Decoding the role of tannic acid in wound healing: a dual‐action mechanism linking IL‐1β modulation and FGF‐driven tissue repair

Dewa Ayu Swastini; Agung Endro Nugroho; Ronny Martien; Jajah Fachiroh; Muhammad Khafi; Komang Dian Aditya Putra

doi:10.22146/ijbiotech.113925

Decoding the role of tannic acid in wound healing: a dual‐action mechanism linking IL‐1β modulation and FGF‐driven tissue repair

https://doi.org/10.22146/ijbiotech.113925

Dewa Ayu Swastini⁽¹⁾, Agung Endro Nugroho^(2*), Ronny Martien⁽³⁾, Jajah Fachiroh⁽⁴⁾, Muhammad Khafi⁽⁵⁾, Komang Dian Aditya Putra⁽⁶⁾

(1) Doctoral Program, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta 55281, Indonesia; Pharmacy Study Programme, Faculty of Mathematics and Natural Sciences, Universitas Udayana, Badung 80361, Bali, Indonesia
(2) Departement of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Gadjah Mada, Indonesia
(3) Departement of Pharmaceutics, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta 55281, Indonesia
(4) Departement of Histology and Cell Biology, Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta 55281, Indonesia
(5) Master in Pharmaceutical Sciences, Faculty of Pharmacy, Universitas Gadjah Mada, Jl. Sekip Utara, Sleman, Yogyakarta 55281, Indonesia
(6) Master in Pharmaceutical Sciences, Faculty of Pharmacy, Universitas Gadjah Mada, Jl. Sekip Utara, Sleman, Yogyakarta 55281, Indonesia
(*) Corresponding Author

Abstract

Tannic acid (TA) has been shown in a previous study to expedite cutaneous wound healing in rats; however, the precise mechanism by which it operates remains poorly understood. This research evaluates the effects of TA on wound healing using both in vitro and in silico methods. In vitro, its influence on the inflammatory cytokine interleukin‐1β (IL‐1β) and the growth factor fibroblast growth factor (FGF) throughout the healing process were assessed. In silico molecular docking was employed to predict direct ligand–protein interactions and to provide a mechanistic insight into whether these proteins represent primary molecular targets or downstream effects. Parameters evaluated included cell viability and proliferation, scratch assays, and the activity of pro‐inflammatory cytokines in the lipopolysaccharide (LPS)‐stimulated RAW 264.7 macrophage cell line, together with growth factors in the NIH 3T3 fibroblast cell line; all were evaluated using enzyme‐linked immunosorbent assay (ELISA). The results indicate that TA significantly facilitates wound closure by promoting NIH 3T3 fibroblast cell proliferation, enhancing FGF expression, and suppressing IL‐1ß synthesis in both in vitro and in silico approaches. These findings suggest that TA may hold considerable promise for wound‐healing management.

Keywords

Growth factors; Inflammatory cytokines ; Mechanism; Tannic acid; Wound healing

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References

Che X, Liu Q, Zhang L. 2023. An accurate and universal proteinsmall molecule batch docking solution using AutoDock Vina. Results Eng. 19:101335. doi:10.1016/j.rineng.2023.101335.

Chen Y, Tian L, Yang F, Tong W, Jia R, Zou Y, Yin L, Li L, He C, Liang X, et al. 2019. Tannic acid accelerates cutaneous wound healing in rats via activation of the ERK 1/2 signaling pathways. Adv. Wound Care 8(7):341–354. doi:10.1089/wound.2018.0853.

Cialdai F, Colciago A, Pantalone D, Rizzo AM, Zava S, Morbidelli L, Celotti F, Bani D, Monici M. 2020. Effect of unloading condition on the healing process and effectiveness of platelet rich plasma as a countermeasure: study on in vivo and in vitro wound healing models. Int. J. Mol. Sci. 21(2). doi:10.3390/ijms21020407.

Cicchese JM, Evans S, Hult C, Joslyn LR, Wessler T, Millar JA, Marino S, Cilfone NA, Mattila JT, Linderman JJ, et al. 2018. Dynamic balance of proand antiinflammatory signals controls disease and limits pathology. Immunol. Rev. 285(1):147–167. doi:10.1111/imr.12671.

de Veras BO, da Silva MV, Cabral Ribeiro PP. 2021. Tannic acid is a gastroprotective that regulates inflammation and oxidative stress. Food Chem. Toxicol. 156:112482. doi:10.1016/j.fct.2021.112482.

Dinarello CA. 2018. Overview of the IL1 family in innate inflammation and acquired immunity. Immunol. Rev. 281(1):8–27. doi:10.1111/imr.12621.

Frenette AP, RodríguezRamos T, Zanuzzo F, Ramsay D, Semple SL, Soullière C, RodríguezCornejo T, Heath G, McKenzie E, Iwanczyk J, et al. 2023. Expression of interleukin1β protein in vitro, ex vivo and in vivo salmonid models. Dev. Comp. Immunol. 147:104767. doi:10.1016/j.dci.2023.104767.

HolzerGeissler JCJ, Schwingenschuh S, Zacharias M, Einsiedler J, Kainz S, Reisenegger P, Holecek C, Hofmann E, WolffWiniski B, Fahrngruber H, et al. 2022. The impact of prolonged inflammation on wound healing. Biomedicines 10(4). doi:10.3390/biomedicines10040856.

