Agkistrodon ameliorates pain response and prevents cartilage degradation in monosodium iodoacetate-induced osteoarthritic rats by inhibiting chondrocyte hypertrophy and apoptosis

Publication type:
Journal article
Metadata:
Autoren
  • Caiwei Wang
  • Li Yan
  • Bo Yan
  • Li Zhou
  • Wan Sun
  • Lingying Yu
  • Fucun Liu
  • Wenxi Du
  • Guangping Yu
  • Zhengyan Hu
  • Qiang Yuan
  • Luwei Xiao
  • Hongwen Li
  • Peijian Tong
  • Jida Zhang
  • Letian Shan
  • Thomas Efferth
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000455692600053&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1016/j.jep.2018.12.004
eISSN
1872-7573
Externe Identifier
  • Clarivate Analytics Document Solution ID: HH4KZ
  • PubMed Identifier: 30529425
ISSN
0378-8741
Zeitschrift
JOURNAL OF ETHNOPHARMACOLOGY
Schlüsselwörter
  • Agkistrodon acutus
  • Osteoarthritis
  • Pain
  • Chondrocyte
  • Hypertrophy
Paginierung
545 - 554
Datum der Veröffentlichung
2019
Status
Published
Titel
<i>Agkistrodon</i> ameliorates pain response and prevents cartilage degradation in monosodium iodoacetate-induced osteoarthritic rats by inhibiting chondrocyte hypertrophy and apoptosis
Sub types
  • Article
Ausgabe der Zeitschrift
231

Data source: Web of Science (Lite)

Other metadata sources:
Autoren
  • Caiwei Wang
  • Li Yan
  • Bo Yan
  • Li Zhou
  • Wan Sun
  • Lingying Yu
  • Fucun Liu
  • Wenxi Du
  • Guangping Yu
  • Zhengyan Hu
  • Qiang Yuan
  • Luwei Xiao
  • Hongwen Li
  • Peijian Tong
  • Jida Zhang
  • Letian Shan
  • Thomas Efferth
DOI
10.1016/j.jep.2018.12.004
ISSN
0378-8741
Zeitschrift
Journal of Ethnopharmacology
Sprache
en
Paginierung
545 - 554
Datum der Veröffentlichung
2019
Status
Published
Herausgeber
Elsevier BV
Herausgeber URL
http://dx.doi.org/10.1016/j.jep.2018.12.004
Datum der Datenerfassung
2020
Titel
Agkistrodon ameliorates pain response and prevents cartilage degradation in monosodium iodoacetate-induced osteoarthritic rats by inhibiting chondrocyte hypertrophy and apoptosis
Ausgabe der Zeitschrift
231

