Antifibrotic effects of Punica granatum peels through stimulation of hepatic stellate cell apoptosis in thioacetamideinduced liver fibrosis in rats

• Published in: Journal of the Arab Society for Medical Research Vol. 12; no. 2; pp. 56 - 67
• Main Authors: Umara, Inayat A., Farraj, Abd al-Raziq H., Jalal, Asma F., al-Tumi, Sayyid A., Hasan, Nabilah S., Sharaf, Hafizah Ali, Nada, Sumayyah A.
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Arab Society for Medical Research 2017
• ISSN: 1687-4293; 2090-3286

Background/aim Liver fibrosis is a major global health problem. The present study aimed to evaluate the antioxidant and antifibrogenic potential of Punica granatum peels extract against thioacetamide (TAA)-induced hepatic fibrosis. Materials and methods Rats were divided into six groups. Group 1 was the control; group 2 was injected with TAA (150 mg/kg, intraperitoneal) (fibrosis group) for 4 weeks; group 3 received P. granatum peels extract only (200 mg/kg); group 4 rats were given oral sliymarin (50 mg/kg) for 4 weeks after withdrawal of TAA; groups 5 and 6 rats were given oral P. granatum peels extract (100 and 200 mg/kg) for 4 weeks after withdrawal of TAA. Fibrosis was assessed histologically and by measuring the hepatic hydroxyproline content. The degree of liver fibrosis was assessed by Masson’s trichrome staining and α-smooth muscle actin as the marker of the activated hepatic stellate cells was detected immunohistochemically. Serum markers of liver damage and oxidative stress were also assessed. Results The biochemical analyses have shown that P. granatum peels extract or sliymarin significantly reduced the progression of hepatic fibrosis. The plant extract or sliymarin resulted in a significant improvement of liver damage by the reduced levels of serum alanine aminotransferase and alkaline phosphatase. Oral administration of P. granatum peels or sliymarin has also restored normal levels of malondialdehyde, hydroxyproline content as markers of fibrosis content (P<0.05) in the liver, and retained control activities of endogenous antioxidants such as superoxide dismutase, nitric oxide, and glutathione. The histological evaluation showed that the plant extract or silymarin treatment maintained the architecture of the liver nearly normal and attenuate the accumulation of excessive collagen in the liver fibrosis caused by TAA. We also observed that P. granatum peels extract or silymarin-treated rats reduced α-smooth muscle actin. Conclusion The obtained results have shown that P. granatum peels extract effectively blocked hepatic stellate cell proliferation and they may be beneficial in the treatment of liver fibrosis.