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Profiling of interactions between diabetic enzymes and natural polyphenols from spices and edible herbs – An in-silico approach

. Beenish Khanzada, Nosheen Akhtar, Shagufta Jabeen & Jawaid Mian Larik


Abstract

Background: Diabetes mellitus (DM) is one of the most prevalent public health concerns globally. Natural products and its derived active compounds may be achievable alternatives for the treatment of type 2 diabetes. Therefore, there is a need to explore natural agents to replace the current standard drugs with anti-diabetic functional food. Current study aimed to screen edible herbs and spices for their antidiabetic activity and docked their selected polyphenols with enzymes associated with diabetes to understand their interaction mechanism and mode of inhibition of respective enzymes. Methods: Alpha amylase and alpha glucosidase inhibition percentage of ethanolic extracts of Cinnamomum zeylanicum, Cinnamomum tamala, Amomum subulatum, Trigonella foenum graecum, Mentha piperita, Coriandrum sativum, Lactuca sativa, and Brassica oleraceavar italic was calculated. Pyrx virtual screening tool was used to dock the selected polyphenols with alpha amylase and human lysosomal alpha glucosidase to examine their binding affinities.  Results: Highest inhibitory potential for alpha glucosidase was observed in case of A. subulatum with IC50 Value 372 µg/ml. However, Cinnamomum zeylanicum and Cinnamomum tamala displayed highest inhibition against Alpha amylase with IC50 68.75 µg/ml. Among selected bioactive compounds, Cinnamtanin B1 and Trigonelloside C exhibited the greatest affinity for Alpha amylase and Alpha glucosidase with lowest Kd (Dissociation constant) Values of -10.2 and -9.1 respectively. Cinnamtannin B1 interacts with aspartate300 at the active site of alpha amylase (serving as antagonist) while it serves as allosteric inhibitor for alpha glucosidase by binding non-competitively on sites other than active site. Conclusion: Such bioactive polyphenols in studied plant extracts may be used as anti-diabetic drugs as they bind competitively at active site of enzyme.

Key words:  Edible herbs, Antidiabetic, polyphenols, molecular docking, alpha glucosidase, alpha amylase.

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