IN SILICO STUDY OF 12 PHYTOSTEROL COMPOUNDS IN MORINGA (MORINGA OLEIFERA LAMK.) SEED OIL ON 5Α-REDUCTASE ENZYME INHIBITION ACTIVITY AS ANTI-ALOPECIA

YULIUS BAKI KORASSA; NYI MEKAR SAPTARINI; RESMI MUSTARICHIE; RINI HENDRIANI; PUTRA JIWAMURWA PAMA TJITDA

doi:10.22159/ijap.2022.v14s4.OP11

Authors

YULIUS BAKI KORASSA Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Padjadjaran University, St. Raya Bandung Sumedang, Km, 21 Jatinangor 45363, Pharmacy Study Program, Health Polytechnic of Ministry of Health, St. Piet A. Tallo, Liliba, Kupang, East Nusa Tenggara
NYI MEKAR SAPTARINI Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Padjadjaran University, St. Raya Bandung Sumedang, Km, 21 Jatinangor 45363
RESMI MUSTARICHIE Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Padjadjaran University, St. Raya Bandung Sumedang, Km, 21 Jatinangor 45363
RINI HENDRIANI Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Padjadjaran University, St. Raya Bandung Sumedang, Km, 21 Jatinangor 45363
PUTRA JIWAMURWA PAMA TJITDA Pharmacy Study Program, Health Polytechnic of Ministry of Health, St. Piet A. Tallo, Liliba, Kupang, East Nusa Tenggara

DOI:

https://doi.org/10.22159/ijap.2022.v14s4.OP11

Keywords:

Moringa oleifera Lamk, Ergostadienol, 5α-reductase, Anti-alopecia

Abstract

Objective: This study aimed to determine the interaction of 12 phytosterol compounds in moringa seed oil to the 5α-reductase enzyme (PDB code: 7BW1) as anti-alopecia by in silico.

Methods: The research was conducted using a molecular docking approach using autodock Tools 1.5.6. Data analysis was carried out by looked at the binding affinity values and inhibition constants (Ki) of 12 phytosterol compounds, as well as visualization of amino acid interactions using Biovia Discovery Studio 2021.

Results: 12 Phytosterol compounds had the potential to be a candidate for anti-alopecia medicines based on in silico test simulations using auto dock with high binding affinity values in the range of-11.47 to-12.76 kcal/mol and stable inhibition constants in the range of 1.87. nM–4.30 nM involving hydrogen bonds with Arg179, Tyr178, Arg105, Arg114, Ser177, Tyr98, Glu57, and Tyr91 amino acids.

Conclusion: Ergostadienol compound in moringa seed oil was predicted to be a better anti-alopecia on the inhibition of 5α-reductase enzyme with binding energy value was-11.60 kcal/mol, inhibition constant was 3.17 nM and interaction of amino acid residues on the inhibition of 5α-reductase enzyme was similar with native finasteride ligands namely Glu57 and Tyr91.

Downloads

Download data is not yet available.

References

McElwee KJ, Sinclair R. Hair physiology and its disorders. Drug Discov Today Dis Mech. 2008;5(2):e163-71. doi: 10.1016/j.ddmec.2008.04.001.

Abbas A, Naqvi SAR, Rasool MH, Noureen A, Mubarik MS, Tareen RB. Phytochemical analysis, antioxidant and antimicrobial screening of seriphidium oliverianum plant extracts. Dose Response. 2021;19(1):15593258211004739. doi: 10.1177/15593258211004739, PMID 33867895.

Mulinari Brenner F, Bergfeld WF. Hair loss: diagnosis and management. Cleve Clin J Med. 2003;70(8):705-12. doi: 10.3949/ccjm.70.8.705, PMID 12959397.

Hariani E, Jusuf NK. Evidence-based treatment of alopecia areata. Period Skin Sex Health Sci Period Dermatol Venereol. 2017;29(2):126-34.

