Honeybee products and edible insect powders improve locomotive and learning abilities of Ubiquilin-knockdown Drosophila

Abstract

Background: Mutations in the human Ubiquilin 2 gene are associated with neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) with or without frontotemporal dementia (FTD), the fatal neurodegenerative disease that progressively affected neuronal cells in both brain and spinal cord. There is currently no effective therapy for these diseases. Over the last decade, researchers have focused on the potential use of natural products especially in neurodegenerative studies. Insect products have been used as traditional medicines, however, scientific information is still lacking. Fruit fly is recently used as a model organism to investigate degenerative diseases related to the nervous system because it has a short life span and produces a large number of offspring. Methods: The present study investigated the effects of honeybee products and edible insect powders on the locomotive and learning abilities, neuromuscular junctions (NMJs) structure, and reactive oxygen species (ROS) in larval brains of Ubiquilinknockdown Drosophila. Results: dUbqn knockdown flies showed defects in locomotive and learning abilities accompanied with structural defects in NMJs. The results obtained revealed that the recovery of locomotive defects was significantly greater in dUbqn knockdown flies fed with coffee honey from Apis cerana (1% v/v) or Apis dorsata melittin (0.5 μg/ml) or wasp powder (2 mg/ml) than that of in untreated dUbqn knockdown flies. Furthermore, dUbqn knockdown flies fed with coffee honey showed the partial rescue of structural defects in NMJs, improved learning ability, and reduced the accumulation of ROS caused by dUbqn depletion in the brain over the untreated group. Conclusion: These results suggest that coffee honey from Apis cerana contains a neuroprotective agent that will contribute to the development of a novel treatment for ALS/FTD.

The Potential Use of Honey as a Neuroprotective Agent for the Management of Neurodegenerative Diseases

“…A total of eight articles were found to use honey or its derivatives as preventive or therapeutic agents via in vivo investigations for various neurodegenerative disorders. Out of these, three in vivo studies [ 35 , 36 , 37 ] investigated the effect of honey on AD, whereas only one in vivo article [ 38 ] investigated the role of honey products on ALS. Mohd Sairazi and his team conducted two in vivo investigations [ 38 , 39 ] on the role of honey in curbing the effect of status epilepticus and other neurodegenerative disorders induced through excitotoxicity.…”

“…Out of these, three in vivo studies [ 35 , 36 , 37 ] investigated the effect of honey on AD, whereas only one in vivo article [ 38 ] investigated the role of honey products on ALS. Mohd Sairazi and his team conducted two in vivo investigations [ 38 , 39 ] on the role of honey in curbing the effect of status epilepticus and other neurodegenerative disorders induced through excitotoxicity. The other two in vivo studies [ 40 , 41 ] investigated the relationship between honey and neurodegeneration.…”

“…However, they did not specifically target a specific neurodegenerative disorder. It was interesting to note that four out of the eight in vivo studies evaluated the effects of Tualang honey (TUH) [ 35 , 39 , 40 , 42 ], while the other in vivo studies utilized Thyme honey (THH) [ 37 ], stingless bee honey (SBH) [ 41 ] and coffee honey [ 38 ]. One article by Campos et al (2022) studied chrysin-a flavonoid found in honey, using both in vitro and in vivo techniques [ 43 ].…”

Potential Therapeutic Benefits of Honey in Neurological Disorders: The Role of Polyphenols

“…Another major hallmark in the early onset of amyotrophic lateral sclerosis is the mutations in the gene encoding ubiquitin chaperone Ubiquilin 2 ( UBQLN2 ), which causes defects in ubiquitin-binding abilities and results in the restricted delivery of ubiquitinated substrates to proteasomes for degradation [ 223 ]. A study by Phokasem et al revealed that coffee honey restored locomotor capacity, increased learning ability, and mitigated oxidative stress in the brain of the Ubiquilin -knockdown Drosophila model [ 224 ].…”

Epigenetic Regulation of ALS and CMT: A Lesson from Drosophila Models

“…Therefore, screening of Food and Drug Administration-approved drugs and natural substances to develop a potential therapy for ALS and CMT would be more extensively performed using Drosophila models. The pioneer studies reported that honeybee products (coffee honey from Apis cerana ) improved locomotive and learning abilities of the Drosophila ALS/FTD model targeting Ubiquilin [ 167 ].…”