Effect of Laggera alata on hepatocyte damage induced by carbon tetrachloride in vitro and in vivo

Department of Pharmacy, College of Life Sciences, China Jiliang University, Xiasha Higher Education Zone, Hangzhou, China.
Journal of ethnopharmacology (Impact Factor: 3). 09/2009; 126(1):50-6. DOI: 10.1016/j.jep.2009.08.030
Source: PubMed


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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    • "Different concentrations of the test compound were applied to the culture wells in triplicate. After the cells were incubated for 8 days, the MTT assay was carried out as described previously [11]. To measure the effect of 3,4-O-dicaffeoylquinic acid on the expression of HBV antigens and HBV DNA, HepG2.2.15 cells were treated with various concentrations of the test compound in the 96-well plates. "
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    ABSTRACT: The anti-hepatitis B activity of 3,4-O-dicaffeoylquinic acid isolated from Laggera alata was studied using the D-galactosamine- (D-GalN-) induced hepatocyte damage model, HepG2.2.15 cells, and with HBV transgenic mice. In vitro results showed that 3,4-O-dicaffeoylquinic acid improved HL-7702 hepatocyte viability and markedly inhibited the production of HBsAg and HBeAg. At a concentration of 100 μg/mL, its inhibitory rates on the expression levels of HBsAg and HBeAg were 89.96% and 81.01%, respectively. The content of hepatitis B virus covalently closed circular DNA (HBV cccDNA) in HepG2.2.15 cells was significantly decreased after the cells were treated with the test compound. In addition, 3,4-O-dicaffeoylquinic acid significantly increased the expression of heme oxygenase-1 (HO-1) in HepG2.2.15 cells. In vivo results indicated that the test compound at concentrations of 100 μg/mL significantly inhibited HBsAg production and increased HO-1 expression in HBV transgenic mice. In conclusion, this study verifies the anti-hepatitis B activity of 3,4-O-dicaffeoylquinic acid. The upregulation of HO-1 may contribute to the anti-HBV effect of this compound by reducing the stability of the HBV core protein, which blocks the refill of nuclear HBV cccDNA. Furthermore, the hepatoprotective effect of this compound may be mediated through its antioxidative/anti-inflammatory properties and by the induction of HO-1 expression.
    Full-text · Article · Jun 2012 · Evidence-based Complementary and Alternative Medicine
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    • "According to the results, Flx caused a slightly decrease in the ALT and AST activities and slightly increased the levels of ALP activity in both sexes in comparison to those of respective control groups. The increased levels of AST and ALT, the decreased level of TP and ALB, and the decrease in A/G ratios are classical indicators of liver damage in the whole animal model (Wu et al. 2009 "
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    ABSTRACT: Gender-related changes in plasma chemistry values were examined in guinea pigs after taking oral fluoxetine hydrochloride (HCl) as a widely prescribed drug for weight reduction and treatment of depressive disorders. Twenty guinea pigs of both sexes were divided into four groups of five animals. For both of the sexes, one group was treated with oral fluoxetine HCl (20 mg/kg/day) and another was used as a control which administered with distilled water. On the last day of the experiment (35th day), blood samples were collected for determining selected plasma biochemical parameters. For lipid profile, increases in high-density lipoprotein cholesterol, very low-density lipoprotein-cholesterol, and triglycerides were seen in both sexes, along with increases in total cholesterol and low-density lipoprotein cholesterol (LDL-C) in males and decreases of LDL-C in females and atherogenic index in both sexes. The levels of total protein, globulins, urea, and creatinine were increased only in the male guinea pigs that received fluoxetine. Although, the levels of creatine phosphokinase and alanine transaminase decreased in the fluoxetine-treated female guinea pigs compared to control. Other parameters like lactate dehydrogenase, alkaline phosphatase, aspartate transaminase, albumin, total bilirubin, (in)direct bilirubin, fasting blood sugar, calcium, and phosphorus did not alter following intake of fluoxetine in both sexes. For hormonal profile, testosterone and tetraiodothyronine (T4) in males and T3 and thyroid-stimulating hormone in both sexes did not change in fluoxetine-treated guinea pigs. However, the level of T4 decreased in fluoxetine-treated female group compared with the control group. Fluoxetine treatment resulted in gender-dependent effects. The decrease of T4 in female guinea pigs that received fluoxetine supports that this drug would be a possible endocrine disruptor.
    Full-text · Article · Dec 2011 · Comparative Clinical Pathology
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    ABSTRACT: The immune factors were the main reasons of hepatic damage in hepatitis. To validate the beneficial effects of Laggera alata on hepatitis in humans, regulatory properties of L. alata extract (LAE) was studied using a Bacillus Calmette-Guerin-Lipopolysaccharide (BCG-LPS) induced immune liver injury model in mice. Quantificational analysis of LAE indicated that isochlorogenic acids were the major components in the extract whose content amounted to 51%. LAE reduced the serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and nitric oxide (NO) levels of the mice, also decreased the malondialdehyde (MDA) level in mouse liver, and increased the levels of total protein and glutathione peroxidase (GSH-PX) in mouse liver. Meanwhile, resulted in significant recovery of immune-mediated hepatocyte injury in the liver sections. The study suggests that the regulatory properties of LAE may be achieved by ameliorating oxidative stress from BCG-LPS-induced immune liver injury or by preventing tissue damage as a result in inflammation. Isochlorogenic acids may be its substance basis responsible for the regulatory potential. Additional, flavonol components may also play important role in the pharmacological activity of L. alata.
    Preview · Article · Jun 2011 · Journal of medicinal plant research
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