PMID- 27172999
OWN - NLM
STAT- MEDLINE
DCOM- 20180327
LR  - 20181113
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 6
DP  - 2016 May 12
TI  - Dual activities of the anti-cancer drug candidate PBI-05204 provide 
      neuroprotection in brain slice models for neurodegenerative diseases and stroke.
PG  - 25626
LID - 10.1038/srep25626 [doi]
LID - 25626
AB  - We previously reported neuroprotective activity of the botanical anti-cancer drug 
      candidate PBI-05204, a supercritical CO2 extract of Nerium oleander, in brain 
      slice and in vivo models of ischemic stroke. We showed that one component of this 
      neuroprotective activity is mediated through its principal cardiac glycoside 
      constituent, oleandrin, via induction of the potent neurotrophic factor 
      brain-derived neurotrophic factor (BDNF). However, we also noted that the 
      concentration-relation for PBI-05204 in the brain slice oxygen-glucose 
      deprivation (OGD) model is considerably broader than that for oleandrin as a 
      single agent. We thus surmised that PBI-05204 contains an additional 
      neuroprotective component(s), distinct from oleandrin. We report here that 
      neuroprotective activity is also provided by the triterpenoid constituents of 
      PBI-05204, notably oleanolic acid. We demonstrate that a sub-fraction of 
      PBI-05204 (Fraction 0-4) containing oleanolic and other triterpenoids, but 
      without cardiac glycosides, induces the expression of cellular antioxidant gene 
      transcription programs regulated through antioxidant transcriptional response 
      elements (AREs). Finally, we show that Fraction 0-4 provides broad 
      neuroprotection in organotypic brain slice models for neurodegeneration driven by 
      amyloid precursor protein (APP) and tau implicated in Alzheimer's disease and 
      frontotemporal dementias, respectively, in addition to ischemic injury modeled by 
      OGD.
FAU - Van Kanegan, Michael J
AU  - Van Kanegan MJ
AD  - Center for Drug Discovery and Department of Neurobiology, Duke University Medical 
      Center, Durham, NC 27710, US.
FAU - Dunn, Denise E
AU  - Dunn DE
AD  - Center for Drug Discovery and Department of Neurobiology, Duke University Medical 
      Center, Durham, NC 27710, US.
FAU - Kaltenbach, Linda S
AU  - Kaltenbach LS
AD  - Center for Drug Discovery and Department of Neurobiology, Duke University Medical 
      Center, Durham, NC 27710, US.
FAU - Shah, Bijal
AU  - Shah B
AD  - Center for Drug Discovery and Department of Neurobiology, Duke University Medical 
      Center, Durham, NC 27710, US.
FAU - He, Dong Ning
AU  - He DN
AD  - Center for Drug Discovery and Department of Neurobiology, Duke University Medical 
      Center, Durham, NC 27710, US.
FAU - McCoy, Daniel D
AU  - McCoy DD
AD  - Center for Drug Discovery and Department of Neurobiology, Duke University Medical 
      Center, Durham, NC 27710, US.
FAU - Yang, Peiying
AU  - Yang P
AD  - Department of Palliative Care, Rehabilitation and Integrative Medicine, 
      University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, US.
FAU - Peng, Jiangnan
AU  - Peng J
AD  - Department of Chemistry and Biochemistry, University of North Carolina at 
      Wilmington, NC 28403, US.
FAU - Shen, Li
AU  - Shen L
AD  - Department of Pharmacy, Medical College of Yangzhou University, Yangzhou, China.
FAU - Du, Lin
AU  - Du L
AD  - Department of Chemistry and Biochemistry, Stephenson Life Sciences Research 
      Center, Natural Products Discovery Group, and Institute for Natural Products 
      Applications and Research Technologies, University of Oklahoma, Norman, Oklahoma 
      73019, US.
FAU - Cichewicz, Robert H
AU  - Cichewicz RH
AD  - Department of Chemistry and Biochemistry, Stephenson Life Sciences Research 
      Center, Natural Products Discovery Group, and Institute for Natural Products 
      Applications and Research Technologies, University of Oklahoma, Norman, Oklahoma 
      73019, US.
FAU - Newman, Robert A
AU  - Newman RA
AD  - Department of Experimental Therapeutics, University of Texas, M. D. Anderson 
      Cancer Center, Houston, TX 77030, US.
FAU - Lo, Donald C
AU  - Lo DC
AD  - Center for Drug Discovery and Department of Neurobiology, Duke University Medical 
      Center, Durham, NC 27710, US.
LA  - eng
GR  - R21 NS080514/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20160512
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Heterocyclic Compounds, 4 or More Rings)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (PBI-05204)
RN  - 0 (Plant Extracts)
RN  - 6SMK8R7TGJ (Oleanolic Acid)
RN  - IY9XDZ35W2 (Glucose)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/chemistry/*pharmacology
MH  - Brain/*drug effects/metabolism/pathology
MH  - Chemical Fractionation/methods
MH  - Disease Models, Animal
MH  - Female
MH  - Glucose/metabolism
MH  - Heterocyclic Compounds, 4 or More Rings/*pharmacology
MH  - Humans
MH  - Male
MH  - Nerium/chemistry
MH  - Neurodegenerative Diseases/*drug therapy
MH  - Neuroprotective Agents/chemistry/pharmacology
MH  - Oleanolic Acid/chemistry/pharmacology
MH  - Organ Culture Techniques
MH  - Oxygen/metabolism
MH  - Plant Extracts/*pharmacology
MH  - Rats, Sprague-Dawley
MH  - Stroke/*drug therapy
PMC - PMC4865873
COIS- P.Y. is a paid consultant of Phoenix Biotechnology. R.A.N. is President and Chief 
      Science Officer of Phoenix Biotechnology.
EDAT- 2016/05/14 06:00
MHDA- 2018/03/28 06:00
PMCR- 2016/05/12
CRDT- 2016/05/14 06:00
PHST- 2015/12/02 00:00 [received]
PHST- 2016/04/20 00:00 [accepted]
PHST- 2016/05/14 06:00 [entrez]
PHST- 2016/05/14 06:00 [pubmed]
PHST- 2018/03/28 06:00 [medline]
PHST- 2016/05/12 00:00 [pmc-release]
AID - srep25626 [pii]
AID - 10.1038/srep25626 [doi]
PST - epublish
SO  - Sci Rep. 2016 May 12;6:25626. doi: 10.1038/srep25626.