Schisandra chinensis Stem Ameliorates 3-Nitropropionic Acid-Induced Striatal Toxicity via Activation of the Nrf2 Pathway and Inhibition of the MAPKs and NF-κB Pathways

Abstract

The beneficial value of the stems of Schisandra chinensis (SSC) in neurological diseases is unclear. We examined whether SSC aqueous extract (SSCE) alleviates striatal toxicity in a 3-nitropropionic acid (3-NPA)-induced mouse model of Huntington's disease (HD). SSCE (75, 150, or 300 mg/kg/day, p.o.) was given daily before or after 3-NPA treatment. Pre- and onset-treatment with SSCE displayed a significant protective effect and pretreatment was more effective as assessed by neurological scores and survival rate. These effects were related to reductions in mean lesion area, cell death, succinate dehydrogenase activity, microglial activation, and protein expression of inflammatory factors including interleukin (IL)−1β, IL-6, tumor necrosis factor-alpha, inducible nitric oxide synthase, and cyclooxygenase-2 in the striatum after 3-NPA treatment. Pretreatment with SSCE stimulated the nuclear factor erythroid 2-related factor 2 pathway and inhibited phosphorylation of the mitogen-activated protein kinase and nuclear factor-kappa B signaling pathways in the striatum after 3-NPA treatment. The gomisin A and schizandrin components of SSCE significantly reduced the neurological impairment and lethality induced by 3-NPA treatment. These results indicate for the first time that SSCE may effectively prevent 3-NPA-induced striatal toxicity during a wide therapeutic time window through anti-oxidative and anti-inflammatory activities. SSCE has potential value in preventive and therapeutic strategies for HD-like symptoms.

C60 Fullerene Reduces 3-Nitropropionic Acid-Induced Oxidative Stress Disorders and Mitochondrial Dysfunction in Rats by Modulation of p53, Bcl-2 and Nrf2 Targeted Proteins

“…The intensification of oxidative processes in brain mitochondria was accompanied by the increase of GSSG content and decrease of GSH concentration as well as decrease of GSH/GSSG ratio, which were additional important indicators of oxidative stress and mitochondrial dysfunction [ 13 , 15 ]. Our findings were in concordance with previous studies where the disturbances in mitochondrial bioenergetics, defects in mitochondrial complexes II–IV, F 1 F 0 ATP-ase, and aconitase, mitochondrial swelling, disbalance in the pro-antioxidant system, excessive mitochondrial fission, and subsequent neuronal cell death in different regions of the brain after prolonged and acute 3-NPA treatment have been demonstrated [ 4 , 38 , 39 , 40 ]. Numerous pieces of evidence from clinical and experimental studies validated the key role of oxidative stress and concomitant mitochondrial dysfunction in mediating the neuronal degeneration and behavioral abnormalities at HD as well as after the exposure to neurotoxin 3-NPA [ 3 , 6 , 8 , 38 , 39 ].…”

“…We consider that in our case, Nrf2 activation with an accumulation of Nrf2 protein in the nucleus, can result from 3-NPA-induced ROS overproduction, especially O 2 •− , GSH/GSSG redox alteration, loss of ATP, or even as a direct response to SDH inhibition. Our findings coincide with previous reports that acute and prolonged 3-NPA administration provokes Nrf2 activation in neuronal cells [ 38 , 53 , 61 ] and this process was ROS-regulated [ 16 , 57 ].…”

Schisandrin ameliorates cognitive deficits, endoplasmic reticulum stress and neuroinflammation in streptozotocin (STZ)-induced Alzheimer’s disease rats

“…Schisandrin is reported to restrain the cartilage degradation and inflammation by inhibiting the MAPK and NF-κB pathway [ 25 ]. Schisandrin reveals the anti-toxicity through the activation of the Nrf2 pathway and inhibition of MAPKs and NF-κB pathway [ 14 ]. In our study, the degradation of IκBα and the phosphorylation of IκBα and IKKα/β in STZ induced group were significantly reversed after schisandrin treatment.…”

Schisandrin Restores the Amyloid β-Induced Impairments on Mitochondrial Function, Energy Metabolism, Biogenesis, and Dynamics in Rat Primary Hippocampal Neurons

“…Schisandrin is a natural active ingredient derived from the Chinese herb fruit, Schisandra chinensis [12]. Numerous studies have reported that schisandrin is beneficial for the central nervous system by inhibiting neuroinflammation [13], relieving endoplasmic reticulum stress [14], and suppressing autophagy [15]. Schisandrin is further reported to exert protective effects against glutamate-induced toxicity through inhibiting intrinsic mitochondria-dependent apoptosis, suggesting the implication of schisandrin in mitochondrial regulation [16].…”