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.
Omeprazole是一种胃H+/K+ ATPase的抑制剂（PPI），对于猪ATPase的IC50值为1.1μM。Omeprazole对CYP2C19活性具有竞争性抑制作用，抑制常数（Ki）为2至6μM [1-2]。Omeprazole能抑制革兰氏阳性和革兰氏阴性细菌的生长 [3]。Omeprazole可用于治疗十二指肠和胃溃疡、胃食管反流病和糜烂性食管炎 [4]。
在体外，Omeprazole（0.1, 1, 2和4μg/ml; 3, 12天）治疗显著降低了破骨细胞和成骨细胞（RAW264.7和MC3T3-E1）中CTR、c-fos、NFATc1和MMP-9的表达，而与Omeprazole浓度无关。随着Omeprazole浓度的增加，成骨细胞中骨钙蛋白和OPG/RANKL比值的表达增加 [5]。Omeprazole（0-300μM; 7天）以浓度依赖性方式破坏HK2、HPC和HEK293T细胞的形态并抑制增殖，但对NRK细胞的影响很小 [6]。
在体内，Omeprazole（20mg/kg/day; 2周; oral）治疗改善了盐酸半胱胺诱导的胃肠道疾病模型小鼠的运动并减少了焦虑行为 [4]。Omeprazole（100mg/kg/day; 1周; i.p.）治疗改善了幽门螺杆菌感染的小鼠胃中的细菌定植量和髓过氧化物酶（MPO）活性，提高了胃黏膜中抗细胞凋亡Bcl-2蛋白的表达 [7]。