Gastroprotective Effects of Nettle- and Carob-Enriched Snail Mucus in a Rat Model of Gastric Injury: Role of Antioxidant and Anti-Inflammatory Mechanisms.
Gharbi Khaoula K, Selmi Slimen S, Wahabi Soumaya S, Kahlaoui Hanen H et al.
Dietary supplementation of Helix aspersa Müller with nettle (Urtica dioica L.) or carob (Ceratonia siliqua L.) has been hypothesized to enhance the biochemical composition and gastroprotective properties of the secreted mucus through enrichment of its polyphenolic, protein, and glycoprotein content. This study presents a comprehensive experimental evaluation of diet-enriched snail mucus preparations across three supplementation levels (10%, 20%, and 30%) in an ethanol-induced rat gastric ulcer model, encompassing phytochemical characterization, in vitro antioxidant assessment, and in vivo biochemical, systemic, and histopathological profiling. A standard snail mucus control group (SSSD) was included to isolate the specific contribution of dietary plant enrichment from the intrinsic properties of snail mucus itself. Analysis revealed that dietary supplementation significantly increased the yield of lyophilised snail mucus as well as its total phenolic, flavonoid, protein, and sugar contents in a dose-dependent manner, with nettle exerting markedly superior effects than carob at all tested doses, attributable to its 33-fold higher phenolic content and 15.5-fold higher flavonoid content relative to carob extract. In vivo, pretreatment with enriched mucus preparations significantly attenuated ethanol-induced gastric injury across all evaluated parameters. The 30% nettle-enriched group (SSUD30%) demonstrated the strongest gastroprotective effect, normalizing gastric pH (3.75 ± 0.074), reducing gastric juice volume (1.59 ± 0.071 mL/100 g), restoring antioxidant enzyme activities (SOD, CAT, GPx) to near-control values, reducing lipid peroxidation markers (MDA: 0.35 nmol/mg protein), and attenuating systemic inflammatory biomarkers including CRP, hepatic enzymes, and lipid profile alterations. Histopathological semi-quantitative scoring confirmed a histological damage score reduction from 11 (ethanol group) to 2 in the SSUD30% group, corresponding to 81.82% protection, significantly exceeding that of famotidine (36.3%). These findings support a comprehensive gastroprotective model based on three complementary and interdependent mechanisms: reinforcement of the physical mucus barrier through increased viscosity and glycoprotein content, enhancement of endogenous antioxidant defenses through restoration of SOD, CAT, and GPx activities via the Nrf2/HO-1 pathway, and attenuation of systemic inflammatory cascades through inhibition of NF-κB-mediated signaling by flavonoids and polyphenols incorporated into the enriched mucus. Overall, diet-enriched snail mucus, particularly SSUD30%, should be conceptualized not merely as a topical mucoprotective agent, but as a multi-target bioactive preparation whose efficacy depends on the complementary contribution of physical barrier reinforcement, antioxidant restoration, and anti-inflammatory modulation. Future studies should prioritize identification of the specific bioactive compounds responsible for the observed effects, assessment of bioavailability under gastrointestinal conditions, and validation of therapeutic potential in human clinical settings.