Molecular Docking Study of Illicium verum Hook f. as Elastase and Collagenase Inhibitor in Anti-aging Mechanism
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Submitted
29 March 2025
29 March 2025
Published
30 May 2025
30 May 2025
Abstract
Skin aging, a natural physiological process intensified by external factors that augment the activity of aging-related enzymes such as elastase and collagenase, leads to the degradation of collagen solubility and the disruption of elastin fiber cross-linking. This study aimed to investigate the potential of secondary metabolites from Illicium verum fruit as inhibitors of both elastase and collagenase through an in silico molecular docking approach. The methodology involved ligand and protein preparation, validation of the docking protocol, the molecular docking simulation itself, and subsequent visualization of amino acid residue interactions. The protein targets utilized were elastase (PDB ID: 1Y93) and collagenase (PDB ID: 2D1N). The docking results identified gingerol as exhibiting the highest binding affinity for elastase (-7.99 kcal/mol), followed by carvacrol (-6.79 kcal/mol) and ferulic acid (-6.24 kcal/mol). Similarly, for collagenase, gingerol displayed the strongest interaction (-8.47 kcal/mol), followed by carvacrol (-6.30 kcal/mol) and α-pinene (-6.24 kcal/mol). Notably, gingerol and carvacrol also demonstrated favorable amino acid similarity scores and promising interactions within the active sites of both elastase and collagenase. In conclusion, this molecular docking study suggests that the secondary metabolites of I. verum fruit possess potential anti-aging activity by inhibiting elastase and collagenase enzymes.
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18. Pratama MRF, Poerwono H, Siswodihardjo S. Molecular docking of novel 5-O-benzoylpinostrobin derivatives as wild type and L858R/T790M/V948R mutant EGFR inhibitor. J Basic Clin Physiol Pharmacol. 2019;30(6): 2019-0301. DOI: 10.1515/jbcpp-2019-0301; PMID: 31855568
19. Hevener KE, Zhao W, Ball DM, Babaoglu K, Qi J, White SW, et al. Validation of Molecular Docking Programs for Virtual Screening against Dihydropteroate Synthase. J Chem Inf Model. 2009;49(2):444–60. DOI: 10.1021/ci800293n; PMCID: PMC2788795; PMID: 19434845
20. Pratama MRF, Poerwono H, Siswodihardjo S. Introducing a two‐dimensional graph of docking score difference vs. similarity of ligand‐receptor interactions. Indones J Biotechnol. 2021;26(1):54-60. DOI: 10.22146/ijbiotech.62194
21. Pratama RR, Sholikhah I, Sukardiman S, Sahu RK, Widyowati R. Phytochemical Compounds Identification From 70% Ethanol Extract of Arcangelesia Flava (L.) Merr Stems Using LC-MS/MS and In-Silico Molecular Docking Approach as Inhibitor Interleukin-1β. Pharmacogn J. 2023;15(4):528–34. DOI: 10.5530/pj.2023.15.114
22. Chen D, Oezguen N, Urvil P, Ferguson C, Dann SM, Savidge TC. Regulation of protein-ligand binding affinity by hydrogen bond pairing. Sci Adv. 2016;2(3):e1501240. DOI: 10.1126/sciadv.1501240; PMCID: PMC4820369; PMID: 27051863
23. Vaou N, Stavropoulou E, Voidarou C (Chrysa), Tsakris Z, Rozos G, Tsigalou C, et al. Interactions between Medical Plant-Derived Bioactive Compounds: Focus on Antimicrobial Combination Effects. Antibiotics. 2022;11(8):1014. DOI: 10.3390/antibiotics11081014; PMCID: PMC9404952; PMID: 36009883
24. Wink M. Modes of Action of Herbal Medicines and Plant Secondary Metabolites. Medicines. 2015;2(3):251–86. DOI: 10.3390/medicines2030251; PMCID: PMC5456217; PMID: 28930211
25. Abdelfattah MAO, Dmirieh M, Bakrim WB, Mouhtady O, Ghareeb MA, Wink M, et al. Antioxidant and anti-aging effects of Warburgia salutaris bark aqueous extract: Evidences from in silico, in vitro and in vivo studies. J Ethnopharmacol. 2022;292:115187. DOI: 10.1016/j.jep.2022.115187
26. Ayustaningwarno F, Anjani G, Ayu AM, Fogliano V. A critical review of Ginger’s (Zingiber officinale) antioxidant, anti-inflammatory, and immunomodulatory activities. Front Nutr. 2024;11:1364836. DOI: 10.3389/fnut.2024.1364836; PMCID: PMC11187345; PMID: 38903613
27. Alipour H, Raz A, Zakeri S, Djadid ND. Therapeutic applications of collagenase (metalloproteases): A review. Asian Pac J Trop Biomed. 2016;6(11):975–81. DOI: 10.1016/j.apjtb.2016.07.017
28. Hwang JH, Jung HW, Oh SY, Kang JS, Kim JP, Park YK. Effects of Zingiber officinale extract on collagen-induced arthritis in mice and IL-1β-induced inflammation in human synovial fibroblasts. Eur J Inflamm. 2017;15(3):168–78. DOI: 10.1177/1721727X17727997
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2. Agrawal R, Hu A, Bollag WB. The Skin and Inflamm-Aging. Biology. 2023;12(11):1396. DOI: 10.3390/biology12111396; PMCID: PMC10669244; PMID: 37997995
3. James WD, Berger TG, Elston DM. Andrews’ Diseases of the Skin: Clinical dermatology. 12th edition. Philadelphia: Elsevier Saunders; 2016.
