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

Figure 4

Probable mechanisms through which propolis and royal jelly (RJ) alleviate symptoms of Parkinson’s disease. Propolis, RJ, and their compounds alleviate oxidative damage directly by scavenging free radicals through the release of an electron from their phenolic group and indirectly through activation of ERK/MAPK signaling, which deactivates Keap1, the molecule that degrades NRF2 resulting in NRF2 translocation into the nucleus to activate ARE, which stimulates the expression of antioxidant genes such as HO-1. On the other hand, NRF2 and HO-1 prevent the transcription of inflammatory pathways such as NF-κB resulting in less production of inflammatory cytokines. Mitigation of oxidative stress and neuroinflammation is associated with less mitochondrial respiration and less production of apoptotic molecules such as caspase-3 and bax, eventually leading to less neurodegeneration. On the other side, chrysin increased the expression of various neurotrophic factors possibly through its contribution to HO-1 production; however, the detailed mechanism is not clearly understood. RJ also stimulates the expression of cerebral and hippocampal GDNF, possibly through activation of estrogen receptors. GDNF is associated with neuroprotective effects: enhancing the survival and morphological differentiation of midbrain dopaminergic neurons and fostering their affinity for dopamine. All these events prevent neuronal degeneration, maintain intact brain structure, keep proper levels of dopamine and acetylcholine, and eventually improve motor and cognitive symptoms of PD. ↑ denotes increase; ↓ denotes decrease; ERK: extracellular signal-regulated kinase; MAPK: mitogen-activated protein kinase; NRF2: nuclear factor erythroid 2; ARE: antioxidant response element; HO-1: heme oxygenease-1; NF-κB: nuclear factor kappa B; TNF-α: tumor necrosis factor alpha; GDNF: glial cell line-derived neurotrophic factor; AIF: apoptosis inducing factor; caspase-3: cysteine-aspartic acid protease 3; bax: bcl-2-associated X protein; SNC: substantia nigra pars compacta; PD: Parkinson’s disease.