Inhibition of human amylin aggregation by Flavonoid Chrysin: An in-silico and in-vitro approach

Abstract

Islet amyloid polypeptide (amylin), consecrated by the pancreatic β-cells with insulin, has a significant role to play in maintaining homeostasis of islet cell hormones. Alzheimer's disease is the predominant source of dementia. However, its etiology remains uncertain; it appears that type 2 diabetes mellitus and other prediabetic states of insulin resistance contribute to the intermittent Alzheimer's disease presence. Amylin is abnormally elevated in Type II diabetes patients, accumulated into amylin aggregates, and ultimately causes apoptosis of the β-cells, and till date, its mechanism remains unclear. Several flavonoids have inhibitory effects on amylin amyloidosis, but its inhibition mechanisms are unknown. Screening a collection of traditional compounds revealed the flavone Chrysin, a potential lead compound. Chrysin inhibits amyloid aggregate formation according to Thioflavin T binding, turbidimetry assay. We report results of molecular interaction analysis of Chrysin with amylin which shows potent binding affinity against amylin. Pharmacokinetics and Drug likeness studies of Chrysin also suggest that it is a potential lead compound. Therefore, Chrysin prevented amylin aggregation.

Impact of Some Natural and Artificial Sweeteners Consumption on Different Hormonal Levels and Inflammatory Cytokines in Male Rats: In Vivo and In Silico Studies

“…Additionally, according to the present study’s findings, the potential clinical implications of these binding interactions in the context of consumption and metabolic health of many additives, such as sweeteners, could be predicted and ensured by both in vitro and in vivo studies. Based on the literature and in agreement with the above results, many natural and synthetic compounds showed a potential inhibition effect against many hormones and enzymes during consumption, such as amylin, , FSH and LH, COX I/II, prostaglandin E2, and antioxidant enzymes . The current study’s findings open the perspectives toward using in silico techniques to predict the negative implications of many food additives, including sweeteners.…”

“…For example, the flavonoid chrysin inhibited amylin through in silico and in vitro approaches, with a binding free energy of −6.45 kcal/mol. 88 Also, Fang et al 89 revealed amylin inhibition using epigallocatechin-3-gallate (−4.28 kcal/mol) and genistein (−5.10 kcal/mol). In the present study, the docking study with amylin (PDB ID: 2L86 ), aspartame (−5.8 kcal/mol), sucralose (−5.5 kcal/mol), and sucrose (−5.4 kcal/mol) showed comparable results to the literature ( Figure 2 ), which may the cause for the lower concentrations of amylin as shown in Table 3 .…”

“…The in vivo results of the present study agree with many published studies on inhibiting human amylin aggregation. For example, the flavonoid chrysin inhibited amylin through in silico and in vitro approaches, with a binding free energy of −6.45 kcal/mol . Also, Fang et al revealed amylin inhibition using epigallocatechin-3-gallate (−4.28 kcal/mol) and genistein (−5.10 kcal/mol).…”

Targeting pancreatic beta cell death in type 2 diabetes by polyphenols

“…Under these conditions, autophagy activation has protective effects and inhibits pancreatic β cell death, being a natural defense ( 42 , 43 ). Flavonoids have also been involved in the protection of the deleterious effects of hIAPP aggregates in these cells ( 105 – 109 ). Apart from the actions of flavonoids already explained, flavonoids have been also involved in an increase in antioxidant enzymes, as a protective mechanism ( 110 , 111 ).…”

5,7- Dimethoxycoumarin Enhances Insulin Release and Stimulates Extrapancreatic Secretion of Amylin.

“…Coumarins due to their aromatic structures, are known to potently inhibit cholinesterases (acetylcholinesterase, and butyrylcholinesterase) enzymes that promote and propagate β -amyloid aggregation (37), and also Monamine Oxidase (MAO) which induces β -amyloid deposition (38) (39). Various avonoids inhibit human amylin amyloidosis through unknown mechanism (40).…”