Antioxidant activity, xanthine oxidase inhibition and acute oral toxicity of Dillenia philippinensis Rolfe (Dilleniaceae) leaf extract

Article published in the Journal of Pharmacy & Pharmacognosy Research 9(6): 846-858, 2021.

Sarah S. Ansari¹*, Patricia H. Diño³, Agnes L. Castillo^1,2,3, Librado A. Santiago^1,2,3

¹The Graduate School, University of Santo Tomas, España, Manila 1008, Philippines.

²Faculty of Pharmacy, University of Santo Tomas, España, Manila 1008, Philippines.

³Research Center for the Natural and Applied Sciences, University of Santo Tomas, España, Manila 1008, Philippines.

Abstract

Context: Hyperuricemia is a metabolic syndrome characterized by a high serum uric acid level with an increased risk of gout, diabetes, cardiovascular and renal disease. Allopurinol is a widely known xanthine oxidase inhibitor that lowers serum uric acid production. Documented adverse effects of the drug raise the need for a natural alternative for xanthine oxidase inhibitor that is safe and effective. This research is driven to address the need by capitalizing on previous studies made on the Dillenia species showing nephroprotective and antihyperuricemic activity.

Aims: To evaluate the antioxidant capacity, xanthine oxidase inhibitory activity, and acute toxicity of Dillenia philippinensis; a plant locally known as Katmon and endemic to the Philippines.

Methods: The D. philippinensis ethanolic leaf extract (DPELE) was partitioned using solvents of different polarities, hexane, ethyl acetate, and butanol. The antioxidant activity of the DPELE and the sub-extracts was assessed using nitric oxide, hydrogen peroxide, and hydroxyl radical scavenging assays against ascorbic acid, while the xanthine oxidase inhibitory activity was examined against allopurinol as a standard. The acute toxicity was performed using Sprague-Dawley rats following OECD 425 guidelines.

Results: The D. philippinensis ethyl acetate fraction (DPEAF) had the highest scavenging activity of nitric oxide, hydrogen peroxide, and hydroxyl (IC₅₀ = 210.00, 70.92 and 59.88 µg/mL) free radicals, respectively. Also, the xanthine oxidase dose-dependent inhibitory activity was observed to be highest in the DPEAF with an IC₅₀ = 23.09 µg/mL. Lastly, neither toxicity nor mortalities were observed in rats treated with the DPELE and the DPEAF for 14 days. The approximate lethal dose for DPELE and DPEAF was higher than 2000 mg/kg BW.

Conclusions: This study shows that the DPELE and DPEAF are potential sources of natural antioxidants and xanthine oxidase inhibitors, which may be used in the treatment of hyperuricemia and are presumed safe to be used orally.