Protective effects of Centella asiatica leaf extract on dimethylnitrosamine‑induced liver injury in rats

Abstract

Oxidative stress in liver injury is a major pathogenetic factor in the progression of liver damage. Centella asiatica (L.) Urban, known in the United States as Gotu kola, is widely used as a traditional herbal medicine in Chinese or Indian Pennywort. The efficacy of Centella asiatica is comprehensive and is used as an anti‑inflammatory agent, for memory improvement, for its antitumor activity and for treatment of gastric ulcers. The present study investigated the protective effects of Centella asiatica on dimethylnitrosamine (DMN)‑induced liver injury in rats. The rats in the treatment groups were treated with Centella asiatica at either 100 or 200 mg/kg in distilled water (D.W) or with silymarin (200 mg/kg in D.W) by oral administration for 5 days daily following intraperitoneal injections of 30 mg/kg DMN. Centella asiatica significantly decreased the relative liver weights in the DMN‑induced liver injury group, compared with the control. The assessment of liver histology showed that Centella asiatica significantly alleviated mass periportal ± bridging necrosis, intralobular degeneration and focal necrosis, with fibrosis of liver tissues. Additionally, Centella asiatica significantly decreased the level of malondialdehyde, significantly increased the levels of antioxidant enzymes, including superoxide dismutase, glutathione peroxidase and catalase, and may have provided protection against the deleterious effects of reactive oxygen species. In addition, Centella asiatica significantly decreased inflammatory mediators, including interleukin (IL)‑1β, IL‑2, IL‑6, IL‑10, IL‑12, tumor necrosis factor‑α, interferon‑γ and granulocyte/macrophage colony‑stimulating factor. These results suggested that Centella asiatica had hepatoprotective effects through increasing the levels of antioxidant enzymes and reducing the levels of inflammatory mediators in rats with DMN‑induced liver injury. Therefore, Centella asiatica may be useful in preventing liver damage.

Figure 1.

Effects of Centella asiatica on DMN-induced liver injury. (A) Morphological analysis of cells exposed to various treatments against DMN-induced liver injury. Centella asiatica was administered at doses of 100 or 200 mg/kg. (B) Body weights and liver weights. Relative liver weights (%) were calculated as the liver weight/body weight. Values are presented as the mean ± standard error of the mean. **P<0.01 and *P<0.05, compared with the negative control; ^#P<0.05, compared with the vehicle control. DMN dimethylnitrosamine.

Figure 2.

Effects of Centella asiatica on DMN-induced changes in liver histology. (A) Representative images at magnification, ×200 and ×400 (insert), (B) Histological activity scores for periportal ± bridging necrosis, intralobular degeneration and focal necrosis, and fibrosis. Animals (n=8/group) were orally administered with Centella asiatica at 100 or 200 mg/kg. The vehicle control comprised DMN with distilled water. Values are presented as the mean ± standard error of the mean. **P<0.01, compared with the negative control: ^##P<0.01 and ^#P<0.05, compared with the vehicle control. DMN dimethylnitrosamine.

Figure 3.

Effects of Centella asiatica on DMN-induced hepatic levels in liver tissue. (A) MDA (nmol/mg tissue), (B) SOD (U/mg tissue), (C) GPx (U/mg tissue) and (D) CAT (U/mg tissue). The animals (n=8/group) were orally administrated with Centella asiatica at 100 or 200 mg/kg. DMN in D.W was used as a vehicle control. Saline in D.W was used as a negative control. Values are presented as the mean ± standard error of the mean. **P<0.01 and *P<0.05, compared with the negative control; ^##P<0.01 and ^#P<0.05, compared with the vehicle control. DMN, dimethylnitrosamine; MDA, malondialdehyde; SOD, superoxide dismutase; GPx, glutathione peroxidase; CAT, catalase; D.W, distilled water.

Figure 4.

Effect of Centella asiatica on DMN-induced inflammatory cytokines and mediators in serum. The animals (n=8/group) were orally administrated with Centella asiatica at 100 or 200 mg/kg. DMN in D.W was used as a vehicle control. Saline in D.W was used as a negative control. Values are presented as the mean ± standard error of the mean. **P<0.01 and *P<0.05, compared with the negative control; ^##P<0.01 and ^#P<0.05, compared with the vehicle control. DMN, dimethylnitrosaminel TNF, tumor necrosis factor-α;, TNF-α; IL, interleukin; IFN-γ, interferon-γ; GM-CSF, granulocyte/macrophage colony-stimulating factor; D.W, distilled water.