Effect of the standardized extract of Centella asiatica (ECa 233) on liver metabolome of rotenone-treated rats

Abstract

Liver plays an important role in the body’s metabolic processes, with many functions including nutrient metabolism and detoxification of xenobiotics. Liver diseases cause serious public health problems worldwide. Several studies of hepatoprotective activities from natural plant extracts have been revealed during recent years. The protective effects of Centella asiatica on the liver have been reported. Centella asiatica (Apiaceae) is a medicinal herb that has been commonly used in many countries in Asia. However, the compositions of the main compounds extracted from the herb were varied across geographical regions. Therefore, the standardized extract of Centella asiatica (ECa 233) contained >80% triterpenoids with a ratio of madecassoside to asiaticoside kept at 1.5(±0.5):1 was developed by the Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand. Previous studies shown therapeutic effects of ECa 233 to various conditions such as memory improvement, anxiolytic and wound healing effect. However, the protective effect of ECa 233 on the liver has not yet been determined. The aim of this study was to investigate the possible protective effect of ECa 233 on liver metabolome of rotenone-induced rats by using GC-MS based metabolomics. Metabolomic analysis was performed to better understand the underlying mechanisms in the liver tissue. Liver enzymes, lipid peroxidation and antioxidant enzymes in liver were analyzed. Adult male Wistar rats were randomly divided into three groups (with six rats/group): control, rotenone and ECa 233 group. Rats in the ECa 233 group received 10 mg/kg of ECa 233 orally for 20 days, followed by 2.5 mg/kg of intraperitoneal rotenone injection to induce toxicity before being sacrificed. Metabolomic analysis showed that supplementation of ECa 233 protected rat liver against rotenone toxicity. Pipecolinic acid appeared to be the most important metabolites; its level was decreased in the rotenone group as compared to the control. Supplementation with ECa 233 before administration of rotenone raised pipecolinic acid to levels intermediate between controls and rotenone alone. Antioxidant tests revealed that ECa 233 inhibited lipid peroxidation and increased catalase activities in liver tissue. The outcomes of this study provide further evidence in support of using Centella asiatica as a value-added component in new dietary supplements or medicines for liver disorders in the future.