Computational Identification of Gingeronone A from Zingiber officinale as a Promising Caspase-1 Inhibitor for Systemic Lupus Erythematosus Treatment: Molecular Docking and ADMET Analysis

Sri Maryam (1) , Ginayanti Hadisoebroto (2) , Femmy Hamidah (3)
(1) Farmasi Universitas Al-Ghifari,
(2) Farmasi Universitas Al-Ghifari,
(3) Farmasi Universitas Al-Ghifari
https://doi.org/10.53675/icosei.v1i1.1634
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Issue
Vol. 1 No. 1 (2025)
Submitted
2025-08-19
Published
2025-10-07
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Abstract

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by multi-organ inflammation mediated by caspase-1, a critical enzyme in inflammasome activation, with current therapeutics facing significant limitations necessitating exploration of natural anti-inflammatory alternatives from Zingiber officinale (ginger) secondary metabolites. This computational study employed systematic molecular docking to evaluate thirteen major ginger metabolites against the caspase-1 receptor (PDB ID: 3GN8) using AutoDock Tools, complemented by comprehensive ADMET profiling via pkCSM and ProTox-II platforms, with dexamethasone as native ligand and colchicine as comparative control. Molecular docking revealed significant binding affinity variations (-5.53 to -10.08 kcal/mol) with strong structure-activity correlation (R² = 0.89), where gingeronone A demonstrated the most promising anti-inflammatory potential with binding energy of -10.08 kcal/mol and inhibition constant of 0.04101 μM, approaching dexamethasone potency (-12.86 kcal/mol, Ki = 0.00037306 μM) while significantly outperforming colchicine (-9.80 kcal/mol, Ki = 0.06593 μM), forming critical hydrophobic interactions with amino acid residues CYS 205 and MET 73 that mirror dexamethasone binding patterns. ADMET analysis revealed superior pharmacokinetic profiles for gingeronone A including excellent human intestinal absorption (91.641%), favorable distribution characteristics (log VDss = 0.021 L/kg), outstanding drug-likeness score (90/100) compared to dexamethasone (64/100) and colchicine (56/100), and acceptable safety profile with LD₅₀ of 2000 mg/kg (class 4) and minimal organ-specific toxicity predictions. This investigation identifies gingeronone A as a promising lead compound from Z. officinale for SLE treatment through caspase-1 inhibition, combining superior binding affinity, favorable pharmacokinetic properties, and acceptable safety profiles, providing robust scientific foundation for experimental validation and demonstrating the value of integrating traditional medicine knowledge with modern computational drug discovery approaches for developing novel anti-inflammatory therapeutics targeting autoimmune diseases.Keywords: systemic lupus erythematosus, caspase-1, molecular docking, Zingiber officinale, gingeronone A, anti-inflammatory, ADMET

Authors

Sri Maryam
Farmasi Universitas Al-Ghifari
Ginayanti Hadisoebroto
Farmasi Universitas Al-Ghifari
Femmy Hamidah
Farmasi Universitas Al-Ghifari

How to Cite

Computational Identification of Gingeronone A from Zingiber officinale as a Promising Caspase-1 Inhibitor for Systemic Lupus Erythematosus Treatment: Molecular Docking and ADMET Analysis. (2025). Proceeding International Conference On Sustainable Environment And Innovation (ICOSEI), 1(1). https://doi.org/10.53675/icosei.v1i1.1634

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References

Aja, P. M., Nwachukwu, N., Ibiam, U. A., Igwenyi, I. O., Orji, O. U., & Orji, B. O. (2021). Identification of natural compounds with analgesic and anti-inflammatory properties using machine learning and molecular docking studies. Journal of Biomolecular Structure and Dynamics, 39(14), 5114-5126. https://doi.org/10.1080/07391102.2020.1764391

Banerjee, P., Eckert, A. O., Schrey, A. K., & Preissner, R. (2018). ProTox-II: A webserver for the prediction of toxicity of chemicals. Nucleic Acids Research, 46(W1), W257-W263. https://doi.org/10.1093/nar/gky318

Chen, K. Q., Tang, W. R., & Liu, X. (2025). Research and progress of cGAS/STING/NLRP3 signaling pathway: a mini review. Frontiers in Immunology, 16, 1594133. https://doi.org/10.3389/fimmu.2025.1594133

Frimayanti, N., Nasution, M. R., & Etavianti, E. (2021). Molecular docking and molecular dynamic simulation of 1,5-benzothiazepine chalcone derivative compounds as potential inhibitors for Zika virus helicase. Jurnal Riset Kimia, 12(1), 44-52. https://doi.org/10.25077/jrk.v12i1.365

