I switched from Google to DuckDuckGo and found this surprising article. hindawi.com/journals/omcl/2...
5. Evidence from Preclinical Studies
The effects of both propolis and its flavonoids and RJ and its lipids on PD were examined both in vivo and in vitro. 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]. This effect is a read out for reduced neurotoxicity demonstrated by CAPE in mice treated with MPTP and rotenone as depicted by increased percentage of viable dopaminergic neurons in the SNC by 73% and 92%, respectively [44, 84].
6.1. Bee Products Protect Neurons against Oxidative Stress
Antioxidants protect neurons against neurotoxins by inhibiting the generation of free radicals. Several lines of evidence denote that flavonoids in propolis and derivatives of RJ lipids demonstrate neuroprotective effects in dopaminergic neurons, to a great extent, through modulation of oxidative stress. CAPE blocked the production of O2− and peroxynitrite in the brain of MPTP-intoxicated mice and inhibited the activity of the prooxidant iNOS in rotenone-induced mouse model of PD [44, 84].
6.2. Bee Products Protect Neurons against Neuroinflammation
Research shows that both central and local inflammation, which involves CD4 T cell infiltration and activation of CD11b+microglia/macrophages, play a key role in neuron loss in PD. Chronic activation of these cells is associated with morphological and functional alterations that promote excessive production of ROS [44, 87].
Research shows that bee products such as RJ display immunomodulatory and anti-inflammatory functions under conditions of neuroinflammation via activation of NRF2 [13]. In addition to being a master pathway that stimulates the release of antioxidants, NRF2 plays a central role in the suppression of inflammatory responses directly through downregulation of the transcription of proinflammatory cytokines such as IL-6 and IL-1β [92]. Moreover, redox control (expression of antioxidant genes such as HO-1) is another mechanism through which RJ might silence neuroinflammation [13]. HO-1 is a main cytoprotective agent not only against oxidative stress but also against inflammation.
6.4. Maintaining Brain Levels of Dopamine
Dopamine is the main neuroactive substance involved in PD [31]. Current PD treatments are based on dopamine replacement [44]. Active compounds in propolis increased dopamine levels in the SNC of experimental models of PD.
6.5. Enhancement of the Production of Neurotrophins in the Brain
Neuronal adversities such as chronic oxidative stress, neuroinflammation, and excitotoxicity are key contributors to progressive neurotoxicity and neurodegeneration. Neurotrophins are compounds that are essential for the survival of specific neurochemical phenotype classes of neurons [42].
6.6. Restoration of Normal Brain Structure
PD involves morphological alterations in different parts of the brain, including reduced volumes of the caudate nucleus, thalamus, and white matter, as well as atrophy of the basal ganglia, contraction in the left cerebellum, decreased gray matter in the right quadrangular lobe, reduced fractional anisotropy, neuromelanin pigmentation, neuronal loss within the SNC, and increased mean and radial diffusivity within the SNC and globus pallidus [108]. Experimental models indicate that RJ induces structural and symptomatic improvements in PD mice by protecting against the histomorphometrical dysfunctions caused by the disease. The effect of RJ on the integrity of brain structure is attributed to its antioxidant, anti-inflammatory, and antiapoptotic effects, which all lower the loss of dopaminergic and cholinergic neurons [99, 109]. 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.
7. Discussion
Few preclinical studies have evaluated the effect of propolis flavonoids, RJ, and RJ lipids on PD. Whole RJ [82], CAPE [44], and chrysin [42] improved motor behavioral alterations in PD animals. The protective effects of these compounds are likely attributed to their ability to reduce the production of free radicals [13, 42, 44, 45, 79, 84, 86], proinflammatory cytokines [42, 44], and mitochondrial proteins [45, 84] involved in cell death as well as their downstream effectors such as caspase-3 [85] and bax [79]. Immunochemistry and cell viability analyses revealed higher survival of dopaminergic neurons treated with these compounds both in vivo [42, 44, 84] and in vitro [13, 45, 79, 84, 86]. These results indicate that bee products such as propolis and RJ can be a potentially safe adjunctive treatment for PD.
And here is a long bonus section for Art and the rest of us microbiome obsessed people:
It is now well-known that altered gut microbiome is a major contributor to the initiation and development of PD pathology [10, 11, 121]. Evolving knowledge implies that dietary interventions such as fatty acids (phospholipid membrane precursors), amino acids, and microbiota-directed therapy (e.g., probiotics, prebiotics, and postbiotics) may correct gut alterations, treat GI symptom, and promote CNS functioning in PD [10, 18, 121, 122]. Propolis and RJ are rich in amino acids, fatty acids, and phospholipids [28, 37, 41, 55]. In addition, they are abundant in beneficial bacteria such as lactic acid bacteria, which is commonly used as probiotics to improve health and enhance growth and reproductive performance—43 species of these bacteria have been identified in bees and bee products such as RJ with 20 of them having inhibitory effects against 28 species of human and animal pathogens, some of which are antibiotic-resistant [123]. Propolis possesses strong antimicrobial properties, and it is used by bee workers as a disinfecting agent to keep integrity of the beehive [40]. Meanwhile, RJ contributes to the diversity and vitality of gut microbiome in queen bees. For example, Lactobacillus apis and Bifidobacterium are abundant in the gut of queen bees, and they produce metabolites that prevent the expression of oxidative stress genes and contribute to the excellent physical and reproductive traits of queen bees. On the other hand, these bacteria are deficient in bee workers, which feast mainly on honey and pollens [124]. The literature denotes that both propolis and RJ contribute to the maintenance of GI function. In this respect, supplementing rats on high fat diet with 0.2% dietary green propolis significantly altered the structure of gut microbiome. This effect was associated with less intestinal permeability, lower levels of lipopolysaccharide in the systemic circulation, and downregulation of activity of toll-like receptor 4 and cytokine expression in skeletal muscle [125]. Propolis was also reported to protect rats against gastric mucosal lesions induced by stress [126]. RJ has been shown to enhance the growth of beneficial gut bacteria such as Bacteroides fragillis and Bacteroides thetaiotaomicron, which colonize in the distal end of the gut to ferment and degrade indigestible proteins and carbohydrates; they also play a role in the activation of the regulatory T cells. In addition, RJ also demonstrates protective effects on the intestinal wall by contributing to the viability of the human epithelial colorectal cell line Caco-2 [127]. Thus, we suggest that propolis and RJ may positively affect the gut-brain axis in PD patients by modulating microbiota composition. Future studies exploring the effect of bee products on microbiota in PD and its association with the molecular and cellular adversities associated with PD will provide insightful information. It might be helpful to compare the effect of combining propolis and RJ with other conventional treatments such as dietary modifications and exercise since these interventions express their effects, in part, through the modulation of gut microflora [128].
A chronological model for the pathogenesis of PD
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