title: Eucommia ulmoides Oliv. bark aqueous extract inhibits osteoarthritis in a rat model of osteoarthritis.
abstract: BACKGROUND
  Eucommia ulmoides Oliv. bark (EU) is a common traditional Chinese herbal medicine for treatment of osteoarthritis (OA), but its therapeutic effect on OA and the underlying mechanisms have not been fully clarified. Our previous study showed that Eucommia ulmoides Oliv. bark aqueous extract (EUE) had a protective effect on cartilage, and this study was aimed to investigate the anti-osteoarthritis effect and mechanisms of EUE in a rat model of osteoarthritis.
  
  
  METHODS
  Thirty-two 5-week-old specific pathogen-free Sprague-Dawley rats which were randomized into four even groups (n=8). Group A received sham operation while the OA model was established using the modified Hulth technique in groups B, C and D. For eight weeks after operation, in addition to routine feeding, group A received gavage with deionized water, group B with deionized water, group C with 1.35 g/kg/day EUE, and group D with 2.7 g/kg/day EUE. Eight weeks postoperatively, all of the animals were euthanized for radiological, gross and histopathological observations to evaluate the effect of EUE on OA and to determine its potential mechanisms.
  
  
  RESULTS
  Radiological and histopathological observations showed that the articular degenerative changes were significantly more alleviated in groups C and D than in group B, while there were no obviously degenerative manifestations in group A. Mankin׳s scores in groups C and D were significantly lower than in group B (P<0.01). The severity of OA was significantly less in group D than in group C (P<0.01). The IL-1β and IL-6 contents in serum and MMP-3 secretion in articular cartilage were significantly lower in groups C and D than those in group B (P<0.01), and significantly lower in group D than those in group C (P<0.01). Compared with group B, phosphorylated Akt was significantly down-regulated in groups C and D.
  
  
  CONCLUSIONS
  EUE may inhibit the progression of osteoarthritis by inhibiting the PI3K/Akt pathway to delay cartilage degeneration, reduce inflammatory cytokines and prevent MMP-3 secretion. Therefore, EU is a potential therapeutic agent for OA, but its efficacy is limited.
authors.affiliation: Department of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical University, PR China; Key laboratory of Bone and Cartilage Regenerative Medicine of Guangdong Province, Nanfang Hospital, Southern Medical University, PR China. Electronic address: xgp19@163.com.
authors.forename: Guo-ping
authors.initials: GP
authors.lastname: Xie
authors.affiliation: Department of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical University, PR China. Electronic address: hnxyjn@smu.edu.cn.
authors.forename: Nan
authors.initials: N
authors.lastname: Jiang
authors.affiliation: Department of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical University, PR China. Electronic address: 151102352@qq.com.
authors.forename: Sheng-nan
authors.initials: SN
authors.lastname: Wang
authors.affiliation: Department of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical University, PR China. Electronic address: siriusjump@hotmail.com.
authors.forename: Rui-zhen
authors.initials: RZ
authors.lastname: Qi
authors.affiliation: Department of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical University, PR China. Electronic address: 35314031@qq.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Key laboratory of Bone and Cartilage Regenerative Medicine of Guangdong Province, Nanfang Hospital, Southern Medical University, PR China. Electronic address: 544592541@qq.com.
authors.forename: Pei-ran
authors.initials: PR
authors.lastname: Zhao
authors.affiliation: Department of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical University, PR China. Electronic address: palatin921@126.com.
authors.forename: Liang
authors.initials: L
authors.lastname: Liang
authors.affiliation: Department of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical University, PR China; Key laboratory of Bone and Cartilage Regenerative Medicine of Guangdong Province, Nanfang Hospital, Southern Medical University, PR China. Electronic address: nanfanghot@126.com.
authors.forename: Bin
authors.initials: B
authors.lastname: Yu
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D019902:Chondrocytes / Q000378:metabolism; D004195:Disease Models, Animal; D031283:Eucommiaceae; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007719:Knee Joint / Q000187:drug effects / Q000473:pathology; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D010003:Osteoarthritis / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008517:Phytotherapy; D024301:Plant Bark; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017207:Rats, Sprague-Dawley
chemical_list: D000893:Anti-Inflammatory Agents; D053583:Interleukin-1beta; D015850:Interleukin-6; D010936:Plant Extracts; D051057:Proto-Oncogene Proteins c-akt; D019278:Matrix Metalloproteinase 3
keywords: Eucommia ulmoides Oliv. bark; IL-1β; IL-6; MMP-3; Osteoarthritis; PI3K/Akt signaling pathway