Antioxidant and Mitochondria-Targeted Activity of Caffeoylquinic-Acid-Rich Fractions of Wormwood (Artemisia absinthium L.) and Silver Wormwood (Artemisia ludoviciana Nutt.)

Caffeoylquinic acids are some of the chemophenetically significant specialized metabolites found in plants of the family Asteraceae Dumort., possessing a broad spectrum of biological activities. As they might be potential mitochondria-targeted antioxidants, effective preparation methods - including extraction, isolation, and purification of caffeoylquinic acids from plant sources - are in great demand. The aim of this study was to fractionate the caffeoylquinic acids from cultivated wormwood (Artemisia absinthium L.) and silver wormwood (Artemisia ludoviciana Nutt.) herb acetone extracts and evaluate their phytochemical profiles, antioxidant activity (radical scavenging and re- ducing activities), effects on kidney mitochondrial functions, and cytochrome-c-reducing properties. The main findings of our study are as follows: (1) Aqueous fractions purified from wormwood and silver wormwood herb acetone extracts are rich in monocaffeoylquinic acids (chlorogenic acid, neochlorogenic acid, 4-O-caffeoylquinic acid), while methanolic fractions purified from wormwood and silver wormwood herb acetone extracts are rich in dicaffeoylquinic acids (4,5-dicaffeoylquinic acid, 3,4-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid). Aqueous fractions purified from worm- wood and silver wormwood herb acetone extracts were solely composed of monocaffeoylquinic acids. Methanolic fractions purified from wormwood and silver wormwood herb acetone extracts con- tained only dicaffeoylquinic acids. (2) Fractions purified from silver wormwood herb acetone extracts stood out as having the greatest content of caffeoylquinic acids. (3) The greatest radical scavenging activity was determined in the dicaffeoylquinic-acid-rich fraction purified from silver wormwood herb acetone extract; the greatest reducing activity was determined in the dicaffeoylquinic-acid- rich fraction purified from wormwood herb acetone extract. (4) The effect of both fractions on mitochondrial functions was dose-dependent; lower concentrations of caffeoylquinic-acid-rich frac- tions had no effect on mitochondrial functions, whereas higher concentrations of caffeoylquinic- acid-rich fractions reduced the state 3 respiration rate (with the complex-I-dependent substrate glutamate/malate). (5) Both monocaffeoylquinic- and dicaffeoylquinic-acid-rich fractions possessed cytochrome-c-reducing properties; the greatest cytochrome c reduction properties were determined in the dicaffeoylquinic-acid-rich fraction purified from wormwood herb acetone extract. In sum- mary, these findings show that caffeoylquinic acids might be beneficial as promising antioxidant and cytochrome-c-reducing agents for the modulation of mitochondria and treatment of various mitochondrial-pathway-associated pathologies

Caffeic Acid Phenethyl Ester Reduces Ischemia-Induced Kidney Mitochondrial Injury in Rats

During partial nephrectomy, the avoidance of ischemic renal damage is extremely important as duration of renal artery clamping (i.e., ischemia) influences postoperative kidney function. Mitochondria (main producer of ATP in the cell) are very sensitive to ischemia and undergo damage during oxidative stress. Finding of a compound which diminishes ischemic injury to kidney is of great importance. Caffeic acid phenethyl ester (CAPE), biologically active compound of propolis, might be one of the promising therapeutic agents against ischemia-caused damage. Despite wide range of biological activities of CAPE, detailed biochemical mechanisms of its action at the level of mitochondria during ischemia are poorly described and need to be investigated. We investigated if CAPE (22 mg/kg and 34 mg/kg, injected intraperitoneally) has protective effects against short (20 min) and longer time (40 min) rat kidney ischemia in an in vitro ischemia model. CAPE ameliorates in part ischemia-induced renal mitochondrial injury, improves oxidative phosphorylation with complex I-dependent substrate glutamate/malate, increases Ca2+ uptake by mitochondria, blocks ischemia-induced caspase-3 activation, and protects kidney cells from ischemia-induced necrosis. The protective effects on mitochondrial respiration rates were seen after shorter (20 min) time of ischemia whereas reduction of apotosis and necrosis and increase in Ca2+ uptake were revealed after both, shorter and longer time of ischemia