A high prevalence of hyperuricemia among adult and older adult populations has intrigued the development of its therapy based on natural products. Our objective was to investigate the antihyperuricemic activity of the natural product from Limonia acidissima L. in vivo. The extract was obtained through the maceration of L. acidissima fruits using an ethanolic solvent and was tested for its antihyperuricemic activity against potassium oxonate-induced hyperuricemic rats. Serum uric acid, creatinine, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and blood urea nitrogen (BUN) were observed before and after the treatment. Expression of urate transporter 1 (URAT1) was also measured using a quantitative polymerase chain reaction. Antioxidant activity based on a 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging assay, along with total phenolic content (TPC) and total flavonoid content (TFC), were measured. Herein, we present the evidence of the serum uric acid lowering effect of the L. acidissima fruit extract along with improved AST and ALT (p < 0.01). The reduction of serum uric acid was in accordance with the decreasing trend of URAT1 (1.02 ± 0.05-fold change in the 200 mg group), except in a group treated with 400 mg/kg body weight extract. At the same time, BUN increased significantly in the 400 mg group (from 17.60 ± 3.286 to 22.80 ± 3.564 mg/dL, p = 0.007), suggesting the renal toxicity of the concentration. The IC50 for DPPH inhibition was 0.14 ± 0.02 mg/L with TPC and TFC of 143.9 ± 5.24 mg GAE/g extract and 390.2 ± 3.66 mg QE/g extract, respectively. Further studies should be carried out to prove this correlation along with the safe concentration range of the extract.
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