Rosmarinic acid prevents gastric ulcers via sulfhydryl groups reinforcement, antioxidant and immunomodulatory effects.

Rosmarinic acid (RA) is a secondary metabolite present in several plant species that has already demonstrated antioxidant, antiallergic, anticancer, antimicrobial, neuroprotective, and hepatoprotective effects experimentally. Due to the promising pharmacological properties found previously, this study aimed to assess the oral acute toxicity and the gastroprotective effect of RA using animal models. Acute toxicity was assessed according to OECD guide 423. Ethanol, stress, NSAIDs, and pylorus ligature-induced gastric ulcer models were used to investigate antiulcer properties. The related mechanisms of action were also evaluated from ethanol-induced gastric lesions protocol. RA (300 and 2000 mg/kg) showed no changes in behavioral, water and food intake, body and organs weight parameters with LD50 set around 2500 mg/kg. RA presented gastroprotective activity in all assessed doses (25, 50, 100, and 200 mg/kg) using different animal models. Besides, it was observed that this effect is not related to the modulation of gastric juice parameters (pH, volume, and [H+]), the participation of nitric oxide, mucus, and prostaglandins. However, increased sulfhydryl groups, GSH and IL-10 levels as well as reduced of proinflammatory cytokine (TNF-α and IL-1ß) levels were found for RA-treated groups. RA presents low acute toxicity and gastroprotective activity, preventing ulcer formation via cytoprotective, antioxidant, and anti-inflammatory mechanisms. Graphical abstract.

Cytoprotective, antioxidant and anti-inflammatory mechanism related to antiulcer activity of Cissampelos sympodialis Eichl. in animal models.

ETHNOPHARMACOLOGICAL RELEVANCE: The leaves and roots of Cissampelos sympodialis (Menispermaceae) are used by indian tribes and in folk medicine to treat genitourinary infections, inflammation, asthma and gastrointestinal disorders. MATERIAL AND METHODS: The standardized ethanolic extract (Cs-EtOHE) and alkaloids total fraction (Cs-TAF) obtained from aerial parts of C. sympodialis were evaluated in several models of acute gastric ulcers. The antisecretory and/or neutralizing mechanisms of the gastric acid secretion, cytoprotective, antioxidant and immunoregulatory mechanisms were also evaluated. RESULTS: Cs-EtOHE and Cs-TAF presented a reduction in gastric mucosa lesions against ethanol, NSAIDs, hypothermic restraint-stress and gastric juice containment induced ulcer models. This activity is related to alkaloids present in the extract, and involves the participation of sulfhydryl compounds, nitric oxide, KATP channels, prostaglandins, decreased levels of IL-1ß and TNF-α and increased levels of GSH and IL-10. CONCLUSION: The data indicate gastroprotective activity, due to the participation of the cytoprotective, antioxidant and immunoregulatory mechanisms.

Activity of alkaloids on peptic ulcer: what's new?

Peptic ulcer is a common disease characterized by lesions that affect the mucosa of the esophagus, stomach and/or duodenum, and may extend into the muscular layer of the mucosa. Natural products have played an important role in the process of development and discovery of new drugs, due to their wide structural diversity and present, mostly specific and selective biological activities. Among natural products the alkaloids, biologically active secondary metabolites, that can be found in plants, animals or microorganisms stand out. The alkaloids are compounds consisting of a basic nitrogen atom that may or may not be part of a heterocyclic ring. This review will describe 15 alkaloids with antiulcer activity in animal models and in vitro studies.