Abstract
Parkinson’s disease (PD) is a major age-related neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra par compacta (SNpc). Rotenone is a neurotoxin that is routinely used to model PD to aid in understanding the mechanisms of neuronal death. Safflower (Carthamus tinctorius. L.) has long been used to treat cerebrovascular diseases in China. This plant contains flavonoids, which have been reported to be effective in models of neurodegenerative disease. We previously reported that kaempferol derivatives from safflower could bind DJ-1, a protein associated with PD, and that a flavonoid extract from safflower exhibited neuroprotective effects in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of PD. In this study, a standardized safflower flavonoid extract (SAFE) was isolated from safflower and found to primarily contain flavonoids. The aim of the current study was to confirm the neuroprotective effects of SAFE in rotenone-induced Parkinson rats. The results showed that SAFE treatment increased body weight and improved rearing behavior and grip strength. SAFE (35 or 70 mg/kg/day) treatment reversed the decreased protein expression of tyrosine hydroxylase, dopamine transporter and DJ-1 and increased the levels of dopamine and its metabolite. In contrast, acetylcholine levels were decreased. SAFE treatment also led to partial inhibition of PD-associated changes in extracellular space diffusion parameters. These changes were detected using a magnetic resonance imaging (MRI) tracer-based method, which provides novel information regarding neuronal loss and astrocyte activation. Thus, our results indicate that SAFE represents a potential therapeutic herbal treatment for PD.
Highlights
Neurodegenerative disorders, such as Parkinson’s disease (PD) and Alzheimer’s disease (AD), affect millions of patients at ever growing numbers in aging societies, and no curative treatments exist [1]
High-performance liquid chromatography (HPLC) analysis showed that the 30% ethanol elutate of safflower contained kaempferol 3-O-rutinoside (K3R) and anhydrosafflor yellow B (AYB), as shown in the standardized HPLC chromatogram of safflower flavonoid extract (SAFE)
The rotenone-induced PD model is associated with neuronal damage in the substantia nigra (SN) and striatum, which can manifest as marked deterioration in motor function, behavioral changes, loss of body which can manifest as marked deterioration in motor function, behavioral changes, loss of body weight weight and altered muscle morphology [28,29,30]
Summary
Neurodegenerative disorders, such as Parkinson’s disease (PD) and Alzheimer’s disease (AD), affect millions of patients at ever growing numbers in aging societies, and no curative treatments exist [1]. Rotenone is a pesticide and toxin that can be used to induce PD in an animal model [10]. Rotenone reproduces many key pathological features of PD such as oxidative damage, α-synuclein aggregation [11], oxidative stress-induced striatal dopaminergic terminal degeneration [12], selective nigrostriatal loss, cognitive deficits and depression-like behavior [13]. Madopar® (levodopa + benserazide) is the gold standard treatment, long-term use of this drug can cause adverse symptoms [14]
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