Effect of Tokishakuyakusan on Anemia in a Rat Model of Salt‐Sensitive Hypertension

ABSTRACT Aim Anemia is prevalent in patients with cardiac and renal diseases and is associated with morbidity and mortality. Consequently, new strategies for managing anemia are expected in these patients. Tokishakuyakusan, a Kampo medicine, is clinically used to treat various conditions, such as anemia and chronic nephritis. However, its effect on anemia in the context of cardiac and renal dysfunction remains unknown. Here, using Dahl salt‐sensitive rats, a model of salt‐sensitive hypertension, we investigated our hypothesis that tokishakuyakusan is effective for anemia in the context of cardiac and renal dysfunction. Methods Six‐week‐old male Dahl salt‐sensitive rats were fed either a normal or a high‐salt diet for 8 weeks. A subset of Dahl salt‐sensitive rats fed a high‐salt diet was administered tokishakuyakusan for 8 weeks. Results Following 8 weeks on a high‐salt diet, Dahl salt‐sensitive rats developed anemia, hypertension, and cardiac and renal dysfunction. Tokishakuyakusan alleviated anemia in the high‐salt diet group. In addition, serum iron, transferrin saturation, and haptoglobin levels decreased in the high‐salt diet group, while these decreases were attenuated by tokishakuyakusan. Hepatic gene expression of hepcidin , a regulator of iron metabolism, was decreased in the high‐salt diet group, with tokishakuyakusan suppressing this decrease. Duodenal gene expression of iron transporters was not altered by tokishakuyakusan. While tokishakuyakusan did not affect the progression of hypertension and cardiac hypertrophy, it reduced renal fibrosis in the high‐salt diet group. Conclusions Tokishakuyakusan alleviated anemia and reduced renal fibrosis in Dahl salt‐sensitive rats fed a high‐salt diet.