Harsaya, I., & Jusup, I. (2020). Systemic lupus eritematosus berhubungan dengan depresi. Jurnal Ilmiah Kesehatan Jiwa, 2(1), 9-12. Available at: https://jurnal.rs-amino.jatengprov.go.id/index.php/JIKJ/article/view/8

Hasanah, N. U., Rahmawati, D., & Sastyarina, Y. (2020). Studi literatur: aktivitas senyawa [6]-gingerol dari rimpang jahe (Zingiber officinale) sebagai imunomodulator. Proceeding of Mulawarman Pharmaceuticals Conferences, 12, 183-189. https://doi.org/10.25026/mpc.v12i1.423

Hasselgren, C., Chavan, S., Laurie, D., McGovern, T., Maurer, M., Raffo, A. J., & Shi, H. (2019). Genetic toxicology in silico protocol. Regulatory Toxicology and Pharmacology, 107, 104403. https://doi.org/10.1016/j.yrtph.2019.104403

Herowati, R., & Widodo, G. P. (2017). Molecular docking analysis: interaction studies of natural compounds to anti-inflammatory targets. International Journal of Applied Chemistry, 13(3), 449-462. https://doi.org/10.37622/IJAC/13.3.2017.449-462

Kahlenberg, J. M., Thacker, S. G., Berthier, C. C., Cohen, C. D., Kretzler, M., & Kaplan, M. J. (2014). An essential role for caspase-1 in the induction of murine lupus and its associated vascular damage. Arthritis & Rheumatism, 66(1), 152-162. https://doi.org/10.1002/art.38225

Krihariyani, D., Ratih, H., Soediro, I., & Darmawan, E. (2019). Studi insilico aktivitas antioksidan dan ADMET brazilein kayu secang (Caesalpinia sappan L.) terhadap Escherichia coli extended spectrum beta-lactamase (ESBL). Prosiding Seminar Nasional Kesehatan, 251-257. Available at: http://www.rcsb.org/pdb/home.do

Li, A., Guo, F., Pan, Q., Chen, S., Chen, J., Liu, H. F., & Pan, Q. (2025). Systemic lupus erythematosus therapies: a decade of progress and prospects in clinical trials. Journal of Translational Medicine, 23, 169. https://doi.org/10.1186/s12967-025-06184-0

Liu, J., Zhou, J., Luan, Y., Li, X., Meng, X., Liao, W., Tang, J., & Wang, Z. (2024). Systemic lupus erythematosus: pathogenesis and targeted therapy. Molecular Biomedicine, 5, 35. https://doi.org/10.1186/s43556-024-00217-8

Luo, J., Liu, J., Peng, H., Smith, D. E., Gonzalez, F. J., & Patterson, A. D. (2025). An abundant ginger compound furanodienone alleviates gut inflammation via the xenobiotic nuclear receptor PXR in mice. Nature Communications, 16, 698. https://doi.org/10.1038/s41467-025-56624-0

Mao, Q. Q., Xu, X. Y., Cao, S. Y., Gan, R. Y., Corke, H., Beta, T., & Li, H. B. (2019). Bioactive compounds and bioactivities of ginger (Zingiber officinale Roscoe). Foods, 8(6), 185. https://doi.org/10.3390/foods8060185

Mathias, L. M., & Stohl, W. (2020). Systemic lupus erythematosus (SLE): emerging therapeutic targets. Expert Opinion on Therapeutic Targets, 24(12), 1283-1302. https://doi.org/10.1080/14728222.2020.1832464

Mir, R. H., Mohi-Ud-Din, R., Al-Keridis, L. A., Ahmad, B., Alshammari, N., Patel, M., Adnan, M., & Masoodi, M. H. (2024). Recent developments in anti-inflammatory natural products. Inflammopharmacology, 32(2), 1593-1606. https://doi.org/10.1007/s10787-023-01419-2

Mo, S., Li, Y., He, J., & Lin, L. (2024). Progress of rituximab in the treatment of systemic lupus erythematosus and lupus nephritis. Frontiers in Medicine, 11, 1472019. https://doi.org/10.3389/fmed.2024.1472019

Muchtaridi, M., Dermawan, D., Yusuf, M., & Sari, I. P. (2017). Molecular docking and 3D-pharmacophore modeling to study the interactions of chalcone derivatives with estrogen receptor alpha. Pharmaceuticals, 10(4), 81. https://doi.org/10.3390/ph10040081

Nancy, N., & Ikawati, Z. (2012). Evaluasi pengobatan systemic lupus erythematosus (SLE) pada pasien SLE dewasa. Jurnal Manajemen dan Pelayanan Farmasi, 2(3), 164-170.

