Hepatoprotective effect of Cichorium intybus L., a traditional Uighur medicine, against carbon tetrachloride-induced hepatic fibrosis in rats

Abstract

Aim: To investigate the hepatoprotective effect of a Cichorium intybus L. extract (CIE) on CCl4-induced hepatic fibrosis in rats.

Methods: Seventy-two male Wistar albino rats were randomly divided into six groups of twelve rats each. The normal control group was allowed free access to food and water. Liver injury was performed in the remaining five groups with an i.p. injection of a 1.0 mL/kg CCl4 and olive oil (2:3 v/v) mixture, twice weekly for 8 weeks. All rats, with the exception of the injury model group, were intragastrically (i.g.,) administered quantum satis (q.s.) dosages [CIE group: 6, 18, and 54 mg/kg, respectively; Fu Fang Bie Jia Ruan Gan Pian (FFBJRGP) group: 780 mg/kg]. The oral administration of different drugs was performed on the day before CCl4 administration and subsequently once per day for 8 wk. The serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), hexadecenoic acid (HA), laminin (LN), hydroxyproline (Hyp), and glutathione (GSH), malondialdehyde (MDA) and superoxide dismutase (SOD) in the rat livers were measured. Histopathological changes in the liver were assessed for each group using HE staining and a Masson Trichrome examination. The expression of transforming growth factor-β1 (TGF-β1) and α-smooth muscle actin (α-SMA) was examined by immunohistochemical analysis.

Results: CIE at oral doses of 6, 18, and 54 g/kg per day showed a significant hepatoprotective effect, especially at a dose of 54 g/kg per day. CIE doses reduced the levels of AST (149.04 ± 34.44, P < 0.01), ALT (100.72 ± 27.19, P < 0.01), HA (548.50 ± 65.09, P < 0.01), LN (28.69 ± 3.32, P < 0.01) and Hyp (263.33 ± 75.82, P < 0.01). With regards to hepatoprotective activity, the CIE dose of 54 g/kg per day produced the largest significant effect by increasing GSH (3.11 ± 0.81), SOD (269.98 ± 33.77, P < 0.01) and reducing MDA (2.76 ± 0.51, P < 0.01) levels in the liver. The expressions of TGF-β1 and α-SMA were measured by immunohistology and found to be significantly reduced by CIE in a dose-dependent manner.

Conclusion: CIE may effectively protect against CCl4-induced hepatic fibrosis in rats; thus, it is a promising anti-fibrotic therapeutic agent.

Keywords: Carbon tetrachloride; Cichorium intybus L. extract; Hepatic fibrosis; Traditional Uighur medicine.

Figure 1

Liver morphology. A: Normal group; B: CCl₄-treated group; C: Positive-drug + CCl₄; D: 6 g/kg CIE + CCl₄; E: 18 g/kg CIE + CCl₄; F: 54 g/kg CIE + CCl₄. CIE: Cichorium intybus L. extract.

Figure 2

Hematoxylin-eosin (original magnification × 100) of liver sections in rats. A: Normal group; B: CCl₄-treated group; C: Positive-drug + CCl₄; D: 6 g/kg CIE + CCl₄; E: 18 g/kg CIE + CCl₄; F: 54 g/kg CIE + CCl₄. CIE: Cichorium intybus L. extract.

Figure 3

Masson Trichrome examinations (original magnification × 40) of liver sections in rats. A: Normal group; B: CCl₄-treated group; C: Positive-drug + CCl₄; D): 6 g/kg CIE + CCl₄; E: 18 g/kg CIE + CCl₄; F: 54 g/kg CIE + CCl₄. CIE: Cichorium intybus L. extract.

Figure 4

Immunohistochemical examination of transforming growth factor-β1 positive cells (original magnification × 200) of liver sections in rats. A: Normal group; B: CCl₄-treated group; C: Positive-drug + CCl₄; D: 6 g/kg CIE + CCl₄; E: 18 g/kg CIE + CCl₄; F: 54 g/kg CIE + CCl₄. CIE: Cichorium intybus L. extract.

Figure 5

Immunohistochemical examination of α-smooth muscle actin positive cells (original magnification × 200) of liver sections in rats. A: Normal group; B: CCl₄-treated group; C: Positive-drug + CCl₄; D: 6 g/kg CIE + CCl₄; E: 18 g/kg CIE + CCl₄; F: 54 g/kg CIE + CCl₄. CIE: Cichorium intybus L. extract.