Different protective capability of chlorogenic acid and quercetin against indomethacin-induced gastrointestinal ulceration.

Autor:	Boonyong C; Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand., Angkhasirisap W; Academic Service Division, National Laboratory Animal Center, Mahidol University, Nakorn Pathom 73170, Thailand., Kengkoom K; Academic Service Division, National Laboratory Animal Center, Mahidol University, Nakorn Pathom 73170, Thailand., Jianmongkol S; Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand.
Jazyk:	angličtina
Zdroj:	The Journal of pharmacy and pharmacology [J Pharm Pharmacol] 2023 Mar 12; Vol. 75 (3), pp. 427-436.
DOI:	10.1093/jpp/rgac098
Abstrakt:	Objectives: The study compared the protective effects against indomethacin-induced GI ulceration of chlorogenic acid with quercetin in rats. Methods: Rats were orally given chlorogenic acid or quercetin (100 mg/kg; 5 days), followed by indomethacin (40 mg/kg; single dose). After 24 h, GI tissues were assessed for histopathological damages, then analysed by ELISA and western blot methods. Cell viability was measured in vitro by MTT assay. Key Findings: Unlike quercetin, chlorogenic acid could not prevent gastric ulcers in indomethacin-treated rats. The levels of gastric prostaglandin E2 (PGE2) and Bax/Bcl-2 ratio in the chlorogenic acid-treated group were not different from those receiving indomethacin alone. Nevertheless, both compounds alleviated jejunum ulcers through suppression of PERK/eIF-2/ATF-4/CHOP-related endoplasmic reticulum (ER) stress and decrease Bax/Bcl-2 ratio. Moreover, at 100 µM, they abolished the cytotoxicity of tunicamycin (an ER stress inducer) in gastric (AGS) and intestinal (Caco-2) cells. In silico docking studies suggested that both compounds could interact with key amino acid residues in the -catalytic domain of PERK. Conclusion: Chlorogenic acid and quercetin exerted comparable protective effects against indomethacin-induced intestinal ulcer through suppression of ER stress-mediated apoptosis but, unlike quercetin, chlorogenic acid offered no protection against gastric ulceration due to its -inability to increase PGE2 production. (© The Author(s) 2023. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
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