Molecular interactions of  Andrographis paniculata  Burm. f. Active Compound with Nuclear Receptor (CAR and PXR): An In Silico Assessment Approach

Elza Sundhani; Agung Endro Nugroho; Arief Nurrochmad; Endang Lukitaningsih

doi:10.22146/ijc.67981

Molecular interactions of Andrographis paniculata Burm. f. Active Compound with Nuclear Receptor (CAR and PXR): An In Silico Assessment Approach

https://doi.org/10.22146/ijc.67981

Elza Sundhani⁽¹⁾, Agung Endro Nugroho^(2*), Arief Nurrochmad⁽³⁾, Endang Lukitaningsih⁽⁴⁾

(1) Doctoral Program in Pharmaceutical Science, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta 55281, Indonesia; Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Muhammadiyah Purwokerto, Jl. KH. Ahmad Dahlan Dukuhwaluh, Purwokerto 53182, Central Java, Indonesia
(2) Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Gadjah Mada, Sekip Utara, Yogyakarta 55281, Indonesia
(3) Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Gadjah Mada, Sekip Utara, Yogyakarta 55281, Indonesia
(4) Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta 55281, Indonesia
(*) Corresponding Author

Abstract

The study aims to analyze the potential Herb-Drug Interactions (HDIs) of the chemical compound in Andrographis paniculate Burm. f. against Constitutive Androstane Receptor (CAR) and Pregnane X Receptor (PXR). The 1XVP and 1SKX obtained from the Protein Data Bank (PDB) were used as the targeted protein. The molecular docking analysis was done using the Molecular Operating Environment (MOE) and molecular dynamics simulation using Gromacs. The results of the docking analysis showed that 14-Deoxy-11,12-didehydroandrographolide had the strongest binding energy (1XVP-21.0998 Å) with the Arene-H binding type on Tyr326 and Andrographidine A had the strongest binding energy (1SKX-24.7363 Å) with the Arene-H binding type on Trp299. While Andrographolide is the major component, it also has a high affinity for the two PDB IDs (1XVP-17.4044 Å and 1SKX-21.8881 Å). Based on the RMSD value, the radius of gyration (Rg), and MM/PBSA on molecular dynamic simulations, it shows that the ligand and protein complex as a whole can bind strongly to amino acid residues at the active site. The complex also has sufficient stability and good affinity. Therefore, this study can predict the mechanism in HDIs, especially in CYP 450 expression through the activation pathways of CAR and PXR receptors.

Keywords

Andrographis paniculata; CAR; PXR; 1XVP; 1SKX

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References

[1] Awortwe, C., Makiwane, M., Reuter, H., Muller, C., Louw, J., and Rosenkranz, B., 2018, Critical evaluation of causality assessment of herb-drug interactions in patients, Br. J. Clin. Pharmacol., 84 (4), 679–693.

[2] Fasinu, P.S., Bouic, P.J., and Rosenkranz, B., 2012, An overview of the evidence and mechanisms of herb-drug interactions, Front. Pharmacol., 3, 69.

[3] Showande, S.J., Fayeke, T.O., Kajula, M., Hokkanen, J., and Tolonen, A., 2018, Potential inhibition of major human cytochrome P450 isoenzymes by selected tropical medicinal herbs-Implication for herb-drug interactions, Food Sci. Nutr., 7 (1), 44–55.

[4] Bo, L., Baosheng, Z., Yang, L., Mingmin, T., Beiran, L., Zhiqiang, L., and Huaqiang, Z., 2016, Herb-drug enzyme-mediated interactions, and the associated experimental methods: A review, J. Tradit. Chin. Med., 36 (3), 392–408.

[5] Buchman, C.D., Chai, S.C., and Chen, T., 2018, A current structural perspective on PXR and CAR in drug metabolism, Expert Opin. Drug Metab. Toxicol., 14 (6) 635–647.

[6] Daujat-Chavanieu, M., and Gerbal-Chaloin, S., 2020, Regulation of CAR and PXR expression in health and disease, Cells, 9 (11), 2395.

[7] Wang, Y.M., Ong, S.S., Chai, S.C., and Chen, T., 2012, Role of CAR and PXR in xenobiotic sensing and metabolism, Expert Opin. Drug Metab. Toxicol., 8 (7), 803–817.

