Hesperidin Protects SH−SY5Y Neuronal Cells against High Glucose−Induced Apoptosis via Regulation of MAPK Signaling

Abstract

Neurodegenerative diseases are associated with neuronal cell death through apoptosis. Apoptosis is tightly associated with the overproduction of reactive oxygen species (ROS), and high glucose levels contribute to higher oxidative stress in diabetic patients. Hesperidin, a natural active compound, has been reported to scavenge free radicals. Only a few studies have explored the protective effects of hesperidin against high glucose−induced apoptosis in SH−SY5Y neuronal cells. Glucose stimulated neuronal cells to generate excessive ROS and caused DNA damage. In addition, glucose triggered endoplasmic reticulum stress and upregulated cytoplasmic as well as mitochondrial calcium levels. Hesperidin inhibited glucose−induced ROS production and mitigated the associated DNA damage and endoplasmic reticulum stress. The downregulation of antiapoptotic protein Bcl−2 following glucose treatment was reversed by a hesperidin treatment. Furthermore, hesperidin repressed the glucose−induced Bcl−2−associated X protein, cleaved caspase−9, and cleaved caspase−3. Hesperidin also suppressed the glucose−induced phosphorylation of extracellular signal−regulated kinase and c−Jun N−terminal kinase. The current results confirmed that hesperidin could protect neuronal cells against glucose−induced ROS. Mechanistically, hesperidin was shown to promote cell viability via attenuation of the mitogen−activated protein kinase signaling pathway.

Alpinetin inhibits neuroinflammation and neuronal apoptosis via targeting the JAK2/STAT3 signaling pathway in spinal cord injury

“…However, microglia overactivation can result in the release of a variety of pro‐inflammatory mediators, which are thought to be markers and drivers of neuroinflammation‐related diseases 58,59 . Microglia‐mediated neuroinflammation is often associated with the abnormal secretion of ROS, 60 which subsequently stimulate associated inflammatory pathways, thereby accelerating oxidative damage to cells and resulting in neuronal damage and death 61 . In addition, neuronal impairment in neurodegenerative diseases can also lead to the activation of resting microglia, 62 which exacerbates the neuroinflammatory response, induces MMP imbalance, and further enhances neuronal apoptosis 63 .…”

“…58,59 Microglia-mediated neuroinflammation is often associated with the abnormal secretion of ROS, 60 which subsequently stimulate associated inflammatory pathways, thereby accelerating oxidative damage to cells and resulting in neuronal damage and death. 61 In addition, neuronal impairment in neurodegenerative diseases can also lead to the activation of resting microglia, 62 which exacerbates the neuroinflammatory response, induces MMP imbalance, and further enhances neuronal apoptosis. 63 Accordingly, drugs that can inhibit microglial overactivation may also exert neuroprotective effects, causing increasing concern in microglia-related neuroinflammatory diseases.…”

Effect of Hesperidin on Barrier Function and Reactive Oxygen Species Production in an Oral Epithelial Cell Model, and on Secretion of Macrophage-Derived Inflammatory Mediators during Porphyromonas gingivalis Infection

“…On the other hand, in vivo studies using models of supplementation in rats have shown that hesperidin reduces the expression of levels of ROS and thiobarbituric acid reactive substances (TBARS) and increases the activity of antioxidants [ 30 , 31 , 32 ]. Additionally, Lim et al [ 33 ] demonstrated the marked ability of hesperidin to inhibit high-glucose-induced intracellular ROS production in SH−SY5Y neuronal cells. Although the literature shows its promising antioxidant properties, our results using P. gingivalis bacteria associated or not with H 2 O 2 are not in accordance.…”