Protective effects of coumarin and coumarin derivatives against carbon tetrachloride-induced acute hepatotoxicity in rats.
ABSTRACT The comparison of the antioxidant activity of some coumarins with their molecular structure is well determined. However, the protective function of coumarins with various chemical structures against liver toxicity has not yet been well established. Therefore, the aim of this study was to evaluate the possible cytoprotective properties of coumarin and some coumarin derivatives against CCl(4) (carbon tetrachloride)-induced hepatotoxicity. Coumarin (1,2-benzopyrone) and coumarin derivatives esculetin (6,7-dihydroxycoumarin), scoparone (6,7-dimethoxycoumarin) and 4-methylumbelliferone (7-hyroxy-4-methyl) were examined for their protective effect against CCl(4)-induced hepatotoxicity in Male Sprague-Dawley rats. A single toxic dose of CCl(4) (1.25 ml kg(-1), orally) produced liver damage in rats, seen histologically as centrilobular necrosis. Administration of CCl(4) increased serum enzyme levels of aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP). Pre-treatment of rats with esculetin (31.15 mg kg(-1), orally) and scoparone (35 mg kg(-1), orally) significantly prevented CCl(4)-induced increase in serum enzymes, whereas 4-methylumbelliferone (35 mg kg(-1)) and coumarin (30 mg kg(-1)) had no effect against CCl(4)-induced rise in serum enzymes. Morphological findings were consistent with the plasma transaminase observations. Among the coumarin analogs, esculetin, which possesses orthodihydroxy coumarins, showed the strongest protective effect against CCl(4)-induced liver damage, followed by scoparone, 4-methylumbelliferone and coumarin, respectively. The results of this study indicate that the chemical structures of coumarins play an important role in the prevention of liver toxicity.
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ABSTRACT: Leishmaniasis is a zoonotic disease that can manifest itself in visceral and cutaneous form. The aim of this study was to search for new leishmanicidal compounds. Preliminarily, Artemia salina assay was applied to compounds from two plants found in Northeastern Brazil, Platymiscium floribundum and Annona muricata. Then these compounds were tested against three Leishmania species (L. donovani, L. mexicana and L. major). A screening assay using luciferase-expressing promastigote form were used to measure the viability of promastigote One coumarin, scoparone, isolated from P. floribundum and two acetogenins, annonacinone and corossolone isolated from A. muricata showed leishmanicidal activity in all species tested. Nevertheless, Leishmania species indicated different susceptibilities in relation to the tested compounds: L. mexicana was more sensitive to scoparone followed by L. major and L. donovani. The three species presented similar inhibition to corossolone and annonacinone. Acetogenin annonacinone (EC(50)= 6.72 - 8.00 μg/mL) indicated high leishmanicidal activity; corossolone (EC(50)= 16.14 - 18.73 μg/mL) and scoparone (EC(50)= 9.11 - 27.51 μg/mL) moderate activity. A. saline larvae were less sensitive to the coumarin scoparone and acetogenin corossolone was the most toxic. In conclusion, the leishmanicidal activity demonstrated by the coumarin and acetogenins indicate these compounds for further studies aiming the development of new leishmanicidal agents.Experimental Parasitology 12/2012; · 2.15 Impact Factor
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ABSTRACT: The available conventional remedies for the treatment of drug-induced liver diseases are highly inadequate and possess serious adverse effects; therefore, the development of new, effective drugs is considered necessary. This article explores the hepatoprotective and antioxidant potential of 7-methylcoumarin (MC) and 7-methoxycoumarin (MOC) in CCl(4)-induced hepatotoxicity in rats. MC and MOC individually, at doses of 50 and 100 mg/kg body weight, were administered orally once-daily for 7 days. The hepatoprotective activity was assessed using various biochemical parameters, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum bilirubin (TB), total protein (TP), and albumin (TA). Serum antioxidant enzyme [e.g., superoxide dismutase (SOD) and catalase (CAT)] levels were determined. Also, thiobarbituric-acid-related substances (TBARS) levels, along with histopathological studies of liver tissue, were scrutinized. Pretreatment with MC and MOC significantly decreased ALT, AST, and TB in the serum of CCl(4)-induced liver damaged rats in a dose-dependent manner. TA and TP levels in the serum were also restored significantly in all presupplemented MC and MOC groups. In addition, oxidative stress induced by CCl(4) was prevented significantly; thereby, increasing SOD and CAT levels and decreasing TBARS levels in liver homogenates. Histopathological studies revealed the ameliorative natures of both the compounds. This study demonstrates the strong hepatoprotective activity of MC and MOC, which could be attributed to their potent antioxidant effects.Drug and Chemical Toxicology 11/2012; · 1.29 Impact Factor
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ABSTRACT: ABSTRACT This study was designed to investigate the potential of Physalis peruviana root as a functional food with hepato-renal protective effects against fibrosis. The chemical composition of the plant root suggested the presence of alkaloids, withanolides and flavonoids. Five compounds were isolated and their structures elucidated by different spectral analysis techniques. One compound was isolated from the roots: cuscohygrine. The biological evaluation was conducted on different animal groups; control rats, control treated with ethanolic root extract, CCl(4) group, CCl(4) treated with root extract, and CCl(4) treated with silymarin as a standard herbal drug. The evaluation used the oxidative stress markers malondialdehyde (MDA), superoxide dismutase (SOD), and nitric oxide (NO). The liver function indices; aspartate and alanine aminotransferases (AST & ALT), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), bilirubin, and total hepatic protein were also estimated. Kidney disorder biomarkers; creatinine, urea, and serum protein were also evaluated. The results suggested safe administration, and improvement of all the investigated parameters. The liver and kidney histopathological analysis confirmed the results. In conclusion, P. peruviana succeeded in protecting the liver and kidney against fibrosis. Further studies are needed to discern their pharmacological applications and clinical uses.Journal of Dietary Supplements 03/2013; 10(1):39-53.