Harnessing Phytochemicals to Regulate Catalytic Residues of Alpha-Amylase and Alpha-Glucosidase in Type 2 Diabetes

Overview

Journal Cell Biochem Biophys

Specialties Biochemistry
Biophysics
Cell Biology

Date 2024 Oct 9

PMID 39384699

Authors

Sivaraman Dhanasekaran

Srikanth Jeyabalan

Abbas Alam Choudhury

Vijayarangan Devi Rajeswari

Gnanasambandan Ramanathan

Tamilanban Thamaraikani

Mahendran Sekar

Vetriselvan Subramaniyan

Wong Ling Shing

Affiliations

Soon will be listed here.

Abstract

Type 2 diabetes (T2D), also known as non-insulin-dependent diabetes mellitus, represents the prevailing manifestation of diabetes, encompassing a substantial majority of cases, ~90-95%. Plant-derived antidiabetic leads are being intensively explored due to their safety and effectiveness. The main objective of the present study is to evaluate the anti-diabetic potential of the traditional formulation Karisalai Karpam through in-vitro and in-silico investigations. The in-vitro and in-silico investigation of traditional polyherbal preparation Karisalai Karpam (KK) chooranam were performed to ascertain its inhibitory potential against α-amylase and α-glucosidase enzymes along with antioxidant (DPPH and ABTS) and phytochemical analysis. The results of enzyme inhibitory activity of KK witnessed highest activity against α-glucosidase enzyme with a percentage inhibition of 84.66 ± 2.50% (IC,187.9 ± 5.79 μg/ml) followed by moderate level of α-amylase inhibition exhibited with 72.94 ± 3.66% (IC, 241.6 ± 9.76 μg/ml). Additionally, the strongest antioxidant activity was observed in quenching DPPH (IC,154.8 ± 14.53 μg/ml) and ABTS radicals (IC,148.6 ± 29.74 μg/ml). The outcome of the molecular docking studies indicated that among the 17 compounds analysed, the lead such as acalyphin, apigenin, humulene, and indirubin exhibited a prominent binding affinity over the residual binding site of α-glucosidase. It's important to note that the catalytic site of the enzyme α-amylase is primarily occupied by amyrin, apigenin, arjunolic acid, β-sitosterol, geraniol, and tricetin. In conclusion, the formulation KK demonstrates robust alpha-glucosidase and alpha-amylase inhibitory activity. It's also worth noting that the formulation exhibits noteworthy antioxidant properties, which could provide additional health benefits. The binding mode and energies of the identified phytochemicals against the target enzymes further support the formulation's antidiabetic potential.

References

Heise T, Nosek L, Ronn B, Endahl L, Heinemann L, Kapitza C . Lower within-subject variability of insulin detemir in comparison to NPH insulin and insulin glargine in people with type 1 diabetes. Diabetes. 2004; 53(6):1614-20. DOI: 10.2337/diabetes.53.6.1614. View

Ahmed Q, Ali A, Mukhtar S, Alsharif M, Parveen H, Mohmad Sabere A . Medicinal Potential of Isoflavonoids: Polyphenols That May Cure Diabetes. Molecules. 2020; 25(23). PMC: 7727648. DOI: 10.3390/molecules25235491. View

Zheng P, Xiong Z, Liao C, Zhang X, Feng M, Wu X . and studies of bis (indol-3-yl) methane derivatives as potential α-glucosidase and α-amylase inhibitors. J Enzyme Inhib Med Chem. 2021; 36(1):1938-1951. PMC: 8409970. DOI: 10.1080/14756366.2021.1971976. View

Dhital S, Lin A, Hamaker B, Gidley M, Muniandy A . Mammalian mucosal α-glucosidases coordinate with α-amylase in the initial starch hydrolysis stage to have a role in starch digestion beyond glucogenesis. PLoS One. 2013; 8(4):e62546. PMC: 3636141. DOI: 10.1371/journal.pone.0062546. View

van de Laar F, Lucassen P, Akkermans R, van de Lisdonk E, Rutten G, van Weel C . Alpha-glucosidase inhibitors for patients with type 2 diabetes: results from a Cochrane systematic review and meta-analysis. Diabetes Care. 2004; 28(1):154-63. DOI: 10.2337/diacare.28.1.154. View

