Anti-amnesic activity of neferine with antioxidant and anti-inflammatory capacities, as well as inhibition of ChEs and BACE1.
OBJECTIVE
the multifunctional potential of neferine derived from the embryo of Nelumbo nucifera seeds for the age-related neurodegenerative disorders, in vivo anti-amnesic activities and in vitro cholinesterases (ChEs)- and β-site APP cleaving enzyme 1 (BACE1)-inhibitory activities, as well as anti-inflammatory and antioxidant activities were investigated.


METHODS
in vivo anti-amnesic activities were performed via the passive avoidance, Y-maze, and Morris water maze tasks in a scopolamine-induced amnesia model. The cell-free antioxidant capacities were evaluated by in vitro scavenging activities against 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) radicals, and peroxynitrite (ONOO(-)), as well as inhibitory activities against nitric oxide (NO), superoxide anion (O(2)(-)), lipid peroxidation, and ONOO(-)-mediated tyrosine nitration. The intracellular antioxidant capacities were also determined via inhibitory activities of lipopolysaccharide (LPS)-induced NO generation and NF-κB activation in RAW 264.7 cells.


RESULTS
neferine showed significant improvement in cognitive impairment in scopolamine-induced amnesia animal models and moderate inhibitory activities in ChEs and BACE1 assays. In addition, it exhibited notable scavenging activities against DPPH, ABTS, NO, and O(2)(-) radicals, as well as ONOO(-). Neferine also demonstrated remarkable inhibitory activity against lipid peroxidation and protein nitration in cell-free antioxidant assays and moderate inhibitory activity of NO generation with exceptional suppression of NF-κB activation in cell-based assays.


CONCLUSIONS
the results demonstrate that the anti-amnesic effect of neferine may be mediated via antioxidant and anti-inflammatory capacities, as well as inhibition of ChEs and BACE1.
Jung
Hyun Ah
HA
Department of Food Science and Human Nutrition, Chonbuk National University, Jeonju 561-756, Republic of Korea.
Jin
Seong Eun
SE
Choi
Ran Joo
RJ
Kim
Dong Hyun
DH
Kim
Yeong Shik
YS
Ryu
Jong Hoon
JH
Kim
Dong-Wook
DW
Son
You Kyung
YK
Park
Jin Ju
JJ
Choi
Jae Sue
JS
D000647:Amnesia / Q000188:drug therapy*; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000975:Antioxidants / Q000627:therapeutic use*; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D044182:Benzylisoquinolines / Q000302:isolation & purification / Q000627:therapeutic use*; D002460:Cell Line; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D002802:Cholinesterases / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D031653:Nelumbo / Q000737:chemistry; D018384:Oxidative Stress / Q000187:drug effects; D008517:Phytotherapy
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D044182:Benzylisoquinolines; D002800:Cholinesterase Inhibitors; D004365:Drugs, Chinese Herbal; C057222:neferine; D002802:Cholinesterases; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509282:Bace1 protein, mouse