Effect of Laggera alata on hepatocyte damage induced by carbon tetrachloride in vitro and in vivo.
ABSTRACT Laggera alata, as a traditional Chinese herbal medicine, has been widely used to ameliorate some ailments associated with inflammation including hepatitis in folk.
Based on anti-inflammatory activity of total phenolics from Laggera alata (TPLA), to further validate the remarkable curative effect Laggera alata in hepatitis, hepatoprotective effect of TPLA was examined.
TPLA was prepared and its principle components were quantificationally analyzed. The hepatoprotective effects of TPLA were studied using a CCl(4)-induced injury model in primary cultured neonatal rat hepatocytes, and a CCl(4)-induced acute and chronic damage model in vivo.
TPLA significantly reduced cellular leakage of hepatocyte aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and improved cell viability in vitro. TPLA markedly decreased the serum AST and ALT levels of the mice, the levels of AST, ALT, total protein, albumin, and sialic acid in rat serum, and the hydroxyproline level in rat liver. Meanwhile, severe hepatic lesions induced by CCl(4) in mice/rats were remarkably improved by the administration of TPLA.
This investigation verifies the hepatoprotective effect of TPLA in vitro/in vivo and clarifies its active components dicaffeoylquinic acids responsible for hepatoprotective potential.
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ABSTRACT: The hepatoprotective activities of total flavonoids of Laggera alata (TFLA) were evaluated by carbon tetrachloride (CCl(4))-induced injury in primary cultured neonatal rat hepatocytes and in rats with hepatic damage. In vitro, TFLA at a concentration range of 1-100 microg/ml improved cell viability and inhibited cellular leakage of two enzymes, hepatocyte aspartate aminotransferase (AST) and alanine aminotransferase (ALT), caused by CCl(4). In vivo, oral treatment with TFLA at doses of 50, 100, and 200 mg/kg significantly reduced the levels of AST, ALT, total protein, and albumin in serum and the hydroxyproline and sialic acid levels in liver. Histopathological examinations revealed that liver damage were improved when treated with TFLA. Meanwhile, 1,1-diphenyl-2-picrylhydrazyl (DPPH) and superoxide radicals scavenging activities of TFLA were also determinated. To understand the exact components of TFLA responsible for the hepatoprotective effect, nine flavonoid compounds were isolated and identified from TFLA. In conclusion, the present investigation was the first to verify the hepatoprotective effect of L. alata in vitro and in vivo. The hepatoprotective action of TFLA is likely related to its potent antioxidative and anti-inflammatory activity. Neutralizing reactive oxygen species by nonenzymatic mechanisms and enhancing the activity of original natural hepatic-antioxidant enzymes may be the main mechanisms of TFLA against CCl(4)-induced injury.Journal of Biomedical Science 08/2006; 13(4):569-78. · 2.46 Impact Factor
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ABSTRACT: Current pharmacological agents for human immunodeficiency virus (HIV) infection include drugs targeted against HIV reverse transcriptase and HIV protease. An understudied therapeutic target is HIV integrase, an essential enzyme that mediates integration of the HIV genome into the host chromosome. The dicaffeoylquinic acids (DCQAs) and the dicaffeoyltartaric acids (DCTAs) have potent activity against HIV integrase in vitro and prevent HIV replication in tissue culture. However, their specificity against HIV integrase in cell culture has been questioned. Thus, the ability of the DCQAs and DCTAs to inhibit binding of HIV type 1 (HIV-1) gp120 to CD4 and their activities against HIV-1 reverse transcriptase and HIV RNase H were studied. The DCQAs and DCTAs inhibited HIV-1 integrase at concentrations between 150 and 840 nM. They inhibited HIV replication at concentrations between 2 and 12 microM. Their activity against reverse transcriptase ranged from 7 microM to greater than 100 microM. Concentrations that inhibited gp120 binding to CD4 exceeded 80 microM. None of the compounds blocked HIV-1 RNase H by 50% at concentrations exceeding 80 microM. Furthermore, when the effects of the DCTAs on reverse transcription in acutely infected cells were measured, they were found to have no activity. Therefore, the DCQAs and DCTAs exhibit > 10- to > 100-fold specificity for HIV integrase, and their activity against integrase in biochemical assays is consistent with their observed anti-HIV activity in tissue culture. Thus, the DCQAs and DCTAs are a potentially important class of HIV inhibitors that act at a site distinct from that of current HIV therapeutic agents.Antimicrobial Agents and Chemotherapy 01/1998; 42(1):140-6. · 4.57 Impact Factor
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ABSTRACT: Three new eudesmane sesquiterpenes, 5 beta-hydroxyilicic acid (1), 5 alpha-hydroxyl-4-epi-ilicic acid methyl ester (2), and 3 alpha-hydroxyilicic acid (3), together with 12 known sesquiterpenes were isolated from the aerial part of Laggera alata. Their structures were elucidated primarily by NMR and mass spectroscopic methods. The structures of 1 and 2 were confirmed by X-ray crystallography.Journal of Natural Products 09/2003; 66(8):1078-81. · 3.29 Impact Factor