Parkinson disease(PD) is characterized by the loss of dopaminergic neurons in the substantia nigra and deposition of cytosolic inclusions in surviving neurons(Lewy bodies),resulting in motor deficits and non-motor sym...Parkinson disease(PD) is characterized by the loss of dopaminergic neurons in the substantia nigra and deposition of cytosolic inclusions in surviving neurons(Lewy bodies),resulting in motor deficits and non-motor symptoms.Although Levodopa remains the gold standard treatment for PD,side effects like dyskinesia followed by long-term use could notbe ignored.Consequently,there is a need for devel.opment new drugs.Baicalein is a flavonoid isolated from traditional Chinese herb,Scutellaria baicalensis Georgi.Our laboratory discovered that baicalein could effectively attenuate neurotoxicity of 6-hydroxydopamine(6-OHDA) and promote the differentiation of PC12 cells through high throughput drug screen.ing at the cellularlevel.In vivo studies have shown that baicalein exerts significant therapeutic effect,particularly in the attenuation of muscle tremor in 6-OHDA-lesioned rats.Based on the result from the so far acquired knowledge and previous findings from our laboratory,we could consider neuroprotec.tive mechanism of baicalein focus on the activities ofanti-oxidation and anti-inflammation.Baicalein could prevent oxidative stress and apoptosis through maintaining the mitochondrial function,inhibition of collapse of mitochondrial membrane potential,increase the activity of antioxidant enzymes and restraint of lipid peroxidation via several pathways such as Keap1/Nrf2/HO-1.Anti-inflammatory activity of baicalein exert by attenuating activation of astrocyte and microglia,as well as the production of cathepsin B and cytokines.Additionally,promoting the degradation of α-synuclein contributes to the neuroprotective effect of baicalein against Lewy bodies toxicity.Furthermore,baicalein also modulates the metabolic balance between glutamate(GLu) and gamma-aminobutyric acid(GABA).Overall,baica.lein could protect nervous systemby inhibiting oxidative damage and neuroinflammation caused by environmental and genetic factors.This article reviewed the developments of studies on pharmacody.namics and mechanism of baicalein in PD therapy and provideda reference for further exploration.展开更多
基金supported by National Key R＆D Plan(2016YFC1000905)
文摘Parkinson disease(PD) is characterized by the loss of dopaminergic neurons in the substantia nigra and deposition of cytosolic inclusions in surviving neurons(Lewy bodies),resulting in motor deficits and non-motor symptoms.Although Levodopa remains the gold standard treatment for PD,side effects like dyskinesia followed by long-term use could notbe ignored.Consequently,there is a need for devel.opment new drugs.Baicalein is a flavonoid isolated from traditional Chinese herb,Scutellaria baicalensis Georgi.Our laboratory discovered that baicalein could effectively attenuate neurotoxicity of 6-hydroxydopamine(6-OHDA) and promote the differentiation of PC12 cells through high throughput drug screen.ing at the cellularlevel.In vivo studies have shown that baicalein exerts significant therapeutic effect,particularly in the attenuation of muscle tremor in 6-OHDA-lesioned rats.Based on the result from the so far acquired knowledge and previous findings from our laboratory,we could consider neuroprotec.tive mechanism of baicalein focus on the activities ofanti-oxidation and anti-inflammation.Baicalein could prevent oxidative stress and apoptosis through maintaining the mitochondrial function,inhibition of collapse of mitochondrial membrane potential,increase the activity of antioxidant enzymes and restraint of lipid peroxidation via several pathways such as Keap1/Nrf2/HO-1.Anti-inflammatory activity of baicalein exert by attenuating activation of astrocyte and microglia,as well as the production of cathepsin B and cytokines.Additionally,promoting the degradation of α-synuclein contributes to the neuroprotective effect of baicalein against Lewy bodies toxicity.Furthermore,baicalein also modulates the metabolic balance between glutamate(GLu) and gamma-aminobutyric acid(GABA).Overall,baica.lein could protect nervous systemby inhibiting oxidative damage and neuroinflammation caused by environmental and genetic factors.This article reviewed the developments of studies on pharmacody.namics and mechanism of baicalein in PD therapy and provideda reference for further exploration.
