PMID- 26083352
OWN - NLM
STAT- MEDLINE
DCOM- 20160503
LR  - 20220310
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 10
IP  - 6
DP  - 2015
TI  - Eupatilin Exerts Antinociceptive and Chondroprotective Properties in a Rat Model 
      of Osteoarthritis by Downregulating Oxidative Damage and Catabolic Activity in 
      Chondrocytes.
PG  - e0130882
LID - 10.1371/journal.pone.0130882 [doi]
LID - e0130882
AB  - Increases in oxidative stress are thought to be associated with the development 
      of osteoarthritis (OA). Eupatilin, one of the major compounds present in 
      artemisia species, was shown to have both anti-oxidative and anti-inflammatory 
      properties. Here, we investigated the in vivo effects of eupatilin on pain 
      severity and cartilage degradation in an experimental rat model of OA, along with 
      the mechanisms of action underlying these effects. Experimental OA was induced 
      via an intra-articular injection of monosodium iodoacetate (MIA), with oral 
      administration of eupatilin initiated on the day of MIA injection. Pain was 
      assessed by measuring the paw withdrawal latency and threshold. Cartilage 
      destruction was analyzed macroscopically and histomorphologically. The effects of 
      eupatilin on mRNA expression were investigated in interleukin-1beta 
      (IL-1beta)-stimulated human OA chondrocytes. Eupatilin treatment exhibited clear 
      antinociceptive effects, along with an attenuation of cartilage degradation in OA 
      rats. Additionally, the number of osteoclasts present in the subchondral bone 
      region was significantly decreased following eupatilin treatment. Eupatilin 
      reduced the expression of interleukin-1beta (IL-1beta), interleukin-6 (IL-6), 
      nitrotyrosine and inducible nitric oxide synthase (iNOS) in cartilage. mRNA 
      levels of matrix metalloproteinase-3 (MMP-3), MMP13, and a disintegrin and 
      metalloproteinase with thrombospondin motifs-5 (ADAMTS-5) were reduced in 
      IL-1beta-stimulated human OA chondrocytes, while tissue inhibitor of 
      metalloproteinases-1 (TIMP-1) was induced. Phosphorylated protein levels of the 
      c-jun N-terminal kinase (JNK) was reduced by eupatilin. Taken together, these 
      results suggest that eupatilin suppresses oxidative damage and reciprocally 
      enhances extracellular matrix production in articular chondrocytes, making 
      eupatilin a promising therapeutic option for the treatment of OA.
FAU - Jeong, Jeong-Hee
AU  - Jeong JH
AD  - The Rheumatism Research Center, Catholic Research Institute of Medical Science, 
      The Catholic University of Korea, Seoul, South Korea.
FAU - Moon, Su-Jin
AU  - Moon SJ
AD  - Division of Rheumatology, Department of Internal Medicine, College of Medicine, 
      The Catholic University of Korea, Seoul, South Korea.
FAU - Jhun, Joo-Yeon
AU  - Jhun JY
AD  - The Rheumatism Research Center, Catholic Research Institute of Medical Science, 
      The Catholic University of Korea, Seoul, South Korea.
FAU - Yang, Eun-Ji
AU  - Yang EJ
AD  - The Rheumatism Research Center, Catholic Research Institute of Medical Science, 
      The Catholic University of Korea, Seoul, South Korea.
FAU - Cho, Mi-La
AU  - Cho ML
AD  - The Rheumatism Research Center, Catholic Research Institute of Medical Science, 
      The Catholic University of Korea, Seoul, South Korea.
FAU - Min, Jun-Ki
AU  - Min JK
AD  - Division of Rheumatology, Department of Internal Medicine, College of Medicine, 
      The Catholic University of Korea, Seoul, South Korea.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150617
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Analgesics)
RN  - 0 (Biomarkers)
RN  - 0 (Flavonoids)
RN  - 4D58O05490 (eupatilin)
SB  - IM
MH  - Analgesics/*pharmacology
MH  - Animals
MH  - Arthritis, Experimental/chemically induced/pathology/*prevention & control
MH  - Biomarkers/metabolism
MH  - Cartilage, Articular/drug effects/metabolism
MH  - Chondrocytes/*drug effects/metabolism/pathology
MH  - Flavonoids/*pharmacology
MH  - Humans
MH  - Immunoenzyme Techniques
MH  - Male
MH  - Osteoarthritis/chemically induced/pathology/*prevention & control
MH  - Pain/*drug therapy
MH  - Rats
MH  - Rats, Wistar
PMC - PMC4471346
COIS- Competing Interests: The authors declare that there is no conflict of interests 
      regarding the publication of this paper.
EDAT- 2015/06/18 06:00
MHDA- 2016/05/04 06:00
PMCR- 2015/06/17
CRDT- 2015/06/18 06:00
PHST- 2014/10/14 00:00 [received]
PHST- 2015/05/26 00:00 [accepted]
PHST- 2015/06/18 06:00 [entrez]
PHST- 2015/06/18 06:00 [pubmed]
PHST- 2016/05/04 06:00 [medline]
PHST- 2015/06/17 00:00 [pmc-release]
AID - PONE-D-14-46062 [pii]
AID - 10.1371/journal.pone.0130882 [doi]
PST - epublish
SO  - PLoS One. 2015 Jun 17;10(6):e0130882. doi: 10.1371/journal.pone.0130882. 
      eCollection 2015.