Predicting ADME and Molecular Docking Analysis of Andrographis paniculata and Strobilanthes crispus Chemical Constituents Againts Antidiabetic Molecular Targets
Abstract
Andrographis paniculata and Strobilanthes crispus are two medicinal plants from Acanthaceae family, known to have antidiabetic activity. This study aimed to investigate the molecular interaction of A. paniculata and S. crispus phytochemical constituents with various macromolecular targets of antidiabetic agent through molecular docking. Nineteen A. paniculata and twenty S. crispus chemical constituents were docked to four macromolecular targets of antidiabetic agent by using AutoDock Vina in PyRx. The results revealed that compounds from A. paniculata that have the best binding affinity protein targets was 19-tripenhyl isoandrographolide to glucokinase (-10.4 kcal/mol), Dipeptidyl peptidase 4 (DPP4) (9.3 kcal/mol) and α-glucosidase (-8.8 kcal/mol), and andrographolactone to Protein Tyrosin Phosphatase1B (PTP1B) (-9.5 kcal/mol). Whereas compounds in the S. crispus derivatives that have the best binding affinity were stigmasterol to glucokinase (-9.9 kcal/mol), rutin to DPP4 (-9.7 kcal/mol), lupeol to α-glucosidase (-8.8 kcal/mol) and luteolin to PTP1B (-8.8 kcal/mol). The differences between the two plants were due to the differences in compounds in each of the plants as well as differences in target proteins. Other than that, profile of absorption, distribution, metabolism, and excretion (ADME) predictions are very important because they play a critical role in assessing the quality of potential clinical candidates for a new drug. Compounds with best binding energy that showed good ADME properties were andrographolactone, stigmasterol, lupeol and luteolin. Deoxyandrographolide was predicted to have the best ADME properties, however its affinity to target proteins was lower than native ligands.
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References
International Diabetes Federation. IDF Diabetes Atlas. International Diabetes Federation Seven Edition. 2015.
N. Kerru, A. Sigh-Pillay, P. Awolade, P. Sigh, Current Anti-Diabetic Agents and Their Molecular Targets A Review, Eur. J. Medicin. Chem., 2018, 152, 436-488, DOI: https://doi.org/10.1016/j.ejmech.2018.04.061.
R. J. Marles, N. R. Fransworth, Antidiabetic Plants and their Active Constituens, Phytomedicine, 1995, 155, 2, 137-189, DOI: https://doi.org/10.1016/S0944-7113(11)80059-0.
A. E. Nugroho, M. Andrie, N. K., Warditiani, E. Siswanto, S. Pramono, E. Lukitaningsih, Antidiabetic and Antihiperlipidemic Effect of Andrographis paniculata (Burm. f.) Nees and Andrographolide in High-fructose-fat-fed Rats. Indian J. Pharmacol., 2012, 44(3), 377-381, DOI: https://doi.org/10.4103/0253-7613.96343.
A. E. Nugroho, N. Y. Lindawati, K. Herlyanti, L. Widyastuti, and S. Pramono, Antidiabetic Effect of a Combination of Andrographolide Enriched Extract of Andrographis paniculata (Burm f.) and Asiaticoside Enriched Extract of Centella asiatia L. in High Fructose Fat Fed Rats, Indian. J. Exp. Biol., 2013, 51, 1101-1108.
A. Chowdhury, and S. K. Biswas, Comparative Study of Hypoglicemic Effect of Ethanolic and Hot Water Extracts of Andrographis paniculata in Alloxan Induced Rat, Intern. J. Pharma. Sci. Res., 2012, 3(3), 771-773, DOI: https://doi.org/10.13040/IJPSR.0975-8232.3(3).815-17.
A. W. Augustine, A. Narashimhan, M. Vishwanathan, and B. Karundevi, Evaluation of Antidiabetic Property of Andrographis paniculata Powder in High Fat and Sucrose-induced Type-2 Diabetic Adult Male Rat, Asian Pac. J. Trop. Dis., 2014, 4(1), S140-S147, DOI: https://doi.org/10.1016/S2222-1808(14)60429-1.
