Development of a neuroprotective potential algorithm for medicinal plants.
Medicinal plants are promising candidates for Alzheimer's disease (AD) research but there is lack of systematic algorithms and procedures to guide their selection and evaluation. Herein, we developed a Neuroprotective Potential Algorithm (NPA) by evaluating twenty-three standardized and chemically characterized Ayurvedic medicinal plant extracts in a panel of bioassays targeting oxidative stress, carbonyl stress, protein glycation, amyloid beta (Aβ) fibrillation, acetylcholinesterase (AChE) inhibition, and neuroinflammation. The twenty-three herbal extracts were initially evaluated for: 1) total polyphenol content (Folin-Ciocalteu assay), 2) free radical scavenging capacity (DPPH assay), 3) ferric reducing antioxidant power (FRAP assay), 4) reactive carbonyl species scavenging capacity (methylglyoxal trapping assay), 5) anti-glycative effects (BSA-fructose, and BSA-methylglyoxal assays) and, 6) anti-Aβ fibrillation effects (thioflavin-T assay). Based on assigned index scores from the initial screening, twelve extracts with a cumulative NPA score ≥40 were selected for further evaluation for their: 1) inhibitory effects on AChE activity, 2) in vitro anti-inflammatory effects on murine BV-2 microglial cells (Griess assay measuring levels of lipopolysaccharide-induced nitric oxide species), and 3) in vivo neuroprotective effects on Caenorhabditis elegans post induction of Aβ1-42induced neurotoxicity and paralysis. Among these, four extracts had a cumulative NPA score ≥60 including Phyllanthus emblica (amla; Indian gooseberry), Mucuna pruriens (velvet bean), Punica granatum (pomegranate) and Curcuma longa (turmeric; curcumin). These extracts also showed protective effects on H2O2induced cytotoxicity in differentiated cholinergic human neuronal SH-SY5Y and murine BV-2 microglial cells and reduced tau protein levels in the SH-SY5Y neuronal cells. While published animal data support the neuroprotective effects of several of these Ayurvedic medicinal plant extracts, some remain unexplored for their anti-AD potential. Therefore, the NPA may be utilized, in part, as a strategy to help guide the selection of promising medicinal plant candidates for future AD-based research using animal models.
Department of Chemistry, University of Rhode Island, Kingston, RI 02881, USA.
Weixi
W
Liu
Bioactive Botanical Research Laboratory, Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, USA.
Hang
H
Ma
Bioactive Botanical Research Laboratory, Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, USA.
Nicholas A
NA
DaSilva
Bioactive Botanical Research Laboratory, Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, USA.
Kenneth N
KN
Rose
Bioactive Botanical Research Laboratory, Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, USA.
Shelby L
SL
Johnson
Bioactive Botanical Research Laboratory, Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, USA.
Lu
L
Zhang
Bioactive Botanical Research Laboratory, Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, USA.
Chunpeng
C
Wan
Department of Chemistry, University of Rhode Island, Kingston, RI 02881, USA. Electronic address: jdain@chm.uri.edu.
Joel A
JA
Dain
Bioactive Botanical Research Laboratory, Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, USA; George & Anne Ryan Institute for Neuroscience, University of Rhode Island, Kingston, RI 02881, USA. Electronic address: nseeram@uri.edu.
