Journal of Ethnopharmacology 103 (2006) 154–159
Effects and mechanisms of crude astragalosides fraction
on liver fibrosis in rats
Shuang-Ying Gui
a,b
, Wei Wei
a,∗
, Hua Wang
a
, Li Wu
a
, Wu-Yi Sun
a
,
Wen-bi Chen
a
, Cheng-Yi Wu
a
a
Institute of Clinical Pharmacology, Key Laboratory of Anti-inflammatory and Immunopharmacology in Anhui Province,
Key Laboratory of Chinese Medicine Research and Development in Anhui Province,
Anhui Medical University, Anhui Province, Hefei 230032, PR China
b
Anhui College of Traditional Chinese Medicine, Hefei 230031, PR China
Received 7 April 2005; received in revised form 8 July 2005; accepted 22 July 2005
Available online 29 September 2005
Abstract
Astragalosides is the major active constituent of Radix Astragali. The present study was carried out to investigate the effect of crude astragalosides
fraction (CAF) on rats liver fibrosis and its possible mechanisms. Hepatic fibrosis was induced by subcutaneous injection with 50% CCl
4
in
Sprague–Dawley rats. The amount of CCl
4
administered was 1 mg kg
-1
. The alanine aminotransferase (ALT), aspartate aminotransferase (AST)
levels in plasma and hydroxyproline (Hyp), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) contents
in liver tissue were assayed by spectrophotometry. The hyaluronic acid (HA) and procollagen III (PC III) were assessed by radioimmunoassay. Tumor
necrosis factor- (TNF-) and transforming growth factor-1 (TGF-1) levels in culture supernatants of Kupffer cells (KCs) were determined with
ELISA. Liver samples collected after 8 weeks of CCl
4
treatment were stained with hematoxylin–eosin (HE) and massion, and scored. Intragastric
administration of CAF (10, 20 and 40 mg kg
-1
) significantly decreased indices of liver and spleen, the serum transaminase activities, HA and PC III
levels, and Hyp and MDA contents in liver tissue in rats of hepatic fibrosis. Decreased SOD and GSH-px levels were reversed after administration
of CAF. Histopathological scores showed CAF had inhibitory effect on the progression of hepatic fibrosis. In the in vitro experiments, CAF
significantly reduced TNF- and TGF-1 levels in culture supernatants of KCs. The results showed CAF significantly inhibited the progression of
hepatic fibrosis induced by CCl
4
, and the inhibitory effect of CAF on hepatic fibrosis might be associated with its ability to scavenge free radical
and inhibit the production of TNF- and TGF-1 from activated KCs.
© 2005 Elsevier Ireland Ltd. All rights reserved.
Keywords: Crude astragalosides fraction; Radix Astragali; Liver fibrosis; Free radicals; Tumor necrosis factor-; Transforming growth factor-1
1. Introduction
Hepatic fibrosis is a dynamic process caused by chronic
liver injury due to various etiologies (viral infections, alcohol
abuse, and metal overload), eventually leading to cirrhosis. It
is predominantly characterized by excessive accumulation of
extracellular matrix (ECM) caused by both an increased syn-
thesis and decreased or unbalanced degradation of ECM. The
accumulation of ECM proteins distorts the hepatic architecture
by forming a fibrous scar, and the subsequent development of
nodules of regenerating hepatocytes defines cirrhosis. Cirrhosis
∗
Corresponding author. Tel.: +86 551 5161208; fax: +86 551 5161208.
E-mail address: wwei@ahmu.edu.cn (W. Wei).
produces hepatocellular dysfunction and increased intrahepatic
resistance to blood flow, which result in hepatic insufficiency
and portal hypertension, respectively (Gines et al., 2004). There
is no standard treatment for liver fibrosis. Although there are a
few anti-inflammatory and anti-fibrotic drugs showing effective-
ness on treating hepatic fibrosis, their side effects and toxicity
call for new and more effective natural drugs.
Radix Astragali (root of Astragalus; Huangqi) is a popular
traditional Chinese medicine, and Astragalus membranaceus
and Astragalus membranaceus var. mongolicus are two com-
monly used species. Astragalosides, extracted from the root of
Astragalus membranaceus, is the active compound, in addition
to astragalus polysaccharides. Investigations revealed that Radix
Astragali has protecting liver lesion and anti-fibrotic properties
(Cheng et al., 2000; Zhang et al., 1992). In vitro, Radix Astra-
0378-8741/$ – see front matter © 2005 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.jep.2005.07.025