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Omeprazole (OPZ) is a proton pump inhibitor commonly used for the treatment of gastric acid hypersecretion. Studies have revealed that use of OPZ can induce hepatotoxicity, but the mechanisms by which it induces liver injury are unclear. This study aimed to identify reactive metabolites of OPZ, determine the pathways of the metabolic activation, and define the correlation of the bioactivation with OPZ cytotoxicity. Quinone imine-derived glutathione (GSH), N-acetylcysteine (NAC), and cysteine (Cys) conjugates were detected in OPZ-fortified rat and human liver microsomal incubations captured with GSH, NAC, or Cys. The same GSH conjugates were detected in bile of rats and cultured liver primary cells after exposure to OPZ. Similarly, the same NAC conjugates were detected in urine of OPZ-treated rats. The resulting quinone imine was found to react with Cys residues of hepatic protein. CYP3A4 dominated the metabolic activation of OPZ. Exposure to OPZ resulted in decreased cell survival in cultured primary hepatocytes. Pretreatment with ketoconazole attenuated the susceptibility of hepatocytes to the cytotoxicity of OPZ.

Conventional methods to extract and recover chlorogenic acid (CGA) from plants exhibit plenty of flaws, like over‐consumption of organic solvents, low extracting rate, and low enrichment efficiency. Herein, an ultrasound‐assisted deep eutectic solvent extraction (UAE‐DESs) was introduced to extract CGA from sunflower disks. And NKA‐II macroporous resin was used as adsorbent to adsorb CGA from dilute DESs extracts. Then NKA‐II was collected by filtration followed by desorption to obtain CGA separated from DESs. The extraction yield of CGA was 6.16 mg/g with liquid–solid ratio 31 ml/g, ultrasonic temperature 47°C, ultrasonic time 54 min, and deep eutectic solvent (DES) composed of choline chloride/1,4‐butanediol (1/2, mol/mol) and water content 30% (w/w). After NKA‐II enrichment, the recovery efficiency of CGA was 80.76% and the purity was 75.84%. Moreover, the recovered DESs could be reused during the extraction. The present research provided a time‐saving, green, and sustainable method for extracting and recovering CGA from sunflower disks. Practical applications The research proposed a method for the extraction and recovery of CGA from sunflower disks by combining UAE‐DESs and NKA‐II macroporous resins. The combination of diluted DESs with macroporous resins can effectively overcome the disadvantages of DESs and provide an efficient method for the recovery of natural products. The CGA extracted can be applied in medicine, food, and other fields.

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