Syringic acid protects against indomethacin-induced gastric injury via NF-κB and apoptotic pathway modulation

Gastric ulcer is a common disorder resulting from impaired mucosal protection due to cyclooxygenase (COX) inhibition. Proton pump inhibitors (PPIs) reduce this damage, but prolonged use has side effects. Syringic acid (SA), a natural polyphenol, shows antioxidant and anti-inflammatory effects, but its gastroprotective role in COX inhibitor-induced injury is not fully understood. This study investigated the protective effects and underlying mechanisms of SA in COX inhibitor-induced gastric injury. Thirty-two male Wistar rats were divided into four groups (n = 8). Rats were pretreated orally for 14 days with saline (Control, Ulcer), syringic acid (50 mg/kg, Ulcer + SA), or omeprazole (30 mg/kg, OMP). Gastric ulcers were then induced using the non-selective COX inhibitor indomethacin (100 mg/kg, single dose) in all groups except Control. Gastric pH, ulcer index, inhibition rate, and lesion area were measured. Histopathological, immunohistochemical, biochemical, and RT-PCR analyses were performed. COX inhibitor exposure caused severe mucosal damage via oxidative stress, inflammation, and apoptosis. SA pretreatment increased gastric pH and reduced ulcer index. The ulcer inhibition rates were 78.5% for SA and 91.5% for OMP. SA markedly improved tissue architecture, restored antioxidant-enzyme activity, reduced MDA levels, and downregulated NF-kappa B, iNOS, and COX-2. It also shifted the Bax/Bcl-2 ratio toward anti-apoptosis and lowered cleaved caspase-3 expression. Syringic acid may confer gastroprotective effects against indomethacin-induced gastric injury by modulating oxidative stress, inflammation, and apoptosis. While less potent than omeprazole, its multi-target actions suggest potential value as an adjunctive strategy for COX inhibitor-induced gastric damage.

Dergi

NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY

Yıl

2026

Cilt

399

Sayı

5

Sayfa

7415-7431

ISSN

0028-1298

eISSN

1432-1912

DOI

10.1007/s00210-025-04881-7

WoS UID

WOS:001635991300001