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

Table 2

Characteristics of included preclinical experiments involving administration of propolis, royal jelly, and their constituents in animal and cell culture models of Parkinson’s disease ().

Animal/cell line model	Treatment	Summary of effects and mechanism	Reference
6-OHDA-induced rat model of PD	Propolis gavage (200 mg/kg/d/40 days)	↑ TH+ neurons; ↓ Striatal fiber degeneration; Propolis restored body weight and reverted 6-OHDA-induced reductions in HR and HRV	[83]
Rotenone-induced mouse model of PD	CAPE (2.5-10 mg/kg/p.o./every other d/17 days)	↓ Motor deficits, microglia activation (CD11b+), TNF-α and IL-1β, COX-2, iNOS, and NF-κB; ↑ Striatal dopamine and TH+ neurons	[44]
MPTP-induced mouse model of PD; MPTP-treated CGNs and RMNs as cellular models of PD	CAPE (2-10 mg/kg/p.o./d/7 days)	↑ Neuronal viability, striatal dopamine, TH+ neurons; ↓ iNOS, caspase-1, cytochrome c, AIF, MPP-induced formation of free radicals and peroxynitrite, and neurotoxicity	[84]
6-OHDA-treated CGNs and hepatic cells as a cellular model of PD and oxidative stress	CAPE (10 μM/4 h) followed by a treatment with 6-OHDA (70 μM for 6 h)	↑ Neuronal viability; ↓ Cytochrome c, caspase-3, and H2O2-induced neurotoxicity	[45]
6-OHDA-treated CGNs and RMNs as a cellular model of PD	CAPE (10 μM) for 2 h	↑ Neuronal viability; ↓ Formation of O2− and peroxynitrite and H2O2-induced neurotoxicity	[88]
MPP+-treated SH-SY5Y cells as a cellular model of PD	PB (1, 10, 20 μM) for 24 h	↑ Neuronal viability, mitochondrial membrane potential, and bcl-2/bax ratio; ↓ ROS, caspase-3, apoptotic rate, and cytochrome c	[85]
MPP+-treated SH-SY5Y cells as a cellular model of PD	PB (20 μM) for 24 h	↓ Neurotoxicity; ↑ ERK/MAPK and HO-1	[86]
6-OHDA-treated SH-SY5Y cells as a cellular model of PD	PB (25 μM) for 4 h	↓ Neurotoxicity, ROS, MDA, and apoptotic rate; ↑ Nrf2/ARE, SOD, HO-1, γ-GCS, bcl-2/bax ratio, and mitochondrial membrane potential	[79]
6-OHDA-induced rat model of PD	Chrysin orally (10 mg/kg/twice a d/28 days)	↓ TNF-α, INF-γ, IL-1β, IL-6, IL-10, NF-κB, TRAP, and S100B; ↑ Dopamine, DOPAC, HVA, BDNF, NGF, GDNF, TAR, and TH+ neurons	[42]
6-OHDA-induced mouse model of PD	Dietary RJ 100 or 200 mg (3 weeks)	↑ Neuronal survival (the number of Nissl-stained neurons in the SNC and CPU) and the thickness of gray and white matter of the cerebral cortex and cerebellum; ↓ Motor deficits and contralateral to striatal lesion induced by apomorphine injection	[82]
6-OHDA-treated SH-SY5Y cells as a cellular model of PD	RJ fatty acids: 10-HDA, 10H2DA, SA, their derivatives DAEE and HPO-DAEE (4 h)	Only HPO-DAEE ↑ cell viability, NRF2-ARE signaling, HO-1, γ-GCL, and NQO1; ↓ ROS emission	[13]

↑ denotes increase; ↓ denotes decrease; RJ: royal jelly; d: day; h: hour; PD: Parkinson’s disease; 6-OHDA: 6-hydroxydopamine; HR: heart rate; HRV: heart rate variability; SNC: substantia nigra pars compacta; CPU: caudate putamen unit; 10-HDA: 10-hydroxy-decanoic acid; 10H2DA: 10-hydroxy-2-decenoic acid; SA: sebacic acid; DAEE: 2-decenoic acid ethyl ester; HPO-DAEE: 4-hydroperoxy-2-decenoic acid ethyl ester; HO-1: heme oxygenase 1; γ-GCL: γ-glutamylcysteine ligase; NQO1: NAD(P)H quinone dehydrogenase 1; ROS: reactive oxygen species; NRF2-ARE: nuclear factor erythroid 2-antioxidant response element; eIF2α-ATF4: eukaryotic initiation factor 2, an upstream effector of the activating transcription factor-4; CAPE: caffeic acid phenethyl ester, genes encoding CD11b (a microglia surface antigen); COX-2: cyclooxygenase-2; iNOS: inducible nitric oxide synthase; NF-κB: nuclear factor-κB; TH: tyrosine hydroxylase; MPTP: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; CGNs: cerebellar granule neurons; RMNs: rostral mesencephalic neurons; p.o.: oral gavage; AIF: apoptosis inducing factor; MPP: 1-methyl-4-phenylpyridinium; caspase-3: cysteine-aspartic acid protease 3; H2O2: hydrogen peroxide; PB: pinocembrin; bcl-2: B cell lymphoma 2; bax: bcl-2-associated X protein; ERK: extracellular signal-regulated kinase; MAPK: mitogen-activated protein kinase; γ-GCS: γ-glutamylcysteine synthetase; MDA: malondialdehyde; SOD: super oxide dismutase; DOPAC: 3,4-dihydroxyphenylacetic acid; HVA: homovanillic acid; BDNF: brain-derived neurotrophic factor; NGF: nerve growth factor; GDNF: glial cell line-derived neurotrophic factor; TNF-α: tumor necrosis factor-α; INF-γ: interferon-gamma; IL-1β: interleukin-1β; IL-2: interleukin-2; IL-6: interleukin-6; IL-10: interleukin-10; NF-κB: nuclear factor-kappa B; S100B: calcium-binding protein B; TRAP: total reactive antioxidant potential; TAR: total antioxidant reactivity.