J. Pharm. Pharmacogn. Res., vol. 14, no. 3, Article ID 2715, May-Jun 2026.
DOI: https://doi.org/10.56499/jppres_14.3.2715
Original Article
Antihyperuricemic effect of ethanol extract of Erythrina subumbrans (Hassk.) Merr. leaves in a fructose–potassium oxonate-induced male Wistar rat model
[Efecto antihiperuricémico del extracto etanólico de hojas de Erythrina subumbrans (Hassk.) Merr. en un modelo de rata Wistar macho inducido por fructosa-oxonato de potasio]
Elis Susilawati1*, Aditya N. Azriq1, Kartikasari1, Marita Kaniawati1, Agus Sulaeman1, Jutti Levita2
1Department of Pharmacology & Clinical Pharmacy, Faculty of Pharmacy, Bhakti Kencana University, Bandung, Indonesia.
2Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang 46363, Indonesia.
*E-mail: elis.susilawati@bku.ac.id
Abstract
Context: Hyperuricemia is associated with gout, oxidative stress, and renal and hepatic dysfunction. Erythrina subumbrans (Hassk.) Merr. contains bioactive metabolites, but its antihyperuricemic activity remains insufficiently evaluated.
Aims: To evaluate the antihyperuricemic activity of the ethanol extract of E. subumbrans leaves in vitro and in a fructose-potassium oxonate-induced hyperuricemic rat model.
Methods: Xanthine oxidase inhibition was assessed colorimetrically. Male Wistar rats were assigned to normal control, negative control, allopurinol, and extract-treated groups (100, 200, and 400 mg/kg body weight) in a preventive/co-treatment design. Serum uric acid, creatinine, aminotransferases, and malondialdehyde were measured and analyzed using repeated measures analysis. Liver and kidney tissues were examined histologically.
Results: The ethanol extract of E. subumbrans leaves inhibited xanthine oxidase in vitro, with a 50% inhibitory concentration of 30.98 ± 0.64 µg/mL, indicating lower activity than allopurinol (1.24 ± 0.64 µg/mL). At day 60, the extract at 100, 200, and 400 mg/kg attenuated serum uric acid levels to 3.28 ± 0.14, 3.26 ± 0.19, and 2.64 ± 0.09 mg/dL, respectively, compared with the negative control group (p<0.05). Lower creatinine, aminotransferase, and malondialdehyde values were observed in the extract-treated groups than in the negative control group. Histopathological alterations of the liver and kidney were numerically reduced, although not all pairwise comparisons reached statistical significance.
Conclusions: The ethanol extract of E. subumbrans leaves showed antihyperuricemic activity in this preventive/co-treatment model. The observed effect may have been partly related to xanthine oxidase inhibition; however, further mechanistic, standardization, and safety studies are required.
Keywords: alanine aminotransferase; creatinine; hyperuricemia; malondialdehyde; rats, Wistar; uric acid.

Resumen
Contexto: La hiperuricemia se asocia con gota, estrés oxidativo y disfunción renal y hepática. Erythrina subumbrans (Hassk.) Merr. contiene metabolitos bioactivos, pero su actividad antihiperuricémica aún no ha sido suficientemente evaluada.
Objetivos: Evaluar la actividad antihiperuricémica del extracto etanólico de hojas de E. subumbrans in vitro y en un modelo de ratas hiperuricémicas inducido por fructosa-oxonato de potasio.
Métodos: La inhibición de la xantina oxidasa se evaluó mediante un ensayo colorimétrico. Ratas Wistar macho fueron distribuidas en grupos control normal, control negativo, alopurinol y grupos tratados con extracto a dosis de 100, 200 y 400 mg/kg de peso corporal, en un diseño preventivo/cotratamiento. Se midieron ácido úrico sérico, creatinina, aspartato aminotransferasa, alanina aminotransferasa y malondialdehído, y se analizaron mediante análisis de medidas repetidas. Los tejidos hepático y renal fueron examinados histológicamente.
Resultados: El extracto etanólico de hojas de E. subumbrans inhibió la xantina oxidasa in vitro, con una concentración inhibitoria del 50% de 30,98 ± 0,64 µg/mL, mostrando menor actividad que el alopurinol (1,24 ± 0,64 µg/mL). En el día 60, el extracto a 100, 200 y 400 mg/kg atenuó los niveles séricos de ácido úrico a 3,28 ± 0,14; 3,26 ± 0,19; y 2,64 ± 0,09 mg/dL, respectivamente, en comparación con el grupo control negativo (p < 0,05). Se observaron valores más bajos de creatinina, aminotransferasas y malondialdehído en los grupos tratados con extracto que en el grupo control negativo. Las alteraciones histopatológicas hepáticas y renales se redujeron numéricamente, aunque no todas las comparaciones por pares alcanzaron significancia estadística.