Kumar N, Rungseevijitprapa W, Narkkhong NA, Suttajit M, Chaiyasut C. 5α-reductase inhibition and hair growth promotion of some Thai plants traditionally used for hair treatment. J Ethnopharmacol. 2012;139(3):765-71. doi: 10.1016/j.jep.2011.12.010. PMID 22178180.

Han A, Mirmirani P. Clinical approach to the patient with alopecia. Semin Cutan Med Surg. 2006;25(1):11-23. doi: 10.1016/j.sder.2006.01.003, PMID 16616299.

Stough D, Stenn K, Haber R, Parsley WM, Vogel JE, Whiting DA. Psychological effect, pathophysiology, and management of androgenetic alopecia in men. Mayo Clin Proc. 2005;80(10):1316-22. doi: 10.4065/80.10.1316.

Bayoumy IA, Hameed E. Effect of oral finasteride on serum androgen levels and androgenetic alopecia in adult men. Department of Dermatology and Venereology. 2007;18(2):37-45.

Prager N, Bickett K, French N, Morcovici G. A randomized, double-blind, placebo-controlled trial to determine the effectiveness of botanically derived inhibitors of 5-α-reductase in the treatment of androgenetic alopecia. The Journal of Alternative and Complementari Medicine. 2002;8(2):143-52.

Kaushik R, Gupta D, Yadaf R. Review article: alopecia: remedies. Int J Pharm Sci Res. 2011;2(7):1631-7.

Roy RK, Thakur M, Dixit VK. Hair growth promoting activity of Eclipta alba in male albino rats. Arch Dermatol Res. 2008;300(7):357-64. doi: 10.1007/s00403-008-0860-3, PMID 18478241.

Gregoriou S, Papafragkaki D, Kontochristopoulos G, Rallis E, Kalogeromitros D, Rigopoulos D. Cytokines and other mediators in alopecia areata. Mediators Inflamm. 2010;2010:928030. doi: 10.1155/2010/928030. PMID 20300578.

Choi HI, Kim DY, Choi SJ, Shin CY, Hwang ST, Kim KH. The effect of cilostazol, a phosphodiesterase 3 (PDE3) inhibitor, on human hair growth with the dual promoting mechanisms. J Dermatol Sci. 2018;91(1):60-8. doi: 10.1016/j.jdermsci.2018.04.005, PMID 29678305.

Legiawati L. Alopesia androgenic. Media Derm Venerelogica Indones (MDVI). 2013;40(2):96-101.

Triarini D, Hendriani R. Review Artikel: tanaman Herbal dengan Aktivitas perangsang pertumbuhan rambut. Farmaka Suplemen. 2017;15(1):105-13.

Kaur A, Singh TG, Dhiman S, Arora S, Babbar R. Novel herbs use din cosmetics for skin an D hair care: a review. Plant Arch. 2020;20:3784-93.

Anwar F, Bhanger MI. Analytical characterization of Moringa oleifera seed oil grown in temperate regions of Pakistan. J Agric Food Chem. 2003;51(22):6558-63. doi: 10.1021/jf0209894, PMID 14558778.

Rahman IMM, Barua S, Nazimuddin M, Begum ZA, Rahman MA, Hasegawa H. Physicochemical properties of Moringa oleifera Lam. Seed oil of the indigenous-cultivar of Bangladesh. J Food Lipids. 2009;16(4):540-53. doi: 10.1111/j.1745-4522.2009.01165.x.

Cabeza M, Bratoeff E, Heuze I, Ramirez E, Sanchez M, Flores E. Effect of β-sitosterol as inhibitor of 5α-reductase in hamster prostate. Proc West Pharmacol Soc. 2003;46:153-5. PMID 14699915.

Goodman DS. Topical preparation for the treatment of hair loss. United States Patent US. 2002;6(358):541 B1.

Pateh UU, Haruna AK, Garba MI, Abubakar MS, Ambi AA. Isolation of stigmasterol, B-sitosterol, and 2 Hydroxyhexadecanoid and methyl ester from rhizomes of Stylochtion lancifolius, Nig. J Pharm Sci. 2009;8(1):19-25.

