Estrogen-like neuroprotection of isopsoralen against spinal cord injury through estrogen receptor ERα.
Isopsoralen is a type of furocoumarin that exhibits estrogen-like activities. The aim of this study was to determine the estrogen-like neuroprotection of isopsoralen in an animal model of spinal cord injury (SCI). Results indicated that isopsoralen (intraperitoneal injection of 5 and 10 mg/kg per day for two weeks) significantly enhanced the hindlimb locomotor functions of mice with SCI, as revealed in the BMS score and angle of inclined plane tests. Morphological data showed that isopsoralen significantly attenuated the injury of the gray matter of spinal cord and induced the up-regulation of ERα levels. The neuroprotective effects of isopsolaren were blocked by the ERα antagonist MPP (0.3 mg/kg), but not by the ERβ receptor antagonist PHTPP (0.3 mg/kg). Isopsolaren treatment increased phosphorylated PI3K and AKT (P-PI3K and P-AKT) in the spinal cord of SCI mice and showed a significant anti-apoptotic activity. These results suggest that isopsoralen performs estrogen-like neuroprotection against SCI-induced apoptosis by activating ERα and regulating the PI3K/AKT pathway.
Department of Orthopedics, Jinling Hospital, Clinical School of Nanjing, Second Military Medical University, Nanjing, 210002, China.
Xiao-Ming
XM
Li
Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China.
Qi
Q
Yang
Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China.
Xu-Bo
XB
Li
Department of Orthopedics, Jinling Hospital, Clinical School of Nanjing, Second Military Medical University, Nanjing, 210002, China.
Qiang
Q
Cheng
Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China.
Kun
K
Zhang
Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China.
Jing
J
Han
Department of Orthopedics, Jinling Hospital, Clinical School of Nanjing, Second Military Medical University, Nanjing, 210002, China. jnzhao2002@163.com.
Jian-Ning
JN
Zhao
Department of Orthopedics, Jinling Hospital, Clinical School of Nanjing, Second Military Medical University, Nanjing, 210002, China. liugene@hotmail.com.|Jinling Hospital, Department of Orthopedics, School of Medicine, Nanjing University, Nanjing, 210002, China. liugene@hotmail.com.
Gang
G
Liu
Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China. minggao@fmmu.edu.cn.
Ming-Gao
MG
Zhao
D000818:Animals; D047628:Estrogen Receptor alpha / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011564:Furocoumarins / Q000494:pharmacology / Q000627:therapeutic use*; D006727:Hormone Antagonists / Q000494:pharmacology; D008297:Male; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
C524478:1,3-bis(4-hydroxyphenyl)-4-methyl-5-(4-(2-piperidinylethoxy)phenol)-1H-pyrazole; D047628:Estrogen Receptor alpha; D011564:Furocoumarins; D006727:Hormone Antagonists; D018696:Neuroprotective Agents; D010880:Piperidines; D011720:Pyrazoles; C011659:angelicin; D019869:Phosphatidylinositol 3-Kinases
ERα; Isopsoralen; Neuroprotection; Spinal cord injury
J Neurotrauma. 2003 Oct;20(10):1017-27
14588118
Crit Care. 2005 Feb;9(1):66-75
15693986
Ann Surg. 2008 Aug;248(2):294-302
18650641
J Neurotrauma. 2006 May;23(5):635-59
16689667
Prog Brain Res. 2009;175:125-37
19660652
Spine J. 2014 Feb 1;14(2):353-60
24269082
Arch Phys Med Rehabil. 2009 Mar;90(3):517-21
19254621
Oncol Rep. 2014 Mar;31(3):1175-82
24366110
Ann N Y Acad Sci. 2010 Jun;1199:90-4
20633113
J Neurotrauma. 2002 Feb;19(2):175-90
11893021
J Neurotrauma. 2001 Nov;18(11):1267-78
11721745
Trends Biochem Sci. 2004 May;29(5):233-42
15130559
Phytomedicine. 2010 Feb;17(2):126-31
19577453
Proc Soc Exp Biol Med. 1995 Jan;208(1):44-50
7892294
Anticancer Agents Med Chem. 2015;15(9):1092-111
25584692
J Neuroinflammation. 2012 Apr 07;9:65
22483094
Oncogene. 2003 Sep 11;22(39):7998-8011
12970748
J Neurotrauma. 2006 Jun;23 (6):830-52
16774470
Cancer Res. 2004 Jan 1;64(1):423-8
14729654
J Surg Res. 2013 Nov;185(1):300-9
23816246
Zhongguo Zhong Yao Za Zhi. 2007 Sep;32(17 ):1789-91
17993004
J Neurosci Res. 2005 Mar 1;79(5):628-37
15668909
Curr Opin Cell Biol. 2006 Dec;18(6):685-9
17046225
J Biol Chem. 2001 Mar 30;276(13):9817-24
11139588
Int J Oncol. 2014 Nov;45(5):1813-9
25174607
Maturitas. 2006 Jun 20;54(3):222-8
16343828
Trends Mol Med. 2004 Dec;10(12):580-3
15567326
World J Emerg Med. 2011;2(1):38-44
25214981
J Biochem Mol Biol. 2002 Jan 31;35(1):94-105
16248974
Neurosci Biobehav Rev. 2008;32(3):550-80
18036661
Spinal Cord. 2007 Mar;45(3):190-205
17179973
J Neurotrauma. 2004 Mar;21(3):293-306
15115604