Antidiabetic Activity of Ethyl Acetate Compounds from Gayam (Inocarpus fagiferus): In Silico and In Vivo Studies

Mus Ifaya, Bai Athur Ridwan, Putri Salsabila Laugi, Apriliani Putri Utami, Syawal Abdurrahman

Abstrak


Diabetes mellitus is characterized by high blood sugar levels. Though many drugs are available, blood glucose control is still challenging to achieve due to decreased beta cell function and side effects of long-term use. Gayam tree bark (Inocarpus fagiferus) has the potential to inhibit digestive enzymes, although the molecular mechanism of its antidiabetic effect has not been ascertained. This study aims to determine the activity of compounds from ethyl acetate extract as antidiabetics, tested in silico and in vivo. The study used molecular docking and in vivo activity analysis. LC-MS analysis was used to determine the content of compounds in the ethyl acetate fraction of gayam bark. Through molecular interaction prediction and ADME-Toxicology, compounds in gayam bark showed antidiabetic activity. In the molecular docking interaction study, the Cochliophilin A compound had a lower binding energy than acarbose on the α-amylase receptor: -9.76 kcal/mol and -8.95 kcal/mol. The ADME-Tox model predicted good skin permeability, absorption, and distribution for Cochliophilin A. The ethyl acetate extract showed antidiabetic activity in lowering blood sugar levels in rats on day 14, respectively by 74% (IV), 72% (V), and 74% (VI). Collectively, compounds in gayam bark are useful in treating diabetes.


Kata Kunci


antidiabetic; Inocarpus fagiferus; mass spectrometry; molecular docking

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Referensi


Saeedi P, Petersohn I, Salpea P, Malanda B, Karuranga S, Unwin N, et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Res Clin Pract. 2019;157:107843.

Thomas RL, Halim S, Gurudas S, Sivaprasad S, Owens DR. IDF diabetes atlas: A review of studies utilising retinal photography on the global prevalence of diabetes related retinopathy between 2015 and 2018. Diabetes Res Clin Pract. 2019;157:107840.

Yuen L, Saeedi P, Riaz M, Karuranga S, Divakar H, Levitt N, et al. Projections of the prevalence of hyperglycaemia in pregnancy in 2019 and beyond: Results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Res Clin Pract. 2019;157:107841.

Padhi S, Nayak AK, Behera A. Type II diabetes mellitus: a review on recent drug-based therapeutics. Biomed Pharmacother. 2020;131:110708.

Hedrington MS, Davis SN. Considerations when using alpha-glucosidase inhibitors in the treatment of type 2 diabetes. Expert Opin Pharmacother. 2019;20(18):2229-35.

Leroux‐Stewart J, Rabasa‐Lhoret R, Chiasson JL. α‐Glucosidase inhibitors. International textbook of diabetes mellitus. 2015:673-85.

Widyawati T, Purnawan WW, Atangsiapa IJ, Yusoff NA, Ahmad M, Asmawi MZ. Aktivitas anti diabetes dari ekstrak daun Syzygium polyanthum (Wight), tanaman herbal yang paling umum digunakan pada pasien diabetes di Medan, Sumatera Utara, Indonesia. Int J Pharm Sci Res. 2015;6(4):1698-704.

Eberhardt J, Santos-Martins D, Tillack AF, Forli S. AutoDock Vina 1.2.0: New Docking Methods, Expanded Force Field, and Python Bindings. J Chem Inf Model. 2021;61(8):3891-8.

Depkes RI. Riset Kesehatan Dasar (Riskesdas): Badan Penelitian dan Pengembangan Kesehatan. Jakarta: Kementerian Kesehatan RI; 2018.

Abdurrahman S, Ruslin R, Hasanah AN, Mustarichie R, Ifaya M. Active Antialopecia Chemical Identification of Merremia peltata Leaves and Computational Study toward Androgen Receptor Using Molecular Docking and Molecular Dynamic Simulation. Sci World J. 2022;2022:1123047.

Abdurrahman S, Ruslin R, Hasanah AN, Mustarichie R. Molecular docking studies and ADME-Tox prediction of phytocompounds from Merremia peltata as a potential anti-alopecia treatment. J Adv Pharm Technol Res. 2021;12:132-9.

Wu Z, Liao Q, Liu B. A comprehensive review and evaluation of computational methods for identifying protein complexes from protein-protein interaction networks. Brief Bioinform. 2020;21(5):1531-48.

Ramirez D, Caballero J. Is It Reliable to Take the Molecular Docking Top Scoring Position as the Best Solution without Considering Available Structural Data. Molecules. 2018;23(5):1038.

Abdurrahman S, Ruslin R, Hasanah AN, Ifaya M, Mustarichie R. Anti-alopecia activity of coumarin derivatives isolated from Merremia peltata leaves and computational study of their binding to androgen receptors using molecular docking and molecular dynamic simulation. Pharmaceuticals (Basel). 2023;16(5):669.

Abraham MJ, Murtola T, Schulz R, Páll S, Smith JC, Hess B, et al. GROMACS: High-performance molecular simulations through multi-level parallelism from laptops to supercomputers. SoftwareX. 2015;1(2):19-25.

Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev. 2001;46:23-6.

Zhou L, Naraharisetti S, Liu L, Wang H, Lin YS. Contribution of human cytochrome P450 enzymes to glyburide metabolism. Seattle: Wiley Inter Science; 2010;31(4):228-41.

Dewick PM. Medicinal Natural Products: A Biosynthetic Approach. 3rd ed. United Kingdom: John Wiley and Sons Ltd; 2009.

Sen P, Sahu K, Prasad P, Chandrakar S, Sahu RK, Roy A. Approach to phytochemistry and mechanism of action of plants having antidiabetic activity. UK J Pharm Biosci. 2016;4(1):82-120.

Ramu R, Shirahatti PS, Swamy N, Zameer F, Dhananjaya BL, Nagendra PMN. Assessment of in vivo antidiabetic properties of umbelliferone and lupeol constituents of banana (Musa sp. var. Nanjangud rasa bale) flower in hyperglycaemic rodent model. PLoS One. 2016;11:1-17.

Liao X, Liu B, Qu H, Zhang L, Lu Y, Xu Y, et al. A high level of circulating valine is a biomarker for type 2 diabetes and is associated with the hypoglycemic effect of sitagliptin. Mediators Inflamm. 2019;2019:8247019.

Ramirez D, Caballero J. Is It Reliable to Take the Molecular Docking Top Scoring Position as the Best Solution without Considering Available Structural Data. Molecules. 2018;23(5):1038.

Camilloni C, Bonetti D, Morrone A, Giri R, Dobson CM, Brunori M, Gianni S, Vendruscolo M. Towards a structural biology of the hydrophobic effect in protein folding. Sci Rep. 2016;6:28285.

Shi X, Bao W. Hydrogen-Bonded Conjugated Materials and Their Application in Organic Field-Effect Transistors. Front Chem. 2021;9:723718.

Sharp KA, Honig B. Electrostatic interactions in macromolecules: theory and applications. Annu Rev Biophys Chem. 1990;19:301-22.

Changeux JP, Christopoulos A. Allosteric Modulation as a Unifying Mechanism for Receptor Function and Regulation. Cell. 2016;166(5):1084-1102.




DOI: https://doi.org/10.24198/ijpst.v12i3.58070

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