Neuroprotective effects of rhynchophylline against ischemic brain injury via regulation of the Akt/mTOR and TLRs signaling pathways

Molecules. 2014 Jul 30;19(8):11196-210. doi: 10.3390/molecules190811196.

Abstract

Rhynchophylline (Rhy) is an alkaloid isolated from Uncaria which has long been recommended for the treatment of central nervous diseases. In our study, the neuroprotective effect of Rhy was investigated in a stroke model, namely permanent middle cerebral artery occlusion (pMCAO). Rats were injected intraperitoneally once daily for four consecutive days before surgery and then received one more injection after surgery. The protein and mRNA levels of p-Akt, p-mTOR, apoptosis-related proteins (p-BAD and cleaved caspase-3), TLR2/4/9, NF-κB, MyD88, BDNF and claudin-5 were examined. Following pMCAO, Rhy treatment not only ameliorated neurological deficits, infarct volume and brain edema, but also increased claudin-5 and BDNF expressions (p < 0.05). Moreover, Rhy could activate PI3K/Akt/mTOR signaling while inhibiting TLRs/NF-κB pathway. Wortmannin, a selective PI3K inhibitor, could abolish the neuroprotective effect of Rhy and reverse the increment in p-Akt, p-mTOR and p-BAD levels. In conclusion, we hypothesize that Rhy protected against ischemic damage, probably via regulating the Akt/mTOR pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Edema / drug therapy
  • Brain Edema / etiology
  • Brain Infarction / drug therapy
  • Brain Infarction / genetics
  • Brain Infarction / metabolism
  • Brain Infarction / pathology
  • Brain Ischemia / drug therapy
  • Brain Ischemia / genetics
  • Brain Ischemia / metabolism*
  • Brain Ischemia / pathology
  • Brain-Derived Neurotrophic Factor / genetics
  • Brain-Derived Neurotrophic Factor / metabolism
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Claudin-5 / genetics
  • Claudin-5 / metabolism
  • Disease Models, Animal
  • Gene Expression
  • Indole Alkaloids / administration & dosage
  • Indole Alkaloids / pharmacology*
  • Male
  • NF-kappa B / metabolism
  • Neuroprotective Agents / administration & dosage
  • Neuroprotective Agents / pharmacology*
  • Oxindoles
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Rats
  • Signal Transduction / drug effects*
  • TOR Serine-Threonine Kinases / metabolism*
  • Toll-Like Receptors / metabolism*
  • bcl-Associated Death Protein / genetics
  • bcl-Associated Death Protein / metabolism

Substances

  • Brain-Derived Neurotrophic Factor
  • Claudin-5
  • Indole Alkaloids
  • NF-kappa B
  • Neuroprotective Agents
  • Oxindoles
  • Toll-Like Receptors
  • bcl-Associated Death Protein
  • rhyncophylline
  • TOR Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Caspase 3