Gastroprotective Effect of Vanillin on Indomethacin-Induced Gastric Ulcer in Rats: Protective Pathways and Anti-Secretory Mechanism

Abstract

Indomethacin provokes aggressive ulcerogenic adverse effects. Natural products with fewer side effects are therefore highly requested to attenuate its gastric ulcer effect. Vanillin is a natural compound widely used as flavoring agent which has antioxidant activity. Therefore, the aim of this study was to investigate its gastroprotective effect against indomethacin induced gastric injury. Rats were divided into four groups; first group served as control, group 2: Treated with indomethacin (25 mg/kg, po.), group 3: Pre-treated with ranitidine (reference drug) (50 mg/kg, po., 5 days) before indomethacin and group 4: Pretreated with vanillin (100 mg/kg, po., 5 days). Pre-treatment with vanillin reduced ulcer index, gastric juice volume, free, total acidity and histopathological changes induced by indomethacin. Although it reduced gastric oxidative stress, it elevated enzymatic antioxidant activity and gastric nitric oxide content. Moreover, it reduced gastric NFκB protein expression and activity as well as inhibition in levels of proinflammatory cytokines, Myeloperoxidase (MPO) and caspase 3 activities. It down regulated gene expression of TNF-α, Cytokine-Induced Neutrophil Chemo Attractant (CINC-2α) and caspase-9 while lacking effect on mucosal prostaglandin E2 (PGE2) level. Collectively, vanillin displayed gastroprotective effects in indomethacin induced gastric ulcer by anti-secretory action and cytoprotective effect via antioxidant and anti-inflammatory activities.

Vanillic Acid Ameliorates Demyelination in a Cuprizone-Induced Multiple Sclerosis Rat Model: Possible Underlying Mechanisms

“…Recently, ELBini and Neili [32] demonstrated that the use of a K channel blocker stimulated the process of the myelination of nerve fibers in a model of multiple sclerosis when introduced early during disease development or during remission and exacerbated the demyelination when introduced in a toxic inflammatory environment during the inflammatory processes. Moreover, vanillic acid treatment significantly decreased these inflammatory markers (IL-17, INF-γ) in the sciatic nerve, which is in parallel with the results of Katary & Salahuddin, [33] that vanillic acid downregulates inflammatory cytokines induced by indomethacin in the gastric mucosa. These findings suggest anti-inflammatory actions of VA in the Cuprizone demyelinating rat model.…”

<p>Novel chitosan oligosaccharide-based nanoparticles for gastric mucosal administration of the phytochemical “apocynin”</p>

“…Several lines of evidence have demonstrated the defensive role of NO as a gastroprotective mediator against gastric ulceration through enhancement of mucosal blood flow, stimulation of gastric mucus secretion, and reduction of leukocytic cells' infiltration 59–61. Notwithstanding, upregulation or downregulation of NO can cause deleterious gastric mucosal damage 62,63. The marked effectiveness of the medicated COS-NP s could be assigned to the activity of the drug and the polymer in normalizing the upregulated NO content in ulcerated gastric tissue 10,17…”

Promising effect of Geranium robertianum L. leaves and Aloe vera gel powder on Aspirin®-induced gastric ulcers in Wistar rats: anxiolytic behavioural effect, antioxidant activity, and protective pathways

“…Additionally, vanillin and catechin are important phenolic compounds found in geranium. Vanillin decreased stomach levels of Thiobarbituric Acid Reactive Substances (TBARs), Lipid peroxidation byproducts and enhanced GSH and SOD, which affected lipid peroxide levels in gastric tissue, according to Katary and Salahuddin ( 2017 ). Using vanillin as a pretreatment can help reduce stomach acid output.…”

“…The antiulcer and gastroprotective effects of Quercetin and its glucosides have also been discovered in numerous studies. Following pretreatment with vanillin, the indomethacin-induced histological changes, free, total acidity levels, ulcer index and gastric juice volume all decreased (Katary and Salahuddin 2017 ). Moreover, catechin showed a potent protective effect against stomach mucosal lesions and reduced the production of histamine, somatostatin, and gastrin.…”