Neuroprotective Effect of Luteolin-7-O-Glucoside against 6-OHDA-Induced Damage in Undifferentiated and RA-Differentiated SH-SY5Y Cells.

Stephanie Cristine Hepp Rehfeldt,Stefan Laufer,Celso Alves,Márcia Inês Goettert,Joana Silva,Rui Pedrosa,Susete Pinteus

doi:10.3390/ijms23062914

Abstract

Luteolin is one of the most common flavonoids present in edible plants and its potential benefits to the central nervous system include decrease of microglia activation, neuronal damage and high antioxidant properties. The aim of this research was to evaluate the neuroprotective, antioxidant and anti-inflammatory activities of luteolin-7-O-glucoside (Lut7). Undifferentiated and retinoic acid (RA)-differentiated SH-SY5Y cells were pretreated with Lut7 and incubated with 6-hydroxydopamine (6-OHDA). Cytotoxic and neuroprotective effects were determined by MTT assay. Antioxidant capacity was determined by DPPH, FRAP, and ORAC assays. ROS production, mitochondrial membrane potential (ΔΨm), Caspase–3 activity, acetylcholinesterase inhibition (AChEI) and nuclear damage were also determined in SH-SY5Y cells. TNF-α, IL-6 and IL-10 release were evaluated in LPS-induced RAW264.7 cells by ELISA. In undifferentiated SH-SY5Y cells, Lut7 increased cell viability after 24 h, while in RA-differentiated SH-SY5Y cells, Lut7 increased cell viability after 24 and 48 h. Lut7 showed a high antioxidant activity when compared with synthetic antioxidants. In undifferentiated cells, Lut7 prevented mitochondrial membrane depolarization induced by 6-OHDA treatment, decreased Caspase-3 and AChE activity, and inhibited nuclear condensation and fragmentation. In LPS-stimulated RAW264.7 cells, Lut7 treatment reduced TNF-α levels and increased IL-10 levels after 3 and 24 h, respectively. In summary, the results suggest that Lut7 has neuroprotective effects, thus, further studies should be considered to validate its pharmacological potential in more complex models, aiming the treatment of neurodegenerative diseases.

Highlights

Neurodegenerative diseases (ND) are comprised of distinct and heterogeneous disorders characterized by the progressive and selective loss of neurons
The capacity of undifferentiated SH-SY5Y cells to recover from 6-OHDA stimuli was evaluated
The results presented here showed that 6-OHDA treatment increased AChE activity in 43.47%

Summary

Introduction

Neurodegenerative diseases (ND) are comprised of distinct and heterogeneous disorders characterized by the progressive and selective loss of neurons. The prevalence and symptoms worsening are intimately related with age, and as the global population gets older, the need for new ND therapeutic alternatives and deeper knowledge of their pathophysiology is urgent. The World Health Organization (WHO) estimates that by 2040, ND such as Alzheimer’s disease (AD), and other types of dementia, or conditions that compromises motor function like Parkinson’s disease (PD) or amyotrophic lateral sclerosis (ALS), will be the second most prevalent cause of death, after cardiovascular diseases [1]. Due to the complexity and heterogeneity of NDs, most of the synthetic drugs evaluated in in vitro models and/or clinical trials end up failing [2], and further efforts must be conducted to develop an efficient disease-modifying treatment. The glycosylated form of luteolin, known as cyranoside or luteolin-7-O-glucoside (Lut7)

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