4. Soheilifar MH, Masoudi-Khoram N, Shirkavand A, Ghorbanifar S. Non-coding RNAs in photoaging-related mechanisms: a new paradigm in skin health. Biogerontology. 2022;23(3):289–306. DOI: 10.1007/s10522-022-09966-x; PMID: 35587318
5. Chu DH. Overview of biology, development, and structure of skin. In: Wolff K, Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Leffell DJ, editors. Fitzpatrick’s dermatology in general medicine. 7th edition. New York: McGraw-Hill; 2008. p. 57–73.
6. Nurrochmad A, Wirasti W, Dirman A, Lukitaningsih E, Rahmawati A, Fakhrudin N. Effects of Antioxidant, Anti-Collagenase, Anti-Elastase, Anti-Tyrosinase of The Extract and Fraction from Turbinaria decurrens Bory. Indones J Pharm. 2018;29(4):188-99. DOI: 10.14499/indonesianjpharm29iss4pp188
7. Papaccio F, Arino AD, Caputo S, Bellei B. Focus on the Contribution of Oxidative Stress in Skin Aging. Antioxidants. 2022;11(6):1121. DOI: 10.3390/antiox11061121; PMCID: PMC9220264; PMID: 35740018
8. Park S. Biochemical, Structural and Physical Changes in Aging Human Skin, and Their Relationship. Biogerontology. 2022;23(3):275–88. DOI: 10.1007/s10522-022-09959-w; PMCID: PMC10316705; PMID: 35292918
9. Guo L, Qi J, Du D, Liu Y, Jiang X. Current advances of Dendrobium officinale polysaccharides in dermatology: a literature review. Pharm Biol. 2020;58(1):664–73. DOI: 10.1080/13880209.2020.1787470; PMCID: PMC7470034; PMID: 32657196
10. Birkedal-Hansen H. Catabolism and turnover of collagens: collagenases. Methods Enzymol. 1987;144:140-71. DOI: 10.1016/0076-6879(87)44177-3; PMID: 3041177
11. Sharafan M, Jafernik K, Ekiert H, Kubica P, Kocjan R, Blicharska E, et al. Illicium verum (Star Anise) and Trans-Anethole as Valuable Raw Materials for Medicinal and Cosmetic Applications. Molecules. 2022;27(3):650. DOI: 10.3390/molecules27030650; PMCID: PMC8839413; PMID: 35163914
12. Lin CY, Kao SH, Hung LC, Chien HJ, Wang WH, Chang YW, et al. Lipopolysaccharide-Induced Nitric Oxide and Prostaglandin E2 Production Is Inhibited by Tellimagrandin II in Mouse and Human Macrophages. Life. 2021;11(5):411. DOI: 10.3390/life11050411; PMCID: PMC8146495; PMID: 33946374
13. Luís Â, Sousa S, Wackerlig J, Dobusch D, Duarte AP, Pereira L, et al. Star anise (Illicium verum Hook. f.) essential oil: Antioxidant properties and antibacterial activity against Acinetobacter baumannii. Flavour Fragr J. 2019;34(4):260–70. DOI: 10.1002/ffj.3498
14. Lee JH, Park J, Shin DW. The Molecular Mechanism of Polyphenols with Anti-Aging Activity in Aged Human Dermal Fibroblasts. Molecules. 2022;27(14):4351. DOI: 10.3390/molecules27144351; PMCID: PMC9322955; PMID: 35889225
15. Jiratchayamaethasakul C, Ding Y, Hwang O, Im ST, Jang Y, Myung SW, et al. In vitro screening of elastase, collagenase, hyaluronidase, and tyrosinase inhibitory and antioxidant activities of 22 halophyte plant extracts for novel cosmeceuticals. Fish Aquatic Sci. 2020;23:6. DOI: 10.1186/s41240-020-00149-8
16. Aly SE, Sabry BA, Shaheen MS, Hathout AS. Assessment of antimycotoxigenic and antioxidant activity of star anise (Illicium verum) in vitro. J Saudi Soc Agric Sci. 2016;15(1):20–7. DOI: 10.1016/j.jssas.2014.05.003
