Molecular docking of sterol derivatives in Tagetes erecta Linn. as an antiatherosclerotic agents through activation of PPARγ and LXRα receptors

I Wayan Surya Rahadi, Ni Kadek Ayu Mas Ratnadewi, Ketut Agus Adrianta

Abstract


Atherosclerosis is a condition characterized by inflammation in the arteries, which is linked with the accumulation of lipids and alterations in metabolism. Considering that atherosclerosis is the main factor causing death in the world, it is necessary to carry out immediate prevention and treatment to reduce the risk of developing clinical severity. The creation of foam cells, which originate from macrophages, is considered a key element in cardiovascular ailments, particularly in the advancement of atherosclerosis. Two types of the nuclear receptors known as Peroxisome proliferator-activated receptor γ (PPARγ) and liver X receptor α (LXRα), which serve as a primary regulator of cholesterol, intracellular lipid homeostasis and they are instrumental in the process of reverse cholesterol transport (RCT). Activation of these receptors could potentially decrease foam cell formation, consequently lowering the risk of atherogenesis and reducing cardiovascular disease risk. This research aims to determine sterol derivative compounds in Tagetes erecta Linn. which have the best interaction and potential as anti-atherosclerosis through peroxisome proliferator-activated receptor γ (PPARγ) and liver X receptor α (LXRα) activation. The analysis of this study is using docking molecular analysis. The parameters observed in this study were docking score, visualization results, absorption, distribution, metabolism, excretion profile, and toxicity value. The molecular docking outcomes indicate that β-sitosterol and 7β-hydroxysitosterol possess the most favorable binding energy values. They exhibit a positive pharmacokinetic profile, with the exception of gastrointestinal absorption and respiratory toxicity.

Keywords


Atherosclerosis; LXR α; Molecular docking; PPARγ; Tagetes erecta Linn.

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Agustin, D.F., & Wahjudi, M. (2023). Studi in silico potensi metabolit sekunder Eleutherine palmifolia (L.) Merr. sebagai inhibitor protein E6 dan E7 dari human Papilloma Virus. Keluwih: Jurnal Kesehatan dan Kedokteran, 4(1), 11–30. https://doi.org/10.24123/kesdok.v4i1.5818

Arifin, N. H., & Febriansah, R. (2022). Uji molecular docking dan bioinformatika terhadap meniran (Phyllanthus niruri L.) sebagai antivirus SARS-CoV-2 dan antikanker serviks. E-Journal Menara Perkebunan, 90(1), 11–22. https://doi.org/10.22302/iribb.jur.mp.v90i1.477

Arifuzzaman, S., Labu, Z. K., Harun-Or-Rashid, Md., Laboni, F. R., Khatun, Mst. R., & Chowdhury, N. S. (2023). Identification of novel compounds targeting the liver X receptor (LXR): in-silico studies, screening, molecular docking, and chemico-pharmacokinetic analysis. https://doi.org/10.21203/rs.3.rs-3688739/v1

Damayanti, S., Khonsa, K., & Amelia, T. (2021). Antiviral activity and toxicity prediction of compounds contained in figs (Ficus carica L.) by in silico method. Indonesian Journal of Pharmaceutical Science and Technology, 8(1), 21. https://doi.org/10.24198/ijpst.v8i1.29868

Fatimah, D. S., Widiyastuti, S., Oktaviani, D. J., Amanda, Q. P., Lestari, S., Ramadhan, S. A., & Megantara, S. (2020). Pemodelan farmakofor, skrining virtual, dan penambatan molekul senyawa metabolit dalam ekstrak daun salam (Syzygium polyanthum (wight) walp.) sebagai senyawa antihipertensi. Jurnal Farmasi Galenika, 7(2), 91–107.