Srivilai J, Minale G, Scholfield CN, Ingkaninan K. Discovery of natural steroid 5 alpha-reductase inhibitors. Assay Drug Dev Technol. 2019;17(2):44-57. doi: 10.1089/adt.2018.870, PMID 30575417.

Xiao Q, Wang L, Supekar S, Shen T, Liu H, Ye F. Structure of human steroid 5α-reductase 2 with the anti-androgen drug finasteride/. Nature Communications Journal. 2020;11(1):5430. doi: 10.1038/s41467-020-19249-z, PMID 33110062.

Suzuki R, Satoh H, Ohtani H, Hori S, Sawada Y. Saturable binding of finasteride to steroid 5α-reductase as determinant of nonlinear pharmacokinetics. Drug Metab Pharmacokinet. 2010;25(2):208-13. doi: 10.2133/dmpk.25.208, PMID 20460827.

Hosking AM, Juhasz M, Atanaskova Mesinkovska N. Complementary and alternative treatments for alopecia: a comprehensive review. Skin Appendage Disord. 2019;5(2):72-89. doi: 10.1159/000492035. PMID 30815439.

Chaterjee S, Agrawala S. Saw palmetto (Serenoa repens) in androgenic alopecia–an effective phytotherapy. Nat Prod Radiance. 2003;2:302-5.

Iehle C, Delos S, Guirou O, Tate R, Raynaud JP, Martin PM. Human prostatic steroid 5 alpha-reductase isoforms–a comparative study of selective inhibitors. J Steroid Biochem Mol Biol. 1995;54(5-6):273-9. doi: 10.1016/0960-0760(95)00134-l, PMID 7577710.

Astuty F, Komari N. Kajian molecular docking senyawa karwinaphthol b dari tanaman bawang dayak (Eleutherine palmifolia (L.) Merr.) sebagai inhibitor enzim glukokinase. J Nat Sci. 2022;2(1):1-9.

Puratchikody A, Sriram D, Umamaheswari A, Irfan N. 3D structural interactions and quantitative structural toxicity studies of tyrosine derivatives intended for safe potent inflammation treatment. Chem Cent J. 2016;10(24):1-19.

Bramasta JS, Sanjaya IGM. Studi in silico phytosterols and their derivatives as candidates for anti-breast cancer drugs. J Appl Chem. 2021;5(1):1-7.

Sari IW, Junaidin PD. Molecular docking study flavonoid compounds from kumis kucing (Orthosiphon stamineus B.) in α-glucosidase receptor as antidiabetic type 2. Farmagazine J. 2020;7(2):54-60.

Nauli T. Determination of the active site of aspergillus niger cellulose by docking ligands. Indonesian J Appl Chem (JKTI). 2014;16(2).

Kontoyianni M, McClellan LM, Sokol GS. Evaluation of docking performance: comparative data on docking algorithms. J Med Chem. 2004;47(3):558-65. doi: 10.1021/jm0302997. PMID 14736237.

Dzubak AL, Mitra C, Chance M, Kuhn S, Jellison GE, Sefat AS. MnNiO3 revisited with modern theoretical and experimental methods. J Chem Phys. 2017;147(17):174703. doi: 10.1063/1.5000847, PMID 29117688.

Fitriasari A, Wijayanti NK, Ismiyati N, Dewi D, Kundarto WA, Sudarmanto BS. Study of the potential of curcumin and its analogs as selective estrogen receptor modulators (SERMs): docking pada reseptor estrogen ß. Pharmacon. 2008;9(1).

Kotrechko S, Timoshevskii A, Kolyvoshko E, Matviychuk Y, Stetsenko N. Thermomechanical stability of carbyne-based nanodevices. Nanoscale Res Lett. 2017;12(1):327. doi: 10.1186/s11671-017-2099-4, PMID 28476087.

