In Silico Study of Gamma-Mangostin Compound from Garcinia Mangostana L. Fruit Skin and Activity Test as an Alpha Amylase Inhibitor

Kurniawan Kurniawan; Nurul  Marfu'ah; Gita  Fazriah D.

doi:10.37899/journallamedihealtico.v6i2.1889

Kurniawan Pharmacy Department, Faculty of Health Science, Universitas Darussalam Gontor, Jl. Raya Siman, Ponorogo, 63471, Indonesia
Nurul Marfu'ah Pharmacy Department, Faculty of Health Science, Universitas Darussalam Gontor, Jl. Raya Siman, Ponorogo, 63471, Indonesia
Gita Fazriah D. Pharmacy Department, Faculty of Health Science, Universitas Darussalam Gontor, Jl. Raya Siman, Ponorogo, 63471, Indonesia

DOI: https://doi.org/10.37899/journallamedihealtico.v6i2.1889

Keywords: α-amylase, diabetic, gamma-mangostin, Garcinia mangostana L.

Abstract

The aim of this study is to determine the interaction between the gamma-mangostin compound and the α-amylase enzyme using molecular docking modeling and in vitro. The results of molecular docking showed that all compounds could interact with the active site of the α-amylase enzyme. The gamma-mangostin compound has a fairly negative binding affinity. The binding affinity score of the compound was then compared with the control, namely the carbohydrate inhibitor acarbose. The results showed that the binding affinity quite close to the control, namely -9.1 kcal/mol, while the control was -16.4 kcal/mol, but the score was not negative enough. Interaction of the target protein with the alpha amylase compound to determine the amino acid residues on the active side of the protein. The results showed that there were hydrogen, alkyl and van der waals bonds on the active side of the protein that were the same as the control. In silico and in vitro, the gamma-mangostin compound has the potential to reduce blood sugar levels with an α-amylase inhibitor, in vitro with percentage of 43.33% approaching the positive control, namely acarbose, which is 56.25% at a concentration of 200 ppm and an IC50 value of 166.06 ppm.

References

Abbas, M. M., Al-Rawi, N., Abbas, M. A., & Al-Khateeb, I. (2019). Naringenin Potentiated β-Sitosterol Healing Effect on the Scratch Wound Assay. Research in pharmaceutical sciences, 14(6), 566–573. http://dx.doi.org/10.4103/1735-5362.272565

Alfiani, L. A. (2022). Uji Aktivitas Penghambatan Enzim α–amilase oleh Ekstrak Herba Ciplukan (Physalis Angulate L) Secara In Vitro. Jurnal Ilmiah Wahana Pendidikan, 8(15), 335–346. https://doi.org/10.5281/zenodo.7049485

Amrulloh, M. H., Noviany, Hadi, S., Rafi’, M., Yandri, Suwandi, J. F., & Aminah, N. S. (2024). In Vitro Alpha-Amylase Inhibitory Activity of Cocoa Pod Husk (Theobroma cacao L.). In AIP Conference Proceedings. https://doi.org/10.1063/5.0208408

Anugrahini, C. P. H., & Wahyuni, A. S. (2021). Narrative Review: Aktivitas Antidiabetes Tanaman Tradisional Di Pulau Jawa. Pharmacon: Jurnal Farmasi Indonesia, Edisi Khus, 120–131.

Chen, S. P., Lin, S. R., Chen, T. H., Ng, H. S., Yim, H. S., Leong, M. K., & Weng, C. F. (2021). Mangosteen xanthone γ-mangostin exerts lowering blood glucose effect with potentiating insulin sensitivity through the mediation of AMPK/PPARγ. Biomedicine & Pharmacotherapy, 144, 112333. https://doi.org/10.1016/j.biopha.2021.112333

Dewi, P., Habibah, N. A., Mustikaningtyas, D., Iswari, R. S., WH, N., Marianti, A., Yuniastuti, A., Widyaningrum, P., Susanti, R., Christijanti, W., Riyaniarti, M. M., & W., E. (2022). Potensi Senyawa Aktif Bahan Alam. Unisma Press.

