The Effects and Mechanism of Scutellaria baicalensis Georgi Stems and Leaves Flavonoids on Myelin Sheath Degeneration Induced by Composite Aβ in Rats.

Abstract

Alzheimer's disease is a degenerative disease of the central nervous system, and its characteristic pathological changes are closely associated with Aβ deposition and neurofibrillary tangles. Many studies have found that malignant changes in the myelin sheath and oligodendrocyte (OL) are accompanied by the occurrence and development of AD. Therefore, any method that can resist myelin sheath and OL disorders may be a potential strategy for AD. To investigate the effects and mechanism of Scutellaria baicalensis Georgi stem and leaf flavonoids (SSFs) on the myelin sheath degeneration induced by Aβ25-35 combined with AlC13 and RHTGF-β1 (composite Aβ) in rats. A rat AD model was established by intracerebroventricular injection of composite Aβ. The Morris water maze was used to screen the memory impairment rat model. The successful model rats were divided into the model group and the 35, 70, and 140 mg/kg SSFS groups. The myelin sheath changes in the cerebral cortex were observed with an electron microscope. The expression of the oligodendrocyte- specific protein claudin 11 was detected with immunohistochemistry. The protein expression levels of myelin oligodendrocyte glycoprotein (MOG), myelin-associated glycoprotein (MAG) and myelin basic protein (MBP), sphingomyelin synthase-1 (SMS1), and sphingomyelinase-2 (SMPD2) were assayed by Western blotting. The intracerebroventricular injection of composite Aβ caused degeneration of the myelin sheath structure and was accompanied by the decreased claudin 11, MOG, MAG, MBP, and SMS1, and increased SMPD2 protein expression in the cerebral cortex. However, 35, 70, and 140 mg/kg SSFs can differentially ameliorate the above abnormal changes induced by composite Aβ. SSFs can alleviate myelin sheath degeneration and increase the protein expression of claudin 11, MOG, MAG, and MBP, and the effective mechanism may be related to the positive regulation of SMS1 and SMPD2 activities.