Arifin SN, Pratiwi D, Setiawan AA. In silico study of flavonoid compounds from long bean extract (Vigna sinensis L.) as hair growth with androgen receptors. J Farmagazine. 2017;4(2):31-7.

Shivanika C, Kumar D, Ragunathan V, Tiwari P, Sumitha A. Molecular docking, validation, dynamics simulations, and pharmacokinetic prediction of natural compounds against the SARSCoV-2 main-protease. J Biomol Struct Dyn. 2020;1:1-27.

Arwansyah A, Ambarsari L, Sumaryada TI. Simulasi docking senyawa kurkumin dan analognya sebagai inhibitor reseptor androgen pada kanker prostat. Curr Biochem. 2014;1(1):11-9. doi: 10.29244/cb.1.1.11-19.

Driani. Prediction of bioactive compounds from sanrego plant (Lunasia amara Blanco) as cyclooxygenase-2 (Cox-2) enzyme inhibitors through molecular docking approach. J Ilmiah Pena. 2018;1(1):9-10.

Sethi A, Joshi K, Sasikala K, Alvala M. Molecular docking in modern drug discovery: principles and recent applications. Intech. 2017:125-41. Available from: https://www.intechopen.com/books/advanced-biometric-technologies/livenessdetection-in-biometri.

Omotayo A, Oyebamiji AK, Oyewole OR, Semire B. A DFT-based QSAR and molecular docking studies on potent anti-colon cancer activity of pyrazole derivatives. Glob J Med Res B Pharm Drug Discov Toxicol Med. 2018;18(2):9-21.

Tambunan USF, Alamudi S. Designing cyclic peptide inhibitor of dengue virus NS3-NS2B protease by using molecular docking approach. Bioinformation. 2010;5(6):250-4. doi: 10.6026/97320630005250, PMID 21364826.

Idrees S, Ashfaq UA. Discovery and design of cyclic peptides as dengue virus inhibitors through structure-based molecular docking. Asian Pac J Trop Med. 2014;7(7):513-6. doi: 10.1016/S1995-7645(14)60085-7, PMID 25063278.

Carlson HA, Smith RD, Khazanov NA, Kirchhoff PD, Dunbar JB, Benson ML. Differences between high- and low-affinity complexes of enzymes and nonenzymes. J Med Chem. 2008;51(20):6432-41. doi: 10.1021/jm8006504, PMID 18826206.

Vargas JAR, Lopez AG, Pinol MC, Froeyen M. Molecular docking study on the interaction between 2-substituted-4,5-difuryl imidazoles with different protein target for antileishmanial activity. J Appl Pharm Sci. 2018;8(3):14-22.

Noviardi H, Fachrurrazie. The Potential of bullatalicin compounds as inhibitors of leukotriene A4 hydrolase protein in colon cancer in silico. Fitofarmaka. 2015;5(2):65-73.

Patrick GL. An introduction to medicinal chemistry. 5th ed. UK: Oxford University Press; 2013. p. 228-9.

Syahputra G. Docking simulation of curcumin compounds and its analogues as inhibitors of the 12-llipoxygenase Eenzyme, Bogor: Institut Pertanian Bogor: Bogor; 2014.

Cosconati S, Forli S, Perryman AL, Harris R, Goodsell DS, Olson AJ. Virtual screening with AutoDock: theory and practice. Expert Opinion on Drug Discovery. 2010;5(6):597-607. doi: 10.1517/17460441.2010.484460, PMID 21532931.

Schwans JP, Sunden F, Lassila JK, Gonzalez A, Tsai Y, Herschlag D. Use of anion–aromatic interactions to position the general base in the ketosteroid isomerase active site. Proc Natl Acad Sci USA. 2013;110(28):11308-13. doi: 10.1073/pnas.1206710110.

Schottel BL, Chifotides HT, Dumnbar KR. Anion-pi interactions. Chem Soc Rev. 2008;37(1):68-83. doi: 10.1039/b614208g, PMID 18197334.