Omeprazole is an inhibitor of gastric H+/K+ ATPase (PPI) with an IC50 value of 1.1μM for porcine ATPase. Omeprazole has competitive inhibitory effects on CYP2C19 activity with an inhibition constant (Ki) of 2 to 6μM [1-2]. Omeprazole can inhibit the growth of Gram-positive and Gram-negative bacteria [3]. Omeprazole can be used to treat duodenal and gastric ulcers, gastroesophageal reflux disease, and erosive esophagitis [4].
In vitro, Omeprazole (0.1, 1, 2, and 4μg/ml; 3 and 12 days) treatment significantly reduced the expression of CTR, c-fos, NFATc1, and MMP-9 in osteoclasts and osteoblasts (RAW264.7 and MC3T3-E1), regardless of the Omeprazole concentration. With the increase in Omeprazole concentration, the expression of osteocalcin and the ratio of OPG/RANKL in osteoblasts increased [5]. Omeprazole (0-300μM; 7 days) disrupted the morphology and inhibited proliferation of HK2, HPC, and HEK293T cells in a concentration-dependent manner, but had little effect on NRK cells [6].
In vivo, Omeprazole (20mg/kg/day; 2 weeks; oral) treatment improved the movement of mice in a gastric and intestinal disease model induced by hydrochloric acid cysteamine and reduced anxiety behavior [4]. Omeprazole (100mg/kg/day; 1 week; i.p.) treatment increased the bacterial colonization and myeloperoxidase (MPO) activity in the stomach of mice with Helicobacter pylori infection, and increased the expression of anti-apoptotic Bcl-2 protein in the gastric mucosa [7].
References:
[1] Smolka, A.J., Goldenring, J.R., Gupta, S., et al. Inhibition of gastric H,K-ATPase activity and gastric epithelial cell IL-8 secretion by the pyrrolizine derivative ML 3000. BMC Gastroenterol. 4(4), 1-11 (2004).
[2] Li XQ, Andersson TB, Ahlström M, Weidolf L. Comparison of inhibitory effects of the proton pump-inhibiting drugs omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole on human cytochrome P450 activities. Drug Metab Dispos. 2004;32(8):821-827.
[3] Jonkers D, Stobberingh E, Stockbrügger R. Omeprazole inhibits growth of gram-positive and gram-negative bacteria including Helicobacter pylori in vitro. J Antimicrob Chemother. 1996;37(1):145-150.
[4] Rethinavel H S, Selvaraj D B, Balakrishnan S J, et al. Omeprazole treatment manifests anxiolytic effects in a cysteamine hydrochloride induced mouse model of gastrointestinal disorder[J]. Heliyon, 2022, 8(6).
[5] Hyun JJ, Chun HJ, Keum B, et al. Effect of omeprazole on the expression of transcription factors in osteoclasts and osteoblasts. Int J Mol Med. 2010;26(6):877-883.
[6] Xiong Z, Lai Z, Li S, et al. Potential Kidney Risks Associated With Clinical Doses of Omeprazole: In Vivo and In Vitro Studies[J]. Clinical and Experimental Pharmacology and Physiology, 2025, 52(8): e70050.
[7] Maróstica M, Arçari D P, Bartchewsky Jr W, et al. Effects of a one-week treatment with acid gastric inhibitors on Helicobacter pylori-infected mice[J]. Scandinavian journal of gastroenterology, 2007, 42(12): 1404-1412.