Medicinal plants are commonly used in Latin American folk medicine for the treatment of gastric problems. In order to understand the properties of some of their chemical constituents, four natural xanthones, an acetylated derivative, two coumarins (mammea A/BA and mammea C/OA) isolated from Calophyllum brasiliense Cambess and two flavonoids (minimiflorin and mundulin) isolated from Lonchocarpus oaxacensis Pittier, and the chalcone lonchocarpin isolated from Lonchocarpus guatemalensis Benth were tested for their activities on gastric H+,K+-ATPase isolated from dog stomach. All the compounds tested inhibited H+,K+-ATPase activity with varied potency. The xanthones inhibited the H+,K+-ATPase with IC50 values ranging from 47 microM to 1.6 mM. Coumarins inhibited H+,K+-ATPase with IC50 values of 110 and 638 microM. IC50 values for the flavonoids ranged from 9.6 to 510 microM among which minimiflorin was the most potent. The results suggest that H+,K+-ATPase is sensitive to inhibition by several types of structurally different natural compounds. The potency of the effects on gastric H+,K+-ATPase depends on the presence, position and number of hydroxyls groups in the molecule. Collectively, these results suggest a potential for important pharmacological and toxicological interactions by these types of natural products at the level of H+,K+-ATPase which may explain, at least in part, the gastroprotective properties, indicated by traditional medicine, of the plants from which these compounds were isolated.
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http://dx.doi.org/10.1016/j.jep.2005.10.014 | DOI Listing |
J Biol Chem
December 2024
Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) - Universidad de Buenos Aires, Instituto de Química y Fisicoquímica Biológicas "Prof. Alejandro C. Paladini" (IQUIFIB), Buenos Aires, Argentina. Electronic address:
The introduction of potassium-competitive acid blockers (P-CABs) has been a major innovation in gastric H,K-ATPase inhibition and many laboratories are actively engaged in the development of novel molecules within this class. This work investigates the interaction between H,K-ATPase and tegoprazan, a representative of the P-CABs group, in terms of K and H binding, through functional and structural analyses. First, by studying the H,K-ATPase activity, we found a model to describe the non-Michaelis-Menten kinetics through a "ping-pong" mechanism that explains a stoichiometry of 1 H, 1 K, and 1 ATP molecule, but also considering the influence of H on the ionization states of the protein.
View Article and Find Full Text PDFInt J Cancer
November 2024
Department of Biology, University of Copenhagen, Copenhagen, Denmark.
Pancreatic ductal adenocarcinoma (PDAC) remains the most lethal cancer type. PDAC is characterized by fibrotic, hypoxic, and presumably acidic tumor microenvironment (TME). Acidic TME is an important player in tumor development, progression, aggressiveness, and chemoresistance.
View Article and Find Full Text PDFClin J Gastroenterol
August 2024
Faculty of Medicine, Department of Gastroenterology, Yamagata University, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan.
A 47-year-old woman presented with multiple gastric tumors, each up to 10 mm in diameter, in the gastric body and fundus without mucosal atrophy. White spots and numerous transparent, light-brownish, small, and rounded spots were observed in the background gastric mucosa. Biopsy specimens obtained from the tumors revealed gastric neuroendocrine tumors.
View Article and Find Full Text PDFWorld J Gastroenterol
March 2024
Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota 55905, United States.
Yu 's study in the (2023) introduced a novel regimen of Vonoprazan-amoxicillin dual therapy combined with () for the rescue therapy against () a pathogen responsible for peptic ulcers and gastric cancer. Vonoprazan is a potassium-competitive acid blocker renowned for its rapid and long-lasting acid suppression, which is minimally affected by mealtime. Compared to proton pump inhibitors, which bind irreversibly to cysteine residues in the H/K-ATPase pump, Vonoprazan competes with the K ions, prevents the ions from binding to the pump and blocks acid secretion.
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