Franceschelli, S., De Cecco, F., Pesce, M., Ripari, P., Guagnano, M. T., Nuevo, A. B., Grilli, A., Sancilio, S., & Speranza, L. (2023). Hydroxytyrosol reduces foam cell formation and endothelial inflammation regulating the PPARγ/LXRα/ABCA1 pathway. International Journal of Molecular Sciences, 24(3). https://doi.org/10.3390/ijms24032057

Fruchart, J. C., Santos, R. D., Aguilar-Salinas, C., Aikawa, M., Al Rasadi, K., Amarenco, P., Barter, P. J., Ceska, R., Corsini, A., Després, J. P., Duriez, P., Eckel, R. H., Ezhov, M. V., Farnier, M., Ginsberg, H. N., Hermans, M. P., Ishibashi, S., Karpe, F., Kodama, T., … Libby, P. (2019). The selective peroxisome proliferator-activated receptor alpha modulator (SPPARMα) paradigm: Conceptual framework and therapeutic potential. Cardiovascular Diabetology, 18(1), 1–20. https://doi.org/10.1186/s12933-019-0864-7

Gholam, G. M. (2022). Molecular docking of the bioactive compound Ocimum sanctum as an inhibitor of Sap 1 Candida albicans. Sasambo Journal of Pharmacy, 3(1), 18–24. https://doi.org/10.29303/sjp.v3i1.157

Ivanović, V., Rančić, M., Arsić, B., & Pavlović, A. (2020). Lipinski’s rule of five, famous extensions and famous exceptions. Chemia Naissensis, 3(1), 171–181. https://doi.org/10.46793/chemn3.1.171i

Jayanto, F., Mustarichie, R., & Kakhar, A. (2020). Virtual Screening Kandungan Senyawa Kipas Laut (Gorgonia mariae) sebagai Antiasma. Alchemy, 16(2), 199–210. https://doi.org/10.20961/alchemy.16.2.3996.199-210

Khan, M. A., Hashim, M. J., Mustafa, H., Baniyas, M. Y., Al Suwaidi, S. K. B. M., AlKatheeri, R., Alblooshi, F. M. K., Almatrooshi, M. E. A. H., Alzaabi, M. E. H., Al Darmaki, R. S., & Lootah, S. N. A. H. (2020). Global Epidemiology of Ischemic Heart Disease: Results from the Global Burden of Disease Study. Cureus, 12(7). https://doi.org/10.7759/cureus.9349

Khotimah, S., Kalim, H., Rohman, M. S., & Soeharto, S. (2020). Anti-atherosclerotic activity of eleutherine americana merr. As the peroxisome proliferated-activated receptor γ agonist: In silico study. Research Journal of Pharmacy and Technology, 13(3), 1423–1428. https://doi.org/10.5958/0974-360X.2020.00260.7

Kresnapati, I. N. B. A., Khaerunnisa, S., & Safitri, I. (2021). Ethanol Extract of Marigold Flower (Tagetes Erecta L.) Decreases The Total Cholesterol, Low Density Lypoprotein (LDL), Malondialdehyde (MDA), and Apoliprotein B (APOB) on Hyperlipidemia Rat Models. Folia Medica Indonesiana, 57(3), 245. https://doi.org/10.20473/fmi.v57i3.23838

Lin, H. C., Lii, C. K., Chen, H. C., Lin, A. H., Yang, Y. C., & Chen, H. W. (2018). Andrographolide Inhibits Oxidized LDL-Induced Cholesterol Accumulation and Foam Cell Formation in Macrophages. American Journal of Chinese Medicine, 46(1), 87–106. https://doi.org/10.1142/S0192415X18500052

Ma, X., Li, S. F., Qin, Z. S., Ye, J., Zhao, Z. L., Fang, H. H., Yao, Z. W., Gu, M. N., & Hu, Y. W. (2015). Propofol up-regulates expression of ABCA1, ABCG1, and SR-B1 through the PPARγ/LXRα signaling pathway in THP-1 macrophage-derived foam cells. Cardiovascular Pathology, 24(4), 230–235. https://doi.org/10.1016/j.carpath.2014.12.004

