Neuroprotective effects of the salidroside derivative SHPL-49 via the BDNF/TrkB/Gap43 pathway in rats with cerebral ischemia.

Autor: You S; The Research Center of Chiral Drugs, Innovation Research Institute of Traditional, Chinese Medicine (IRI), Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China., Ma Z; The Research Center of Chiral Drugs, Innovation Research Institute of Traditional, Chinese Medicine (IRI), Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China., Zhang P; The Research Center of Chiral Drugs, Innovation Research Institute of Traditional, Chinese Medicine (IRI), Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China., Xu W; Shanghai Hutchison Pharmaceuticals Co., Ltd, Shanghai 201203, China., Zhan C; Shanghai Hutchison Pharmaceuticals Co., Ltd, Shanghai 201203, China., Sang N; The Research Center of Chiral Drugs, Innovation Research Institute of Traditional, Chinese Medicine (IRI), Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China., Xu J; The Research Center of Chiral Drugs, Innovation Research Institute of Traditional, Chinese Medicine (IRI), Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China., Wang F; The Research Center of Chiral Drugs, Innovation Research Institute of Traditional, Chinese Medicine (IRI), Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China., Zhang J; The Research Center of Chiral Drugs, Innovation Research Institute of Traditional, Chinese Medicine (IRI), Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address: jgzhang@shutcm.edu.cn.
Jazyk: angličtina
Zdroj: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2024 May; Vol. 174, pp. 116460. Date of Electronic Publication: 2024 Mar 22.
DOI: 10.1016/j.biopha.2024.116460
Abstrakt: Ischemic stroke is a common intravascular disease and one of the leading causes of death and disability. The salidroside derivative SHPL-49, which we previously synthesized, significantly attenuates cerebral ischemic injury in a rat model of permanent middle cerebral artery occlusion. To explore the neuroprotective mechanism of SHPL-49, the effects of SHPL-49 on the expression levels of neurotrophic factors in neurons and microglia and the polarization of microglia were investigated in the present study. SHPL-49 activated the brain-derived neurotrophic factor (BDNF) pathway, decreased the number of degenerated neurons, and accelerated neurogenesis in rats with cerebral ischemia. In addition, SHPL-49 promoted the polarization of microglia toward the M2 phenotype to alleviate neuroinflammation. In BV2 cells, SHPL-49 upregulated CD206 mRNA and protein levels and inhibited CD86 mRNA and protein levels. SHPL-49 also increased neurotrophic factor secretion in BV2 cells, which indirectly promoted the survival of primary neurons after oxygen-glucose deprivation (OGD). Proteomics analysis revealed that SHPL-49 promoted growth-associated protein 43 (Gap43) expression. SHPL-49 enhanced synaptic plasticity and increased Gap43 protein levels via activation of the BDNF pathway in the OGD primary neuron model. These results indicate that SHPL-49 prevents cerebral ischemic injury by activating neurotrophic factor pathways and altering microglial polarization. Thus, SHPL-49 is a potential neuroprotective agent.
Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
Databáze: MEDLINE
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