Nutritional, Bioactive, and Therapeutic Potential of Senna alexandrina Leaf Extract: Anti-Inflammatory Effects and Enhanced Anti-Helicobacter pylori Activity in Combination with Omeprazole–Amoxicillin–Rifabutin Therapy

Senna alexandrina is recognized for its medicinal uses, yet its multi-target therapeutic potential remains insufficiently characterized. To the best of our knowledge, this is the first study to investigate the anti-inflammatory and anti-Helicobacter pylori activities of S. alexandrina leaf extract in combination with the omeprazole–amoxicillin–rifabutin regimen, commercially known as Talicia. The study further evaluates whether the extract enhances the antibacterial activity of this established H. pylori treatment. Bioactivity of a methanolic leaf extract from Al-Qassim, Saudi Arabia, was evaluated using membrane stabilization, broth microdilution checkerboard assays, butyrylcholinesterase (BChE) inhibition, MTT assays on WI-38 human fibroblasts, and HPLC profiling. The extract exhibited protection against hypotonicity-induced erythrocyte hemolysis (IC50 = 8.44 µg/mL) and bactericidal activity against H. pylori ATCC 43504 (MIC = 31.25 µg/mL; MBC = 62.50 µg/mL; MBC/MIC = 2.0). Combining the extract with Talicia yielded a Fractional Inhibitory Concentration Index (FICI) of 0.75, indicating an additive to weakly synergistic interaction (7.81 µg/mL extract and 8.00 µg/mL Talicia). HPLC identified rosmarinic acid (16.05 mg/g dry extract) and quercetin (15.90 mg/g dry extract) as primary polyphenols. The extract showed cell-free BChE inhibition (IC50 = 31.8 µg/mL) and low cytotoxicity on WI-38 fibroblasts under tested conditions (IC50 = 191.1 µg/mL). Overall, S. alexandrina leaf extract displays preliminary in vitro membrane-stabilizing, antibacterial, and cholinesterase-inhibitory activities, enhancing Talicia activity via additive interaction. These findings justify further mechanistic, pharmacokinetic, toxicological, and in vivo investigations before any therapeutic or clinical relevance can be proposed.