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  • The causes of POD are complex and not entirely

    2020-09-15

    The causes of POD are complex, and not entirely clear. Androsova et al, believed that the main molecular mechanism of POD is a central cholinergic deficiency caused by deregulation of cholinergic anti-inflammatory pathways Agar synthesis leading to increased inflammation. The cholinergic anti-inflammatory pathway, mediated by acetylcholine, suppresses NF-kappa B activation and inhibits the release of inflammatory cytokines (e.g., tumor necrosis factor, interleukin [IL]-1β, IL-6, and IL-18). Decreased cholinesterase activity in delirious patients was correlated with elevated levels of C-reactive protein and IL-6. From the literature analysis, the mechanisms for POD patients having decreased cholinesterase activity may be related to the following factors: (1) The reducing cholinesterase activity could prevent the production of inflammatory markers, which is the body\'s self-protection. However, if the cholinesterase activity decreases significantly, it will in turn inhibit the cholinergic anti-inflammatory pathway, and thus increase the body\'s inflammatory response. In our subsequent research, we would analyze the relationship between enzyme activity and plasma inflammatory markers. (2) Acetylcholine plays an important role in memory, associative learning and selective attention. Cholinesterase terminates the action of Agar synthesis by hydrolyzing this neurotransmitter to produce inactive products. Cerejeira et al reported that preoperatively, plasma cholinesterase activity was significantly lower in patients who developed delirium compared with the remaining subjects. We assumed that the decreased AChE and BChE activity might be a response to already decreased acetylcholine levels even preoperatively in POD patients. Thus lower levels of plasma cholinesterase activity might due to pre-existing differences already present before surgery. Unfortunately, in our study, we did not measure preoperative values of cholinesterase activity, which is the direction of our future research. (3) Polymorphisms in cholinesterase genes lead to decreased activity. (4) The body was in negative nitrogen balance, and the production of cholinesterase was lower, which can reduce cholinesterase activity.
    Introduction Search for inhibitors of cholinesterases has been driven by their pivotal role as a drug category that helps to slow down the debilitating symptoms of neurodegenerative conditions, such as Alzheimer\'s disease (AD). The cognitive impairment, developing towards severe dementia can be temporarily managed by one of the few available Acetylcholinesterase (AChE) inhibitors based on natural structures - galanthamine and physostigmine. However, many other natural compounds exert such action in vitro and in vivo but clinical evidence is missing and their activity is usually rather moderate (Perry and Howes, 2011). Natural compounds usually differ in their selectivity to one of the two forms, i.e AChE and butyrylcholinesterase (BChE), while the typically preferred is rather AChE targeting. BChE, which is also considered as promising target for drug discovery since it enzymatic activity upsurges in the late stages of AD. In fact, it has been reported that BChE inhibitors can also act in a similar way to those of AChE inhibitors and slow down cognitive decline (Li et al., 2008). Among a huge number of natural products that have been shown to be inhibitors of in vitro activity of cholinesterases (Orhan et al., 2017, 2018), several classes of polyphenols are usually considered promising (Pinho et al., 2013; Politeo et al., 2018). On the other hand, polyphenols showing such activity could also contribute to the dementia prevention via their well-established antiinflammatory properties (Sawikr et al., 2017). Thereof, stilbenoids, such as resveratrol, and isoflavonoids, such as genistein are mentioned as markedly active and as potential lead structures. However, among these two structural classes, there are many more compounds that have not been studied. This drew our attention to the traditional medicinal plant that contains both isoflavonoids and stilbenoids, among others.