Journal of Liver

Matrine eliminates hepatosteatosis and glucose intolerance in high fructose-fed mice by suppressing ER stress associated de novo lipogenesis in the liver

3^rd World Congress on Hepatitis and Liver Diseases

October 10-12, 2016 Dubai, UAE

Ali Mahzari, XiaoyiZeng, Songpei Li, Charlie Changli Xue and Jiming Ye

RMIT University, Australia

Scientific Tracks Abstracts: J Liver

Abstract:

Matrine is a small molecule (MW: 248) isolated from a natural product and used as a prescribed hepatoprotective drug in humans with little adverse effect. Our recent work shows that matrine can reduce glucose intolerance in mice caused by excess lipid intake directly from diet. Here, we investigated whether matrine may also be efficacious for hepatosteatosis and glucose intolerance due to hepatic de novo lipogenesis from high carbohydrate. This study was performed in high fructose-fed mice for 8 weeks with matrine treatment (100 mg/kg/d) administered in the last 2 weeks. We found that matrine markedly reduced hepatosteatosis (100% reduction in triglyceride content, p<0.01 vs. untreated group) and glucose intolerance (ACU: HFru+HuM1 vs. untreated, P<0.05) without affecting caloric intake. Fructose-induced increases in SREBP1c (by 66%) and SCD1 (by 72%) in the hepatic lipogenic pathway were all suppressed by the treatment with matrine (all p<0.05). As our earlier work revealed ER stress as a mechanism of fructose-induced de novo lipogenesis, we examined hepatic ER stress following matrine treatment. Indeed, matrine significantly decreased IRE1 by 2 fold (p<0.01 vs. untreated group) in the ER stress pathway. These results together suggest that matrine eliminates hepatosteatosis and glucose intolerance by suppressing ER stress associated lipogenesis in the liver. To further assess the implications of these findings to the glycemic control for diabetes, we generated a type-2 diabetes model in mice by high fat feeding (to produce insulin resistance) plus low doses of streptozotocin (to decrease plasma insulin by 50%). Consistent with the effects in high fructose-fed mice, matrine reduced hepatic triglyceride content (by 60%) and SREBP1c level (by 57%, p<0.05) in the liver and significantly lowered the hyperglycaemia. Collectively, our findings indicate that the hepatoprotective drug matrine may be repurposed for the treatment of hepatosteatosis and type-2 diabetes associated de novo lipogenesis in the liver.

Biography :

Ali Mahzari has received his Bachelor of Clinical Laboratory Sciences from College of Applied Medical Sciences of King Saud University in Riyadh, KSA in 2005 and Master’s degree of Laboratory Medicine from RMIT University in 2010 and did research in the Cytogenetics and Molecular Cytogenetics Laboratories of the Murdoch Children Research Institute in Melbourne. He has worked as a Medical Technologist 1 in Biochemistry Lab in King Fahad Medical City from 2006-2008 and in 2011. His work involved the testing of quality control of the automated machines, blood sample for clinical chemistry, liver and lipid profile tests. He is currently a PhD student at RMIT University and a Lecturer in the Laboratory Medicine Department at Al-Baha University. His current research interest is in the evaluation of effectiveness and safety of Chinese medicine in the treatment of non-alcoholic fatty liver disease and liver-related disease.

Email: m6m12@hotmail.com