Abstract
In this study, we investigated whether phloroglucinol (1, 3, 5 - trihydroxybenzene) has therapeutic effects in cellular and animal model of Parkinson's disease (PD). PD is the second most common, chronic and progressive neurodegenerative disease, and is clinically characterized with motor dysfunctions such as bradykinesia, rigidity, postural instability, gait impairment, and resting tremor. In the brains of PD patients, dopaminergic neuronal loss is observed in the Substantia nigra. Although the exact mechanisms underlying PD are largely unknown, mitochondrial dysfunction and oxidative stress are thought to be critical factors that induce the onset of the disease. Here, phloroglucinol administration was shown to attenuate motor functional deficits evaluated with rota-rod and apomorphine-induced rotation tests in 6-hydroxydopamine (6-OHDA)-induced PD animal models. Moreover, phloroglucinol ameliorated the loss of synapses as assessed with protein levels and immunoreactivity against synaptophysin in the midbrain region of the 6-OHDA-lesioned rats. In addition, in SH-SY5Y cultures, the cytotoxicity of 6-OHDA was reduced by pre-treatment with phloroglucinol. The increase in the reactive oxygen species, lipid peroxidation, protein carbonyl formation and 8-hydroxyguanine caused by treatment with 6-OHDA was attenuated by phloroglucinol in SH-SY5Y cells. Furthermore, phloroglucinol treatment rescued the reduced levels of nuclear Nrf2, antioxidant enzymes, i.e., catalase and glutathione peroxidase, in 6-OHDA-treated cells. Taken together, phloroglucinol has a therapeutic potential for treatment of PD.
Highlights
Parkinson’s disease (PD) is a progressive neurodegenerative disorder mainly characterized by the loss of dopaminergic neurons in the midbrain and the presence, in the affected brain regions, of protein inclusions called Lewy bodies [1]
Rats that were co-administered with phloroglucinol and 6-OHDA showed improved motor function compared with the 6-OHDAlesioned group (p,0.05) and reached significant recovery at similar levels to the control group, the administration of phloroglucinol alone was not found to affect the motor function assessed with rota-rod (Figure 1A)
We demonstrated that phloroglucinol, a component from the edible brown algae, Ecklonia cava can attenuate motor functional deficits as assessed with the rota-rod and apomorphine-induced rotation tests in a 6-OHDA-lesioned rat PD model (Figure 1)
Summary
Parkinson’s disease (PD) is a progressive neurodegenerative disorder mainly characterized by the loss of dopaminergic neurons in the midbrain and the presence, in the affected brain regions, of protein inclusions called Lewy bodies [1]. We investigated whether phloroglucinol (1, 3, 5trihydroxybenzene) affects motor functional deficits in a unilaterally 6-hydroxydopamine (6-OHDA)-injected rat PD model. Because it shares a similarity with the endogenous neurotransmitter dopamine, 6-OHDA can enter dopaminergic neurons via the dopamine transporter. Several published reports have described the protective effects of phloroglucinol against H2O2-induced oxidative stress in in vitro and in vivo [7,8]
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