In Silico Study of Propolis Bioactive Compounds as Topical Treatment of Atopic Dermatitis

Tantri Liris Nareswari

doi:10.20884/1.api.2025.13.2.17894

Tantri Liris Nareswari Institut Teknologi Sumatera

DOI: https://doi.org/10.20884/1.api.2025.13.2.17894

Abstract

Background: Atopic dermatitis is a chronic inflammatory skin disease characterized by eczematous lesions, and recurrent pruritus. Atopic dermatitis is a global health burden, highlighting the need for novels with better safety profiles. Current topical therapies, such as corticosteroid and calcineurin inhibitors are effective agents but limited by adverse effects upon its long-term use. Propolis, a natural resinous product of bees, possesses diverse pharmacological activities including antimicrobial, anti-inflammatory, antioxidant, and immunomodulatory properties. However, its therapeutic potential in atopic dermatitis treatment remains underexplored.

Objective: This study aimed to investigate the potential of propolis bioactive compounds as topical therapeutic agents for dermatitis atopic through molecular docking analysis.

Methods: Selected bioactive compounds from propolis were screened for pharmacokinetic and ADMET properties relevant to topical application. Molecular docking analysis was conducted against key protein targets implicated in atopic dermatitis pathogenesis to evaluate their binding affinities and interaction profiles compared with reference ligands.

Results: Thirty compounds met the pharmacokinetic and toxicity criteria for topical use. Molecular docking results indicate that tschimgin showed interactions with SPLA-2 and Calcineurin-NFAT pathway, demonstrating that tschimgin is a multitarget compound although its binding affinities did not surpass the reference drug (hydrocortisone, tacrolimus). While suberosin demonstrated high binding affinity to PDE4, suggesting potential PDE4 inhibitory activity. Overall, pharmacokinetic predictions indicated favorable skin permeability and low systemic toxicity.

Conclusion: Propolis bioactive compounds show promise as potential topical therapeutic candidates for AD by targeting multiple inflammatory pathways. Further in vitro and in vivo validation is needed to confirm their pharmacological efficacy and safety.

