RESUMO
BACKGROUND AND PURPOSE: Paracetamol is the most implicated xenobiotic in inducing hepatotoxicity. Our study aimed to determine the impact of some kaempferol glycosides isolated from the leaves of Cedrela odorata L. on paracetamol hepatotoxicity. EXPERIMENTAL APPROACH: The methanolic extract of dried leaves of C. odorata L. was subjected to the combination of spectroscopic methods (1H and 13CNMR). Six kaempferol glycosides were isolated: kaempferol-3-O-ß-D-glycopyranoside (astragalin), kaempferol-3-O-ß-L-rhamnopyranoside, kaempferol-3-O-ß-D-rutinoside, kaempferide-3-O-ß-D-rutinoside, kaempferide-3-O-ß-Drutinosyl-7-O-ß-D-rhamnopyranoside, and kaempferol-3-O-ß-D- rutinosyl-7-O-a-D-arabinopyranoside. Fifty-four female Swiss Albino mice were divided randomly into 9 groups including (1) control negative (1 mL/kg saline; IP), (2) control positive (paracetamol 300 mg/kg; IP), (3) silymarin 50 mg/kg (IP). Animals of groups 4-9 were injected with 6 different samples of isolated compounds at 100 mg/kg (IP). One h later, groups 3-9 were injected with paracetamol (300 mg/kg IP). Two h later, tissue samples were taken from all animals to assess nitrotyrosine, c-Jun N-terminal protein kinase (c-JNK), Raf -1kinase, and oxidative stress biomarkers viz. reduced glutathione (GSH) and malondialdehyde (MDA). FINDINGS/RESULTS: Isolated glycosides had a prominent anti-apoptotic effect via inhibition of c-JNK and Raf-1 kinase. They also exerted a powerful antioxidant effect by modulating the oxidative stress induced by paracetamol via increasing GSH, reducing MDA and nitrotyrosine concentrations compared to positive control. The glycoside (1) showed a better effect than silymarin (standard) in ameliorating the formation of nitrotyrosine, Raf-1 kinase, c-JNK, and GSH. CONCLUSION AND IMPLICATION: Kaempferol glycosides isolated for the first time from C. odorata L. leaves exerted antioxidant and antiapoptotic effects via amelioration of oxidative stress and inhibition of Raf/MAPK pathway.
RESUMO
Despite the traditional use of Solidago canadensis L. (Asteraceae) as a diuretic drug, there is a scarcity in scientific data concerning the activity of its different extracts and fractions as well as the class of constituents responsible for this diuretic action. A comparative study was carried out for the diuretic activities of the different standardized extracts and fractions of the flowering aerial parts of S. canadensis, as well as isolation of compounds from the most biologically active fraction. The ethanol extract and its ethyl acetate fraction (EA) showed the highest aquaretic activities (91 and 58% at a dose of 400 mg/Kg b.wt., respectively) compared to 100% of furosemide at 20 mg/Kg b.wt.. Their activities were higher than Cystinol® and spironolactone reference standards (74% and 59% of furosemide, respectively). EA showed the highest total phenolic and flavonoid contents among the tested fractions of the ethanol and aqueous extracts (9.38 ± 0.004 g GAE and 39.75 ± 0.005 g RE/100 g dried extract, respectively). Eight flavonoids, 2 phenolic acids and 1 nucleoside were isolated from EA. This is the first report of a comparative study between the aquaretic activities of the different extracts, fractions and essential oil of S. canadensis, as well as isolation of thyimidine (1), isorhamnetin-3-O-ß-á´ -glucopyranoside (2), kaempferol-3-O-(6"-O-acetyl)-ß-á´ -glucopyranoside (4), quercetin-3-O-(6"-O-acetyl)-ß-á´ -glucopyranoside (5), and kaempferol-3-O-ß-á´ -apiofuranoside (7) from genus Solidago.
