Protective effects of the bacterial pigment violacein against gastric ulceration: Inhibition of acid-related enzymes, activation of protective pathways, and reduction of inflammation and oxidative stress

This study investigated, for the first time, the oral effects of violacein (VIO) on key enzymes involved in gastric ulceration. Daily administration of VIO at 40 mg/kg body weight reduced neutrophil infiltration and inflammation, demonstrated by a 64 % decrease in gastric mucosa myeloperoxidase (MPO) activity (p = 0.02). VIO also markedly decreased oxidative stress markers: hydrogen peroxide (H₂O₂) by 62 % (p = 0.03), total oxidant status (TOS) by 64 % (p = 0.02), and thiobarbituric acid reactive substances (TBARS) by 74 % (p = 0.02), while increasing total antioxidant status (TAS) by 217 % (p = 0.006), indicating strong protection against oxidative gastric damage. Furthermore, VIO inhibited key gastric enzymes related to acid secretion and mucosal degradation. It reduced H⁺/K⁺-ATPase activity by 52 %, pepsin (PEP) by 72 %, and overall peptic activity by 60 % (p ≤ 0.03), resulting in a 110 % increase in gastric mucosa pH (p = 0.01) and a 61 % reduction in total acidity (TA) (p = 0.02). VIO also suppressed mucin-degrading enzymes, mucinase and β-glucuronidase, by 63 and 48 %, respectively (p ≤ 0.03). Simultaneously, VIO enhanced protective enzyme activities, increasing heme oxygenase (HO) by 190 % and carbonic anhydrase (CA) by 157 % (p ≤ 0.009), which led to elevated levels of gastric mucin, glycoproteins, and hexosamines, reinforcing mucosal integrity. Finally, VIO demonstrated dose-dependent gastroprotection, with a 40 mg/kg dose reducing ulcer area (UA) by 71.8 % (p = 0.02). These findings suggest that VIO offers a promising natural alternative to synthetic drugs by enhancing mucosal defense mechanisms in gastric ulcer management.