Antihyperuricemic Effect of Dendropanax morbifera Leaf Extract in Rodent Models

Abstract

Dendropanax morbifera is a well-known traditional medicine used in China and Korea to treat intestinal disorders, urosis, diuresis, and chronic glomerulonephritis. Hyperuricemia is a metabolic disorder characterized by a high uric acid level in serum due to an imbalance between uric acid production and excretion and causes gout. Recently, the prevalence of hyperuricemia worldwide has been continuously increasing. Xanthine oxidase (XOD) inhibitors (allopurinol (ALP) and febuxostat) and uricosuric agents (benzbromarone and probenecid) are used to treat hyperuricemia clinically. However, because these drugs are poorly tolerated and cause side effects, such as kidney diseases, hepatotoxicity, gastrointestinal symptoms, and hypersensitivity syndrome, only a limited number of drugs are available. We investigated the antihyperuricemic effects of Dendropanax morbifera leaf ethanol extract (DMLE) and its underlying mechanisms of action through in vitro and in vivo studies. We evaluated uric acid levels in serum and urine, and xanthine oxidase (XOD) inhibition activity in the serum and liver tissue of a hyperuricemic rat model of potassium oxonate (PO)-induced hyperuricemic rats. In vitro study, XOD-inhibitory activity was the lowest among the test substances at the IC50 of ALP. However, the IC50 of DMLE-70 was significantly low compared with that of other DMLEs ( p < 0.05 ). In PO-induced hyperuricemic rats, uric acid (UA) levels in serum and urine were significantly reduced in all DMLE-70 and allopurinol-treated (ALT) groups than in the PC group ( p < 0.05 ). UA levels in urine were lower than those in serum in all DME groups. In PO-induced hyperuricemic rats, DMEE-200 reduced UA concentration in serum and increased UA excretion in the urine. These findings suggest that DMLE exerts antihyperuricemic and uricosuric effects on promoting UA excretion by enhanced secretion and inhibition of UA reabsorption in the kidneys. Thus, DMLE may be a potential treatment for hyperuricemia and gout.

Targeting Neutrophil Extracellular Traps in Gouty Arthritis: Insights into Pathogenesis and Therapeutic Potential

“…Benzbromarone has been linked to potential hepatic toxicity and cardiovascular risk, whereas probenecid may exhibit significant central nervous system toxicity and hypersensitivity syndrome, particularly when administered at higher dosages. [227][228][229][230][231] These observations highlight the importance of vigilant monitoring and cautious dose adjustments to mitigate the risk of adverse reactions, ensuring the safe and effective utilization of these agents in the management of hyperuricemia and gout. As such, a balanced assessment of risks and benefits is essential to optimize patient outcomes and uphold safety in clinical practice.…”

Dendropanoxide Attenuates High Glucose-induced Oxidative Damage in NRK-52E Cells via AKT/mTOR Signaling Pathway

“…Dendropanoxide (DPx) is a triterpenoid compound primarily found in the plants of Dendropanax morbifera (D. morbifera). D. morbifera has been reported to exhibit various pharmacological activities including anti-inflammatory, antioxidant, anti-fibrotic, antidiabetic, and antihyperuricemic activities [19][20][21][22]. In addition, the aquatic extract of D. morbifera protects against nephropathy in animals with diabetes by reducing oxidative stress [22,23].…”