IN SILICO ASSESSMENT OF AMELIORATIVE EFFECTS OF POLYUNSATURATED FATTY ACID (PUFAS) FROM NAVICULA SALINICOLA AS AN INHIBITOR OF BENIGN PROSTATE HYPERPLASIA

ELLIN FEBRINA; ANNE YULIANTINI; DEWI KURNIA; AIYI ASNAWI

doi:10.22159/ijap.2023.v15s2.16

Authors

ELLIN FEBRINA Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Jatinangor-45363, West Java, Indonesia https://orcid.org/0000-0003-3004-5069
ANNE YULIANTINI Department of Pharmacochemistry, Faculty of Pharmacy, Universitas Bhakti Kencana, Bandung-40617, West Java, Indonesia
DEWI KURNIA Department of Pharmacochemistry, Faculty of Pharmacy, Universitas Bhakti Kencana, Bandung-40617, West Java, Indonesia
AIYI ASNAWI Department of Pharmacochemistry, Faculty of Pharmacy, Universitas Bhakti Kencana, Bandung-40617, West Java, Indonesia

DOI:

https://doi.org/10.22159/ijap.2023.v15s2.16%20

Keywords:

Benign prostatic hyperplasia (BPH), Inhibitor, Molecular docking, Navicula salinicola, Polyunsaturated fatty acids (PUFAs)

Abstract

Objective: Benign prostatic hyperplasia (BPH) is a prevalent, non-cancerous condition affecting aging men worldwide. As an alternative approach to conventional treatment options, polyunsaturated fatty acids (PUFAs) have gained attention for their potential therapeutic effects on various health conditions. This study investigated the interaction of PUFAs obtained from Navicula salinicola with the macromolecule associated with BPH, represented by STAT3, that is involved in the androgen signaling pathway in BPH (PDB ID 6NJS), using molecular docking simulations.

Methods: The docking simulations revealed the interaction patterns and binding affinities of 14 PUFAs with the amino acid residues of STAT3. The calculated binding energies and inhibition constants provided insights into the potential inhibitory effects of PUFAs on BPH.

Results: Results indicated that g-linolenic acid exhibited a strong binding affinity, forming hydrogen bonds with ARG609 and hydrophobic interactions with VAL637 and PRO639, highlighting its potential as a potent inhibitor. Docosahexaenoic acid also showed favorable interactions with ARG609 and hydrophobic residues, suggesting its potential therapeutic relevance.

Conclusion: g-Linolenic acid from N. salinicola exhibited a strong molecular interaction with STAT3.

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References

Speakman M, Kirby R, Doyle S, Ioannou C. Burden of male lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH)-focus on the UK. BJU Int. 2015;115(4):508-19. doi: 10.1111/bju.12745, PMID 24656222.

Madersbacher S, Sampson N, Culig Z. Pathophysiology of benign prostatic hyperplasia and benign prostatic enlargement: a mini-review. Gerontology. 2019;65(5):458-64. doi: 10.1159/000496289, PMID 30943489.

Nunes Xavier CE, Angulo JC, Pulido R, Lopez JI. A critical insight into the clinical translation of PD-1/PD-L1 blockade therapy in clear cell renal cell carcinoma. Curr Urol Rep. 2019;20(1):1. doi: 10.1007/s11934-019-0866-8, PMID 30645700.

Mohammed M, Bayissa B, Getachew M, Adem F. Drug-related problems and determinants among elective surgical patients: a prospective observational study. SAGE Open Med. 2022;10:20503121221122438. doi: 10.1177/20503121221122438, PMID 36093421.

Rodrigues SP, Wever AM, Dankelman J, Jansen FW. Risk factors in patient safety: minimally invasive surgery versus conventional surgery. Surg Endosc. 2012;26(2):350-6. doi: 10.1007/s00464-011-1874-z, PMID 21898021.

Li Y, Shi B, Dong F, Zhu X, Liu B, Liu Y. Effects of inflammatory responses, apoptosis, and STAT3/NF-κB- and Nrf2-mediated oxidative stress on benign prostatic hyperplasia induced by a high-fat diet. Aging (Albany, NY). 2019;11(15):5570-8. doi: 10.18632/aging.102138, PMID 31412319.

Huang HF, Murphy TF, Shu P, Barton AB, Barton BE. Stable expression of constitutively activated STAT3 in benign prostatic epithelial cells changes their phenotype to that resembling malignant cells. Mol Cancer. 2005;4(1):2. doi: 10.1186/1476-4598-4-2, PMID 15647107.

