Su-Jin Noh

Phloroglucinol Attenuates Motor Functional Deficits in an Animal Model of Parkinson's Disease by Enhancing Nrf2 Activity

In this study, we investigated whether phloroglucinol (1, 3, 5 - trihydroxybenzene) has therapeutic effects in cellular and animal model of Parkinsons 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.

SF-6 attenuates 6-hydroxydopamine-induced neurotoxicity: An in vitro and in vivo investigation in experimental models of Parkinson's disease

ETHNOPHARMACOLOGICAL RELEVANCE Indigofera tinctoria Linn. (I. tinctoria, Fabaceae) has been widely used for several years in the traditional Indian and Chinese system of Medicine for the treatment of epilepsy, nervous and brain disorders. AIM OF THE STUDY The effect of SF-6, a compound isolated from I. tinctoria to exhibit neuroprotection in in vitro and in vivo models of Parkinsons disease (PD), was investigated. MATERIALS AND METHODS Using human neuroblastoma SH-SY5Y cells, the effect of SF-6 on α-synuclein- or 6-hydroxydopamine (6-OHDA)-, hydrogen peroxide (H(2)O(2))-induced cytotoxicity in vitro was investigated. In in vivo studies SF-6 was challenged against 6-OHDA-induced neuronal damage and behavioral deficits in mice. RESULTS SF-6 (1, 5 and 10 μg/mL) significantly inhibited α-synuclein- or 6-OHDA-, H(2)O(2)-induced cytotoxicity and decreased the reactive oxygen species production in SH-SY5Y cells. SF-6 also scavenged hydroxyl free radicals. In in vivo evaluation, SF-6 attenuated the contralateral rotational asymmetry observed by apomorphine challenge in 6-OHDA-lesioned mice. Further, the behavioral deficits evaluated by rotarod test, Y-maze and passive avoidance tasks were reversed by SF-6 and was found more potent compared with standard compound deprenyl. CONCLUSION Data suggest that SF-6 showed neuroprotection in experimental models of PD due to its potent antioxidant action supporting the traditional claim for its use in nervous and brain disorders.

SP-8203 shows neuroprotective effects and improves cognitive impairment in ischemic brain injury through NMDA receptor

The extracts of earth worms, Eisenia andrei, have been used as a therapeutic agent for stroke in the traditional medicine. It is also reported that the protease fraction separated from the extracts has strong anti-thrombotic activity. Besides anti-thrombotic actions, we found that SP-8203, N-[3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propyl]-N-{4-[3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propylamino]butyl}acetamide, derived from the extracts of earth worms blocked N-methyl-(D)-aspartate (NMDA) receptor-mediated excitotoxicity in a competitive manner. The neuroprotective effects of SP-8203 were attributable to prevention of Ca(2+) influx through NMDA receptors. The systemic administration of SP-8203 markedly reduced neuronal death following middle cerebral artery occlusion in rats. SP-8203 significantly improved spatial learning and memory in the water maze test. These results provided strong pharmacological basis for its potential therapeutic roles in cerebral ischemia.

Methylparaben protects 6-hydroxydopamine-induced neurotoxicity in SH-SY5Y cells and improved behavioral impairments in mouse model of Parkinson's disease

Parkinsons disease (PD) is a progressive neurodegenerative disorder of unknown etiology. Considerable evidence suggests that free radical formation and oxidative stress might play an important role in the pathogenesis of PD. In the present investigation we evaluated the therapeutic potential of methylparaben (MP) a well known pharmaceutical preservative against 6-hydroxydopamine (6-OHDA) neurotoxicity in SH-SY5Y cells and in a mouse model of PD. At nanomolar concentrations MP (0.01, 0.1 and 1 nM) significantly attenuated the 6-OHDA- and hydrogen peroxide-induced cytotoxicity in SH-SY5Y cells. The reactive oxygen species generated by 6-OHDA in SH-SY5Y cells was also inhibited by MP in a concentration dependent fashion. Further, intranigral damage induced by stereotaxically injecting 6-OHDA in mouse brain was significantly attenuated by MP treatment. MP (1, 10 or 50 μg/kg, i.p.) prevented apomorphine-induced rotational behavior and significantly improved motor deficits in 6-OHDA-lesioned mice. The cognitive impairments as evaluated by passive avoidance and Y-maze task in mice were also attenuated by MP concentration dependently. Immunohistochemical analysis of substantia nigra in MP treated mice showed significantly higher number of surviving tyrosine hydroxylase positive cells. Furthermore, MP also suppressed the lipid peroxidation products in 6-OHDA-lesioned mouse brain tissues. Considering the results obtained, the marked neuroprotection exhibited by MP might be attributed to its potent antioxidant property. In conclusion, this study reports the neuroprotective properties of MP in experimental models of PD for the first time and can be developed as a potential therapeutic agent.

Dehydroevodiamine attenuates cognitive dysfunction and neuronal damages in Tg2576 mice

Dehydroevodiamine (DHED), derived from Evodia rutaecarpa, was synthesized and it was previously reported that DHED has anti-dementic activities through various tests. In the present study, it was investigated whether DHED could attenuate cognitive deficits and A proudction in Tg2576 mice. We used memory tests, A 40 and A 42 ELISA kit, and western blotting to confirm total A proteins. The cognitive impairments in Tg2576 mice were significantly improved by DHED treatment. Interestingly, DHED significantly lowered the soluble A 40 and A 42 levels and total A proteins in the cerebral cortex of Tg2576 mice. These results show that DHED might attenuate cognitive dysfunction through blocking production of A . Thus DHED might be one of the potential therapeutic candidates for Alzheimer’s disease.