Manisha, R. L., Riyaz, S., Satyanarayana, B., Nazma, S. K., Nadeem, S. K., Vidhyadhararao, B., Vijay Kumar, J., Venkateswara Rao, I., & Sadhik, S. K. (2013). Evaluation of anxiolytic activity of flower extracts of Tagetes Erecta Linn (Asteraceae) in rats. Journal of Applied Pharmaceutical Science, 3(12), 75–82. https://doi.org/10.7324/JAPS.2013.31214

Mardianingrum, R., Endah, S. R. N., Suhardiana, E., Ruswanto, R., & Siswandono, S. (2021). Docking and molecular dynamic study of isoniazid derivatives as anti-tuberculosis drug candidate. Chemical Data Collections, 32, 100647. https://doi.org/10.1016/j.cdc.2021.100647

Naufa, F., Mutiah, R., Yen, Y., & Indrawijaya, A. (2022). Studi in Silico Potensi Senyawa Katekin Teh Hijau (Camellia sinensis) sebagai Antivirus SARS CoV-2 terhadap Spike Glycoprotein (6LZG) dan Main Protease (5R7Y). Jurnal of Food and Pharmaceutical Sciences, 10(1), 584–596. https://doi.org/10.22146/jfps.3580

Pramatama, A., Susianti, & Windarti. (2014). Noni Fruits (Morinda citrifolia) as Atherosclerosis Inhibitor. Jurnal Penelitian Perawat Indonesia, 18–26. https://doi.org/10.37287/jppp.v2i4.209

Prasetiawati, R., Damayanti, A., & Suwandi, D. W. (2023). Prosiding Seminar Nasional Diseminasi Penelitian Volume 3 Program Studi S1 Farmasi 2023 Simulasi Dinamika Molekuler Senyawa Aktif Akar Pakis Tangkur (Polypodium feei METT) Sebagai Inhibitor Enzim Inducible Nitric Oxide Synthase (iNOS). Prosiding Seminar, 3(September), 390–400.

PubChem. (2023). National Center of Biotechnology Information.

Rachmawati, E., Rohman, M. S., Sishartami, L. W., Sargowo, D., & Kalsum, U. (2022). In Silico Modelling, Regulation of Cell Viability and Anti Atherosclerotic Effect in Macrophage by Decaffeinated Coffee and Green Tea Extract. Pharmacognosy Journal, 14(1), 46–55. https://doi.org/10.5530/pj.2022.14.7

Ramadhian, M. R., & Rahmatia, N. (2017). Potensi Cabai sebagai Anti-Aterosklerosis. Journal of Majority, 6(2), 55–59.

Ravi, L., & Krishnan, K. (2016). a Handbook on Protein-Ligand Docking Tool: Autodock4. 4(3), 1–6.

Rimac, H., Grishina, M., & Potemkin, V. (2021). Use of the Complementarity Principle in Docking Procedures: A New Approach for Evaluating the Correctness of Binding Poses. Journal of Chemical Information and Modeling, 61(4), 1801–1813. https://doi.org/10.1021/acs.jcim.0c01382

Ruswanto, R., Mardianingrum, R., Siswandono, S., & Kesuma, D. (2020). Reverse Docking, Molecular Docking, Absorption, Distribution, and Toxicity Prediction of Artemisinin as an Anti-diabetic Candidate. Molekul, 15(2), 88. https://doi.org/10.20884/1.jm.2020.15.2.579

Rosenblat, M., Volkova, N., & Aviram, M. (2013). Pomegranate phytosterol (β-sitosterol) and polyphenolic antioxidant (punicalagin) addition to statin, significantly protected against macrophage foam cells formation. Atherosclerosis, 226(1), 110–117. https://doi.org/10.1016/j.atherosclerosis.2012.10.054

Sahoo, S., Sinha, S., & Singh, A. (2022). Molecular Docking Study Reveals α-Santalol from Santalum album Linn. as Promising Inhibitor of CD36 for Atherosclerosis. Cardiometry, 24, 353–359. https://doi.org/10.18137/cardiometry.2022.24.353359

