Morin exerts neuroprotective actions in Parkinson disease models in vitro and in vivo

Abstract

Aim: To investigate the neuroprotective effects of morin on 1-methyl-4-phenylpyridinium ion (MPP + )-induced apoptosis in neuronal differentiated PC12 cells as well as in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson disease (PD). Methods: PC12 cells were challenged with MPP + in the presence or absence of morin. Cell viability was determined using MTT assay. Cell apoptosis was measured using flow cytometry. Generation of reactive oxygen species (ROS) was assayed using fluorescence assay. In an MPTP mouse model of PD, behavioral deficits, striatal dopamine content, and number of dopaminergic neurons were measured. Results: MPP + induced apoptosis and ROS formation in PC12 cells. Concomitant treatment with morin (5-50 μmol/L) significantly attenuated the loss of cell viability and apoptosis when compared with MPP + treatment alone. Morin also attenuated ROS formation induced by MPP + . MPTP induced permanent behavioral deficits and nigrostriatal lesions in mice. When administered prior to MPTP, morin (20 to 100 mg/kg) attenuated behavioral deficits, dopaminergic neuronal death and striatal dopamine depletion in the MPTP mouse model. Conclusion: The findings suggest that morin has neuroprotective actions both in vitro and in vivo, and may provide a novel therapeutic agent for the treatment of PD and other neurodegenerative diseases.

Protective effect of Bu-7, a flavonoid extracted from Clausena lansium, against rotenone injury in PC12 cells

“…This kind of dose-response relationship has been reported previously [21,35,36] . It is common that a chemical binds to two or more targets/receptors with different affinities.…”

“…It is well known that rotenone, 6-OHDA, and MPP + cause neurotoxicity in cells in vitro [21,22] ; thus, our previous data suggested that Bu-7 may have a positive effect on anti-apoptosis and mitochondrial protection. Therefore, in our present study, we utilized rotenone to create an in vitro cell model to study the protective effects of Bu-7 in PC12 cells and tried to find the possible underlying mechanisms.…”

Phenolics

“…Acacetin at a dose of 200 nM protected in vitro and in vivo mesencephalic cells against MPP + insults with decrease of NO, prostaglandin E2 (PGE2), and TNF-α. 24 Hydroxylation of acacetin in C5′ yields diosmetin (CS 3.12), which at a dose of 500 nM protected hippocampal neurons against glutamate insults. 24 Hydroxylation of acacetin in C5′ yields diosmetin (CS 3.12), which at a dose of 500 nM protected hippocampal neurons against glutamate insults.…”

Naturally occurring polyphenol, morin hydrate, inhibits enzymatic activity of N-methylpurine DNA glycosylase, a DNA repair enzyme with various roles in human disease

“…Also, many studies have demonstrated that polyphenols sensitize cancer cells to chemotherapy via effects on survival and growth signaling pathways [35, 36]. Moreover, morin hydrate has been shown to exert a neuroprotective effect via its antioxidant properties in mouse models of Parkinson’s disease [37] and against excitotoxic neuronal death in culture [38]. However, the relatively high IC 50 in live cells and in extracts would not be conducive to using morin hydrate to inhibit MPG-induced carcinogenesis, resistance to chemotherapy, or alkylation damage-induced neurotoxicity.…”