Sappanwood extract modulates hepatic structure–function in hepatomegaly and hepcidin related iron regulatory pathways in a phenylhydrazine induced hemolytic anemia rat model relevant to thalassemia
Mohammad Indra Pratama, Ratu Safitri, Desak Made Malini, Mas Rizky A. A. Syamsunarno, Mohammad Ghozali, Madihah MadihahAbstract
Background
Hepatomegaly in hemolytic disorders, including in thalassemia, is a common complication, primarily due to hemosiderosis and activation of extramedullary hematopoiesis. Globin chain imbalance leads to chronic hemolysis and ineffective erythropoiesis, which are associated with suppression of hepcidin expression. Reduced hepcidin levels may increase iron absorption and accumulation, contributing to oxidative stress and liver tissue damage. Iron chelation therapy, such as deferipron, is effective but has side effects, so safer alternatives are needed. Sappanwood ( Caesalpinia sappan L.) contains the active compound brazilin, which chelates iron and exhibits antioxidant activity, potentially reducing oxidative stress, improving iron metabolism disorders, and reducing hepatomegaly. This study aims to evaluate the potential of sappanwood extract as a natural iron chelator and antioxidant.
Methods
This experimental study used male Wistar rats (180–250 g) with a model of iron overload hemolytic anemia, which were divided into normal controls, negative controls (phenylhydrazine 40 mg/kg BW), positive controls (deferiprone 75 mg/kg BW), and sappanwood extract (SWE) treatment (50, 100, 200 mg/kg BW) for 14 days. The parameters measured included iron metabolism, hepatomegaly, liver function, hepcidin‐related gene expression, and oxidative stress. Data were analyzed using ANOVA, with p < 0.05 considered significant.
Results
The results showed that administration of 100 mg/kg BW SWE provided optimal improvement ( p < 0.05), including reductions in hepatomegaly, SGPT, hemosiderin, lipid peroxidation, bilirubin, extramedullary hematopoiesis, and modulation in iron‐related gene expression, including Hamp, Bmp6, Epo , and Ftl .
Conclusions
These findings confirm the potential of sappanwood as a potential therapeutic candidate for the management of iron overload in thalassemia.