Abstract
Luteolin, a 3’,4’,5,7-tetrahydroxyflavone, is a plant flavonoid and pharmacologically active agent that has been isolated from several plant species. In the present study, the effects of luteolin obtained from the medicinal plant Elsholtzia rugulosa and the related mechanisms were examined in an Alzheimer's disease (AD) cell model. In this model, copper was used to exacerbate the neurotoxicity in β-amyloid precursor protein Swedish mutation stably overexpressed SH-SY5Y cells (named “APPsw cells” for short). Based on this model, we demonstrated that luteolin increased cell viability, reduced intracellular ROS generation, enhanced the activity of SOD and reversed mitochondrial membrane potential dissipation. Inhibition of caspase-related apoptosis was consistently involved in the neuroprotection afforded by luteolin. Furthermore, it down-regulated the expression of AβPP and lowered the secretion of Aβ1-42. These results indicated that luteolin from the Elsholtzia rugulosa exerted neroprotective effects through mechanisms that decrease AβPP expression, lower Aβ secretion, regulate the redox imbalance, preserve mitochondrial function, and depress the caspase family-related apoptosis.
Highlights
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the progressive loss of memory and cognitive decline
Our findings indicate that copper triggers the neurotoxicity in APPsw overexpressing cells, which exacerbates the Aβ neurotoxicity and can be taken as a model of AD
Dysfunction of mitochondrial membrane and caspase-related apoptosis were seen in copper-treated APPsw cells, indicating that copper plays a role on neurotoxicity in this model
Summary
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the progressive loss of memory and cognitive decline. Elsholtzia rugulosa (Labiatae), which is distributed in the Sichuan, Yunnan and Guizhou provinces of China, is known as a herbal tea, medicinal herb and honey plant [18]. In these regions, the title plant is widely used by local people in the treatment of colds, headaches, pharyngitis, coughs and fever [19]. The effects of luteolin isolated from Elsholtzia rugulosa were evaluated on copper-induced neurotoxicity in the β-amyloid precursor protein Swedish mutation stably overexpressing SH-SY5Y cells
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