Baicalin attenuated substantia nigra neuronal apoptosis in Parkinson’s disease rats via the mTOR/AKT/GSK-3β pathway

Abstract

This focus of our research is to investigate the protective effect of Baicalin on apoptosis and mTOR/AKT/GSK-3β pathway in substantia nigra neurons in a rat model for Parkinson's disease, induced by 6-Hydroxydopamine. Thirty healthy female Sprague-Dawley rats were randomly divided into control group, model group, and Baicalin group. The Parkinson model was established by injecting 6-Hydroxydopamine into the right substantia nigra of rats in model and Baicalin group. The rats in Baicalin group were intragastrically administered with Baicalin (25 mg/kg/day) for four weeks. At the same time, the rats in control and model groups were intragastrically administered with equivalent solvents. We observed the rat turns, rotation speed and left forelimb usage. The protein expression levels of α-SYN, mTOR, AKT, and GSK-3β in substantia nigra were detected by immunohistochemistry and Western blotting. Compared with model group, Baicalin significantly reduced the number of rotation speeds and neuron apoptosis (P < 0.001, respectively). However, the left forelimb use rate was notably increased after treatment with Baicalin (P < 0.001, respectively). Also, Baicalin decreased the expression levels of α-SYN, mTOR, AKT, and GSK-3β in rats when compared with those in model group (P < 0.001, respectively).

PI3K/AKT Signal Pathway: A Target of Natural Products in the Prevention and Treatment of Alzheimer’s Disease and Parkinson’s Disease

“…Zhang et al showed that the anti-PD function of baicalein is probably related to the activation of Nrf2/HO-1, protein kinase C (PKC) and PI3K/AKT signaling pathways (Zhang et al, 2012). Baicalin has one more glucuronide in the seven hydroxyl group than baicalein (Figure 2), which inhibit 6-OHDA-induced apoptosis of substantia nigra neurons in PD rats through mTOR/AKT/GSK-3β pathway (Zhai et al, 2019). Apigenin has been shown to remarkably reduce the effects of 1methyl-4-phenylpyridine (MPP + )-induced apoptosis in experimental models of PD.…”

Do Naturally Occurring Antioxidants Protect Against Neurodegeneration of the Dopaminergic System? A Systematic Revision in Animal Models of Parkinson's Disease

“…Consequently, decreased levels of this protein can rescue dopaminergic neurons from cell death. This property has been demonstrated for polyphenols such as astilbin, baicalein, baicalin, chrysin, curcumin, 7,8-dihydroxyflavone, naringenin and resveratrol [ 45 , 52 , 54 , 57 , 58 , 86 , 118 , 119 ].…”

“…The apoptosis process is closely related to neuronal death in PD, as high levels of Bax and caspase 3 have been detected in the brains of patients with it [ 157 ]. Several of the polyphenols studied, such as baicalein, baicalin, curcumin, ferulic acid, icariin, lutein, polydatin, puerarin and resveratrol have the ability to inhibit apoptosis in dopaminergic neurons by reducing the expression of proapoptotic factors (Bax, cytochrome C, caspases 3, 8, 9 and 12) and increase levels of the anti-apoptotic protein Bcl-2 [ 48 , 49 , 56 , 86 , 91 , 118 , 119 , 158 - 160 ]. These antioxidant substances and their effects are summarized in Table 7 .…”

“…In addition, this signaling pathway is associated with the mammalian target of rapamycin complex 1 (mTORC1), indispensable for the survival and neuroprotection of dopaminergic neurons [ 168 ], and whose activation was induced by myricitrin and the naringin [ 89 , 90 ]. Similarly, baicalin treatment was associated with activation of the mTOR/Akt/glycogen synthase kinase-3β (GSK-3β) signaling pathway [ 119 ]. GSK-3β is an important gene tightly related to the loss of dopaminergic neurons in PD models and it can be inactivated by Akt [ 169 ].…”

Baicalin Coadministration with Lithium Chloride Enhanced Neurogenesis <i>via</i> GSK3β Pathway in Corticosterone Induced PC-12 Cells

“…Recent emerging studies have shown that baicalin can exhibit antidepressant effects by promoting hippocampal neurogenesis and exhibit an almost consistent effect with lithium chloride. [29][30][31] Lithium, as a known GSK3β inhibitor, has significant antidepressant effect. It is one of the commonly used prescription drugs for the treatment of bipolar disorder.…”