The effect of cinnamic acid-isatin hybrid and/or vonoprazan on indomethacin-induced gastric ulcer in rats

Excessive use of nonsteroidal anti-inflammatory drugs (NSAIDs) has a major role in gastric ulcer (GU) development. Cinnamic acid and Isatin have anti-inflammatory and antioxidant effects. This work was conducted to assess the therapeutic effect of a cinnamic acid-isatin hybrid on indomethacin-induced GU, comparing its efficacy to the standard novel drug, vonoprazan. Thirty-five healthy mature male albino rats were randomly split into 7 groups (5 animals/group) as follows: control (Ctrl), cinnamic acid hybrid (CAH) , vonoprazan (VPZ) , indomethacin (INDO), CAH-treated (INDO + CAH), vonoprazan-treated (INDO + VPZ), and combined treatment (INDO + CAH + VPZ) groups. After two weeks, anti-inflammatory [interleukin 1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), and nuclear factor kappa B (NF-κB)], oxidative stress [myeloperoxidase (MPO), malondialdehyde (MDA)], and antioxidant enzymes [catalase (CAT), superoxide dismutase (SOD)], caspase-3 immunohistochemical staining, and morphometric analysis of histological activity index ( HAI) were assessed. Both light and transmission electron microscopy techniques were used to examine the stomach tissue. Indomethacin caused severe erosion and distortion of the normal architecture in the gastric mucosa as revealed under light and electron microscopes, confirming the biochemical results. While treatment with CAH and VPZ caused marked improvement in the damaged gastric mucosa noticed under light and electron microscopes, and confirmed the biochemical results in the form of a significant (P < 0.5) increase in the antioxidant enzymes (SOD and CAT) levels, a significant (P < 0.5) decrease in oxidative stress markers (MDA, MPO), inflammatory markers (TNF-α, IL-1β, and NF-κB), and caspase-3 immunostaining. Morphometric results revealed a significant (P < 0.05) reduction in the HAI score of the treated groups. The combination of both cinnamic acid hybrid and vonoprazan has a synergistic effect on improving the outcomes of indomethacin-induced gastric ulcer.