[8] Lynch, C., Mackowiak, B., Huang, R., Li, L., Heyward, S., Sakamuru, S., Wang, H., and Xia, M., 2018, Identification of modulators that activate the constitutive androstane receptor from the Tox21 10K compound library, Toxicol. Sci., 167 (1), 282–292.

[9] Hossain, M.S., Urbi, Z., Sule, A., and Rahman, K.M.H., 2014, Andrographis paniculata (Burm. f.) Wall. ex Nees: A Review of ethnobotany, phytochemistry, and pharmacology, Sci. World J., 2014, 274905.

[10] Kumar, S., Singh, B., and Bajpai, V., 2021, Andrographis paniculata (Burm.f.) Nees: Traditional uses, phytochemistry, pharmacological properties and quality control/quality assurance, J. Ethnopharmacol., 275, 114054.

[11] Dai, Y., Chen, S.R., Chai, L., Zhao, J., Wang, Y., and Wang, Y., 2019, Overview of pharmacological activities of Andrographis paniculata and its major compound andrographolide, Crit. Rev. Food Sci. Nutr., 59 (Suppl. 1), S17–S29.

[12] Kandanur, S.G.S., Tamang, N., Golakoti, N.R., and Nanduri, S., 2019, Andrographolide: A natural product template for the generation of structurally and biologically diverse diterpenes, Eur. J. Med. Chem., 176, 513–533.

[13] Balap, A., Lohidasan, S., Sinnathambi, A., and Mahadik, K., 2017, Herb-drug interaction of Andrographis paniculata (Nees) extract and andrographolide on pharmacokinetic and pharmacodynamic of naproxen in rats, J. Ethnopharmacol., 195, 214–221.

[14] Balap, A., Atre, B., Lohidasan, S., Sinnathambi, A., and Mahadik, K., 2016, Pharmacokinetic and pharmacodynamic herb-drug interaction of Andrographis paniculata (Nees) extract and andrographolide with etoricoxib after oral administration in rats, J. Ethnopharmacol., 183, 9–17.

[15] Chien, C.F., Wu, Y.T., Lee, W.C., Lin, L.C., and Tsai, T.H., 2010, Herb–drug interaction of Andrographis paniculata extract and andrographolide on the pharmacokinetics of theophylline in rats, Chem. Biol. Interact., 184 (3), 458–465.

[16] Pan, Y., Abd-Rashid, B.A., Ismail, Z., Ismail, R., Mak, J.W., Pook, P.C.K., Er, H.M., and Ong, C.E., 2011, In vitro determination of the effect of Andrographis paniculata extracts and andrographolide on human hepatic cytochrome P450 activities, J. Nat. Med., 65 (3-4), 440–447.

[17] Pekthong, D., Blanchard, N., Abadie, C., Bonet, A., Heyd, B., Mantion, G., Berthelot, A., Richert, L., and Martin, H., 2009, Effects of Andrographis paniculata extract and andrographolide on hepatic cytochrome P450 mRNA expression and monooxygenase activities after in vivo administration to rats and in vitro in rat and human hepatocyte cultures, Chem. Biol. Interact., 179 (2-3), 247–255.

[18] Pekthong, D., Martin, H., Abadie, C., Bonet, A., Heyd, B., Mantion, G., and Richert, L., 2008, Differential inhibition of rat and human hepatic cytochrome P450 by Andrographis paniculata extract and andrographolide, J. Ethnopharmacol., 115 (3), 432–440.

[19] Qiu, F., Hou, X.L., Takahashi, K., Chen, L.X., Azuma, J., and Kang, N., 2012, Andrographolide inhibits the expression and metabolic activity of cytochrome P450 3A4 in the modified Caco-2 cells, J. Ethnopharmacol., 141 (2), 709–713.

[20] Ooi, J.P., Kuroyanagi, M., Sulaiman, S.F., Tengku Muhammad, T.S., and Tan, M.L., 2011, Andrographolide and 14-Deoxy-11,12-didehydroandrographolide inhibit cytochrome P450s in HepG2 hepatoma cells, Life Sci., 88 (9-10), 447–454.

