Apigenin Attenuates Functional and Structural Alterations via Targeting NF-kB/Nrf2 Signaling Pathway in LPS-Induced Parkinsonism in Experimental Rats: Apigenin Attenuates LPS-Induced Parkinsonism in Experimental Rats.

Parkinson's disease (PD) is a progressive hypokinetic movement disorder caused by selective degeneration of dopaminergic neurons in striatum and dopamine deficiency in a region of the midbrain. LPS is an endotoxin, used as animal model to induce microglial activation, neuroinflammation, oxidative stress, and neurotransmitter alteration with PD-like symptoms. Therefore, to prevent neuroinflammation and neurotransmitter changes and to restore normal brain physiology, we tried apigenin (AGN) alone and in combination with piperine (bioenhancer), in LPS experimental model of rats. In this study, rats were treated with single unilateral intranigral injection of LPS at a dose of 5 μg/5 μl on day 0. The oral administration of AGN (25 and 50 mg/kg; p.o.) alone, AGN (25 mg/kg; p.o.) in combination with piperine (2.5 mg/kg; p.o.), and bromocriptine (10mg/kg; p.o.) started from day 7th once in a day. Intranigral injection of LPS significantly altered body weight and behavioral parameters assessed on weekly basis. Furthermore, the biochemical and neuroinflammatory analysis confirmed (on day 22nd) increased level of nitrite, MDA, SOD, TNF-α, IL-1β, IL-6, and caspase-1, and decreased level of CAT, GSH, and complex-I. Furthermore, altered level of neurotransmitters (DA, GABA, and glutamate) and cellular changes were observed from histopathological and immunohistochemistry (NF-kB and Nrf-2) analysis. Treatment with AGN (25 and 50 mg/kg; p.o.) alone and AGN (25 mg/kg; p.o.) in combination with piperine (2.5 mg/kg; p.o.) significantly attenuated the alteration in body weight, motor impairments, oxidative stress, neuroinflammation, and neurotransmitters in rat brain. The neuroprotective effect of AGN against LPS-induced cell death is attributed by modulating NF-kB and Nrf2 signaling pathway in the striatum. [ABSTRACT FROM AUTHOR]