Tumor Necrosis Factor-Alpha in NSAID-Induced Gastropathy and the Immunomodulatory Potential of Propolis: A Literature Review

Rania Syafira Putri Widyanti¹, Willy Sandhika²*

Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs) remain widely used analgesic and anti-inflammatory agents, yet their gastric toxicity is a persistent clinical problem. Cyclooxygenase (COX) inhibition and prostaglandin depletion explain only part of NSAID-induced gastropathy. Epithelial injury, oxidative stress, and altered mucosal permeability release damage-associated molecular patterns that engage pattern recognition receptors, activate NF-κB and MAPK signaling, and drive pro-inflammatory cytokine production. Tumor necrosis factor-alpha (TNF-α) is a central cytokine in this response. It is produced by macrophages, T-cells, and, under inflammatory conditions, epithelial cells, and it signals through TNFR1 and TNFR2 to promote inflammation, apoptosis, or survival depending on the signaling complexes formed. This review summarizes the immunological mechanisms linking NSAID exposure to TNF-α expression and examines propolis, including nano-formulated propolis, as a candidate immunomodulatory agent. Experimental and in vitro studies suggest that propolis constituents, particularly flavonoids, suppress pro-inflammatory cytokines in activated macrophages and modulate NF-κB and Nrf2 pathways, and a systematic review reports gastroprotective effects in NSAID-induced gastric injury. Nano-formulation may improve solubility and bioavailability. However, evidence that propolis lowers TNF-α specifically in NSAID gastropathy is limited; much of the mechanistic reasoning is inferred, and propolis composition varies with origin. Controlled in vivo studies using standardized preparations, with TNF-α measured alongside histopathology, are needed.

Keywords

healthy lifestyle; NSAID-induced gastropathy; TNF-α; nano propolis; aspirin

Cite This Article

Widyanti, R. S. P., Sandhika, W. (2026). Tumor Necrosis Factor-Alpha in NSAID-Induced Gastropathy and the Immunomodulatory Potential of Propolis: A Literature Review. International Journal of Scientific Advances (IJSCIA), Volume 7| Issue 6: Nov – Dec 2026, Pages 1008-1013. URL: https://www.ijscia.com/wp-content/uploads/2026/11/Volume7-Issue6-Nov-Dec-No.1123-1008-1013.pdf

Volume 7 | Issue 6: Nov – Dec 2026