Hepatoprotective constituents of the edible brown alga Ecklonia stolonifera on tacrine-induced cytotoxicity in Hep G2 cells.
ABSTRACT In this study, ethanolic extracts from 18 seaweed variants were assessed for hepatoprotective activity against tacrine-induced cytotoxicity in Hep G2 cells. Only one of these, Ecklonia stolonifera Okamura (Laminariaceae), a member of the brown algae, exhibited promising hepatoprotective activity. Bioassay-guided fractionation of the active ethyl acetate (EtOAc) soluble fraction obtained from the ethanolic extract of E. stolonifera, resulted in the isolation of several phlorotannins [phloroglucinol (1), eckstolonol (2), eckol (3), phlorofucofuroeckol A (4), and dieckol (5)]. Compounds 2 and 4 were determined to protect Hep G2 cells against the cytotoxic effects of tacrine, with EC50 values of 62.0 and 79.2 microg/mL, respectively. Silybin, a well characterized hepatoprotective agent, was used as a positive control, and exhibited an EC50 value of 50.0 microg/mL. It has been suggested that the phlorotannins derived from marine brown algae might prove useful sources in the development of novel hepatoprotective agents.
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ABSTRACT: In the course of searching for hepatoprotective agents from natural products, six compounds were isolated from the MeOH extract of the leaves of Juglans sinensis, as guided by their DPPH free radical scavenging activity. The structures were determined as juglanoside B (1), quercetin 3-O-alpha-L-arabinofuranoside (avicularin, 2), quercetin 3-O-alpha-L-arabinopyranoside (guaijaverin, 3), quercetin 3-O-alpha-L-rhamnopyranoside (quercitrin, 4), (+)-catechin (5) and quercetin 3-O-beta-D-galactopyranoside (hyperin, 6). Compounds 2-6 showed significant DPPH free radical scavenging effects. An evaluation for the hepatoprotective activity of the isolated compounds on drug-induced cytotoxicity was conducted, and compounds 1, 2, and 5 showed protective effects against nitrofurantoin-induced cytotoxicity, and compound 5 also exhibited a moderate protective effect on amiodarone-induced cytotoxicity in Hep G2 cells.Archives of Pharmacal Research 06/2005; 28(5):529-33. · 1.54 Impact Factor
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ABSTRACT: Eckol (1), a novel phlorotannin with a dibenzo-1,4-dioxin skeleton, has been isolated from the brown alga Ecklonia kurome Okamura as a potent and specific anti-plasmin inhibitor. Its structure has been elucidated based on the spectral data, in particular, by means of negative nuclear Overhauser effect (NOE), and finally established as 1-(3,5-dihydroxyphenoxy)-2,4,7,9-tetrahydroxydibenzo-1,4-dio xin by X-ray analysis. Some partially methoxylated derivatives of eckol were prepared by methylation with diazomethane and also by selective dimethylation of eckol permethylate (1b) to establish the structural requirements for inhibitory activities on alpha 2-macroglobulin and alpha 2-plasmin inhibitor, the main plasmin inhibitors in plasma.CHEMICAL & PHARMACEUTICAL BULLETIN 03/1989; 37(2):349-53. · 1.56 Impact Factor
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ABSTRACT: To characterize the hepatic effects of tacrine treatment in patients with Alzheimer's disease. Controlled trials of tacrine therapy consisting of two blinded, parallel-group trials; three blinded, enrichment-design trials; and their respective open-label extensions. Multicenter clinical trials in the United States, France, and Canada. A total of 2446 men and women at least 50 years of age with a diagnosis of probable Alzheimer's disease of mild to moderate severity and in good health without significant hepatic, cardiovascular, or renal disease. Administration of tacrine vs placebo, with weekly measurement of serum hepatic enzymes. Incidence, maximum severity, and timing of event for serum alanine aminotransferase (ALT) elevation. Among the 2446 patients who received tacrine in clinical trials, ALT levels greater than the upper limit of normal (ULN) occurred on at least one occasion in 1203 patients (49%), ALT levels greater than three times the ULN occurred in 621 patients (25%), and ALT levels greater than 20 times the ULN occurred in 40 patients (2%). The elevated ALT levels were generally asymptomatic and occurred more frequently in women than men. The mean time from initiation of tacrine treatment to first ALT level greater than three times the ULN was 50 days, and 90% of all initial ALT levels greater than three times the ULN occurred during the first 12 weeks of treatment. Of 145 patients who discontinued tacrine treatment because of an ALT level greater than three times the ULN and were rechallenged, 127 (88%) were able to resume long-term therapy with the drug. In all instances, discontinuing tacrine completely reversed elevations in ALT levels, and no deaths related to hepatotoxicity occurred. These data suggest that the potential for serious hepatic toxicity can be reduced through careful monitoring of ALT levels in patients who may benefit from tacrine therapy.JAMA The Journal of the American Medical Association 05/1994; 271(13):992-8. · 29.98 Impact Factor