Trends in Immunotherapy

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Predicted Immunomodulatory and Anti-Inflammatory Potential of Ficus carica Phytochemicals Targeting NF-kB and TNF-α Signaling Pathways: An In-Silico Investigation

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https://doi.org/10.54963/ti.v10i2.2420
Mezouara, M., Aouji , M., Mouniane, Y., Belmejdoub, N., El Bakkali, M., Aboussaleh, Y., & Hmouni, D. (2026). Predicted Immunomodulatory and Anti-Inflammatory Potential of Ficus carica Phytochemicals Targeting NF-kB and TNF-α Signaling Pathways: An In-Silico Investigation. Trends in Immunotherapy, 10(2), 154–177. https://doi.org/10.54963/ti.v10i2.2420
Volume 10, Issue 2 (2026)
Copyright (c) 2026 Mounia Mezouara, Marouane Aouji , Yassine Mouniane, Nada Belmejdoub, Mohamed El Bakkali, Youssef Aboussaleh, Driss Hmouni
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Authors

  • Mounia Mezouara

    Laboratory of Natural Resources and Sustainable Development, Department of Biology, Faculty of Sciences, Ibn Tofail University, Kenitra 14000, Morocco
  • Marouane Aouji

    Laboratory of Natural Resources and Sustainable Development, Department of Biology, Faculty of Sciences, Ibn Tofail University, Kenitra 14000, Morocco
  • Yassine Mouniane

    Scientific Research and Innovation Laboratory (SRILab), Higher School of Technology, Ibn Tofail University, Kenitra 14000, Morocco
  • Nada Belmejdoub

    Laboratory of Natural Resources and Sustainable Development, Department of Biology, Faculty of Sciences, Ibn Tofail University, Kenitra 14000, Morocco
  • Mohamed El Bakkali

    Laboratory of Natural Resources and Sustainable Development, Department of Biology, Faculty of Sciences, Ibn Tofail University, Kenitra 14000, Morocco
    Higher Institute of Nursing and Health Techniques (ISPITS-Kenitra), Kenitra 14000, Morocco
  • Youssef Aboussaleh

    Laboratory of Natural Resources and Sustainable Development, Department of Biology, Faculty of Sciences, Ibn Tofail University, Kenitra 14000, Morocco
  • Driss Hmouni

    Laboratory of Natural Resources and Sustainable Development, Department of Biology, Faculty of Sciences, Ibn Tofail University, Kenitra 14000, Morocco

Received: 10 May 2026; Revised: 29 May 2026; Accepted: 25 June 2026; Published: 29 June 2026

Chronic inflammation and immune dysregulation are key contributors to the development and progression of metabolic diseases, including type 2 diabetes mellitus (T2DM). Natural phytochemicals capable of modulating inflammatory signaling pathways have attracted increasing interest as potential multi-target therapeutic agents. This study investigated the predicted immunomodulatory and antidiabetic potential of major Ficus carica leaf phytochemicals using an integrated in silico approach combining molecular docking, physicochemical characterization, pharmacokinetic analysis, and toxicity prediction. Six bioactive compounds (quercetin, kaempferol, chlorogenic acid, caffeic acid, rutin, and gallic acid) were evaluated against four key inflammatory and metabolic targets: NF-κB p50, TNF-α, DPP-4, and α-glucosidase. Molecular docking demonstrated that quercetin and kaempferol exhibited the strongest binding affinities toward both inflammatory and metabolic targets. Quercetin showed the highest affinity for NF-κB p50 (−7.39 kcal/mol) and DPP-4 (−7.00 kcal/mol), forming stable complexes through hydrogen bonds, hydrophobic interactions, π–π stacking, and electrostatic contacts. Physicochemical and pharmacokinetic analyses indicated favorable drug-likeness and acceptable aqueous solubility for most compounds. Toxicity prediction suggested low acute toxicity (classes 4–5) but indicated potential cardiotoxicity, cytotoxicity, and immunotoxicity, emphasizing the need for cautious interpretation. Overall, the predicted interactions with NF-κB and TNF-α support the potential immunomodulatory properties of Ficus carica phytochemicals, particularly quercetin and kaempferol, as promising multi-target candidates for inflammation-associated metabolic disorders. However, these computational findings remain hypothesis-generating and require validation through in vitro and in vivo studies to confirm their biological activity, safety, and therapeutic potential.

Keywords:

Ficus carica Immunomodulation Chronic Inflammation NF-kB TNF-α Flavonoids Molecular Docking Inflammatory Signaling Pathways

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