Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0847097 (acidity)
 15,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Butein, a natural chalcone, has anti-inflammatory and hepatoprotective activity. One synthetic derivative of butein, 2',4',6'-tris(methoxymethoxy)chalcone (TMMC), has potent anti-inflammatory activity via an HO-1 (heme oxygenase 1) dependent pathway. The alpha,beta-unsaturated ketone moiety in both TMMC and chalcones could be important in mediating this effect. To investigate the structural requirements of TMMC derivatives for anti-inflammatory effects, we modified the alpha,beta-unsaturated ketone moiety through catalytic hydrogenation, hydride reduction, or introduction of a triple bond. In addition, we performed structural modifications such as converting the -OMOM group to an -OMe or -OH group. Generally, modifications in the alpha,beta-unsaturated ketone caused a significant decrease or loss of anti-inflammatory activity, which is consistent with the role of the alpha,beta-unsaturated ketone group acting as a Michael acceptor of nucleophilic species like glutathione or cysteine residues on proteins. Chemically, the electron-donating substituents could make the thiol-adduct more stable by decreasing the acidity of the alpha-hydrogen and slowing the speed of the retro-Michael reaction. Also, like previous studies, the 2'-hydroxy group was crucial in increasing the anti-inflammatory effect. The 2'-hydroxy group produced potent anti-inflammatory effects by increasing the electrophilic properties of alpha,beta-unsaturated ketones due to hydrogen bonding between the 2'-hydroxy group and the ketone moiety.
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PMID:Structural requirements of 2',4',6'-tris(methoxymethoxy) chalcone derivatives for anti-inflammatory activity: the importance of a 2'-hydroxy moiety. 1808 1

Although its role and importance is less well studied, carbon monoxide (CO) has been identified as the second gasotransmitter in the GI tract. This study was performed to investigate the effect of modifying the endogenous CO production by altering heme oxygenase (HO) activity either by induction through hemin administration or inhibition by zinc mesoporphyrin administration on gastric secretion and ulceration induced by either cold restraint stress (CRS) or indomethacin (IND) treatment in adult male albino rats. Our results revealed that hemin significantly increased HO-1 levels with an increase in carboxyhemoglobin (COHb) level while zinc mesoporphyrin significantly decreased HO-1 levels with a decrease in COHb level in all groups. Hemin pretreatment significantly attenuated the gastric mucosal lesions induced by CRS and IND administration, which was accompanied by significant reduction in free and total acidity of gastric secretion, decreased proteolytic activity and marked attenuation of lipid peroxidation inspite of decreased NO and PGE2 levels. On the other hand, Inhibition of HO-1 activity by zinc mesoporphyrin prevented most of the effects caused by hemin administration except for its similar reduction in gastric mucosal NO and PGE2 levels. On conclusion, Hemin exerts a protective effect against CRS and IND-induced gastric ulcers possibly via inducing HO-1 and increasing endogenous production of CO (Tab. 2, Fig. 4, Ref. 75).
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PMID:The effect of induction of endogenous CO by heme-oxygenase inducer, hemin versus heme-oxygenase blocker, zinc mesoporphyrin on gastric secretion and ulceration under different conditions in adult male albino rats. 2502 20