References

[1] N. Gołuchowska, A. Ząber, A. Będzichowska, A. Tomaszewska, A. Rustecka, and B. Kalicki, “The Role of MicroRNA in the Pathogenesis of Atopic Dermatitis,” Int J Mol Sci, vol. 26, no. 12, pp. 1–15, 2025, doi: 10.3390/ijms26125846.
[2] L. M. Pinto, A. Chiricozzi, L. Calabrese, M. Mannino, and K. Peris, “Novel Therapeutic Strategies in the Topical Treatment of Atopic Dermatitis,” Dec. 01, 2022, MDPI. doi: 10.3390/pharmaceutics14122767.
[3] S. Meledathu, M. P. Naidu, and P. M. Brunner, “Update on atopic dermatitis,” Apr. 01, 2025, Elsevier Inc. doi: 10.1016/j.jaci.2025.01.013.
[4] S. A. Khan, Y. Wu, A. S. M. Li, X. Q. Fu, and Z. L. Yu, “Network pharmacology and molecular docking-based prediction of active compounds and mechanisms of action of Cnidii Fructus in treating atopic dermatitis,” BMC Complement Med Ther, vol. 22, no. 1, Dec. 2022, doi: 10.1186/s12906-022-03734-7.
[5] A. Courtney and J. C. Su, “The Psychology of Atopic Dermatitis,” Mar. 01, 2024, Multidisciplinary Digital Publishing Institute (MDPI). doi: 10.3390/jcm13061602.
[6] H. Yang et al., “Application of Topical Phosphodiesterase 4 Inhibitors in Mild to Moderate Atopic Dermatitis: A Systematic Review and Meta-analysis,” JAMA Dermatol, vol. 155, no. 5, pp. 585–593, May 2019, doi: 10.1001/jamadermatol.2019.0008.
[7] J. Jeskey et al., “Atopic Dermatitis: A Review of Diagnosis and Treatment,” Journal of Pediatric Pharmacology and Therapeutics, vol. 29, no. 6, pp. 587–603, 2024, doi: 10.5863/1551-6776-29.6.587.
[8] B. A. Martin et al., “A new approach to atopic dermatitis control with low-concentration propolis-loaded cold cream,” Pharmaceutics, vol. 13, no. 9, Sep. 2021, doi: 10.3390/pharmaceutics13091346.
[9] L. Tang, J. Gao, X. Li, X. Cao, and B. Zhou, “Molecular Mechanisms of Luteolin Against Atopic Dermatitis Based on Network Pharmacology and in vivo Experimental Validation,” Drug Des Devel Ther, vol. 16, pp. 4205–4221, 2022, doi: 10.2147/DDDT.S387893.
[10] N. Shin et al., “Pimecrolimus interferes the therapeutic efficacy of human mesenchymal stem cells in atopic dermatitis by regulating NFAT-COX2 signaling,” Stem Cell Res Ther, vol. 12, no. 1, pp. 1–16, 2021, doi: 10.1186/s13287-021-02547-8.
[11] W. Frazier and N. Bhardwaj, “Atopic Dermatitis: Diagnosis and Treatment,” Am Fam Physician, vol. 101, no. 10, pp. 590–598, 2020.
[12] V. R. Pasupuleti, L. Sammugam, N. Ramesh, and S. H. Gan, “Honey, Propolis, and Royal Jelly: A Comprehensive Review of Their Biological Actions and Health Benefits,” Oxid Med Cell Longev, vol. 2017, 2017, doi: 10.1155/2017/1259510.
[13] A. Salatino, M. L. F. Salatino, and G. Negri, “How diverse is the chemistry and plant origin of Brazilian propolis?,” Apidologie, vol. 52, no. 6, pp. 1075–1097, 2021, doi: 10.1007/s13592-021-00889-z.
[14] E. N. Yanti and P. M. Kustiawan, “Study of Indonesian Stingless Bee Propolis Potential as Antioxidant: A Review,” Jurnal Farmasi Sains dan Praktis, pp. 261–269, Dec. 2023, doi: 10.31603/pharmacy.v9i3.7105.
[15] F. Zulhendri et al., “Recent Update on the Anti-Inflammatory Activities of Propolis,” Dec. 01, 2022, MDPI. doi: 10.3390/molecules27238473.
[16] K. Y. Liew et al., “Anti-Allergic Properties of Propolis: Evidence From Preclinical and Clinical Studies,” Jan. 21, 2022, Frontiers Media S.A. doi: 10.3389/fphar.2021.785371.
[17] M. Roney and M. F. F. Mohd Aluwi, “The importance of in-silico studies in drug discovery,” Aug. 01, 2024, KeAi Publishing Communications Ltd. doi: 10.1016/j.ipha.2024.01.010.
[18] M. M. de Souza, A. L. R. Gini, J. A. Moura, C. B. Scarim, C. M. Chin, and J. L. dos Santos, “Prodrug Approach as a Strategy to Enhance Drug Permeability,” Mar. 01, 2025, Multidisciplinary Digital Publishing Institute (MDPI). doi: 10.3390/ph18030297.
