Cinnamic Acid Protects the Nigrostriatum in a Mouse Model of Parkinson’s Disease via Peroxisome Proliferator-Activated Receptorα

Abstract

Parkinson's disease (PD) is the second most common devastating human neurodegenerative disorder and despite intense investigation, no effective therapy is available for PD. Cinnamic acid, a naturally occurring aromatic fatty acid of low toxicity, is a precursor for the synthesis of a huge number of plant substances. This study highlights the neuroprotective effect of cinnamic acid in 1methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. Oral administration of cinnamic acid protected tyrosine hydroxylase (TH)-positive dopaminergic neurons in the substantia nigra pars compacta (SNpc) and TH fibers in the striatum of MPTP-insulted mice. Accordingly, oral cinnamic acid also normalized striatal neurotransmitters and improved locomotor activities in MPTP-intoxicated mice. While investigating mechanisms, we found that cinnamic acid induced the activation of peroxisome proliferator-activated receptor α (PPARα), but not PPARβ, in primary mouse astrocytes. Cinnamic acid mediated protection of the nigrostriatal system and locomotor activities in WT and PPARβ (−/−), but not PPARα (−/−) mice from MPTP intoxication suggests that cinnamic acid requires the involvement of PPARα in protecting dopaminergic neurons in this model of PD. This study delineates a new function of cinnamic acid in protecting dopaminergic neurons via PPARα that could be beneficial for PD.

Propolis as a Potential Disease-Modifying Strategy in Parkinson’s disease: Cardioprotective and Neuroprotective Effects in the 6-OHDA Rat Model

“…Similarly, the neuroprotective roles of chrysin, a flavonoid encountered in propolis, were achieved through mechanisms involving inflammatory mediators and neurotrophic factors in the unilateral 6-OHDA model of PD [ 73 ]. Cinnamic acid, another component present in green propolis, showed neuroprotective effects in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD, detected by the attenuation of the nigrostriatal cell loss via activation of peroxisome proliferator-activated receptor alpha, which is involved in regulation of energy homeostasis and is known to have anti-inflammatory and antioxidative stress properties [ 79 ]. The existing literature has suggested important biological activities of propolis, including its antioxidant, anti-inflammatory, analgesic, and antimicrobial properties, which may contribute to its neuroprotective and cardioprotective roles [ 69 , 80 ].…”

Overview of Beneficial Effects of (Poly)phenol Metabolites in the Context of Neurodegenerative Diseases on Model Organisms

“…In a mouse model of MPTP induced PD cinnamic acid reduced TH cell death, while increasing dopamine levels and locomotion. Interestingly the authors identified peroxisome proliferator-activated receptor α (PPARα) but not PPARβ as crucial for cinnamic acid effects [ 173 ]. Moreover, using a transgenic model of Alzheimer’s disease with cinnamic acid showed reduced plaque formation and increased memory and learning while the same model using knock—out PPARα showed no effects [ 174 ].…”

Cinnamic acid ameliorate gentamicin-induced liver dysfunctions and nephrotoxicity in rats through induction of antioxidant activities

“…Other valuable characteristics such as splenoprotective [26], hepatoprotective and cardioprotective [27,28], functions have been attributed to CA. Ameliorative effects of CA on neuroinflammation [29], memory deficits [23], and neurodegenerative disorders such as Alzheimer's disease [30] and Parkinson's disease [31] have been investigated in several studies. Furthermore, there is evidence about the vasodilator activity of CA through the nitric oxide (NO)-cGMP-PKG pathway [32].…”