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Bruceine D elevates Nrf2 activation to restrain Parkinson's disease in mice through suppressing oxidative stress and inflammatory response.

Abstract：

:Parkinson's disease (PD) is neurodegenerative disease, featured by a loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc), characteristic motor symptoms and cognitive impairment. Development of effective therapeutic drugs for PD is necessary. In this study, we investigated the potential of Bruceine D (BD) during PD progression. After establishment of PD mouse models, we found that BD markedly improved the motor function of mice and alleviated chemically induced dopaminergic neuron loss of tyrosine hydroxylase (TH) in the SNpc area. BD treatments markedly repressed the neuroinflammation in SNpc by restricting nuclear factor κB (NF-κB) activation, accompanied with the reduced activity of astrocytes and microglial. BD also improved the antioxidant system in MPTP-challenged mice, as proved by the up-regulated superoxide dismutase (SOD) and glutathione (GSH), and down-regulated malondialdehyde (MDA) in SNpc and striatum (STR). The anti-oxidant effects of BD were regulated by the activation of nuclear factor E2-related factor 2 (Nrf2) signaling, contributing to the expression of Nrf2 down-streaming signals such as heme oxygenase-1 (HO-1), NAD(P)H: quinone oxidoreductase 1 (NQO1) and glutathione cysteine ligase modulatory subunit (GCLM). In MPP+-challenged mouse neurons, BD exhibited cytoprotective effects by improving the Nrf2-meditated antioxidant system and abolished the MPP+-triggered inflammatory response through hindering the activation of the NF-κB signal. The pharmacokinetic parameters and organ distribution findings demonstrated that BD showed a brain tissue targeting function. Moreover, both in vivo and in vitro analysis indicated that BD had few side effects. Collectively, results here demonstrated that BD was effective for the inhibition of dopaminergic neuronal loss and PD progression by activating Nrf2 without toxicity.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Yang Y,Kong F,Ding Q,Cai Y,Hao Y,Tang B

doi

10.1016/j.bbrc.2020.03.097

subject

Has Abstract

pub_date

2020-06-11 00:00:00

pages

1013-1020

issue

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(20)30588-X

journal_volume

526

pub_type

杂志文章

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Bruceine D elevates Nrf2 activation to restrain Parkinson's disease in mice through suppressing oxidative stress and inflammatory response.