Navindra P
NP
Seeram
D000465:Algorithms; D016229:Amyloid beta-Peptides / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D017628:Microglia / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology; D020258:Neurotoxicity Syndromes / Q000188:drug therapy; D018384:Oxidative Stress / Q000187:drug effects*; D010946:Plants, Medicinal / Q000378:metabolism
D016229:Amyloid beta-Peptides; D000975:Antioxidants; D018696:Neuroprotective Agents; D006861:Hydrogen Peroxide
Alzheimer's disease (AD); Antioxidant; Beta amyloid (Aβ); Caenorhabditis elegans; Glycation; Neuroinflammation
Curr Alzheimer Res. 2005 Apr;2(2):131-6
15974909
Nat Rev Drug Discov. 2010 May;9(5):387-98
20431570
FEBS Lett. 2006 Sep 4;580(20):4842-50
16914144
J Agric Food Chem. 2005 Apr 20;53(8):3167-73
15826074
Alzheimers Dement. 2015 Mar;11(3):332-84
25984581
Neurochem Int. 2016 May;95:100-8
26550708
Nat Rev Neurosci. 2011 Feb;12(2):65-72
21193853
J Agric Food Chem. 2008 Jul 9;56(13):4855-73
18557624
Int Psychogeriatr. 2001 Dec;13(4):439-50
12003250
Acta Neuropathol. 2006 Oct;112(4):405-15
16865397
Neurobiol Aging. 2011 May;32(5):763-77
19464758
J Pathol. 2010 May;221(1):13-25
20186922
Mol Biosyst. 2015 May;11(5):1338-47
25789915
J Neurosci. 2005 Aug 24;25(34):7709-17
16120771
Amino Acids. 2012 Apr;42(4):1221-36
20949363
Curr Pharm Des. 2012;18(1):27-33
22211686
Front Aging Neurosci. 2014 Mar 14;6:42
24672477
J Neurol Neurosurg Psychiatry. 2004 Dec;75(12):1672-7
15548480
Biochem Pharmacol. 2014 Apr 15;88(4):640-51
24398425
Biochim Biophys Acta. 2000 Jul 26;1502(1):139-44
10899439
J Berry Res. 2016 Jun 16;6(2):149-158
28649289
Brain Res Bull. 2012 Feb 10;87(2-3):144-53
22155297
Neurology. 2001 Sep 25;57(6):985-9
11571321
Bioresour Technol. 2005 May;96(8):873-7
15627557
Cochrane Database Syst Rev. 2006 Jan 25;(1):CD005593
16437532
J Neural Transm (Vienna). 2006 Nov;113(11):1685-95
17036175
Cochrane Database Syst Rev. 2000;(4):CD001190
11034704
Nat Neurosci. 2010 Jul;13(7):812-8
20581818
Biochem Pharmacol. 1961 Jul;7:88-95
13726518
Neurochem Int. 2016 May;95:63-74
26529297
Toxicol Appl Pharmacol. 2002 Nov 1;184(3):187-97
12460747
ACS Chem Neurosci. 2016 Jan 20;7(1):26-33
26559394
Proc Natl Acad Sci U S A. 1999 Aug 31;96(18):9989-90
10468546
Lancet Neurol. 2014 Aug;13(8):788-94
25030513
Glia. 2002 Nov;40(2):232-9
12379910
Mol Nutr Food Res. 2015 Jun;59(6):1025-40
25689033
Behav Brain Res. 2014 Jul 1;267:55-65
24667360
Neurochem Int. 2013 Apr;62(5):522-9
22982670
Nature. 2006 Oct 19;443(7113):787-95
17051205
Arch Biochem Biophys. 2003 Nov 1;419(1):31-40
14568006
Ageing Res Rev. 2012 Apr;11(2):329-45
22336470
J Agric Food Chem. 2008 Feb 27;56(4):1415-22
18220345
Am J Clin Nutr. 2000 Feb;71(2):621S-629S
10681270
Neurochem Res. 2016 Nov;41(11):2836-2847
27418278
Curr Alzheimer Res. 2014;11(9):834-43
25274111
Phytother Res. 2009 Jan;23(1):14-9
19048607
Science. 2010 Dec 24;330(6012):1774
21148344
Cell Death Dis. 2013 Jun 13;4:e673
23764854
Neurotoxicology. 2009 Nov;30(6):986-95
19744518
Ann N Y Acad Sci. 2008 Dec;1147:70-8
19076432
J Neurochem. 2005 Jan;92(2):255-63
15663474
J Neurosci. 2001 Nov 1;21(21):8370-7
11606625
Free Radic Res. 2002 Dec;36(12):1307-13
12607822
J Neurochem. 2006 Dec;99(5):1413-24
17074066
Food Funct. 2016 May 18;7(5):2213-22
27101975
Food Funct. 2014 Nov;5(11):2996-3004
25233108
J Agric Food Chem. 2012 Jun 13;60(23):5755-62
22111586
J Neural Transm (Vienna). 2007;114(6):835-9
17401529