Protection by and Anti‐oxidant Mechanism of Berberine Against Rat Liver Fibrosis Induced by Multiple Hepatotoxic Factors

Abstract

1. The aim of the present study was to investigate the effect and mechanism of berberine, an alkaloid extracted from the traditional Chinese medicine coptis, on rat liver fibrosis induced by multiple hepatotoxic factors. 2. Male Wistar rats were separated into five groups, a normal control group, a fibrotic control group and fibrotic groups treated with three different doses of berberine. The fibrotic models were established by introduction of multiple hepatotoxic factors, including CCl(4), ethanol and high cholesterol. Rats in the treatment groups were administered 50, 100 or 200 mg/kg berberine, intragastrically, daily for 4 weeks. Serum levels of alanine aminotransferase (ALT) and serum aspartate aminotransferase (AST), hepatic activity of superoxide dismutase (SOD) and hepatic malondialdehyde (MDA) and hepatic hydroxyproline (Hyp) content were determined. Liver biopsies were obtained for histological and immunohistochemical studies to detect the expressions of alpha-smooth muscle actin (SMA) and transforming growth factor (TGF)-beta1. 3. The results showed that, compared with the fibrotic control group, serum levels of ALT and AST and hepatic content of MDA and Hyp were markedly decreased, but the activity of hepatic SOD was significantly increased in berberine-treated groups in a dose-dependent manner. In addition, histopathological changes, such as steatosis, necrosis and myofibroblast proliferation, were reduced and the expression of a-SMA and TGF-b1 was significantly downregulated in the berberine-treated groups (P < 0.01). 4. These results suggest that berberine could be used to prevent experimental liver fibrosis through regulation of the anti-oxidant system and lipid peroxidation.

Berberine Ameliorates Intestinal Mucosal Barrier Damage Induced by Peritoneal Air Exposure

“…2,3) Many studies have shown that BBR exhibits multiple pharmacological activities including antioxidant, anti-microbial, anti-tumor, and cholesterol-lowering effects. [4][5][6][7] Our previous studies found that BBR could reinforce the intestinal epithelial tight junction and reduce epithelial intestinal permeability in vitro and in vivo, which is important to maintain the intestinal mucosal barrier function. [8][9][10] Therefore, in order to further explore the protective effect of BBR on the intestinal mucosal barrier damage induced by peritoneal air exposure, it is important to determinate the changes in the intestinal mucosa barrier function during peritoneal air exposure under experimental conditions mimicking clinical operation room atmosphere.…”

Isolation and Identification of Urinary Metabolites of Berberine in Rats and Humans

“…Its chemical structure is 5,8-dihydro-9,10-dimethoxy-6H-benzo(g)-1,3-benzodioxolo(5,6-a)quinolizine. Berberine exhibits a wide variety of bioactivities such as antidiarrheic (Sack and Froehlich, 1982;Taylor and Greenough, 1989), antimicrobial (Yan et al, 2008), hypolipidemic (Kong et al, 2004;Doggrell, 2005;Brusq et al, 2006;Cicero et al, 2007), hypoglycemic (Yin et al, 2002;Pan et al, 2003;Zhou et al, 2007;Turner et al, 2008;Yin et al, 2008), antiarrhythmic (Wang et al, 1994;Lau et al, 2001), anticancer (Inoue et al, 2005;Lanvers-Kaminsky et al, 2006;Lin et al, 2006Lin et al, , 2007Piyanuch et al, 2007;Serafim et al, 2008;Yu et al, 2007), anti-inflammatory (Kuo et al, 2004Lee et al, 2007), antiviral (Hayashi et al, 2007), antidepressant (Kulkarni and Dhir, 2007), and hepatoprotective (Zhang et al, 2008) effects. Its chloride salt has been used for several decades in clinical situations to treat gastroenteritis and secretory diarrhea in China.…”

Plant derived antioxidants and antifibrotic drugs: past, present and future

“…Studies have clearly demonstrated that berberine exerted anti-fibrotic effects possibly through activation of AMP-activated protein kinase, blocking NADPH oxidase 4 and Akt expression and reduction in the expression of α-SMA [51]. The effect of berberine on rat liver fibrosis induced by multiple hepatotoxic factors, including CCl 4 , ethanol, and high cholesterol, demonstrated that berberine could prevent experimental liver fibrosis by regulating the anti-oxidant system and lipid peroxidation [52] .…”

“…Moreover, berberine dramatically decreased the number of activated HSCs, the amount of fibrotic septa, and the content of hepatic collagen prevents CCl 4 induced experimental liver fibrosis. Berberine treatment also caused the decrease in the secreation of TGF-β1 and inhibits HSC activation [52] . Further clinical investigations would be necessary to determine whether berberine could be effective for the prevention of liver fibrosis in humans.…”