17. Noumi E, Ahmad I, Adnan M, Patel H, Merghni A, Haddaji N, et al. Illicium verum L. (Star Anise) Essential Oil: GC/MS Profile, Molecular Docking Study, In Silico ADME Profiling, Quorum Sensing, and Biofilm-Inhibiting Effect on Foodborne Bacteria. Molecules. 2023;28(23):7691. DOI: 10.3390/molecules28237691; PMCID: PMC10707387; PMID: 38067422
18. Pratama MRF, Poerwono H, Siswodihardjo S. Molecular docking of novel 5-O-benzoylpinostrobin derivatives as wild type and L858R/T790M/V948R mutant EGFR inhibitor. J Basic Clin Physiol Pharmacol. 2019;30(6): 2019-0301. DOI: 10.1515/jbcpp-2019-0301; PMID: 31855568
19. Hevener KE, Zhao W, Ball DM, Babaoglu K, Qi J, White SW, et al. Validation of Molecular Docking Programs for Virtual Screening against Dihydropteroate Synthase. J Chem Inf Model. 2009;49(2):444–60. DOI: 10.1021/ci800293n; PMCID: PMC2788795; PMID: 19434845
20. Pratama MRF, Poerwono H, Siswodihardjo S. Introducing a two‐dimensional graph of docking score difference vs. similarity of ligand‐receptor interactions. Indones J Biotechnol. 2021;26(1):54-60. DOI: 10.22146/ijbiotech.62194
21. Pratama RR, Sholikhah I, Sukardiman S, Sahu RK, Widyowati R. Phytochemical Compounds Identification From 70% Ethanol Extract of Arcangelesia Flava (L.) Merr Stems Using LC-MS/MS and In-Silico Molecular Docking Approach as Inhibitor Interleukin-1β. Pharmacogn J. 2023;15(4):528–34. DOI: 10.5530/pj.2023.15.114
22. Chen D, Oezguen N, Urvil P, Ferguson C, Dann SM, Savidge TC. Regulation of protein-ligand binding affinity by hydrogen bond pairing. Sci Adv. 2016;2(3):e1501240. DOI: 10.1126/sciadv.1501240; PMCID: PMC4820369; PMID: 27051863
23. Vaou N, Stavropoulou E, Voidarou C (Chrysa), Tsakris Z, Rozos G, Tsigalou C, et al. Interactions between Medical Plant-Derived Bioactive Compounds: Focus on Antimicrobial Combination Effects. Antibiotics. 2022;11(8):1014. DOI: 10.3390/antibiotics11081014; PMCID: PMC9404952; PMID: 36009883
24. Wink M. Modes of Action of Herbal Medicines and Plant Secondary Metabolites. Medicines. 2015;2(3):251–86. DOI: 10.3390/medicines2030251; PMCID: PMC5456217; PMID: 28930211
25. Abdelfattah MAO, Dmirieh M, Bakrim WB, Mouhtady O, Ghareeb MA, Wink M, et al. Antioxidant and anti-aging effects of Warburgia salutaris bark aqueous extract: Evidences from in silico, in vitro and in vivo studies. J Ethnopharmacol. 2022;292:115187. DOI: 10.1016/j.jep.2022.115187
26. Ayustaningwarno F, Anjani G, Ayu AM, Fogliano V. A critical review of Ginger’s (Zingiber officinale) antioxidant, anti-inflammatory, and immunomodulatory activities. Front Nutr. 2024;11:1364836. DOI: 10.3389/fnut.2024.1364836; PMCID: PMC11187345; PMID: 38903613
27. Alipour H, Raz A, Zakeri S, Djadid ND. Therapeutic applications of collagenase (metalloproteases): A review. Asian Pac J Trop Biomed. 2016;6(11):975–81. DOI: 10.1016/j.apjtb.2016.07.017
28. Hwang JH, Jung HW, Oh SY, Kang JS, Kim JP, Park YK. Effects of Zingiber officinale extract on collagen-induced arthritis in mice and IL-1β-induced inflammation in human synovial fibroblasts. Eur J Inflamm. 2017;15(3):168–78. DOI: 10.1177/1721727X17727997
Authors
1.
Rahman A, Widiandani T, Widyowati R. Molecular Docking Study of Illicium verum Hook f. as Elastase and Collagenase Inhibitor in Anti-aging Mechanism. Borneo J Pharm [Internet]. 2025May30 [cited 2025Aug.2];8(2):176-83. Available from: https://journal.umpr.ac.id/index.php/bjop/article/view/9574
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