[19] M. Abbas, A. R. Alanzi, K. I. Sahibzada, M. Nawaz, G. Fatima, and D. Q. Wei, “Identification of novel inhibitors targeting Mycobacterium abscessus InhA through virtual screening, docking, and molecular dynamic simulations,” Sci Rep, vol. 15, no. 1, Dec. 2025, doi: 10.1038/s41598-025-97513-2.
[20] S. Rammali et al., “In vitro and computational investigation of antioxidant and anticancer properties of Streptomyces coeruleofuscus SCJ extract on MDA-MB-468 triple-negative breast cancer cells,” Sci Rep, vol. 14, no. 1, Dec. 2024, doi: 10.1038/s41598-024-76200-8.
[21] D. M. Hasyim, I. Musfiroh, R. Hendra, T. M. Fakih, N. K. K. Ikram, and M. Muchtaridi, “In Silico Approaches for the Discovery of Novel Pyrazoline Benzenesulfonamide Derivatives as Anti-Breast Cancer Agents Against Estrogen Receptor Alpha (ERα),” Applied Sciences, vol. 15, no. 15, p. 8444, Jul. 2025, doi: 10.3390/app15158444.
[22] K. Gayathri et al., “Computational analysis of phytocompounds in Centella asiatica for its antifibrotic and drug-likeness properties - Herb to drug study,” Heliyon, vol. 10, no. 13, Jul. 2024, doi: 10.1016/j.heliyon.2024.e33762.
[23] A. H. Saputro et al., “Alpha-mangostin, piperine and beta-sitosterol as hepatitis C antivirus (HCV): In silico and in vitro studies,” Heliyon, vol. 9, no. 9, Sep. 2023, doi: 10.1016/j.heliyon.2023.e20141.
[24] N. Andrýsková, J. Motyčka, M. Babincová, P. Babinec, and M. Šimaljaková, “Computational Design of a Novel Dithranol–Salicylic Acid Antipsoriatic Prodrug for Esterase-Activated Topical Drug Delivery,” Applied Sciences (Switzerland), vol. 14, no. 3, Feb. 2024, doi: 10.3390/app14031094.
[25] J. Y. Lim, L. T. Gew, and Y. Q. Tang, “Biocomputational-mediated screening and molecular docking platforms for discovery of coumarin-derived antimelanogenesis agents,” Dermatologica Sinica, vol. 41, no. 1, pp. 8–17, Jan. 2023, doi: 10.4103/ds.DS-D-22-00087.
[26] M. E. Herbig, D. H. Evers, S. Gorissen, and M. Köllmer, “Rational Design of Topical Semi-Solid Dosage Forms-How Far Are We?,” Jul. 01, 2023, Multidisciplinary Digital Publishing Institute (MDPI). doi: 10.3390/pharmaceutics15071822.
[27] H. Khachatryan et al., “Computational evaluation and benchmark study of 342 crystallographic holo-structures of SARS-CoV-2 Mpro enzyme,” Sci Rep, vol. 14, no. 1, pp. 1–14, 2024, doi: 10.1038/s41598-024-65228-5.
[28] W. N. Auli et al., “Study of Gnetum gnemon metabolites as potential anti-breast and prostate cancer by metabolomic and molecular docking,” J Appl Pharm Sci, vol. 14, no. 12, pp. 120–130, 2024, doi: 10.7324/JAPS.2024.170723.
[29] K. Yamamoto, H. Hakoi, S. Nomura, and M. Murakami, “The Roles of sPLA2s in Skin Homeostasis and Disease,” Biomolecules, vol. 13, no. 4, 2023, doi: 10.3390/biom13040668.
[30] Y. J. Park, S. A. Yoo, M. Kim, and W. U. Kim, “The Role of Calcium–Calcineurin–NFAT Signaling Pathway in Health and Autoimmune Diseases,” Front Immunol, vol. 11, no. March, pp. 1–14, 2020, doi: 10.3389/fimmu.2020.00195.
[31] M. Shah, M. Patel, M. Shah, M. Patel, and M. Prajapati, “Computational transformation in drug discovery: A comprehensive study on molecular docking and quantitative structure activity relationship (QSAR),” Oct. 01, 2024, KeAi Publishing Communications Ltd. doi: 10.1016/j.ipha.2024.03.001.
[32] B. Chibuye, I. Sen Singh, L. Chimuka, and K. K. Maseka, “In silico and ADMET molecular analysis targeted to discover novel anti-inflammatory drug candidates as COX-2 inhibitors from specific metabolites of Diospyros batokana (Ebenaceae),” Biochem Biophys Rep, vol. 39, Sep. 2024, doi: 10.1016/j.bbrep.2024.101758.