Dinnar, N. L. (2022). Uji Aktivitas Penghambatan Enzim Alfa Amilase Ekstrak dan Fraksi Daun Binahong Merah (Anredera cordifolia (Ten.) Steenis). Jurnal Indonesia Sosial Sains, 3(10), 1361–1376. https://doi.org/10.59141/jiss.v3i10.718

Fadlan, A., Warsito, T., & Sarmoko, S. (2022). Evaluasi Parameter Fisikokimia, Farmakokinetika, dan Farmakodinamika Senyawa Fisetin Dalam Desain Obat. Akta Kimia Indonesia, 7(1), 1–13. https://doi.org/10.12962/j25493736.v7i1.10879

Fandinata, S. S., & Ernawati, I. (2020). Manajemen Terapi pada Penyakit Degeneratif (Diabetes Mellitus dan Hipertensi): Mengenal, Mencegah, dan Mengatasi Penyakit Degeneratif (Diabetes Mellitus dan Hipertensi). Penerbit Graniti.

Filimonov, D. A., Druzhilovskiy, D. S., Lagunin, A. A., Gloriozova, T. A., Rudik, A. V., Dmitriev, A. V., Pogodin, P. V., & Poroikov, V. V. (2018). Computer-Aided Prediction of Biological Activity Spectra for Chemical Compounds: Opportunities and Limitations. Biomedical Chemistry: Research and Methods, 1(1), e00004. https://doi.org/10.18097/BMCRM00004

Gaspersz, N., & Sohilait, M. R. (2019). Penambatan Molekuler α, β, dan γ-mangostin Sebagai Inhibitor α-amilase Pankreas Manusia. Indonesian Journal of Chemical Research, 6(2), 59–66. https://doi.org/10.30598/ijcr.2019.6-nel

Godavari, A., & Amutha, K. (2017). In vitro Antidiabetic Activity of Garcinia mangostana by Enzymatic Inhibition Assay. Research Journal of Pharmacy and Technology, 10(2), 508–512. https://doi.org/10.5958/0974-360X.2017.00101.9

Kartini, S., Juariah, S., Mardhiyani, D., Bakar, M. F. A., Bakar, F. I. A., & Endrini, S. (2023). Phytochemical Properties, Antioxidant Activity and α- Amilase Inhibitory of Curcuma Caesia. Advanced Research in Applied Sciences and Engineering Technology, 30(1), 255–263. https://doi.org/10.37934/araset.30.1.255263

Kemenkes RI. (2014). Profil kesehatan Indonesia. Kementrian Kesehatan Republik Indonesia.

Kurnia, D. (2020). Aktivitas Inhibisi α-Amilase Ekstrak Mikroalga Chlorella Vulgaris sebagai Kandidat Antidiabetes. Indonesia Natural Research Pharmaceutical Journal, 5(1), 105–113. https://doi.org/10.52447/inspj.v5i1.2321

Kusmiyati, M., Sudaryat, Y., Rismiarti, Z., & Sari, E. D. (2023). Uji Aktivitas Ekstrak Daun dan Buah Belimbing Wuluh (Averrhoa Bilimbi) sebagai Antidiabetes Melalui Inhibisi α-Amilase. Jurnal Riset Kesehatan Poltekkes Depkes Bandung, 15(1), 163–171. https://doi.org/10.34011/juriskesbdg.v15i1.2118

Laakso, M., & Fernandes Silva, L. (2022). Genetics of type 2 diabetes: past, present, and future. Nutrients, 14(15), 3201. https://doi.org/10.3390/nu14153201

Ladeska, V., Lusi, P. T., & Shela, F. (2017). Potensi Ekstrak Etanol 70% Daun Sukun (Artocarpus altilis) terhadap Penurunan Kadar Glukosa Darah pada Tikus Hiperglikemia dan Hiperlipidemia. Prosiding Seminar Nasional POKJANAS TOI, 56–61.

