Upregulation and/or maintenance of Parkinson's disease (PD)-related beneficial proteins such as Parkin and DJ-1 in astrocytes during neurodegenerative insults may have therapeutic efficacy in PD. Cinnamon is a commonly used natural spice and flavoring material throughout the world. Here we have explored a novel use of cinnamon in upregulating Parkin and DJ-1 and protecting dopaminergic neurons in MPTP mouse model of PD. Recently we have delineated that oral feeding of cinnamon (Cinnamonum verum) powder produces sodium benzoate (NaB) in blood and brain of mice. Proinflammatory cytokine IL-1β decreased the level of Parkin/DJ-1 in mouse astrocytes. However, cinnamon metabolite NaB abrogated IL-1β-induced loss of these proteins. Inability of TNF-α to produce nitric oxide (NO) and decrease the level of Parkin/DJ-1 in wild type (WT) astrocytes, failure of IL-1β to reduce Parkin/DJ-1 in astrocytes isolated from iNOS (-/-) mice, and decrease in Parkin/DJ-1 in WT astrocytes by NO donor DETA-NONOate suggest that NO is a negative regulator of Parkin/DJ-1. Furthermore, suppression of IL-1β-induced expression of iNOS in astrocytes by NaB and reversal of NaB-mediated protection of Parkin/DJ-1 by DETA-NONOate in astrocytes indicate that NaB protects Parkin/DJ-1 in activated astrocytes via suppressing iNOS. Similarly MPTP intoxication also increased the level of iNOS and decreased the level of Parkin/DJ-1 in vivo in the nigra. However, oral treatment of MPTP-intoxicated mice with cinnamon powder and NaB reduced the expression of iNOS and protected Parkin/DJ-1 in the nigra. These findings paralleled dopaminergic neuronal protection, normalized striatal neurotransmitters, and improved motor functions by cinnamon in MPTP-intoxicated mice. These results suggest that cinnamon may be beneficial for PD patients.