Ameliorative Effects and Mechanism of Aqueous Extract of Moringa oleifera Leaves on Hepatic Fibrosis in Rats

Abstract

To investigate the ameliorative effects and mechanism of Moringa oleifera Lam (LM) leaf aqueous extract on hepatic fibrosis (HF) in rats. 60 male SD rats were randomly divided into normal group, model group, colchicine group (100 mg/kg), and LM high, medium and low dose groups (200, 100 and 50 mg/kg), except for the normal group, rats in the remaining groups were established as HF model by intraperitoneal injection of thioacetamide (TAA) and the corresponding drugs were administered from the 5 th week. At the end of drug administration, rats were examined for body weight, liver index, liver function indexes, including serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST). HF indices including serum procollagen type III (PCIII), collagen type IV (IV-C), laminin (LN), hyaluronic acid (HA), liver hydroxyproline acid (HYP). Masson staining was used to observe liver fibrotic tissue lesions. Indicators of Liver oxidative stress, including hepatic reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD), were also detected. Real-time quantitative fluorescence PCR and protein immunoblotting were performed to detect hepatic TGF-β1/Smads pathway gene expression. Rats in the HF model group had significantly lower body weight, highly significantly increased liver index, serum ALT, AST, PCIII, IV-C, LN, HA and liver HYP concentrations compared with rats in the normal group (P<0.01). In addition, the liver tissue of rats in the model group showed a significant increase in collagen fibre deposition, severe liver fibrosis, highly significant increase in liver ROS and MDA content, and a highly significant decrease in SOD activity (P<0.01), indicating that the liver of rats in the model group was in a state of oxidative stress and fibrotic lesions, and liver function was impaired. Compared with the model group, serum ALT, AST, PCIII, IV-C, LN, HA and hepatic HYP concentrations were reduced to varying degrees in the LM group rats. In addition, collagen fibre deposition in liver tissue was significantly reduced, liver ROS and MDA content were significantly decreased, and SOD activity was significantly increased in the LM group rats, indicating that LM could reduce the level of liver oxidative stress, ameliorate liver fibrosis and protect liver function in rats (P<0.05, P<0.01). Gene expression detection of the TGF-β1/Smads pathway showed that the mRNA and protein expression of TGF-β1, Smad2, Smad3 and α-SMA genes were significantly increased in the model group compared with the control group. Compared with the model group, the liver TGF-β1, Smad2, Smad3 and α-SMA gene expressions were significantly lower in the LM high and medium dose groups (P<0.05, P<0.01), and the liver Smad3 and α-SMA gene expressions were significantly lower in the LM low dose group (P<0.05, P<0.01), indicating that LM could downregulate liver TGF-β1/Smads pathway gene expression in HF rats. LM would ameliorate TAA-induced liver fibrosis in rats by down-regulating the ROS-TGF-β1/Smads pathway.

Keywords

• liver fibrosis
• moringa oleifera leaf
• oxidative stress
• liver function