Park WY, Song G, Park JY, Ahn KS, Kwak HJ, Park J. Ellagic acid improves benign prostate hyperplasia by regulating androgen signaling and STAT3. Cell Death Dis. 2022;13(6):554. doi: 10.1038/s41419-022-04995-3, PMID 35715415.

Lin J, Zhou J, Zhong X, Hong Z, Peng J. Inhibition of the signal transducer and activator of transcription 3 signaling pathway by qianliening capsules suppresses the growth and induces the apoptosis of human prostate cells. Mol Med Rep. 2015;11(3):2207-14. doi: 10.3892/mmr.2014.2946, PMID 25394909.

Lin J, Zhou J, Xu W, Zhong X, Hong Z, Peng J. Qianliening capsule treats benign prostatic hyperplasia via suppression of the EGF/STAT3 signaling pathway. Exp Ther Med. 2013;5(5):1293-300. doi: 10.3892/etm.2013.1008, PMID 23737867.

Duan J, Song Y, Zhang X, Wang C. Effect of ω-3 polyunsaturated fatty acids-derived bioactive lipids on metabolic disorders. Front Physiol. 2021;12:646491. doi: 10.3389/fphys.2021.646491, PMID 34113260.

Saini RK, Keum YS. Omega-3 and omega-6 polyunsaturated fatty acids: dietary sources, metabolism, and significance-a review. Life Sci. 2018;203:255-67. doi: 10.1016/j.lfs.2018.04.049, PMID 29715470.

Ventura S, Oliver Vl, White CW, Xie JH, Haynes JM, Exintaris B. Novel drug targets for the pharmacotherapy of benign prostatic hyperplasia (BPH). Br J Pharmacol. 2011;163(5):891-907. doi: 10.1111/j.1476-5381.2011.01332.x, PMID 21410684.

Sandhya S. Phylogenetic diversity, significance and future prospects of heterotrophic bacteria associated with marine microalgae; 2018.

Renugadevi K, Nachiyar CV, Nellore J, Sunkar S, Namasivayam SKR. Nutraceutical compounds from marine microalgae. Handbook of Nutraceuticals and Natural Products: Biological, Medicinal, and Nutritional Properties and Applications. 2022;1:245-55.

Kurnia D, Idar V, Angraeni VJ, Hendriani R, Asnawi A, Nurachman Z. Potential of navicula salinicola extract, a microalgae from maluku islands, as an anti-inflammatory agent using the human red blood cells (HRBC) method. Rasayan J Chem. 2022;15(2):1174-81. doi: 10.31788/RJC.2022.1526913.

Pekkoh J, Phinyo K, Thurakit T, Lomakool S, Duangjan K, Ruangrit K. Lipid profile, antioxidant and antihypertensive activity, and computational molecular docking of diatom fatty acids as ACE inhibitors. Antioxidants (Basel). 2022;11(2):186. doi: 10.3390/antiox11020186, PMID 35204069.

Jiang G, Sun C, Wang X, Mei J, Li C, Zhan H. Hepatoprotective mechanism of Silybum marianum on nonalcoholic fatty liver disease based on network pharmacology and experimental verification. Bioengineered. 2022;13(3):5216-35. doi: 10.1080/21655979.2022.2037374, PMID 35170400.

Pereira H, Barreira L, Figueiredo F, Custodio L, Vizetto Duarte C, Polo C. Polyunsaturated fatty acids of marine macroalgae: potential for nutritional and pharmaceutical applications. Mar Drugs. 2012;10(9):1920-35. doi: 10.3390/md10091920, PMID 23118712.

Gu Z, Suburu J, Chen H, Chen YQ. Mechanisms of omega-3 polyunsaturated fatty acids in prostate cancer prevention. BioMed Res Int. 2013;2013:824563. doi: 10.1155/2013/824563, PMID 23762859.

Veras ASC, Gomes RL, Almeida Tavares ME, Giometti IC, Cardoso APMM, da Costa Aguiar Alves B. Supplementation of polyunsaturated fatty acids (PUFAs) and aerobic exercise improve functioning, morphology, and redox balance in prostate obese rats. Sci Rep. 2021;11(1):6282. doi: 10.1038/s41598-021-85337-9, PMID 33737530.

Guertin MH, Robitaille K, Pelletier JF, Duchesne T, Julien P, Savard J. Effects of concentrated long-chain omega-3 polyunsaturated fatty acid supplementation before radical prostatectomy on prostate cancer proliferation, inflammation, and quality of life: study protocol for a phase IIb, randomized, double-blind, placebo-controlled trial. BMC Cancer. 2018;18(1):64. doi: 10.1186/s12885-017-3979-9, PMID 29321047.

