Apitherapy in Post-Ischemic Brain Neurodegeneration of Alzheimer’s Disease Proteinopathy: Focus on Honey and Its Flavonoids and Phenolic Acids

Abstract

Neurodegeneration of the brain after ischemia is a major cause of severe, long-term disability, dementia, and mortality, which is a global problem. These phenomena are attributed to excitotoxicity, changes in the blood–brain barrier, neuroinflammation, oxidative stress, vasoconstriction, cerebral amyloid angiopathy, amyloid plaques, neurofibrillary tangles, and ultimately neuronal death. In addition, genetic factors such as post-ischemic changes in genetic programming in the expression of amyloid protein precursor, β-secretase, presenilin-1 and -2, and tau protein play an important role in the irreversible progression of post-ischemic neurodegeneration. Since current treatment is aimed at preventing symptoms such as dementia and disability, the search for causative therapy that would be helpful in preventing and treating post-ischemic neurodegeneration of Alzheimer’s disease proteinopathy is ongoing. Numerous studies have shown that the high contents of flavonoids and phenolic acids in honey have antioxidant, anti-inflammatory, anti-apoptotic, anti-amyloid, anti-tau protein, anticholinesterase, serotonergic, and AMPAK activities, influencing signal transmission and neuroprotective effects. Notably, in many preclinical studies, flavonoids and phenolic acids, the main components of honey, were also effective when administered after ischemia, suggesting their possible use in promoting recovery in stroke patients. This review provides new insight into honey’s potential to prevent brain ischemia as well as to ameliorate damage in advanced post-ischemic brain neurodegeneration.

Emerging Role of Plant-Based Bioactive Compounds as Therapeutics in Parkinson’s Disease

“…In vivo findings have shown that p-CA supplementation diminishes the degeneration of axon in sciatic nerves of rat and OS, followed by ischemia or reperfusion [136]. p-CA has also exhibited neuroprotective potential in models of global and local cerebral ischemia by preventing apoptosis and ROS generation [137].…”

The Dual Role of Autophagy in Postischemic Brain Neurodegeneration of Alzheimer’s Disease Proteinopathy

“…On the other hand, older patients show a marked decline in overall performance between 6 and 30 months poststroke [ 29 ]. According to recent projections, by 2030, the number of stroke survivors is predicted increase to 77 million [ 10 , 30 , 31 ]. Despite this, the global death rate due to cerebral ischemia has decreased significantly [ 12 ].…”

“…Despite this, the global death rate due to cerebral ischemia has decreased significantly [ 12 ]. If these global stroke trends continue, by 2030 there is predicted to be approximately 70 million stroke cases, approximately 12 million deaths and more than 200 million disability-adjusted life years annually [ 30 , 31 ]. Despite significant progress in the diagnosis and treatment of brain ischemia, it is assumed that around 2050, the number of brain ischemia cases is likely to double, and disability after stroke is predicted to also increase due to the increasing number of patients whom are likely to survive an ischemic episode [ 32 , 33 ].…”

“…Cerebral ischemia has been found to trigger a sequence of pathological events that can last from minutes to the remaining years of life [ 8 , 38 , 39 , 40 , 41 ]. These pathologies include energy failure, oxidative stress, excitotoxicity, neuroinflammation, cortical and subcortical infarcts, white matter rarefaction, blood–brain barrier damage, microbleeding and cerebral amyloid angiopathy [ 8 , 14 , 30 , 31 , 42 , 43 , 44 , 45 ]. The consequence of the above changes is additional hypoperfusion, causing the ischemia of the adjacent areas, gliosis, the accumulation of amyloid plaques and neurofibrillary tangles, neuronal death and, ultimately, brain atrophy [ 38 , 39 , 41 , 46 , 47 , 48 , 49 ].…”