Evaluation of Long-Time Decoction-DetoxicatedHei-Shun-Pian(ProcessedAconitum carmichaeliDebeaux Lateral Root With Peel) for Its Acute Toxicity and Therapeutic Effect on Mono-Iodoacetate Induced Osteoarthritis

Publication type:

Journal article

Metadata:

Autoren

Lei Zhang
Ting Li
Rongrong Wang
Jiaan Xu
Li Zhou
Li Yan
Zhengyan Hu
Hongwen Li
Fucun Liu
Wenxi Du
Peijian Tong
Huiling Wu
Shanxing Zhang
Letian Shan
Thomas Efferth

Autoren-URL

https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000560782000001&DestLinkType=FullRecord&DestApp=WOS_CPL

DOI

10.3389/fphar.2020.01053

Externe Identifier

Clarivate Analytics Document Solution ID: NB8RJ
PubMed Identifier: 32848727

ISSN

1663-9812

Zeitschrift

FRONTIERS IN PHARMACOLOGY

Schlüsselwörter

Aconitum carmichaeli
traditional Chinese medicine
osteoarthritis
monosodium iodoacetate
pain behaviour
analgesia

Artikelnummer

ARTN 1053

Datum der Veröffentlichung

2020

Status

Published

Titel

Evaluation of Long-Time Decoction-DetoxicatedHei-Shun-Pian(ProcessedAconitum carmichaeliDebeaux Lateral Root With Peel) for Its Acute Toxicity and Therapeutic Effect on Mono-Iodoacetate Induced Osteoarthritis

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Article

Ausgabe der Zeitschrift

Data source: Web of Science (Lite)

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Autoren

Lei Zhang
Ting Li
Rongrong Wang
Jiaan Xu
Li Zhou
Li Yan
Zhengyan Hu
Hongwen Li
Fucun Liu
Wenxi Du
Peijian Tong
Huiling Wu
Shanxing Zhang
Letian Shan
Thomas Efferth

DOI

10.3389/fphar.2020.01053

eISSN

1663-9812

Zeitschrift

Frontiers in Pharmacology

Online publication date

2020

Status

Published online

Herausgeber

Frontiers Media SA

Herausgeber URL

http://dx.doi.org/10.3389/fphar.2020.01053

Datum der Datenerfassung

2020

Titel

Evaluation of Long-Time Decoction-Detoxicated Hei-Shun-Pian (Processed Aconitum carmichaeli Debeaux Lateral Root With Peel) for Its Acute Toxicity and Therapeutic Effect on Mono-Iodoacetate Induced Osteoarthritis

Ausgabe der Zeitschrift

Data source: Crossref

Abstract

<h4>Background</h4>As a degenerative joint disease with severe cartilage destruction and pain, osteoarthritis (OA) has no satisfactory therapy to date. In traditional Chinese medicine (TCM), Aconitum carmichaeli Debeaux derived Hei-shun-pian (Hsp) has been developed for joint pain treatment. However, it causes adverse events in OA patients. Long-time decoction has been traditionally applied to reduce the aconite toxicity of Hsp and other aconite herbs, but its detoxifying effect is uncertain.<h4>Methods</h4>Hsp was extracted with dilute decoction times (30, 60, and 120 min) and evaluated by toxicological, chemical, pharmacological assays. Acute toxicity assay and chemical analysis were employed to determine the toxicity and chemoprofile of Hsp extracts, respectively. Since the detoxified Hsp (dHsp) was defined, its therapeutic effect was evaluated by using an OA rat model induced by monosodium iodoacetate. dHsp at 14 g/kg was orally administered for 28 days, and the pain assessments (mechanical withdrawal threshold and thermal withdrawal latency) and histopathological analyses (HE and safranin-O staining) were performed. Real-time PCR (qPCR) was applied to determine the molecular actions of dHsp on cartilage tissue and on chondrocytes. MTT assay was conducted to evaluate the effect of dHsp on the cell viability of chondrocytes. The cellular and molecular assays were also conducted to analyze the functions of chemical components in dHsp.<h4>Results</h4>The chemoprofile result showed that the contents of toxic alkaloids (aconitine, mesaconitine, and hypaconitine) were decreased but that of non-toxic alkaloids (benzoylaconitine, benzoylmesaconitine, and benzoylhypaconitine) were increased with increasing decoction time. Acute toxicity assay showed that only Hsp extract with 120 min decoction was non-toxic within the therapeutic dose range. Thus, it was defined as dHsp for further experiment. In OA experiment, dHsp significantly attenuated joint pain and prevented articular degeneration from MIA attack. qPCR data showed that dHsp restored the abnormal expressions of Col10, Mmp2, Sox5, Adamts4/5/9, and up-regulated Col2 expression in rat cartilage. In vitro, dHsp-containing serum significantly proliferated rat chondrocytes and regulated the gene expressions of Col2, Mmp1, Adamts9, and Aggrecan in a similar way as the in vivo data. Moreover, aconitine, mesaconitine, and hypaconitine exerted cytotoxic effects on chondrocytes, while benzoylaconitine and benzoylhypaconitine except benzoylmesaconitine exhibited similar molecular actions to dHsp, indicating contributions of benzoylaconitine and benzoylhypaconitine to dHsp.<h4>Conclusions</h4>This study defined dHsp and demonstrated dHsp as a potential analgesic and disease modifying agent against OA with molecular actions on the suppression of chondrocyte hypertrophy and extracellular matrix degradation, providing a promising TCM candidate for OA therapy.

Addresses

School of Biological and Chemical Engineering, Zhejiang University of Science and Technology, Hangzhou, China.

