7,8-Dihydroxyflavone Protects Nigrostriatal Dopaminergic Neurons from Rotenone-Induced Neurotoxicity in Rodents

Abstract

7,8-Dihydroxyflavone (7,8-DHF) is thought to be a promising therapeutic agent for various neurodegenerative diseases. The major purpose of this study was to investigate the neuroprotective effects of 7,8-DHF on the rotenone-induced motor deficit of Parkinson’s disease. Nine-month-old rats were treated with rotenone (2 mg/kg/day, i.h.) for 5 weeks to establish the animal model of Parkinson’s disease (PD), and 7,8-DHF (5 mg/kg, i.p.) was administrated daily throughout the whole period of rotenone injection. Five weeks later, an open field test was used to assess the motor ability of the animals. TH immunostaining was performed to evaluate rotenone-induced neurotoxicity on substantia nigra (SN) dopaminergic neurons and the DA terminals in the striatum. Western blot analyses were used to examine the expressions of TH, BDNF/TrkB signaling cascades, phospho-α-synuclein (Ser129), α-synuclein, and phospho-tau (Ser396) in SN. The results revealed that treatment with 7,8-DHF improved PD model’s behavioral performance and reduced dopaminergic neuron loss in the SN and striatum, associated with the activation of TrkB receptors and its signaling cascades, and reduced p-MAPK, p-α-synuclein, and p-tau. Collectively, these results indicated that 7,8-DHF displayed prominent neuroprotective properties, providing a promising therapeutic strategy for PD treatment.

The protective effect of natural compounds against rotenone‐induced neurotoxicity

“…[112,113] 7,8-DHF has been shown to display its protective effect on rotenone-induced neurotoxicity in rats through activation of TrkB receptors and the corresponding signaling pathways. [114] 3.3.…”

TrkB signaling regulates the cold-shock protein RBM3-mediated neuroprotection

“…The data thus support targeting the pathway pharmacologically at various levels—from TrkB downwards—for the induction of RBM3. Of course, TrkB activators including 7,8-DHF and related molecules ( Jang et al, 2010 ; Chen et al, 2018 ) are well known to have neuroprotective effects on synapses, improving learning and memory and reducing neuronal loss in various disease models ( Devi & Ohno, 2012 ; Wu et al, 2014 ; Zhang et al, 2014 ; Barriga et al, 2017 ; Nie et al, 2019 ), which may, at least in part be due to RBM3 induction. A number of anti-depressants are known to induce TrkB activation ( Björkholm & Monteggia, 2016 ), and it will be interesting to test their capacity to induce RBM3 through this pathway.…”

The TrkB agonist 7,8-dihydroxyflavone improves sensory-motor performance and reduces lipid peroxidation in old mice

“…7,8-DHF has been shown to improve motor function and prolongs survival in Huntington's disease (Jiang et al 2013). In fact, 7,8-DHF has been shown to have a therapeutic effect when administered chronically in animal models such as Parkinson (Nie et al 2019 al. 2014), and depression models (Liu et al 2013).…”