Chromone derivatives suppress neuroinflammation and improve mitochondrial function in the sporadic form of Alzheimer’s disease under experimental conditions

Objective(s): The study aims to estimate the neuroprotective effect of chromone derivatives in the sporadic form of Alzheimer’s disease in the context of the relationship between changes in mitochondrial function and neuroinflammation.Materials and Methods: Alzheimer’s disease was modeled by injecting Aβ ۱-۴۲ fragments into the CA۱ part of the hippocampus of animals. The test compounds and memantine were administered orally for ۶۰ days from the moment the pathology was reproduced. The change in cognitive deficit in rats was assessed in the Y-maze test. In the hippocampus of rats, intensity of cellular respiration, activity of mitochondrial enzymes (citrate synthase, aconitase, cytochrome-c-oxidase, and succinate dehydrogenase), concentrations of IL - ۶; IL -۱β; TNF -α; IL – ۱۰, and cardiolipin were determined.Results: Of the ۱۸ substances, only C۳AACP۶ and C۳AACP۷ compounds contributed to the recovery of aerobic metabolism, increased activity of mitochondrial enzymes, and reduced neuroinflammation in the hippocampus of rats. Furthermore, administration of these substances reduced the manifestation of cognitive deficit in animals with Alzheimer’s disease to a degree comparable with memantine. Moreover, in terms of the effect on changes in the activity of mitochondrial enzymes and aerobic metabolism, these substances significantly exceeded memantine.Conclusion: The study showed that from the analyzed chromone derivatives, two compounds C۳AACP۶ and C۳AACP۷ could have a neuroprotective effect in Alzheimer’s disease, which is realized through the axis: recovery of mitochondrial function, decrease extramitochondrial cardiolipin, decrease neuroinflammation, neuroprotection.

Keywords:

Alzheimer’s disease , Chromone derivatives , Mitochondrial dysfunction , Neuroinflammation , Neuroprotection