A standardized extract of Centella asiatica (ECa 233) alleviates brain injury and improves brain function in β-thalassemia mice with iron overload

Abstract

BACKGROUND: Iron overload plays a role in the pathogenesis of neurodegenerative disorders by inducing oxidative injury in the brain. Centella asiatica (L.) Urb. It is a medicinal plant with neuroprotective effects that exhibits antioxidant and anti-inflammatory activities. A standardized extract of C. asiatica (ECa 233) has high concentrations of the bioactive compounds madecassoside and asiaticoside. It may have potential for use in iron overload conditions. OBJECTIVES: This study aimed to investigate the effects of ECa 233 on iron-induced brain injury, memory deficits, and impaired locomotor activity in 12-month-old wild-type (WT) and β-thalassemia (β-globin knockout, BKO) mice with iron overload. METHODS: WT and BKO mice were intraperitoneally (i.p.) injected with 100 mg of iron, followed by i.p. injection of 20 mg/kg body weight of ECa 233 for 10 days. Iron accumulation and injury in the brain were evaluated via hematoxylin and eosin (H&E) and Prussian blue staining. The Morris water maze (MWM) and open field tests were performed to evaluate spatial learning and memory and locomotor activity, respectively. RESULTS: Aging BKO mice resulted in spontaneous iron accumulation in the brain and poor performance in the MWM test. Iron overload significantly increased brain iron content and worsened brain injury, locomotor activity, and performance in the MWM test in both WT and BKO mice. Treatment with ECa 233 significantly decreased iron accumulation in the brain and reversed brain damage in WT and BKO mice to the same extent. In addition, ECa 233 improved iron-induced memory deficits in WT mice and locomotor activity in iron-overloaded WT and BKO mice. CONCLUSION: These results suggest that the beneficial effect of ECa 233 may be partially due to decreased iron accumulation in the brain. ECa 233 may be used as an adjuvant with an iron chelator to prevent iron-induced neurodegenerative complications in individuals with β-thalassemia.