Antidiabetic Formulation Development Based on Natural Materials As α-Glucosidase Enzyme Inhibitor

Lilik Sulastri, Partomuan Simanjuntak, Wahono Sumaryono, Ratna Djamil, Danang Ardiaynto, Syamsudin Abdillah


Salam (Syzygium polyanthum), stevia (Stevia rebaudiana), tea (Camellia sinensis), and yakon (Smallanthus sonchifolius) leaves act as inhibitors of the α-glucosidase enzyme. The aims of this research were to (i) determine the best combination of polyherbals that could inhibit the α-glucosidase enzyme, (ii) determine the phytochemical content of the teraactive fraction, and (iii) predict potential bioactive compounds that were responsible for the inhibition of the α-glucosidase enzyme. The novelty of this research was its use of several types of herbs, combined with various compositions, to obtain the IC50 value. Also, this research predicted the activity of the compound through a molecular docking approach with Molegro Virtual Docker software. The extraction was carried out with the maceration method with 96% ethanol and then partitioned with ethyl acetate and water. Two fractions with high inhibition percentages were combined with a ratio of 1:1, 1:2, 2:1, 1:3, and 3:1, and they were tested against the α-glucosidase inhibitory enzyme. The best fraction was identified for chemical compound content by Liquid Chromatography Mass Spectroscopy (LC-MS/MS). The compounds were analyzed in silico by using Molegro Virtual Docker software, which obtained the best reranc score. The results showed that the ethanol extract of tea leaves had the highest activity, at 65.51%, and salam, stevia, and yakon leaves had inhibition percentages of 44.11%, 34.74%, and 28.85%, respectively. The combination of water fractions of tea and salam leaves had the best activity at a ratio of 3:1 with IC50 of 16.53 ppm, which was almost equivalent to acarbose as a positive control with IC50 of 14.62 ppm. The analysis of LC-MS/MS for the water fraction of tea contained nicotiflorin with m/z 594, a reranc score of -118.24, and amino acid residues Arg, Asp, Asn, Cys, Glu, His, Thr, and Tyr. The water fraction of salam leaves contained quercetagetin with m/z 319, the reranc score was –89.123, and the amino acid residues Asn, Asp, Gln, Lys, Phe, Pro, Thr, and Trp.


Keywords: Syzygium polyanthum, Stevia rebaudiana, Camellia sinensis, Smallanthus sonchifolius, α-glucosidase enzyme inhibitor, acarbose.


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MCCAA R. E., MCCAA C. S., READ D. G., BOWER J. D., and GUYTON A. C. International Diabetes Federation Diabetes Atlas, Vol. 31. 7th ed. Karakas, 2015.

COMMITTEE OF THE JAPAN DIABETES SOCIETY ON THE DIAGNOSTIC CRITERIA OF DIABETES MELLITUS, SEINO Y., NANJO K., TAJIMA N., KADOWAKI T., KASHIWAGI A., ARAKI E., ITO C., INAGAKI N., IWAMOTO Y., KASUGA M., HANAFUSA T., HANEDA M., and UEKI K. Report of the Committee on the Classification and Diagnostic Criteria of Diabetes Mellitus. Journal of Diabetes Investigation, 2010, 1(5): 212–228.

LIU Y., SUN J., RAO S., SU Y., and YANG Y. Antihyperglycemic, Antihyperlipidemic and Antioxidant Activities of Polysaccharides from Catathelasma Ventricosum in Streptozotocin-Induced Diabetic Mice. Food and Chemical Toxicology, 2013, 57: 39–45.

DEACON C. F. A Review of Dipeptidyl Peptidase-4 Inhibitors. Hot Topics from Randomized Controlled Trials. Diabetes, Obesity and Metabolism, 2018, 20(S1): 34–46.

KANTOROVICH M. M. Camellia Sinensis: A Review. Russian Military Medical Journal, 2012, 8(2): 78–79.

ZANG L.-Y., COSMA G., GARDNER H., SHI X., CASTRANOVA V., and VALLYATHAN V. Effect of Antioxidant Protection by p-Coumaric Acid on Low-Density Lipoprotein Cholesterol Oxidation. American Journal of Physiology-Cell Physiology, 2017, 279(4): C954–C960.

DEWIJANTI I., MANGUNWARDOYO W., DWIRANTI A., HANAFI M., and ARTANTI N. Short Communication: Effects of the Various Source Areas of Indonesian Bay Leaves (Syzygium Polyanthum) on Chemical Content and Antidiabetic Activity. Biodiversitas, Journal of Biological Diversity, 2020, 21(3): 1190–1195.

LELONO R. A. A., & TACHIBANA S. Preliminary Studies of Indonesian Eugenia Polyantha Leaf Extracts as Inhibitors of Key Enzymes for Type 2 Diabetes. Journal of Medical Science, 2013, 13(2): 103–110.

DEBNATH M. Clonal Propagation and Antimicrobial Activity of an Endemic Medicinal Plant Stevia Rebaudiana. Journal of Medicinal Plants Research, 2008, 2(2): 045-051.

SCARIA A., KAMATH J. V, and CHAKRABORTY M. Anti Hyperglycemic, Anti Oxidant, Anti Hyperlipidemic & Nephroprotective Effect of Stevioside in Diabetic Rats. International Journal of Ayurvedic Medicine, 2017, 8(4): 169-173.