Jayakumari S, Vijayalakshmi A, Anandhi N, Mounisha B, Sameer MHM, Yogeshwaran V. 2023. Wound healing and cytotoxic effects of tannin rich fraction of Psidium guajava L. leaves. Ann. Phytomed. Int. J. 12(2):707– 712. doi:10.54085/ap.2023.12.2.83.

Kim S, Chen J, Cheng T, Gindulyte A, He J, He S, Li Q, Shoemaker BA, Thiessen PA, Yu B, et al. 2025. PubChem 2025 update. Nucleic Acids Res. 53(D1):D1516–D1525. doi:10.1093/nar/gkae1059.

Knoedler S, Broichhausen S, Guo R, Dai R, Knoedler L, KaukeNavarro M, Diatta F, Pomahac B, Machens HG, Jiang D, et al. 2023. Fibroblasts: the cellular choreographers of wound healing. Front. Immunol. 14:1233800. doi:10.3389/fimmu.2023.1233800.

KołtunJasion M, Dudek MK, Kiss AK. 2025. Eucommiae cortex comprehensive phytochemical analysis connected with its in vitro antiinflammatory activity in human immune cells. Molecules 30(6):1–19. doi:10.3390/molecules30061364.

Landén NX, Li D, Ståhle M. 2016. Transition from inflammation to proliferation: a critical step during wound healing. Cell. Mol. Life Sci. 73(20):3861– 3885. doi:10.1007/s0001801622680.

Lavoie H, Gagnon J, Therrien M. 2020. ERK signalling: a master regulator of cell behaviour, life and fate. Nat. Rev. Mol. Cell Biol. 21(10):607–632. doi:10.1038/s4158002002557.

Luo M, Wang M, Niu W, Chen M, Cheng W, Zhang L, Xie C, Wang Y, Guo Y, Leng T, et al. 2021. Injectable selfhealing antiinflammatory europium oxidebased dressing with high angiogenesis for improving wound healing and skin regeneration. Chem. Eng. J. 412:128471. doi:10.1016/j.cej.2021.128471.

Maddaluno L, Urwyler C, Werner S. 2017. Fibroblast growth factors: key players in regeneration and tissue repair. Development 144(22):4047–4060. doi:10.1242/dev.152587.

McNutt AT, Li Y, Meli R, Aggarwal R, Koes DR. 2025. GNINA 1.3: the next increment in molecular docking with deep learning. J. Cheminform. 17(1):28. doi:10.1186/s1332102500973x.

O’Boyle NM, Banck M, James CA, Morley C, Vandermeersch T, Hutchison GR. 2011. Open Babel: an open chemical toolbox. J. Cheminform. 3(1):33. doi:10.1186/17582946333.

Orlowski P, Zmigrodzka M, Tomaszewska E, RanoszekSoliwoda K, Czupryn M, AntosBielska M, Szemraj J, Celichowski G, Grobelny J, Krzyzowska M. 2018. Tannic acidmodified silver nanoparticles for wound healing: the importance of size. Int. J. Nanomedicine 13:991–1007. doi:10.2147/IJN.S154797.

Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, Ferrin TE. 2004. UCSF Chimera–a visualization system for exploratory research and analysis. J. Comput. Chem. 25(13):1605–1612. doi:10.1002/jcc.20084.

Song X, Chen Y, Chen X, Zhao X, Zou Y, Li L, Zhou X, Li M, Zhang D, Ye G, et al. 2023. Exosomes from tannic acidstimulated macrophages accelerate wound healing through miR2213p mediated fibroblasts migration by targeting CDKN1b. Int. J. Biol. Macromol. 244:125088. doi:10.1016/j.ijbiomac.2023.125088.

Su X, Liu X, Wang S, Li B, Pan T, Liu D, Wang F, Diao Y, Li K. 2017. Woundhealing promoting effect of total tannins from Entada phaseoloides (L.) Merr. in rats. Burns 43(4):830–838. doi:10.1016/j.burns.2016.10.010.

Swastini DA, Martien R, Fachiroh J, Nugroho AE. 2025. Ethnopharmacology and bioactive evidence of medicinal plants for wound healing in Indonesia: a scoping review. J. Appl. Pharm. Sci. 15(6):10–30. doi:10.7324/JAPS.2025.211952.

Velnar T, Bailey T, Smrkolj V. 2009. The wound healing process: an overview of the cellular and molecular mechanisms. J. Int. Med. Res. 37(5):1528–1542. doi:10.1177/147323000903700531.

Zhang M, Zhao X. 2020. Alginate hydrogel dressings for advanced wound management. Int. J. Biol. Macromol. 162:1414–1428. doi:10.1016/j.ijbiomac.2020.07.311.

Zhu J, Liu B, Wang Z, Wang D, Ni H, Zhang L, Wang Y. 2019. Exosomes from nicotinestimulated macrophages accelerate atherosclerosis through miR213p/PTENmediated VSMC migration and proliferation. Theranostics 9(23):6901– 6919. doi:10.7150/thno.37357.

DOI: https://doi.org/10.22146/ijbiotech.113925