[21] Hafid, A.F., Rifai, B., Tumewu, L., Widiastuti, E., Dachliyati, L., Primaharinastiti, R., and Widyawaruyanti, A., 2015, Andrographolide determination of Andrographis paniculata extracts, ethyl acetate fractions and tablets by thin-layer chromatography, J. Chem. Pharm. Res., 7 (12), 557–561.

[22] Wang, J., Yang, W., Wang, G., Tang, P., and Sai, Y., 2014, Determination of six components of Andrographis paniculata extract and one major metabolite of andrographolide in rat plasma by liquid chromatography-tandem mass spectrometry, J. Chromatogr. B, 951-952, 78–88.

[23] Liu. Y.H., Mo, S.L., Bi, H.C., Hu, B.F., Li, C.G., Wang, Y.T., Huang, L., Huang, M., Duan, W., Liu, J.P., Wei, M.Q., and Zhou, S.F., 2011, Regulation of human pregnane X receptor and its target gene cytochrome P450 3A4 by Chinese herbal compounds and a molecular docking study, Xenobiotica, 41 (4), 259–280.

[24] Küblbeck, J., Niskanen, J., and Honkakoski, P, 2020, Metabolism-disrupting chemicals and the constitutive androstane receptor CAR, Cells, 9 (10), 2306.

[25] Borse, S.P., Singh, D.P., and Nivsarkar, M., 2019, Understanding the relevance of herb-drug interaction studies with special focus on interplays: A prerequisite for integrative medicine, Porto Biomed. J., 4 (2), e15.

[26] Pitaloka, D.A.E. Ramadhan, D.S.F., Arfan, A., Chaidir, L., and Fakih, T.M., 2021, Docking-based virtual screening and molecular dynamics simulations of quercetin analogs as enoyl-acyl carrier protein reductase (InhA) inhibitors of Mycobacterium tuberculosis, Sci. Pharm., 89 (2), 20.

[27] Pitaloka, D.A.E., Damayanti, S., Artarini, A.A., and Sukandar, E.Y., 2019, Molecular docking, dynamics simulation, and scanning electron microscopy (SEM) examination of clinically isolated Mycobacterium tuberculosis by ursolic acid: A pentacyclic triterpenes, Indones. J. Chem., 19, (2), 328–336.

[28] Shivanika, C., Deepak Kumar, S., Ragunathan, V., Tiwari, P., Sumitha, A., and Devi, P.B, 2020, Molecular docking, validation, dynamics simulations, and pharmacokinetic prediction of natural compounds against the SARS-CoV-2 main-protease, J. Biomol. Struct. Dyn., 0 (0), 1–27.

[29] Lee, H.S., Jo, S., Lim, H.S., and Im, W., 2012, Application of binding free energy calculations to prediction of binding modes and affinities of MDM2 and MDMX inhibitors, J. Chem. Inf. Model., 52 (7), 1821–1832.

[30] Maglich, J.M., Parks, D.J., Moore, L.B., Collins, J.L., Goodwin, B., Billin, A.N., Stoltz, C.A., Kliewer, S.A., Lambert, M.H., Willson, T.M., and Moore., J.T., 2003, Identification of a novel human constitutive androstane receptor (CAR) agonist and its use in the identification of CAR target genes, J. Biol. Chem., 278 (19), 17277–17283.

[31] Chen, J., and Raymond, K., 2006, Roles of Rifampicin in drug-drug interactions: underlying molecular mechanisms involving the nuclear pregnane X receptor, Ann. Clin. Microbiol. Antimicrob., 5 (1), 3.

[32] Chrencik, J.E., Orans, J., Moore, L.B., Xue, Y., Peng, L., Collins, J.L., Wisely, G.B., Lambert, M.H., Kliewer, S.A., and Redinbo, M.R., 2005, Structural disorder in the complex of human pregnane X receptor and the macrolide antibiotic Rifampicin, Mol. Endocrinol., 19 (5) 1125–1134.

[33] Damayanti, S., Martak, N.A.S., Permana, B., Suwandi, A., Hartati, R., and Wibowo, I., 2020, In silico study on interaction and preliminary toxicity prediction of Eleutherine Americana components as an antifungal and antitoxoplasmosis candidate, Indones. J. Chem., 20 (4), 899–910.

[34] Hollingsworth, S.A., and Dror, R.O., 2018, Molecular dynamics simulation for all, Neuron, 99 (6), 1129–1143.