Maliangkay, H. P., Rumondor, R., & Walean, M. (2018). Uji Efektivitas Antidiabetes Ekstrak Etanol Kulit Buah Manggis (Garcinia mangostana L.) pada Tikus Putih (Rattus norvegicus) yang Diinduksi Aloksan. Chemistry Progress, 11(1), 15–21.

Muchtaridi, M., Puteri, N. A., Milanda, T., & Musfiroh, I. (2017). Validation Analysis Methods of a-Mangostin, ?-Mangostin and Gartanin Mixture in Mangosteen (Garcinia mangostana L.) Fruit Rind Extract from West Java with HPLC. Journal of Applied Pharmaceutical Science, 7(10), 125–130. https://doi.org/10.7324/JAPS.2017.71018

Nugraha, M. R., & Hasanah, A. N. (2018). Review Artikel: Pengujian Aktivitas Antidiabetes. Farmaka, 16(3), 28–34.

Nursamsiar, N., M. Mangande, M., Awaluddin, A., Nur, S., & Asnawi, A. (2020). In Silico Study of Aglycon Curculigoside A and Its Derivatives as α-Amilase Inhibitors. Indonesian Journal of Pharmaceutical Science and Technology, 7(1), 29. https://doi.org/10.24198/ijpst.v7i1.23062

Pangemanan, K., Datu, O. S., Fatimawali, F., Kalalo, M. J., & Windah, A. L. (2022). Uji Aktivitas Antidiabetes Daging Buah Alpukat Mentega (Persea americana) sebagai Inhibitor Enzim Î±-Glukosidase Secara In Silico. Jurnal Farmasi Medica/Pharmacy Medical Journal (PMJ), 5(2), 15–21. https://doi.org/10.35799/pmj.v5i2.42124

Prahesti, D. A., Pujiyanto, S., & Rukmi, M. G. I. (2018). Isolasi, Uji Aktivitas, dan Optimasi Inhibitor α-Amilase Isolat Kapang Endofit Tanaman Binahong (Anredera cordifolia)(Ten.) Steenis. Jurnal Akademika Biologi, 7(1), 43–51.

Pujiyanto, S., Wijanarka, W., Raharjo, B., & Anggraeni, V. (2019). Aktivitas Inhibitor α-Amilase Ekstrak Etanol Tanaman Brotowali (Tinospora crispa L.). Bioma : Berkala Ilmiah Biologi, 21(2), 91–99. https://doi.org/10.14710/bioma.21.2.91-99

Putri, E. D. T. (2022). Uji Penghambatan Senyawa Aktif Fermentasi Biji Kacang Merah (Phaseolus vulgaris L.) sebagai Antidiabetes Secara In Silico. STIKes Bhakti Husada Mulia Madiun.

Rahmadi, I., Nurdin, S. U., & Astuti, S. (2016). Pengaruh Ekstrak Daun Salam (Syzygium polyanthum (Wight.) Walp.) Terhadap Tingkat Hidrolisis Pati, Aktivitas Antioksidan, dan Sifat Sensori Nasi Instan. Jurnal Teknologi & Industri Hasil Pertanian, 21(1), 28–41. http://dx.doi.org/10.23960/jtihp.v21i1.28%20-%2041

Rijai, A. J., Suganda, A. G., & Iskandar, E. Y. (2018). Aktivitas Inhibitor Alfa-Amilase Beberapa Tumbuhan Obat Indonesia. Jurnal Sains dan Kesehatan, 1(10), 517–524. https://doi.org/10.25026/jsk.v1i10.97

Rivero, B., & Garibay, I. (2019). Development and Validation of a Stability-Indicating HPLC Method for the Quantification of α-Mangostin in Dietary Supplements. Natural Product Communications, 14(7). https://doi.org/10.1177/1934578X19863948

