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

Abstract

Patients with Parkinson’s disease (PD) manifest nonmotor and motor symptoms. Autonomic cardiovascular dysregulation is a common nonmotor manifestation associated with increased morbimortality. Conventional clinical treatment alleviates motor signs but does not change disease progression and fails in handling nonmotor features. Nutrition is a key modifiable determinant of chronic disease. This study aimed to assess the effects of propolis on cardiological features, heart rate (HR) and heart rate variability (HRV) and on nigrostriatal dopaminergic damage, detected by tyrosine hydroxylase (TH) immunoreactivity, in the 6-hydroxydopamine (6-OHDA) rat model of PD. Male Wistar rats were injected bilaterally with 6-OHDA or saline into the striatum and were treated with propolis or water for 40 days. Autonomic function was assessed by time domain parameters (standard deviation of all normal-to-normal intervals (SDNN) and square root of the mean of the squared differences between adjacent normal RR intervals (RMSSD)) of HRV calculated from electrocardiogram recordings. Reductions in HR (p = 1.47 × 10−19), SDNN (p = 3.42 × 10−10) and RMSSD (p = 8.2 × 10−6) detected in parkinsonian rats were reverted by propolis. Propolis attenuated neuronal loss in the substantia nigra (p = 5.66 × 10−15) and reduced striatal fiber degeneration (p = 7.4 × 10−5) in 6-OHDA-injured rats, which also showed significant weight gain (p = 1.07 × 10−5) in comparison to 6-OHDA-lesioned counterparts. Propolis confers cardioprotection and neuroprotection in the 6-OHDA rat model of PD.

Apitherapy for Parkinson’s Disease: A Focus on the Effects of Propolis and Royal Jelly

“…From a theoretical point of view, propolis and RJ may be beneficial not only for the main motor symptoms of PD but also for other nonmotor symptoms such as cardiac, autonomic, GI, depressive, and cognitive symptoms [ 19 , 83 , 110 ]. In connection with this standpoint, propolis (200 mg/kg/40 days) increased the survival of dopaminergic neurons and maintained striatal structure in a PD rat model induced by bilateral injection of 6-OHDA in the striatum.…”

“…In connection with this standpoint, propolis (200 mg/kg/40 days) increased the survival of dopaminergic neurons and maintained striatal structure in a PD rat model induced by bilateral injection of 6-OHDA in the striatum. Along with such neurological improvements, propolis also restored body weight and reverted the cardiological and autonomic alterations caused by 6-OHDA treatment as detected by increased heart rate and heart rate variability compared with the placebo treatment [ 83 ]. Existing knowledge emphasizes an association between PD and cardiac disorders as they share common pathologies such as inflammation, cellular stress, and impaired metabolism of lipids and glucose.…”

“…Rotenone was used in one study to induce PD in rodents via inhibition of mitochondrial complex I of the mitochondrial respiratory chain, which was associated with high emission of mitochondrial ROS and induction of apoptosis via activation of caspase-3 [ 44 ]. 6-Hydroxydopamine (6-OHDA) has been used both in vivo and in vitro in 6 studies to induce PD [ 13 , 42 , 45 , 79 , 82 , 83 ]. It selectively provokes apoptosis of dopaminergic neurons via mechanisms that involve increasing the production of ROS, accelerating lipid peroxidation (production of malondialdehyde (MDA)), and evoking an imbalance between the antiapoptotic B cell lymphoma 2 (bcl-2) and the proapoptotic bcl-2-associated X protein (bax) [ 79 ].…”

“…The findings indicate that these bee products can induce both structural and symptomatic improvements and reduce the behavioral and histomorphometrical dysfunctions that are caused by PD in rodents. In this regard, a water extract of propolis (200 mg/kg/d/40 days) reduced dopaminergic neurodegeneration and striatal fiber degeneration induced by 6-OHDA along with maintenance of body weight and improvement of cardiac and autonomic functions [ 83 ]. CAPE (10 mg/kg) significantly decreased stepping ratio, improved coordination, shortened the latency to orient downwards on pole test, prolonged the permanence time, and increased the activity index and rears in rotenone-challenged mice [ 44 ].…”

“…The effect of propolis on brain structure was evaluated in 6-OHDA-challenged rats. Compared with the sham and placebo (water) groups, propolis significantly reduced striatal fiber degeneration [ 83 ]. However, the effect of active compounds in propolis on anatomical structures in the brain needs to be explored in future studies.…”