Data source: Crossref

Abstract
<h4>Ethnopharmacological relevance</h4>Osteoarthritis (OA), characterized by joint pain and cartilage degradation, is the most common form of joint disease worldwide but with no satisfactory therapy available. The ethanol extract of Agkistrodon acutus (EAA) has been widely used as a traditional Chinese medicine (TCM) for the treatment of arthralgia and inflammatory diseases, but there is no report regarding its efficacy on OA to date. Here, we determined the effects of EAA on the pain behavior and cartilage degradation in vivo and clarified its target genes and proteins associated with chondrocyte hypertrophy and apoptosis in vitro.<h4>Materials and methods</h4>In vivo OA model was established by intra-articular injection (1.5 mg) of monosodium iodoacetate (MIA) into rats and weekly treated by intra-articular administration of EAA at a dose range from 0.3 to 0.9 g/kg for four weeks. The pain behavior parameters, thermal withdrawal latency (TWL) and mechanical withdrawal threshold (MWT) were tested before and after the treatment. Then histopathologic, immunohistochemical and TUNEL analyses of the articular cartilage were conducted, followed by Mankin's scoring. In vitro, the effects of EAA on chondrocytes were evaluated via assays of cell viability, immunofluorescence, real time PCR, and Western blot. UPLC-MS was applied to determine the chemical composition of EAA.<h4>Results</h4>The animal data showed that EEA not only attenuated the pain hypersensitivity but also blocked the cartilage degeneration by improving chondrocyte survival and suppressing chondrocyte apoptosis at a dose-dependent manner in OA rats. Furthermore, EAA remarkably restored the abnormal expression of collagen type II (Col2) and matrix metalloproteinase-13 (MMP13) in cartilage of OA rats. The cellular data showed that EAA significantly increased the cell viability of chondrocytes against OA-like damage and restored the abnormal expressions of Col2 and MMP13 in damaged chondrocytes. The molecular data showed that EAA significantly restored the abnormal mRNA expressions of Col2, Col10, MMP2 and MMP13 as well as the abnormal protein expressions of MMP13, PARP (total and cleaved) in chondrocytes under pathological condition. UPLC-MS analysis showed the known main components of EAA, including amino acides (glycine, L-aspartic acid, L-glutamic acid, and L-hydroxyproline), nucleoside (uridine), purines (xanthine and hypoxanthine), and pyrimidine (uracil).<h4>Conclusions</h4>Our data demonstrate that EAA exerts antinociceptive and chondroprotective effects on OA through suppressing chondrocyte hypertrophy and apoptosis with restoration of the molecular expressions of anabolism and catabolism in chondrocytes. It provides a promising TCM candidate of novel agent for OA therapy.
Addresses
  • The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, China.
Autoren
  • Caiwei Wang
  • Li Yan
  • Bo Yan
  • Li Zhou
  • Wan Sun
  • Lingying Yu
  • Fucun Liu
  • Wenxi Du
  • Guangping Yu
  • Zhengyan Hu
  • Qiang Yuan
  • Luwei Xiao
  • Hongwen Li
  • Peijian Tong
  • Jida Zhang
  • Letian Shan
  • Thomas Efferth
DOI
10.1016/j.jep.2018.12.004
eISSN
1872-7573
Externe Identifier
  • PubMed Identifier: 30529425
Funding acknowledgements
  • Zhejiang Provincial Science and Technology Project of Traditional Chinese Medicine of China: 2013ZQ007
  • Zhejiang Provincial Natural Science Foundation of China: LY14H270009
  • Zhejiang Provincial Science and Technology Project of Traditional Chinese Medicine of China: 2016ZZ011
  • Ningbo Natural Science Foundation: 2014A610277
  • National Natural Science Foundation of China: 81774331
  • Major Science and Technology Special Project of Zhejiang Province: 2014C03035
  • Zhejiang Provincial Science and Technology Project of Traditional Chinese Medicine of China: 2016ZQ010
  • National Natural Science Foundation of China: 81673997
  • Zhejiang Provincial Major Science and Technology Project of Medical and Health of China: 201487674
  • Zhejiang Provincial Natural Science Foundation of China: LY16H060005
  • Zhejiang Provincial Natural Science Foundation of China: LY16H270011
  • Zhejiang Provincial Natural Science Foundation of China: LY17H270016
Open access
false
ISSN
0378-8741
Zeitschrift
Journal of ethnopharmacology
Schlüsselwörter
  • Cartilage, Articular
  • Chondrocytes
  • Animals
  • Rats, Sprague-Dawley
  • Agkistrodon
  • Osteoarthritis
  • Pain
  • Hypertrophy
  • Iodoacetic Acid
  • Analgesics
  • Complex Mixtures
  • Apoptosis
  • Male
Sprache
eng
Medium
Print-Electronic
Online publication date
2018
Paginierung
545 - 554
Datum der Veröffentlichung
2019
Status
Published
Datum der Datenerfassung
2018
Titel
Agkistrodon ameliorates pain response and prevents cartilage degradation in monosodium iodoacetate-induced osteoarthritic rats by inhibiting chondrocyte hypertrophy and apoptosis.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
231

