Naphthazarin has a protective effect on the 1‐methyl‐4‐phenyl‐1,2,3,4‐tetrahydropyridine‐induced Parkinson's disease model

Abstract

"Neurohormesis" refers to a response to a moderate level of stress that enhances the ability of the nervous systems to resist more severe stress that might be lethal or cause dysfunction or disease. Neurohormetic phytochemicals, such as, resveratrol, sulforaphane, curcumin, and catechins, protect neurons against injury and disease. Naphthoquinones, such as, juglone and plumbagin, induce robust hormetic stress responses. However, the possibility that subtoxic dose of 5,8-dihydroxy-1,4-naphthoquinone (naphthazarin) may protect against brain diseases via the activation of an adaptive stress response pathway in the brain has not been investigated. In this study, we examined the neurohormetic effect of a subtoxic dose of naphthazarin in a Parkinson's disease model. It was found that, under these conditions, naphthazarin enhanced movement ability, prevented loss of dopaminergic neurons, and attenuated neuroinflammation in a 1-methyl-4-phenyl-1,2,3,4-tetrahydropyridine-induced Parkinson's disease model. Furthermore, it was found that the neuroprotective effect of naphthazarin was mediated by the suppression of astroglial activation in response to 1-methyl-4-phenylpyridine treatment. In conclusion, we suggest that naphthazarin, in view of its hormetic effect on neuroprotection, be viewed as a potential treatment for Parkinson's disease and other neurodegenerative diseases associated with neuroinflammation.

A survey from 2012 of evidence for the role of neuroinflammation in neurotoxin animal models of Parkinson's disease and potential molecular targets

“…In a different study, the plant root extract napthazarin was investigated for its therapeutic potential following MPTP exposure in mice. Napthazarin was found to reduce astrogliosis and microglial activation in addition to ameliorating DA neuron loss (Choi et al, 2012). However, in the same study by Choi et al, napthazarin was not shown to have direct neuroprotective function, suggesting that the reduction of astrogliosis and microglial activation by napthazarin was sufficient to protect against MPTP-induced DA neurotoxicity.…”

Naphthazarin suppresses cell proliferation and induces apoptosis in human colorectal cancer cells via the B-cell lymphoma 2/B-cell associated X protein signaling pathway

“…Naphthazarin is an important active ingredient, which exhibits extensive pharmacological activities, including antitumor activity, and due to its low toxicity, it has gained considerable attention (9,10). However, to date the anticancer effects of naphthazarin on human colorectal cancer cells have not been reported.…”

The attenuating effects of plumbagin on pro-inflammatory cytokine expression in LPS-activated BV-2 microglial cells

“…Up-regulated Nrf2 protects the brain against blood-brain barrier breakdown (Alfieri et al, 2011), spinal cord injury (Zhang et al, 2015) and cerebral ischemia (Son et al, 2010). Therefore, Nrf2 may have a protective role in neurodegenerative diseases, including PD (Choi et al, 2012; Cuadrado et al, 2009), AD (Kanninen et al, 2008), and HD (Stack et al, 2010) as well as traumatic brain injury (Yan et al, 2008). Also, in-vivo and in-vitro studies indicated the potent anti-inflammatory and protective effects of PL by inhibiting nitric oxide production, iNOS expression, prostaglandin-E2 production, TNF-α, IL-1β, IL-6, as well as an NF-κB release in mice and RAW 264.7 macrophage cells (Checker et al, 2014; Luo et al, 2010; T.…”