In-depth molecular assessment of Hedera helix's L. α - Hederin & Hederacoside C as a gastroprotective & a possible safe Omeprazole phyto-alternative in ethanol-induced gastric ulcer mice model.

Hedera helix L. is among the most popular over-the-counter formulations for effectively alleviating respiratory disorders in adults & children due to its unique active constituents such as α - Hederin & Hederacoside C. Even though its respiratory pharmacological activity is thoroughly researched, its other pharmacological activities remain relatively unexplored. Alcoholism is a Western cultural habit that is associated with various side effects, including peptic ulcer disease (PUD) & drug interaction. The PUD is commonly & recurrently presented clinically, increasing the load on healthcare systems. PUD not only negatively affects the quality of life but is also associated with serious complications such as bleeding, penetration, perforation, pyloric stenosis, & gastric cancer. Alcohol interaction with drugs could either lead to therapeutic failure, accumulation of drug-toxic metabolites, or disturbance of the alcohol detoxification pathway, putting the treatment of alcoholism-induced PUD with a drug-interacting medication such as Omeprazole under the limelight. In line with that, finding plant-derived molecules with the potency of Omeprazole but without its associated side effects & drug-interacting property is a desperate clinical need. In this regard, we aimed to investigate the gastroprotective effect, potency, & molecular mechanism of α - Hederin & Hederacoside C pretreatment against ethanol-induced gastric ulcer in mice model. These compounds were tested in two upgrading doses (50 mg/kg & 75 mg/kg) compared to negative, positive, & Omeprazole groups. Our study revealed that daily oral administration of α - Hederin or Hederacoside C protected the stomach against ethanol-induced gastric ulcers in a dose-dependent manner. The potency of high doses of both compounds was comparable to Omeprazole. Their effectiveness was related to their ability to set the activated invasive forces, including CYP1A2, neutrophils, MDA, leptin, TNF-α, IL-6, IL-12, & NF-κB-p65 & to amplify the intrinsic defensive forces, including COX-2, PGE-2, CAT, & SOD. These intertwined actions were reflected in maintaining vibrant stomach architecture, such as mucosal layer re-epithelization, gland reconstruction, & restoring tunica muscularis normal thickness. Moreover, they limited the exaggeration of the repairing system, including HSP-70, VEGF, & Annexin-1, where their forge was positively correlated with damage depth. Therefore, we compendiously deduced that herbal-based medicine could face the constraints of synthesized medicine satisfactorily without their culminating side effects.