Rollando, R. (2018). Pendekatan Struktur-Aktivitas dan Penambatan Molekul Senyawa 2-Iminoethyl 2-(2-(1-Hydroxypentan-2-yl) Phenyl)acetate Hasil Isolasi Fungi Endofit Genus Fusarium sp pada Enzim β-Ketoasil-ACP KasA Sintase dan Enzim Asam Mikolat Siklopropana Sintase. Pharmaceutical Journal of Indonesia, 3(2), 39–45. http://dx.doi.org/10.21776/ub.pji.2017.003.02.2

Rosalina, V., & Mahendra, R. (2021). Aktivitas Antibakteri Ekstrak dan Fraksi dari Ekstrak Metanol Daun Manggis (Garcinia mangostana) pada Bakteri Penyebab Ulkus Diabetik. Jurnal Surya Medika, 7(1), 31–38. https://doi.org/10.33084/jsm.v7i1.2203

Saeedi, P., Petersohn, I., Salpea, P., Malanda, B., Karuranga, S., Unwin, N., Colagiuri, S., Guariguata, L., Motala, A. A., Ogurtsova, K., Shaw, J. E., Bright, D., & Williams, R. (2019). 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 Research and Clinical Practice, 157, 107843. https://doi.org/10.1016/j.diabres.2019.107843

Santoso, A. P. R., & Wulandari, D. D. (2020). Pengaruh Pemberian Alfa Mangostin Terhadap Kadar Glukosa pada Tikus yang Diinduksi Diet Tinggi Fruktosa. Medical Technology and Public Health Journal, 4(2), 127–133. https://doi.org/10.33086/mtphj.v4i2.1710

Saudale, F. Z., Tokan, M. B., Leo, S. Y., & Ati, S. P. (2020). FFAR4/GPR120 sebagai Target Desain dan Pengembangan Obat Diabetes Melitus Tipe 2 in silico: Suatu Tinjauan dan Perspektif. Chemistry Notes, 2(1), 12–35. https://doi.org/10.35508/cn.v2i1.2338

Spronk, I., Legemate, C., Oen, I., van Loey, N., Polinder, S., & van Baar, M. (2018). Health-Related Quality of Life in Adults After Burn Injuries: A Systematic Review. PLOS ONE, 13(5), 1–21. https://doi.org/10.1371/journal.pone.0197507

Sumarmin, R. (2018). Pengaruh Ekstrak Kulit Buah Manggis (Garcinia mangostana L.) terhadap Histologis Pankreas Mencit (Mus musculus L. Swiss Webster) yang Diinduksi Sukrosa. Eksakta: Berkala Ilmiah Bidang MIPA, 19(1), 100–112. https://doi.org/10.24036/eksakta/vol19-iss1/123

Wahyuningsih, S. (2019). Pengaruh Konsentrasi Enzim α-Amilase pada Hidrolisis Pati Labu Jepang (Kabocha). Chemical Engineering Research Article, 2(1), 26–32. https://doi.org/10.25273/cheesa.v2i1.4433

Wardani, T. S., Aziz, Y. S., & Kurniawan. (2022). Fitokimia untuk Mahasiswa. Lontar Mediatama.

Wirasti, W., Lestari, T., & Isyti’aroh, I. (2021). Penghambatan Ekstrak Daun Kremah (Alternanthera sessilis) terhadap Enzim α-amilase secara In-Vitro. Pharmacon: Jurnal Farmasi Indonesia, 18(1), 68–74. https://doi.org/10.23917/pharmacon.v18i01.14657

Zhu, H., Ye, L., Richard, A., Golbraikh, A., Wright, F. A., Rusyn, I., & Tropsha, A. (2009). A Novel Two-Step Hierarchical Quantitative Structure–Activity Relationship Modeling Work Flow for Predicting Acute Toxicity of Chemicals in Rodents. Environmental Health Perspectives, 117(8), 1257–1264. https://doi.org/10.1289/ehp.0800471