N. Prem Kumar, S. K. Vijayan, J. N. Dharsana, K. X. Seena, and A. K. Anjana, Comparing the Effect of Antidiabetic Activity of Andrographis paniculata, Salacia reticulata and Ocimum sanctum by Invitro Screening, Asian J. Pharma. Clin. Res., 2012, 5(4), 146-149.
S. M. Rammohan, A. Zaini, and S. Amirin, In Vitro α-Glucosidase and α-Amylase Inhibitory Effects of Andrographis paniculata Extract and Andrographolactone, Acta Biochimica Polonica, 2008, 55(2), 391-398.
B. M. F. Abu, A. H. Teg, A. Rahmat, and F. Osman, Effects of Strobilanthes crispus Tea Aqueous Extracts on Glucose and Lipid Profile in Normal and Streptozotocin-induced Hyperglycemic Rat., Plant Foods Human Nutrion, 2006, 61, 7-12.
A. B. Mohd Fadzelly, and R. O. F. Asmah, Effects of Strobilantes crispus Tea Aqueous Extracts on Glucose and Lipid Profile in Normal and Streptozotocin-induced Hyperglycemic Rats, Plant Foods Human Nutrition, 2010, 1(2), 7-12, DOI: https://doi.org/10.1007/s11130-006-0002-z.
N. A. Norfarizan-Hannon, R. Asmah, M. Y. Rokiah, Fauziah, and H. Faridah, Effects of Strobilanthes crispus Juice on Wound Healing and Antioxidant Enzymes in Normal and Streptozotocin-induced Diabetic Rats, J. Bio. Sci., 2009, 9 (7), 662-668, DOI: https://doi.org/10.3923/jbs.2009.662.668.
H. Sun, D. Wang, X. Song, Y. Zhang, W. Ding, X. Peng, X. Zhang, Y. Li, Y. Ma, R. Wang, and P. Yu, Natural Phenylcalconaringenins and Phenylnaringenins as Antidiabetic Agents; α-Glucosidase an α-Amilase Inhibition an In vivo Anthyperglycemic and Anthyperlipidemic Effects, J.Agric. Food Chem., 2017, 65, 1574-1581, DOI: https://doi.org/10.1021/acs.jafc.6b05445.
D. J. Drucker, Enhancing Incretin Action for the Treatment of Type 2 Diabetes, Diabetes Care., 2003, 26(10), 2929-40, DOI: https://doi.org/10.2337/diacare.26.10.2929.
A. S. Al-Zubari, and E. E. M. Eid, Molecular Targets in Development of Antidiabetic Drugs, Inter. J. Pharmacol., 2010, 6(6), 784-795, DOI: https://doi.org/10.3923/ijp.2010.784.795.
D. W. Young, A. Bender, J. Hoyt, E. McWhinnie, G. W. Chirn, C. Y. Tao, J. A. Tallarico, M. Labow, J. L. Jenkins, T. J. Mitchison, and Y. Feng, Integrating High-content Screening and Ligand-Target Prediction to Identify Mechanism of Action, Nature Chem. Bio., 2007, 4, 59-68, DOI: https://doi.org/10.1038/nchembio.2007.53.
Z. Y. Meng, H. X. Zhang, Meizai, and M. Cui, Molecular Docking: A Powerfull Approach for Structure-based Drug Discovery, Curr. Comput. Aided Drug Des., 2011, 7, 146-157, DOI: https://doi.org/10.2174/157340911795677602.
S. Cosconati, S. Forli, A. L. Perryman, R. Harris, D. S. Goodsell, and A. J. Olson, Virtual Screening with AutoDock: Theory and Practice, Expert. Opin. Drug Discovery, 2011, 5, 597–607, DOI: https://doi.org/10.1517/17460441.2010.484460.
O. Rabal, P. Fernando, V. Helena, M. S. Mario, H. Sandra, and O. Julen, In silico Aptamer Docking Studies: from a Retrospective Validation to a Prospective Case Study-TIM3 Aptamers Binding, Molecular Therapy—Nucleic Acids, 2016, 5, e376, DOI: https://doi.org/10.1038/mtna.2016.84.
M. Kontoyianni, L. M. McClellan, and G. S. Sokol, Evaluation of Docking Performance: Comparative Data on Docking Algorithms, J. Med. Chem., 2004, 47(3), 558-65.

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