Setiawan, E., Marpaung, F. R., Sukandar, E., Lukas, L., Wijono, H., Warindra, T., Kurniawan, R., Wibowo, T., Costa, M. O., & Roberts, J. (2019). Kajian Narrative terhadap Profil Farmakokinetik Antibiotik pada Pasien Kritis: Implikasi terhadap Ketercapaian Target Narrative Study on Pharmacokinetics of Antibiotics among Critically Ill Patients: the Implication on the Pharmacokinetics-Pharmacodynami. Pharmaceutical Sciences and Research, 6(1), 1–12. https://doi.org/10.7454/psr.v6i1.4274

Shah, K., Mujwar, S., Gupta, J. K., Shrivastava, S. K., & Mishra, P. (2019). Molecular Docking and in Silico Cogitation Validate Mefenamic Acid Prodrugs as Human Cyclooxygenase-2 Inhibitor. Assay and Drug Development Technologies, 17(6), 285–291. https://doi.org/10.1089/adt.2019.943

Shetty, L. J., Sakr, F. M., Al-Obaidy, K., Patel, M. J., & Shareef, H. (2015). A brief review on medicinal plant Tagetes erecta Linn. Journal of Applied Pharmaceutical Science, 5(Suppl 3), 091–095. https://doi.org/10.7324/JAPS.2015.510.S16

Singh, Y., Gupta, A., & Kannojia, P. (2020). Tagetes erecta (Marigold) - A review on its phytochemical and medicinal properties. Current Medical and Drug Research, 4(01). https://doi.org/10.53517/cmdr.2581-5008.412020201

Susanti, E. (2019). In silico analysis of bioactive compounds of Hibiscus sabdariffa as potential agonists of LXR to inhibit the atherogenesis process. AIP Conference Proceedings, 2108(June). https://doi.org/10.1063/1.5109983

Suwandi, D. W., Wahyuni, N., & Intan, S. A. (2023). Simulasi in silico senyawa aktif daun jambu mawar (Syzygium jambos L. Alston) sebagai obat antiinflamasi. Jurnal Farmamedika (Pharmamedica Journal), 8(1), 7–16. https://doi.org/10.47219/ath.v8i1.205

Tsou, C. Y., Chen, C. Y., Zhao, J. F., Su, K. H., Lee, H. T., Lin, S. J., … Lee, T. S. (2014). Activation of soluble guanylyl cyclase prevents foam cell formation and atherosclerosis. Acta Physiologica, 210(4), 799–810. https://doi.org/10.1111/apha.12210

Weni, M., Safithri, M., & Seno, D. S. H. (2020). Molecular Docking of Active Compounds Piper crocatum on the A-Glucosidase Enzyme as Antidiabetic. Indonesian Journal of Pharmaceutical Science and Technology, 7(2), 64. https://doi.org/10.24198/ijpst.v7i2.21120

Winardi, D. O., Alliyah, S. A., Fadilah, S. N., Sirait, J., Putra, H. B. A., Puspitadewi, N., Neli, N., Muchtaridi, M., & Zuhrotun, A. (2023). Studi In Silico dan In Vitro Senyawa Aktif pada Rimpang Kunyit (Curcuma domestica) sebagai Antiinflamasi pada Cyclooxygenase-2 (COX-2). Indonesian Journal of Pharmaceutical Science and Technology, 1(1). https://doi.org/10.24198/ijpst.v0i0.47171

World Health Organization. (2023). Cardiovascular Diseases.

Yang, H., Sun, L., Li, W., Liu, G., & Tang, Y. (2018). In Silico Prediction of Chemical Toxicity for Drug Design Using Machine Learning Methods and Structural Alerts. Frontiers in Chemistry, 6(February), 1–12. https://doi.org/10.3389/fchem.2018.00030




DOI: https://doi.org/10.24114/jpkim.v16i2.57455

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