Data source: Europe PubMed Central

Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Osteoarthritis (OA), characterized by joint pain and cartilage degradation, is the most common form of joint disease worldwide but with no satisfactory therapy available. The ethanol extract of Agkistrodon acutus (EAA) has been widely used as a traditional Chinese medicine (TCM) for the treatment of arthralgia and inflammatory diseases, but there is no report regarding its efficacy on OA to date. Here, we determined the effects of EAA on the pain behavior and cartilage degradation in vivo and clarified its target genes and proteins associated with chondrocyte hypertrophy and apoptosis in vitro. MATERIALS AND METHODS: In vivo OA model was established by intra-articular injection (1.5 mg) of monosodium iodoacetate (MIA) into rats and weekly treated by intra-articular administration of EAA at a dose range from 0.3 to 0.9 g/kg for four weeks. The pain behavior parameters, thermal withdrawal latency (TWL) and mechanical withdrawal threshold (MWT) were tested before and after the treatment. Then histopathologic, immunohistochemical and TUNEL analyses of the articular cartilage were conducted, followed by Mankin's scoring. In vitro, the effects of EAA on chondrocytes were evaluated via assays of cell viability, immunofluorescence, real time PCR, and Western blot. UPLC-MS was applied to determine the chemical composition of EAA. RESULTS: The animal data showed that EEA not only attenuated the pain hypersensitivity but also blocked the cartilage degeneration by improving chondrocyte survival and suppressing chondrocyte apoptosis at a dose-dependent manner in OA rats. Furthermore, EAA remarkably restored the abnormal expression of collagen type II (Col2) and matrix metalloproteinase-13 (MMP13) in cartilage of OA rats. The cellular data showed that EAA significantly increased the cell viability of chondrocytes against OA-like damage and restored the abnormal expressions of Col2 and MMP13 in damaged chondrocytes. The molecular data showed that EAA significantly restored the abnormal mRNA expressions of Col2, Col10, MMP2 and MMP13 as well as the abnormal protein expressions of MMP13, PARP (total and cleaved) in chondrocytes under pathological condition. UPLC-MS analysis showed the known main components of EAA, including amino acides (glycine, L-aspartic acid, L-glutamic acid, and L-hydroxyproline), nucleoside (uridine), purines (xanthine and hypoxanthine), and pyrimidine (uracil). CONCLUSIONS: Our data demonstrate that EAA exerts antinociceptive and chondroprotective effects on OA through suppressing chondrocyte hypertrophy and apoptosis with restoration of the molecular expressions of anabolism and catabolism in chondrocytes. It provides a promising TCM candidate of novel agent for OA therapy.
Date of acceptance
2018
Autoren
  • Caiwei Wang
  • Li Yan
  • Bo Yan
  • Li Zhou
  • Wan Sun
  • Lingying Yu
  • Fucun Liu
  • Wenxi Du
  • Guangping Yu
  • Zhengyan Hu
  • Qiang Yuan
  • Luwei Xiao
  • Hongwen Li
  • Peijian Tong
  • Jida Zhang
  • Letian Shan
  • Thomas Efferth
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/30529425
DOI
10.1016/j.jep.2018.12.004
eISSN
1872-7573
Zeitschrift
J Ethnopharmacol
Schlüsselwörter
  • Agkistrodon acutus
  • Chondrocyte
  • Hypertrophy
  • Osteoarthritis
  • Pain
  • Agkistrodon
  • Analgesics
  • Animals
  • Apoptosis
  • Cartilage, Articular
  • Chondrocytes
  • Complex Mixtures
  • Hypertrophy
  • Iodoacetic Acid
  • Male
  • Osteoarthritis
  • Pain
  • Rats, Sprague-Dawley
Sprache
eng
Country
Ireland
Paginierung
545 - 554
PII
S0378-8741(18)32192-5
Datum der Veröffentlichung
2019
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2019
Titel
Agkistrodon ameliorates pain response and prevents cartilage degradation in monosodium iodoacetate-induced osteoarthritic rats by inhibiting chondrocyte hypertrophy and apoptosis.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
231

Data source: PubMed

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