Abstract
Parkinson’s disease (PD) is an age-related neurological disorder characterized by a loss of dopaminergic neurons within the midbrain. Neuroinflammation has been nominated as one of the key pathogenic features of PD. Recently, the inadequate pharmacotherapy and adverse effects of conventional drugs have spurred the development of unconventional medications in the treatment of PD. The purpose of this study is to investigate the anti-neuroinflammatory mechanisms of Atractylenolide-I (ATR-I) in in vivo and in vitro models of PD. Nitrite assay was measured via Griess reaction in lipopolysaccharide (LPS) stimulated BV-2 cells. mRNA and protein levels were determined by a reverse transcription-polymerase chain reaction (RT-PCR) and immunoblot analysis, respectively. Further, flow cytometry, immunocytochemistry, and immunohistochemistry were employed in BV-2 cells and MPTP-intoxicated C57BL6/J mice. Pre-treatment with ATR-I attenuated the inflammatory response in BV-2 cells by abating the nuclear translocation of nuclear factor-κB (NF-κB) and by inducing heme oxygenase-1 (HO-1). The intraperitoneal administration of ATR-I reversed MPTP-induced behavioral deficits, decreased microglial activation, and conferred protection to dopaminergic neurons in the mouse model of PD. Our experimental reports establish the involvement of multiple benevolent molecular events by ATR-I in MPTP-induced toxicity, which may aid in the development of ATR-I as a new therapeutic agent for the treatment of PD.
Highlights
Parkinson’s disease (PD) is a progressive, neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and microglial malfunction.Accumulating evidence from various scientific studies suggests that neuroinflammation is one of the important factors involved in the selective degeneration of the nigral neurons in PD [1,2,3,4]
Our experimental reports establish the involvement of multiple benevolent molecular events by ATR-I in MPTP-induced toxicity, which may aid in the development of ATR-I as a new therapeutic agent for the treatment of PD
Our results demonstrate the involvement of multiple molecular events mediated by ATR-I for its anti-neuroinflammatory effect in LPS-induced BV-2 cells and MPTP-induced neurotoxicity
Summary
Parkinson’s disease (PD) is a progressive, neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and microglial malfunction.Accumulating evidence from various scientific studies suggests that neuroinflammation is one of the important factors involved in the selective degeneration of the nigral neurons in PD [1,2,3,4]. A. macrocephala is popularly known as “Baizhu” in traditional Chinese medicine and has long been used for a variety of corresponding medicinal properties [6] This species of plant belongs to the Asteraceae family, and its distribution has been found in some Asian countries, such as Japan, China, and Korea. In terms of the activities elicited by ATR-I in a biological system, pharmacological studies have demonstrated its gastrointestinal inhibitory effects [7], anti-oxidant activity [8], and anti-cancer activity [9]. ATR-I has been reported to increase the hunger and mid-arm muscle circumference of patients with cachectic cancer, and it can significantly inhibit serum levels of interleukin-1 (IL-1), tumor necrosis factor-α (TNF-α), and urine proteolysis-inducing factors [10].
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