SHIVANNA N., NAIKA M., KHANUM F., and KAUL V. K. Antioxidant, Anti-Diabetic and Renal Protective Properties of Stevia Rebaudiana. Journal of Diabetes and Its Complications, 2013, 27(2): 103–113.

AZIZ Z., AL QISTHI F. H., YULIANA N. D., and SIMANJUNTAK P. Identification of α-Glucosidase Enzyme Inhibitor Compound from Ethanol 96% Extract of Yakon Leaves (Smallanthus Sonchifolius [Poepp.& Endl.] H. Robinson). Jurnal Ilmu Kefarmasian Indonesia, 2019, 17(1): 21-26.

SERRA-BARCELLONA C., ARÁOZ M. V. C., CABRERA W. M., HABIB N. C., HONORÉ S. M., CATALÁN C. A. N., GRAU A., GENTA S. B., and SÁNCHEZ S. S. Smallanthus Macroscyphus: A New Source of Antidiabetic Compounds. Chemico-Biological Interactions, 2014, 209(1): 35–47.

HARBORNE J. B. Phytochemical Methods. 3rd ed. Chapman and Hall, London, New York, 2006.

ELYA B., HANDAYANI R., SAURIASARI R., AZIZAHWATI, HASYYATI U. S., PERMANA I. T., and PERMATASARI Y. I. Antidiabetic Activity and Phytochemical Screening of Extracts from Indonesian Plants by Inhibition of Alpha Amylase, Alpha Glucosidase and Dipeptidyl Peptidase IV. Pakistan Journal of Biological Sciences, 2015, 18(6): 273–278.

CAHYANA Y., and ADIYANTI T. Review: Flavonoids as Antidiabetic Agents. Indonesian Journal of Chemistry, 2021, 21(2): 512–526.

HIDAYATI M. D., ERSAM T., SHIMIZU K., and FATMAWATI S. Antioxidant Activity of Syzygium Polynthum Extracts. Indonesian Journal of Chemistry, 2017, 17(1): 49–53.

HOLIDAH D., & CHRISTIANTY F. M. Uji Aktivitas Antidiabetes Ekstrak Teh Hitam, the Oolong, dan Teh Hijau Secara in Vivo. Prosiding. Jember University Press, Jember, 2015.

VINHOLES J., & VIZZOTTO M. Synergisms in Alpha-Glucosidase Inhibition and Antioxidant Activity of Camellia Sinensis L. Kuntze and Eugenia Uniflora L. Ethanolic Extracts. Pharmacognosy Research, 2017, 9(1): 101–107.

MARYAM S. M., SUHAENAH A., and AMRULLAH N. F. Uji Aktivitas Penghambatan Enzim Α-Glukosidase Ekstrak Etanol Biji Buah Alpukat Sangrai (Persea Americana Mill.) Secara in Vitro. Jurnal Ilmiah As-Syifaa, 2020, 12(1): 51–56.

XIANG Z., HE F., KANG T. G., DOU D. Q., GAI K., SHI Y. Y., KIM Y. H., and DONG F. Anti-diabetes constituents in leaves of Smallanthus sonchifolius. Natural Product Communications, 2010, 5(1): 95-98.

KANG G. J., HAN S. C., OCK J. W., KANG H. K., and YOO E. S. Anti-Inflammatory Effect of Quercetagetin, an Active Component of Immature Citrus Unshiu, in HaCaT Human Keratinocytes. Biomolecules and Therapeutics, 2013, 21(2): 138–145.

WANG W., XU H., CHEN H., TAI K., LIU F., and GAO Y. In Vitro Antioxidant, Anti-Diabetic and Antilipemic Potentials of Quercetagetin Extracted from Marigold (Tagetes Erecta L.) Inflorescence Residues. Journal of Food Science and Technology, 2016, 53(6): 2614–2624.

THOMSEN R., & CHRISTENSEN M. H. MolDock: A New Technique for High-Accuracy Molecular Docking. Medicinal Chemistry, 2006, 49(11): 3315–3321.

HABTEMARIAM S. α-Glucosidase Inhibitory Activity of Kaempferol-3-O-Rutinoside. Natural Product Communications, 2011, 6(2): 201–203.

SULASTRI L., SIMANJUNTAK P., SUMARYONO W., and SYAMSUDIN. Prediction of toxicity and inhibition activities of a-glucosidase enzyme of the chemical compounds isolated from Indonesian medicinal plants using Molegro Virtual Docking. International Journal of Chemical Science, 2020, 4(2): 1–7.

MOLEGRO. Molegro Virtual Docker User Manual. CLC Bio Company, 2013.

PROENÇA C., FREITAS M., RIBEIRO D., OLIVEIRA E. F. T., SOUSA J. L. C., TOMÉ S. M., RAMOS M. J., SILVA A. M. S., FERNANDES P. A., and FERNANDES E. α-Glucosidase Inhibition by Flavonoids: An in Vitro and in Silico Structure–Activity Relationship Study. Journal of Enzyme Inhibition and Medicinal Chemistry, 2017, 32(1): 1216–1228.

NURMAYLINDHA V., WIDODO G. P., and HEROWATI R. Molecular Docking Analysis of Leucaena Leucocephala and Trigonella Foenum-Graecum Chemical Constituents on Antidiabetic Macromolecular Targets and Prediction of the Pharmacokinetic Profiles. AIP Conference Proceedings, 2020, 2243: 020015.



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