Conclusiones: El extracto etanólico de hojas de E. subumbrans mostró actividad antihiperuricémica en este modelo preventivo/cotratamiento. El efecto observado puede haber estado parcialmente relacionado con la inhibición de la xantina oxidasa; sin embargo, se requieren estudios mecanísticos, de estandarización y de seguridad adicionales.
Palabras Clave: ácido úrico; alanina aminotransferasa; creatinina; hiperuricemia; malondialdehído; ratas Wistar.

Citation Format: Susilawati E, Azriq AN, Kartikasari, Kaniawati M, Sulaeman A, Levita J (2026) Antihyperuricemic effect of ethanol extract of Erythrina subumbrans (Hassk.) Merr. leaves in a fructose–potassium oxonate-induced male Wistar rat model. J Pharm Pharmacogn Res 14(3): 2715. https://doi.org/10.56499/jppres_14.3.2715
References
Abdel Mageed SS, Mohamed FA, Sobhy M, Elosaily AH, El-Dessouki AM, Ghaiad HR, Abd-Elmawla MA, Fahmy MI, Hassan MAM, El-Shiekh RA, Abdelmaksoud NM (2025) Integrating natural products with modern medicine in the treatment of gouty arthritis: A review. Inflammopharmacology. https://doi.org/10.1007/s10787-025-01784-0
Abdulhafiz F, Mohammed A, Reduan MFH, Hamzah Z, Kari ZA, Téllez-Isaías G (2023) Evaluation of anti-hyperuricemic effects of Alocasia longiloba Miq. (Keladi Candik) extracts in potassium oxonate induced rat model. Heliyon 9(7): e18069. https://doi.org/10.1016/j.heliyon.2023.e18069
An MF, Shen C, Zhang SS, Wang MY, Sun ZR, Fan MS, Zhang LJ, Zhao YL, Sheng J, Wang XJ (2023) Anti-hyperuricemia effect of hesperetin is mediated by inhibiting the activity of xanthine oxidase and promoting excretion of uric acid. Front Pharmacol 14: 1128699. https://doi.org/10.3389/fphar.2023.1128699
Ayala A, Muñoz MF, Argüelles S (2014) Lipid peroxidation: production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal. Oxid Med Cell Longev 2014: 360438. https://doi.org/10.1155/2014/360438
Bajaj P, Kaur T, Singh AP, Kaur G (2024) Acute sleep deprivation-induced hepatotoxicity and dyslipidemia in middle-aged female rats and its amelioration by butanol extract of Tinospora cordifolia. Lab Anim Res 40(1): 24. https://doi.org/10.1186/s42826-024-00216-4
Caliceti C, Calabria D, Roda A, Cicero AFG (2017) Fructose intake, serum uric acid, and cardiometabolic disorders: A critical review. Nutrients 9(4): 395. https://doi.org/10.3390/nu9040395
Das M, Borah NC, Ghose M, Choudhury N (2014) Reference ranges for serum uric acid among healthy Assamese people. Biochem Res Int 2014: 171053. https://doi.org/10.1155/2014/171053
Dehlin M, Jacobsson L, Roddy E (2020) Global epidemiology of gout: prevalence, incidence, treatment patterns and risk factors. Nat Rev Rheumatol 16(7): 380–390. https://doi.org/10.1038/s41584-020-0441-1
Dhammaraj T, Kotseekieo P, Chotikarn T, Phosrithong N, Praison W, Prasomsub T, Lumthong P, Supaporn W, Sungthong B, Mudjupa C, Pulbutr P (2024) In vitro investigation of xanthine oxidase inhibitory and antioxidant activities of 3,4,5-trihydroxycinnamic acid. J Herbmed Pharmacol 13(3): 439–449. https://doi.org/10.34172/jhp.2024.49420
Du L, Zong Y, Li H, Wang Q, Xie L, Yang B, Pang Y, Zhang C, Zhong Z, Gao J (2024) Hyperuricemia and its related diseases: mechanisms and advances in therapy. Signal Transduct Target Ther 9: 212. https://doi.org/10.1038/s41392-024-01916-y
Ejaz AA, Nakagawa T, Kanbay M, Kuwabara M, Kumar A, Garcia Arroyo FE, Roncal-Jimenez C, Sasai F, Kang DH, Jensen T, Hernando AA, Rodriguez-Iturbe B, Garcia G, Tolan DR, Sanchez-Lozada LG, Lanaspa MA, Johnson RJ (2020) Hyperuricemia in kidney disease: A major risk factor for cardiovascular events, vascular calcification, and renal damage. Semin Nephrol 40(6): 574–585. https://doi.org/10.1016/j.semnephrol.2020.12.004
