Impact of select Polyphenols on α-amylase Activity under In vitro Conditions Khasan Y. Kayumov1*, Lubov S. Kuchkarova1, Jakhongir S. Abdurakhmonov1, Rashidbek Kh. Achilov1, Shoaib Khan2, Teodoro Durá-Travé3, Manzura A. Agzamova4, Komila A. Eshbakova4, Sh

Background: Flavonoids have been extensively researched for their ability to modulate enzyme activity, particularly in relation to controlling blood sugar and carbohydrates metabolism. However, there is limited information on the tissue-specific effects of structurally diverse flavonoids on α-amylase activity. This study aimed to investigate and compare rutin, quercetin, luteolin, chrysosplenetin, and thamiflaside affects on α-amylase activity in various parts of the digestive system. Methods: We used homogenates from pancreatic tissue, parotid gland, intestinal mucosa, and chyme during in vitro assays. Flavonoids were tested at different levels and α-amylase activity was measured using a spectrophotometer. The Student-Fisher t-test was used to run a statistical analysis to determine dose and tissue-dependent effects. Results: Rutin, quercetin, luteolin, and chrysosplenetin significantly and dose-dependently inhibited the α-amylase activity. The parotid gland and intestinal mucosa were more sensitive (p<0.05). Luteolin had the strongest inhibitory impact, perhaps because of its hydroxylation patterns. On the other hand, thamiflaside had a distinct influence on α-amylase activity, particularly in the salivary and intestinal compartments suggesting allosteric activation pathways. The varied modulatory profiles were correlated with flavonoid structure-function relationships, where the distribution of hydroxyl and methoxyl groups determines the enzyme binding and outcomes. Conclusion: The results showed that some flavonoids might be used as natural α-amylase inhibitors to regulate blood sugar levels and treat metabolic disorders. They also showed that thamiflaside could help those who need better carbohydrate digestion. These findings revealed that flavonoids might be added to nutraceutical formulations in an organized way. Furthermore, in vivo and clinical studies are needed to determine their safety and efficacy as therapeutic agents.