[35] Bao, L., Wang, J., and Xiao, Y., 2019, Molecular dynamics simulation of the binding process of ligands to the add adenine riboswitch aptamer, Phys. Rev. E, 100 (2), 022412.

[36] Ravi, S., Priya, B., Dubey, P., Thiruvenkatam, V., and Kirubakaran, S., 2021, Molecular docking and molecular dynamics simulation studies of quinoline-3-carboxamide derivatives with DDR kinases–selectivity studies towards ATM kinase, Chemistry, 3 (2), 511–524.

[37] Bai, B., Zou, R., Chan, H.C.S., Li, H., and Yuan, S., 2021, MolADI: A web server for automatic analysis of protein-small molecule dynamic interactions, Molecules, 26 (15), 4625.

[38] Dash, R., Ali, M.C., Dash, N., Azad, M.A.K., Hosen, S.M.Z., Hannan, M.A., and Moon, I.S., 2019, Structural and dynamic characterizations highlight the deleterious role of SULT1A1 R213H polymorphism in substrate binding, Int. J. Mol. Sci., 20 (24), 6256.

[39] Dewi, M.L., Fakih, T.M., and Sofyan, R.I., 2021, The discovery of tyrosinase enzyme inhibitors activity from polyphenolic compounds in red grape seeds through in silico study, J. Pure Appl. Chem. Res., 10 (2), 104–112.

[40] Khanal, S.P., Koirala, R.P., Mishra, E., and Adhikari, N.P., 2021, Molecular dynamics study of structural properties of γ-aminobutyric acid (GABA), BIBECHANA, 18 (1), 67–74.

[41] Zhang, X., Liu, X., He, M., Zhang, Y., Sun, Y and Lu, X, 2020, A molecular dynamics simulation study of KF and NaF ion pairs in hydrothermal fluids, Fluid Phase Equilib., 518, 112625.

[42] Levine, B.G., Stone, J.E., and Kohlmeyer, A., 2011, Fast analysis of molecular dynamics trajectories with graphics processing units—Radial distribution function histogramming, J. Comput. Phys., 230 (9), 3556–3569.

[43] Zikri, A.T., Pranowo, H.D., and Haryadi, W., 2020, Stability, hydrogen bond occupancy analysis and binding free energy calculation from flavonol docked in DAPK1 active site using molecular dynamics simulation approaches, Indones. J. Chem., 21 (2), 383–390.

[44] Subash, K.R., 2020, In silico pharmacokinetic and toxicological properties prediction of bioactive compounds from Andrographis paniculata, Natl. J. Physiol., Pharm. Pharmacol., 10 (7), 537–542.

[45] Julaiha, J., Widodo, G.P., and Herowati, R., 2019, Predicting ADME and molecular docking analysis of Andrographis paniculata and Strobilanthes crispus chemical constituents against antidiabetic molecular targets, J. Idn. Chem. Soc., 2 (2), 66–125.

[46] Lindawati, N.Y., Nugroho, A.E., and Pramono, S., 2015, Pengaruh kombinasi ekstrak terpurifikasi herba sambiloto (Andrographis paniculata (Burm. f.) Nees) dan herba pegagan (Centella asiatica (L.) Urban) terhadap translokasi protein GLUT-4 pada tikus diabetes mellitus tipe 2 resisten insulin, Trad. Med. J., 19 (2), 62–69.

[47] Nugroho, A.E., Rais, I.R., Setiawan, I., Pratiwi, P.Y., Hadibarata, T., Maulana, T., and Pramono, S., 2014, Pancreatic effect of andrographolide isolated from Andrographis paniculata (Burm. f.) Nees, Pak. J. Biol. Sci., 17 (1), 22–31.

[48] Samala, S. and Veeresham, C., 2015, Andrographolide pretreatment enhances the bioavailability and hypoglycemic action of glimepiride and metformin, Int. J. Phytomed., 7 (3), 254–264.

[49] Zhang, X., Zhang, X., Wang, X., and Zhao, M., 2018, Influence of andrographolide on the pharmacokinetics of warfarin in rats, Pharm. Biol., 56 (1), 351–356.

DOI: https://doi.org/10.22146/ijc.67981