Gumbar S, Bhardwaj S, Mehan S, Khan Z, Narula AS, Kalfin R, Tabrez S, Zughaibi TA, Wasi S (2023) Renal mitochondrial restoration by gymnemic acid in gentamicin-mediated experimental nephrotoxicity: evidence from serum, kidney and histopathological alterations. Front Pharmacol 14: 1218506. https://doi.org/10.3389/fphar.2023.1218506
Herlina T, Akili AWR, Nishinarizki V, Hardianto A, Latip JB (2025) Review on antibacterial flavonoids from genus Erythrina: structure-activity relationship and mode of action. Heliyon 11(1): e41395. https://doi.org/10.1016/j.heliyon.2024.e41395
Liu N, Xu H, Sun Q, Yu X, Chen W, Wei H, Jiang J, Xu Y, Lu W (2021) The role of oxidative stress in hyperuricemia and xanthine oxidoreductase inhibitors. Oxid Med Cell Longev 2021: 1470380. https://doi.org/10.1155/2021/1470380
Lubawy M, Formanowicz D (2023) High-fructose diet-induced hyperuricemia accompanying metabolic syndrome: mechanisms and dietary therapy proposals. Int J Environ Res Public Health 20(4): 3596. https://doi.org/10.3390/ijerph20043596
National Institute of Health Research and Development (2019) Laporan Nasional Riskesdas 2018 [National Report of Basic Health Research 2018]. Jakarta: Publishing Agency of the National Institute of Health Research and Development. https://repository.badankebijakan.kemkes.go.id/id/eprint/3514/ [Consulted 17 May, 2026].
Phukhatmuen P, Meesakul P, Suthiphasilp V, Charoensup R, Maneerat T, Cheenpracha S, Limtharakul T, Pyne SG, Laphookhieo S (2021) Antidiabetic and antimicrobial flavonoids from the twigs and roots of Erythrina subumbrans (Hassk.) Merr. Heliyon 7(4): e06904. https://doi.org/10.1016/j.heliyon.2021.e06904
Qurie A, Preuss CV, Musa R (2023) Allopurinol. In: StatPearls. Treasure Island (FL): StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK499942/
Suntornsaratoon P, Bulanawichit W, Siricoon S, Saengsirisuwan V, Panupinthu N, Krishnamra N, Charoenphandhu N (2025) Uricosuric, antioxidant, and anti-inflammatory properties of Pandanus amaryllifolius Roxb. extract against potassium oxonate-induced hyperuricemia in rats. Sci Rep 15: 45700. https://doi.org/10.1038/s41598-025-27933-7
Susilawati E, Levita J, Susilawati Y, Sumiwi SA (2024) Erythrina subumbrans (Hassk.) Merr. (Fabaceae) inhibits insulin resistance in the adipose tissue of high fructose-induced Wistar rats. Drug Des Devel Ther 18: 3825–3839. https://doi.org/10.2147/DDDT.S472660
Timsans J, Palomäki A, Kauppi M (2024) Gout and hyperuricemia: A narrative review of their comorbidities and clinical implications. J Clin Med 13(24): 7616. https://doi.org/10.3390/jcm13247616
Zhang P, Sun H, Cheng X, Li Y, Zhao Y, Mei W, Wei X, Zhou H, Du Y, Zeng C (2022) Dietary intake of fructose increases purine de novo synthesis: A crucial mechanism for hyperuricemia. Front Nutr 9: 1045805. https://doi.org/10.3389/fnut.2022.1045805
Zardooz H, Rostamkhani F, Zaringhalam J, Faraji Shahrivar F (2010) Plasma corticosterone, insulin and glucose changes induced by brief exposure to isoflurane, diethyl ether and CO₂ in male rats. Physiol Res 59(6): 973–978. https://doi.org/10.33549/physiolres.931896
Zhou H, Yang J, Yuan X, Song X, Zhang X, Cao T, Zhang J (2024) Hyperuricemia research progress in model construction and traditional Chinese medicine interventions. Front Pharmacol 15: 1294755. https://doi.org/10.3389/fphar.2024.1294755
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