 at a dose range from 288 to 896 μg/ml caused considerable adverse events including arrhythmia, liver degeneration, yolk sac absorption delay, length decrease, and swim bladder loss, which clearly speak for acute toxicity on cardiovascular, digestive, development, and respiratory systems. The dose range of FZ-120 was lower than that used for clinical application in human beings. Moreover, UPLC-MS revealed that FZ-120 still contained toxic aconitines that were not detectable by HPLC, which might explain its acute toxicity in zebrafish. We concluded that Fuzi is not sufficiently safe even after long-time decoction. The zebrafish model combined with UPLC-MS assay may represent an appropriate test system to unravel aconitine-related acute toxicity.

Date of acceptance

2018

Autoren

Wan Sun
Bo Yan
Rongrong Wang
Fucun Liu
Zhengyan Hu
Li Zhou
Li Yan
Kang Zhou
Jiawei Huang
Peijian Tong
Letian Shan
Thomas Efferth

Autoren-URL

https://www.ncbi.nlm.nih.gov/pubmed/30564068

DOI

10.17179/excli2018-1607

Externe Identifier

PubMed Central ID: PMC6295630

ISSN

1611-2156

Zeitschrift

EXCLI J

Schlüsselwörter

Aconitum carmichaeli
UPLC-MS
aconitine
acute toxicity
zebrafish

Sprache

eng

Country

Germany

Paginierung

889 - 899

PII

2018-1607

Datum der Veröffentlichung

2018

Status

Published online

Titel

In vivo acute toxicity of detoxified Fuzi (lateral root of Aconitum carmichaeli) after a traditional detoxification process.

Sub types

Journal Article

Ausgabe der Zeitschrift

Data source: PubMed

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Property of

Pharmazeutische Biologie

IN VIVO ACUTE TOXICITY OF DETOXIFIED FUZI (LATERAL ROOT OF ACONITUM CARMICHAELI) AFTER A TRADITIONAL DETOXIFICATION PROCESS

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