title: Protective effects of matrine on experimental autoimmune encephalomyelitis via regulation of ProNGF and NGF signaling.
abstract: Inflammation, demyelination, oligodendrocyte (OLG) death, and axonal degeneration are primary characteristics of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). OLGs generate myelin sheaths that surround axons, while damage to OLGs leads to demyelination and neurological functional deficit. Matrine (MAT), a quinolizidine alkaloid derived from the herb Radix Sophorae Flave, has been recently found to effectively ameliorate clinical signs in EAE. Its therapeutic mechanism has, however, not been completely elucidated. In the present study, we found that MAT retarded the disease process, attenuated the clinical severity of EAE rats, ameliorated inflammation and demyelination, and suppressed the apoptosis of OLGs in the central nervous system (CNS) of EAE rats. In addition, MAT markedly blocked increased expression of the proNGF-p75(NTR) death signaling complex, which is known to mediate OLG death in EAE animals. At the same time, MAT also prevented a decrease in the levels of NGF and its receptor TrkA, which together mediate the cell survival pathway and differentiation of OLGs. ProNGF, NGF, and the downstream effector proteins play an important role in the growth, differentiation, and apoptosis of OLGs as well as the reparative response to neuronal damage. These findings thus indicate that MAT improves clinical severity of EAE in part by reducing OLG apoptosis via restoring the ratios of proNGF:NGF and the respective receptors p75(NTR):TrkA in vivo. Taken together, these results suggest that MAT may be a promising agent for MS treatment based on its protective effect on OLGs.
authors.affiliation: Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
authors.forename: Qing-xia
authors.initials: QX
authors.lastname: Pan
authors.affiliation: Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
authors.forename: Xiao-Jian
authors.initials: XJ
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
authors.forename: Yu-Ming
authors.initials: YM
authors.lastname: Xu
authors.affiliation: Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
authors.forename: Yao-juan
authors.initials: YJ
authors.lastname: Chu
authors.affiliation: Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Liu
authors.affiliation: Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Lv
authors.affiliation: Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107, USA. Electronic address: Guang-Xian.Zhang@jefferson.edu.
authors.forename: Guang-Xian
authors.initials: GX
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China. Electronic address: johnyuem@zzu.edu.cn.
authors.forename: Quan-Cheng
authors.initials: QC
authors.lastname: Kan
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001369:Axons / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003711:Demyelinating Diseases / Q000378:metabolism / Q000517:prevention & control; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism / Q000517:prevention & control*; D005260:Female; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D009414:Nerve Growth Factors / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology; D009836:Oligodendroglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008517:Phytotherapy / Q000379:methods; D011498:Protein Precursors / Q000378:metabolism*; D011807:Quinolizines / Q000494:pharmacology*; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects*; D029909:Sophora / Q000737:chemistry; D000093842:Matrines
chemical_list: D000470:Alkaloids; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D011498:Protein Precursors; D011807:Quinolizines; C514218:pro-nerve growth factor, rat; D000093842:Matrines
keywords: MS/EAE; NGF; Oligodendrocytes; ProNGF; TrkA; p75(NTR)