Autoren

Lei Zhang
Ting Li
Rongrong Wang
Jiaan Xu
Li Zhou
Li Yan
Zhengyan Hu
Hongwen Li
Fucun Liu
Wenxi Du
Peijian Tong
Huiling Wu
Shanxing Zhang
Letian Shan
Thomas Efferth

DOI

10.3389/fphar.2020.01053

eISSN

1663-9812

Externe Identifier

PubMed Identifier: 32848727
PubMed Central ID: PMC7396609

Open access

true

ISSN

1663-9812

Zeitschrift

Frontiers in pharmacology

Sprache

eng

Medium

Electronic-eCollection

Online publication date

2020

Open access status

Open Access

Paginierung

1053

Datum der Veröffentlichung

2020

Status

Published

Publisher licence

CC BY

Datum der Datenerfassung

2020

Titel

Evaluation of Long-Time Decoction-Detoxicated Hei-Shun-Pian (Processed Aconitum carmichaeli Debeaux Lateral Root With Peel) for Its Acute Toxicity and Therapeutic Effect on Mono-Iodoacetate Induced Osteoarthritis.

Sub types

research-article
Journal Article

Ausgabe der Zeitschrift

Files

https://www.frontiersin.org/articles/10.3389/fphar.2020.01053/pdf https://europepmc.org/articles/PMC7396609?pdf=render

Data source: Europe PubMed Central

Abstract

BACKGROUND: As a degenerative joint disease with severe cartilage destruction and pain, osteoarthritis (OA) has no satisfactory therapy to date. In traditional Chinese medicine (TCM), Aconitum carmichaeli Debeaux derived Hei-shun-pian (Hsp) has been developed for joint pain treatment. However, it causes adverse events in OA patients. Long-time decoction has been traditionally applied to reduce the aconite toxicity of Hsp and other aconite herbs, but its detoxifying effect is uncertain. METHODS: Hsp was extracted with dilute decoction times (30, 60, and 120 min) and evaluated by toxicological, chemical, pharmacological assays. Acute toxicity assay and chemical analysis were employed to determine the toxicity and chemoprofile of Hsp extracts, respectively. Since the detoxified Hsp (dHsp) was defined, its therapeutic effect was evaluated by using an OA rat model induced by monosodium iodoacetate. dHsp at 14 g/kg was orally administered for 28 days, and the pain assessments (mechanical withdrawal threshold and thermal withdrawal latency) and histopathological analyses (HE and safranin-O staining) were performed. Real-time PCR (qPCR) was applied to determine the molecular actions of dHsp on cartilage tissue and on chondrocytes. MTT assay was conducted to evaluate the effect of dHsp on the cell viability of chondrocytes. The cellular and molecular assays were also conducted to analyze the functions of chemical components in dHsp. RESULTS: The chemoprofile result showed that the contents of toxic alkaloids (aconitine, mesaconitine, and hypaconitine) were decreased but that of non-toxic alkaloids (benzoylaconitine, benzoylmesaconitine, and benzoylhypaconitine) were increased with increasing decoction time. Acute toxicity assay showed that only Hsp extract with 120 min decoction was non-toxic within the therapeutic dose range. Thus, it was defined as dHsp for further experiment. In OA experiment, dHsp significantly attenuated joint pain and prevented articular degeneration from MIA attack. qPCR data showed that dHsp restored the abnormal expressions of Col10, Mmp2, Sox5, Adamts4/5/9, and up-regulated Col2 expression in rat cartilage. In vitro, dHsp-containing serum significantly proliferated rat chondrocytes and regulated the gene expressions of Col2, Mmp1, Adamts9, and Aggrecan in a similar way as the in vivo data. Moreover, aconitine, mesaconitine, and hypaconitine exerted cytotoxic effects on chondrocytes, while benzoylaconitine and benzoylhypaconitine except benzoylmesaconitine exhibited similar molecular actions to dHsp, indicating contributions of benzoylaconitine and benzoylhypaconitine to dHsp. CONCLUSIONS: This study defined dHsp and demonstrated dHsp as a potential analgesic and disease modifying agent against OA with molecular actions on the suppression of chondrocyte hypertrophy and extracellular matrix degradation, providing a promising TCM candidate for OA therapy.

Date of acceptance

2020

Autoren

Lei Zhang
Ting Li
Rongrong Wang
Jiaan Xu
Li Zhou
Li Yan
Zhengyan Hu
Hongwen Li
Fucun Liu
Wenxi Du
Peijian Tong
Huiling Wu
Shanxing Zhang
Letian Shan
Thomas Efferth

Autoren-URL

https://www.ncbi.nlm.nih.gov/pubmed/32848727

DOI

10.3389/fphar.2020.01053

Externe Identifier

PubMed Central ID: PMC7396609

ISSN

1663-9812

Zeitschrift

Front Pharmacol

Schlüsselwörter

Aconitum carmichaeli
analgesia
monosodium iodoacetate
osteoarthritis
pain behaviour
traditional Chinese medicine

Sprache

eng

Country

Switzerland

Paginierung

1053

Datum der Veröffentlichung

2020

Status

Published online

Titel

Sub types

Journal Article

Ausgabe der Zeitschrift

Data source: PubMed

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Pharmazeutische Biologie

Evaluation of Long-Time Decoction-DetoxicatedHei-Shun-Pian(ProcessedAconitum carmichaeliDebeaux Lateral Root With Peel) for Its Acute Toxicity and Therapeutic Effect on Mono-Iodoacetate Induced Osteoarthritis

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