A Standardized Extract of Centella asiatica (ECa 233) Protects Against Liver Injury and Fatty Liver in Wild-Type and Beta-Thalassemia Mice With Iron Overload

Abstract

Iron overload leads to liver damage by promoting free radical reactions and triggering an inflammatory process. Excess iron has been implicated in the progression of nonalcoholic fatty liver (NAFL), liver fibrosis, and ultimately liver cancer in thalassemia. Centella asiatica is known for its anti-inflammatory properties. Therefore, the effects of a standardized extract of C. asiatica (ECa 233) on liver injury in iron overload were evaluated in comparison with an iron chelator, deferiprone, in wild-type (WT) and beta-globin gene-knockout (BKO) mice. The mice received intraperitoneal injections of iron dextran for 5 days, totaling 100 mg/mouse of iron, followed by daily injections of either deferiprone (80 mg/kg/day) or ECa 233 (20 mg/kg/day) for 10 days. Biochemical and histological analyses revealed that deferiprone and ECa 233 reduced iron accumulation and oxidative stress parameters, TBARs and GPX, in the liver. More significantly, both treatments decreased the levels of serum proinflammatory markers, IL-6 and TNF-α, and improved lipid profiles by lowering serum triglyceride, cholesterol, and low-density lipoprotein (LDL) levels. Additionally, ultrasonography demonstrated an improvement in fatty liver associated with iron overload. There was no significant difference in the treatment response between the WT and BKO mice. While deferiprone had a more pronounced effect on the iron parameters than ECa 233, no differences were observed in the other parameters. We hypothesized that the effects of ECa 233 may be primarily due to its anti-inflammatory activity, which in turn affects iron metabolism and reduces the level of labile iron in the liver. Our results suggest that ECa 233 benefits iron-overloaded conditions.