Sofowora A, Ogunbodede E, Onayade A . The role and place of medicinal plants in the strategies for disease prevention. Afr J Tradit Complement Altern Med. 2013; 10(5):210-29. PMC: 3847409. DOI: 10.4314/ajtcam.v10i5.2. View

Sen S, Chakraborty R, Thangavel G, Logaiyan S . Hepatoprotective and antioxidant activity of Karisalai Karpam, a polyherbal Siddha formulation against acetaminophen-induced hepatic damage in rats. Anc Sci Life. 2015; 34(4):198-202. PMC: 4535067. DOI: 10.4103/0257-7941.160863. View

Soobrattee M, Neergheen V, Luximon-Ramma A, Aruoma O, Bahorun T . Phenolics as potential antioxidant therapeutic agents: mechanism and actions. Mutat Res. 2005; 579(1-2):200-13. DOI: 10.1016/j.mrfmmm.2005.03.023. View

Arvouet-Grand A, Vennat B, Pourrat A, Legret P . [Standardization of propolis extract and identification of principal constituents]. J Pharm Belg. 1994; 49(6):462-8. View

10.

Matotoka M, Mashabela G, Masoko P . Phytochemical Content, Antibacterial Activity, and Antioxidant, Anti-Inflammatory, and Cytotoxic Effects of Traditional Medicinal Plants against Respiratory Tract Bacterial Pathogens. Evid Based Complement Alternat Med. 2023; 2023:1243438. PMC: 10247327. DOI: 10.1155/2023/1243438. View

11.

Biswas B, Golder M, Abid M, Mazumder K, Sadhu S . Terpenoids enriched ethanol extracts of aerial roots of (Griff.) and (Perr.) promote diuresis in mice. Heliyon. 2021; 7(7):e07580. PMC: 8318864. DOI: 10.1016/j.heliyon.2021.e07580. View

12.

Hassan H, Raja N, Abasi F, Mehmood A, Qureshi R, Manzoor Z . Comparative Study of Antimicrobial and Antioxidant Potential of Fruit Extract and Its Mediated Selenium Nanoparticles. Molecules. 2022; 27(16). PMC: 9415542. DOI: 10.3390/molecules27165194. View

13.

Hussen E, Endalew S . In vitro antioxidant and free-radical scavenging activities of polar leaf extracts of Vernonia amygdalina. BMC Complement Med Ther. 2023; 23(1):146. PMC: 10157976. DOI: 10.1186/s12906-023-03923-y. View

14.

Zheleva-Dimitrova D, Nedialkov P, Kitanov G . Radical scavenging and antioxidant activities of methanolic extracts from Hypericum species growing in Bulgaria. Pharmacogn Mag. 2010; 6(22):74-8. PMC: 2900065. DOI: 10.4103/0973-1296.62889. View

15.

Kifle Z, Yesuf J, Atnafie S . Evaluation of in vitro and in vivo Anti-Diabetic, Anti-Hyperlipidemic and Anti-Oxidant Activity of Flower Crude Extract and Solvent Fractions of (Rosaceae). J Exp Pharmacol. 2020; 12:151-167. PMC: 7293407. DOI: 10.2147/JEP.S249964. View

16.

Morris G, Huey R, Lindstrom W, Sanner M, Belew R, Goodsell D . AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. J Comput Chem. 2009; 30(16):2785-91. PMC: 2760638. DOI: 10.1002/jcc.21256. View

17.

Binkowski T, Naghibzadeh S, Liang J . CASTp: Computed Atlas of Surface Topography of proteins. Nucleic Acids Res. 2003; 31(13):3352-5. PMC: 168919. DOI: 10.1093/nar/gkg512. View

18.

Hollingsworth S, Karplus P . A fresh look at the Ramachandran plot and the occurrence of standard structures in proteins. Biomol Concepts. 2011; 1(3-4):271-283. PMC: 3061398. DOI: 10.1515/BMC.2010.022. View

19.

Williams C, Headd J, Moriarty N, Prisant M, Videau L, Deis L . MolProbity: More and better reference data for improved all-atom structure validation. Protein Sci. 2017; 27(1):293-315. PMC: 5734394. DOI: 10.1002/pro.3330. View

20.

Wang Y, Xiao J, Suzek T, Zhang J, Wang J, Bryant S . PubChem: a public information system for analyzing bioactivities of small molecules. Nucleic Acids Res. 2009; 37(Web Server issue):W623-33. PMC: 2703903. DOI: 10.1093/nar/gkp456. View