Studi Biokemoinformatika Kandungan Kimia Daun Sambiloto (Andrographis paniculata (Burm.f.) Nees) sebagai Antihiperglikemia serta Prediksi Parameter Farmakokinetik dan Toksisitas
DOI:
https://doi.org/10.30595/pharmacy.v17i2.8944Keywords:
Andrographis paniculata (Burm.f.) Nees, antihiperglikemia, docking molekuler, SwissADME, ToxtreeAbstract
Berdasarkan studi in vitro, in vivo dan uji klinis, sambiloto (Andrographis paniculata (Burm.f.) Nees) terbukti memiliki aktivitas sebagai antihiperglikemia. Namun, mekanisme aksi dan zat aktif yang bertanggung jawab terhadap aktivitas antihiperglikemia dari sambiloto belum diketahui secara pasti. Penelitian ini bertujuan untuk mengetahui interaksi kandungan kimia dari daun sambiloto dengan beberapa target molekuler yang terlibat dalam penyakit diabetes mellitus (DM) serta prediksi parameter farmakokinetik dan toksisitas dari senyawa-senyawa tersebut. Pada penelitian ini sebanyak 14 kandungan kimia daun sambiloto ditambatkan pada 6 target molekuler yaitu aldosa reduktase, α-glukosidase, protein tyrosine phosphatase 1B, peroxisome proliferator-activated receptor gamma, reseptor insulin dan glycogen sintase kinase 3B menggunakan metode docking molekuler yakni Autodock 4.2 yang sebelumnya telah divalidasi. Senyawa kimia dari daun sambiloto yang memiliki interaksi terbaik, selanjutnya diprediksi profil farmakokinetik dan toksisitasnya menggunakan SwissADME dan Toxtree. Berdasarkan hasil docking molekuler dapat diketahui bahwa senyawa yang diprediksi memiliki afinitas pengikatan terbaik dengan target molekuler DM adalah 19-O-asetilanhidroandrografolid, β-sitosterol, neoandrografolid, daukosterol dan asam oleanolat. Hasil prediksi SwissADME menunjukkan bahwa kelima senyawa ini memiliki peluang untuk menjadi obat oral, beberapa diantaranya merupakan substrat Pglikoprotein dan mampu menembus sawar darah otak. Sementara hasil prediksi Toxtree menunjukkan toksisitas yang rendah sampai tinggi dan semua senyawa tidak berpotensi dalam menyebabkan karsinogenisitas baik melalui mekanisme genotoksik maupun non genotoksik.References
Daina, A., Michielin, O., Zoete, V. 2017. SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Scientific Reports, 7: 1-13.
Ferwadi, S., Rahmat, G., Winni, A. 2017. Studi docking molekuler senyawa asam sinamat dan derivatnya sebagai inhibitor protein 1j4x pada sel kanker serviks. Jurnal Kimia Mulawarman, 14(2): 84-90.
Frengki, Saura, E.R., Rinidar. 2013. Studi interaksi kurkumin-artemisin dan turunannya terhadap reseptor sarcoendoplasma reticulum Ca2+ secara in silico. Jurnal Medika Veterinaria, 7(2): 138-141.
Guedes, I.A., Magalhaes, C.S., Dardenne, L.E. 2013. Receptor-ligand molecular docking. Biophysical Review, 6: 75-87.
Ighodaro, O.M. 2018. Molecular pathway associated with oxidative stress in diabetes mellitus. Biomedicine & Pharmacotherapy, 108: 656-662.
Kerru, N., Singh-Pillay, A., Awolade, P., Singh, P. 2018. Current anti-diabetic agents and their molecular targets: a review. European Journal of Medicinal Chemistry, 152: 436-488.
Lipinski, C.A., Lombardo, F., Dominy, B.W., Feeney, F.J. 1997. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Advanced Drug Delivery Reviews, 23: 3-25.
Pebriana, R.B. et al. 2008. Docking kurkumin dan senyawa analognya pada reseptor progesterone: studi interaksinya sebagai selective progesterone receptor modulators (SPRMs). Pharmacon, 9(1): 14-20.
Saeedi, P. et al. 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, 30: 1-10.
Subarmanian, R., Asmawi, M.Z., Sadikun, A. 2008. In vitro α-glukosidase and α-amylase enzym inhibitory effects of Andrographis paniculata extract and andrografolid. Acta Biochimica Polonica, 55(2): 391-398.
Tan, M.C.S., Oyong, G.G., Shen, C.C., Ragasa, C.Y. 2016. Chemical constituents of Andrographis paniculata (Burm. f.) Nees. International Journal of Pharmacognosy and Phytochemical Research, 8: 1398-1402.
Widjajakusuma, E.C. et al. 2018. Phytochemical screening and preliminary clinicals trials of the aqueous extract mixture of Andrographis paniculata (Burm. f.) Wall. Ex Nees and Syzygium polyanthum (Wight.) Walp leaves in metformin treated patients with type 2 diabetes. Phytomedicine, 55: 137-147.
Yu, B.C., Hung, C.R., Chen, W.C., Cheng, J.T. 2003. Antihyperglycaemic effect of andrografolid in streptozotocin-induced diabetic rats. Planta Medica, 69: 1075-1079.
Zhang, X.F., Tan, B.K.H. 2000. Antihyperglycaemic and antioxidant properties of Andrographis paniculata in normal and diabetic rats. Clinical and Experimental Pharmacology and Physiology, 27: 358-363.
Downloads
Published
How to Cite
Issue
Section
License
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution 4.0 International License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).
