title: Oleanolic acid rejuvenates testicular function through attenuating germ cell DNA damage and apoptosis via deactivation of NF-κB, p53 and p38 signalling pathways.
abstract: OBJECTIVE
  Inflammation can cause degenerative changes of reproductive function. Oleanolic acid (OA), the effective component from Ligustrum lucidum Ait., exhibits significantly anti-inflammation and antiageing activity. However, whether OA restores testicular dysfunction via inhibition of inflammation with ageing is unclear. Here, in a natural ageing rat model, we investigated the protection effects of OA and its mechanism of action.
  
  
  METHODS
  Eighteen-month-old Sprague Dawley (SD) rats were randomly divided into ageing control group and two OA-treated groups (5 and 25 mg/kg). Nine-month-old SD rats were used as adult controls. All rats were received either vehicle or OA for 6 months. Then, histomorphology, weight and index of testis, protein expression and immunohistochemistry were examined.
  
  
  RESULTS
  Oleanolic acid significantly restored testicular morphology and improved testicular weight and index. Moreover, OA significantly inhibited phospho-NF-κB p65 and its downstream proinflammatory cytokines' expressions, including IL-1β, COX-2 and TNF-α in testis tissues. Similarly, OA remarkably inhibited IL-1β and TNF-α production. OA significantly attenuated germ cells' DNA damage and apoptosis. Such changes were accompanied by downregulation of γH2AX, p-P53 and Bax expressions, and upregulation of Bcl-2 and Bcl-2/Bax ratio. In addition, OA remarkably inhibited p38 signalling.
  
  
  CONCLUSIONS
  Oleanolic acid effectively rejuvenates testicular function via attenuating germ cell DNA damage and apoptosis through deactivation of NF-κB, p53 and p38 signalling pathways.
authors.affiliation: Medical College of China Three Gorges University, Yichang, China.
authors.forename: Haixia
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Medical College of China Three Gorges University, Yichang, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Medical College of China Three Gorges University, Yichang, China.
authors.forename: Laixin
authors.initials: L
authors.lastname: Song
authors.affiliation: Medical College of China Three Gorges University, Yichang, China.
authors.forename: Zhencai
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Medical College of China Three Gorges University, Yichang, China.
authors.forename: Guifang
authors.initials: G
authors.lastname: Han
authors.affiliation: RENHE Hospital of China Three Gorges University, Yichang, China.
authors.forename: Ding
authors.initials: D
authors.lastname: Yuan
authors.affiliation: Medical College of China Three Gorges University, Yichang, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.affiliation: Medical College of China Three Gorges University, Yichang, China.
authors.forename: Yaoyan
authors.initials: Y
authors.lastname: Dun
authors.affiliation: Medical College of China Three Gorges University, Yichang, China.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Medical College of China Three Gorges University, Yichang, China.
authors.forename: Zhaoqi
authors.initials: Z
authors.lastname: Liu
authors.affiliation: LONGHUA Hospital Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Medical College of China Three Gorges University, Yichang, China.|LONGHUA Hospital Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Changcheng
authors.initials: C
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D004249:DNA Damage / Q000187:drug effects*; D015536:Down-Regulation / Q000187:drug effects; D005854:Germ Cells / Q000187:drug effects* / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D009828:Oleanolic Acid / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013737:Testis / Q000187:drug effects* / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D053583:Interleukin-1beta; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D016159:Tumor Suppressor Protein p53; D009828:Oleanolic Acid; D048051:p38 Mitogen-Activated Protein Kinases
keywords: DNA damage; ageing; apoptosis; oleanolic acid; testis