摘要：Acacetin (5,7-dihydroxy-4′-methoxyflavone), a constituent of flavone naturally present in plants, has anti-cancer and anti-inflammatory activities. Neuroinflammation is thought to be one of the major pathological mechanisms responsible for Parkinson’s disease (PD), and has been a primary target in the development of treatment for PD. In the present study, we evaluated the neuroprotective effect of acacetin in PD induced by 1-methyl-4-phenylpyridine (MPP+)/or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and examined the related pathways in vitro and in vivo . In primary mesencephalic culture, acacetin protected dopaminergic (DA) cells and inhibited production of inflammatory factors such as nitric oxide, prostaglandin E2, and tumor necrosis factor-α against MPP+-induced toxicity in a dose-dependent manner. Then, we confirmed the effect of acacetin (10 mg/kg/d for 3 d, per os ( p.o. )) in a mouse model of PD induced by MPTP (30 mg/kg/d for 5 d, intraperitoneally (i.p.)). In the behavioral test (pole test), the acacetin-treated mice showed decreased time of turning and locomotor activity, which were longer in MPTP-only treated mice. In addition, the acacetin-treated group inhibited degeneration of DA neurons and depletion of dopamine level induced by MPTP toxicity in the substantia nigra and striatum of the brain. Moreover, the acacetin-treated group inhibited microglia activation, accompanied by production of inducible nitric oxide synthases and cyclooxygenase-2. These results suggest that acacetin can protect DA neurons against the neurotoxicity involved in PD via its anti-inflammatory action.