Nursamsiar, N., Parawansah, P., Rahmawati, R., & Tahir, M. (2021). Docking senyawa aglikon kurkuligosida A dan turunannya terhadap enzim aldosa reduktase. FITOFARMAKA: Jurnal Ilmiah Farmasi, 11(2), 136-146. https://doi.org/10.33751/jf.v11i2.3072

Nursanti, O. (2019). Validasi penambatan molekul untuk mendapatkan ligan aktif pada reseptor cyclooxygenase 2. Prosiding Seminar Informasi Kesehatan Nasional, 411-430.

Pázmándi, K., Szöllősi, A. G., & Fekete, T. (2024). The "root" causes behind the anti-inflammatory actions of ginger compounds in immune cells. Frontiers in Immunology, 15, 1400956. https://doi.org/10.3389/fimmu.2024.1400956

Pires, D. E. V., Blundell, T. L., & Ascher, D. B. (2015). pkCSM: Predicting small-molecule pharmacokinetic and toxicity properties using graph-based signatures. Journal of Medicinal Chemistry, 58(9), 4066-4072. https://doi.org/10.1021/acs.jmedchem.5b00104

Ramadhani, N., Marlina, M., Agustina, E., & Ramadhani, D. (2018). Aktivitas antiinflamasi berbagai tanaman diduga berasal dari flavonoid. Farmaka, 14, 111-123.

Ruswanto, R. (2015). Molecular docking empat turunan isonicotinohydrazide pada Mycobacterium tuberculosis enoyl-acyl carrier protein reductase (InhA). Jurnal Kesehatan Bakti Tunas Husada, 13(1), 204-210. https://doi.org/10.36465/jkbth.v13i1.25

Ruswanto, R., Nazaruddin, N., Simbolon, S., & Moektiwardoyo, M. (2015). Sintesis dan studi in silico senyawa 3-nitro-N'-[(pyridin-4-yl) carbonyl]benzohydrazide sebagai kandidat antituberkulosis. Chimica et Natura Acta, 3(2), 57-63. https://doi.org/10.24198/cna.v3.n2.9183

Salama, A. A., Allam, R. M., Fattah, M. A., Farouk, A., & Mostafa, Y. A. (2024). Network pharmacology, molecular docking, and dynamics analyses to predict the antiviral activity of ginger constituents against coronavirus infection. Scientific Reports, 14, 12059. https://doi.org/10.1038/s41598-024-60721-3

Shin, M. S., Kang, Y., Lee, N., Wahl, E. R., Kim, S. H., Kang, K. S., Lazova, R., Kang, I., & Crafts, P. (2021). Activation of caspase-1 is mediated by stimulation of interferon genes and NLR family pyrin domain containing 3 in monocytes of active systemic lupus erythematosus. Clinical Immunology, 227, 108730. https://doi.org/10.1016/j.clim.2021.108730

Siegel, C. H., & Sammaritano, L. R. (2024). Systemic lupus erythematosus: a review. JAMA, 331(17), 1480-1491. https://doi.org/10.1001/jama.2024.2315

Supandi, S., Yeni, Y., & Merdekawati, F. (2018). In silico study of pyrazolylaminoquinazoline toxicity by lazar, protox, and admet predictor. Journal of Applied Pharmaceutical Science, 8(9), 119-129. https://doi.org/10.7324/JAPS.2018.8918

Syahputra, G., Ambarsari, L., & Sumaryada, T. (2014). Simulasi docking kurkumin enol, bisdemetoksikurkumin dan analognya sebagai inhibitor enzim 12-lipoksigenase. Journal Biofisika, 10(1), 55-67.

You, R., He, X., Zeng, Z., Zhan, Y., Xiao, Y., & Xiao, R. (2022). Pyroptosis and its role in autoimmune disease: a potential therapeutic target. Frontiers in Immunology, 13, 841732. https://doi.org/10.3389/fimmu.2022.841732

Yücel, Ç., Karatoprak, G. Ş., Açıkara, Ö. B., Akkol, E. K., Barak, T. H., Sobarzo-Sánchez, E., Aschner, M., & Shirooie, S. (2022). Immunomodulatory and anti-inflammatory therapeutic potential of gingerols and their nanoformulations. Frontiers in Pharmacology, 13, 902551. https://doi.org/10.3389/fphar.2022.902551