Sophora Tomentosa Extract Prevents MPTP-Induced Parkinsonism in C57BL/6 Mice Via the Inhibition of GSK-3β Phosphorylation and Oxidative Stress

Abstract

Sophora species are used as dietary medicines in aging-associated symptoms. Sophora tomentosa L. (ST) is a native medicinal plant in Southeast Asia; however, there is no pharmacological literature about ST extract. The present study evaluates the antioxidant phytoconstituent contents and radical scavenging capacities of ST extract. The further investigation was to clarify the neuroprotective mechanism of ST extract against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinsonism by assaying the activities of the dopaminergic system and antioxidant defenses, glycogen synthase kinase 3β (GSK3-β) phosphorylation, and α-synuclein levels in C57BL/6 mice. The results show that ST extract alleviated the motor deficits in MPTP-induced Parkinsonism with four behavioral tests, including a rearing locomotor, catalepsy test, balance beam walking test, and pole test. ST extract reversed the number of tyrosine hydroxylase (TH)-positive neurons in substantia nigra (SN) that had decreased by MPTP. ST extract also restored the decreased levels of dopamine and the expression of tyrosine hydroxylase (TH) in the striatum. Furthermore, ST extract restored the levels of glutathione (GSH) and the activities of antioxidant enzymes, and decreased the elevated levels of malondialdehyde (MDA) in mouse striatum. ST extract also decreased α-synuclein overexpression and GSK-3β phosphorylation in mouse striatum. In vitro, ST extract exerted higher 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) radical scavenging capacities through its higher phenolic contents, especially protocatechuic acid and epicatechin. These results suggest that ST extract has the potential to counteract MPTP-induced motor deficit. The neuroprotective mechanism of ST extract against MPTP-induced Parkinsonism might be related to decreasing GSK-3β phosphorylation and restoring the activities of striatal antioxidant defenses to restore the nigrostriatal dopaminergic function and decrease α-synuclein accumulation.

Anthocyanins and Their Metabolites as Therapeutic Agents for Neurodegenerative Disease

“…Beneficial effects were also observed in this model using an extract from Sophora tomentosa , which contains high levels of PCA [220]. In addition to preserving dopaminergic neurons, this extract enhanced antioxidant status in the striatum and significantly reduced the expression of alpha-synuclein and phosphorylated (active) glycogen synthase kinase 3-β (GSK3-β), which can activate pro-apoptotic signaling cascades [220]. Syringic acid was also shown to improve outcomes in the MPTP mouse model by preserving dopaminergic neurons through activation of antioxidant enzymes and reductions in pro-inflammatory markers [221].…”

“…These observations correlated with improved motor function in rotarod testing. Beneficial effects were also observed in this model using an extract from Sophora tomentosa , which contains high levels of PCA [220]. In addition to preserving dopaminergic neurons, this extract enhanced antioxidant status in the striatum and significantly reduced the expression of alpha-synuclein and phosphorylated (active) glycogen synthase kinase 3-β (GSK3-β), which can activate pro-apoptotic signaling cascades [220].…”

The Underlying Mechanism of Paeonia lactiflora Pall. in Parkinson’s Disease Based on a Network Pharmacology Approach

“…Kaempferol can also maintain the stability of blood-brain barrier and down-regulate HMGB1/TLR4 pathway to reduce striatal injury in mice ( Yang et al, 2019 ). A number of studies showed that paeoniflorin protects PC12 cells against MPP+, acid, and glutamate induced neuron injury via regulating autophagy, apoptosis, and mitochondrial membrane potential ( Cao et al, 2010 ; Sun et al, 2012 ; Zheng et al, 2016 ). It also reduces dopaminergic neurodegeneration in MPTP model by inhibition of neuroinflammation and suppression of the accelerated dopamine catabolism via Amine oxidase B (MAOB) inhibition ( Liu et al, 2006 ; Zheng et al, 2017 ).…”

“…P. lactiflora and Mucuna pruriens seeds have similar mechanism in ameliorating neuroinflammation and apoptosis, while the latter contains natural levodopa used as a dopamine supplement in India (Lieu et al, 2012;Rai et al, 2017). Both P. lactiflora and Sophora Tomentosa exert antioxidant properties, which might be associated with their common component, catechin (Chang et al, 2019). Although P. lactiflora is a major component in several formulas reported to be neuroprotective in vivo (Ahn et al, 2019;Tang et al, 2020), this is the first time to explore its mechanism alone from a systematic level, which may benefit further drug manufacturing.…”

Neuroprotective Activities of Boophone haemanthoides (Amaryllidaceae) Extract and Its Chemical Constituents

“…However, the prolonged use of levodopa has been shown to be associated with some side effects, including the enhancement of oxidative stress and the acceleration of degeneration of residual dopaminergic neurons in PD patients using this medication [ 9 ], thus necessitating the search for alternative treatment options. A number of in vitro and in vivo studies have shown that herbal medicines, phytochemicals, and other plant-derived bioactive compounds and dietary supplements could ameliorate the effects of PD [ 13 , 14 , 15 ].…”