Ursodeoxycholic Acid Ameliorates Apoptotic Cascade in the Rotenone Model of Parkinson's Disease: Modulation of Mitochondrial Perturbations

Mol Neurobiol. 2016 Mar;53(2):810-817. doi: 10.1007/s12035-014-9043-8. Epub 2014 Dec 15.


The recent emergence of ursodeoxycholic acid (UDCA) as a contender in modifying neurotoxicity in human dopaminergic cells as well as its recognized anti-apoptotic and anti-inflammatory potentials in various hepatic pathologies raised impetus in investigating its anti-parkinsonian effect in rat rotenone model. UDCA prominently improved motor performance in the open field test and halted the decline in the striatal dopamine content. Meanwhile, it improved mitochondrial function as verified by elevation of ATP associated with preservation of mitochondrial integrity as portrayed in the electron microscope examination. In addition, through its anti-inflammatory potential, UDCA reduced the rotenone-induced nuclear factor-κB expression and tumor necrosis factor alpha level. Furthermore, UDCA amended alterations in Bax and Bcl-2 and reduced the activities of caspase-8, caspase-9, and caspase-3, indicating that it suppressed rotenone-induced apoptosis via modulating both intrinsic and extrinsic pathways. In conclusion, UDCA can be introduced as a novel approach for the management of Parkinson's disease via anti-apoptotic and anti-inflammatory mechanisms. These effects are probably linked to dopamine synthesis and mitochondrial regulation.

Keywords: ATP; Caspases; Dopamine; Nuclear factor-κB; Rotenone; Ursodeoxycholic acid.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Apoptosis / drug effects*
  • Behavior, Animal / drug effects
  • Caspases / metabolism
  • Disease Models, Animal
  • Dopamine / metabolism
  • Gene Expression Regulation / drug effects
  • Male
  • Mitochondria / drug effects
  • Mitochondria / metabolism*
  • Mitochondria / ultrastructure
  • Neostriatum / drug effects
  • Neostriatum / enzymology
  • Neostriatum / metabolism
  • Neostriatum / pathology
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurons / pathology
  • Neurons / ultrastructure
  • Parkinson Disease / metabolism*
  • Parkinson Disease / pathology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats, Wistar
  • Rotenone
  • Ursodeoxycholic Acid / pharmacology*


  • RNA, Messenger
  • Rotenone
  • Ursodeoxycholic Acid
  • Adenosine Triphosphate
  • Caspases
  • Dopamine