Ghadian A, Rezaei M. Combination therapy with omega-3 fatty acids plus tamsulocin and finasteride in the treatment of men with lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH). Inflammopharmacology. 2017;25(4):451-8. doi: 10.1007/s10787-017-0343-2, PMID 28391389.

Bercea CI, Cottrell GS, Tamagnini F, McNeish AJ. Omega‐3 polyunsaturated fatty acids and hypertension: a review of vasodilatory mechanisms of docosahexaenoic acid and eicosapentaenoic acid. Br J Pharmacol. 2021;178(4):860-77. doi: 10.1111/bph.15336, PMID 33283269.

Alexander W. Prostate cancer risk and omega-3 fatty acid intake from fish oil: a closer look at media messages versus research findings. Pharm Ther. 2013;38:561.

Chen Z, Ge M. Discovering pathways in benign prostate hyperplasia: a functional genomics pilot study. Exp Ther Med. 2021;21(3):242. doi: 10.3892/etm.2021.9673, PMID 33603850.

Saah SA, Sakyi PO, Adu-Poku D, Boadi NO, Djan G, Amponsah D. Docking and molecular dynamics identify leads against 5 alpha-reductase 2 for benign prostate hyperplasia treatment. J Chem. 2023;2023:1-20. doi: 10.1155/2023/8880213.

Kim S, Chen J, Cheng T, Gindulyte A, He J, He S. PubChem 2019 update: improved access to chemical data. Nucleic Acids Res. 2019;47(D1):D1102-9. doi: 10.1093/nar/gky1033, PMID 30371825.

Bai L, Zhou H, Xu R, Zhao Y, Chinnaswamy K, McEachern D. A potent and selective small-molecule degrader of STAT3 achieves complete tumor regression in vivo. Cancer Cell. 2019;36(5):498-511.e17. doi: 10.1016/j.ccell.2019.10.002, PMID 31715132.

Balint M, Jeszenoi N, Horvath I, van der Spoel D, Hetenyi C. Systematic exploration of multiple drug binding sites. J Cheminform. 2017;9(1):65. doi: 10.1186/s13321-017-0255-6, PMID 29282592.

Jejurikar BL, Rohane SH. Drug designing in discovery studio. Asian J Res Chem. 2021;14(2):2-8.

Asnawi A, Nedja M, Febrina E, Purwaniati P. Prediction of a stable complex of compounds in the ethanol extract of celery leaves (Apium graveolens l.) Function as a vkorc1 antagonist. Trop J Nat Prod Res. 2023;7:2362-70.

Febrina E, Asnawi A, Abdulah R, Lestari K, Supratman U. Identification of flavonoids from Acalypha indica l. (euphorbiaceae) as caspase-3 activators using molecular docking and molecular dynamics. Int J Appl Pharm. 2022:162-6.

Febrina E, Alamhari RK, Abdulah R, Lestari K, Levita J, Supratman U. Molecular docking and molecular dynamics studies of Acalypha indica l. Phytochemical constituents with caspase-3. Int J App Pharm. 2021;13(4):210-5. doi: 10.22159/ijap.2021.v13s4.43861.

Peng T, Wonganan O, Zhang Z, Yu J, Xi R, Cao Y. A 2-benzylmalonate derivative as stat3 inhibitor suppresses tumor growth in hepatocellular carcinoma by upregulating β-TrCP e3 ubiquitin ligase. Int J Mol Sci. 2021;22(7):3354. doi: 10.3390/ijms22073354, PMID 33805945.

Du X, Li Y, Xia YL, Ai SM, Liang J, Sang P. Insights intoprotein–ligand interactions: mechanisms, models, and methods. Int J Mol Sci. 2016;17(2):144. doi: 10.3390/ijms17020144, PMID 26821017.

Etesami E, Saba F, Noroozi M, Amoozegar MA, Khaniki GB, Fazeli SAS. Caspian Sea’s Navicula salinicola Hustedt 1939 and effect of the prolonged culture on its fatty acid profile. Int J Aquat Biol. 2017;5:268-74.

Remize M, Planchon F, Loh AN, Grand FL, Bideau A, Goic NL. Study of synthesis pathways of the essential polyunsaturated fatty acid 20:5n-3 in the diatom chaetoceros muelleri using 13C-isotope labeling. Biomolecules. 2020;10(5):797. doi: 10.3390/biom10050797, PMID 32455747.

Oppedisano F, Macri R, Gliozzi M, Musolino V, Carresi C, Maiuolo J. The anti-inflammatory and antioxidant properties of n-3 PUFAs: their role in cardiovascular protection. Biomedicines. 2020;8(9):306. doi: 10.3390/biomedicines8090306, PMID 32854210.