New insight into the management of renal excretion and hyperuricemia: Potential therapeutic strategies with natural bioactive compounds

Abstract

Hyperuricemia is the result of increased production and/or underexcretion of uric acid. Hyperuricemia has been epidemiologically associated with multiple comorbidities, including metabolic syndrome, gout with long-term systemic inflammation, chronic kidney disease, urolithiasis, cardiovascular disease, hypertension, rheumatoid arthritis, dyslipidemia, diabetes/insulin resistance and increased oxidative stress. Dysregulation of xanthine oxidoreductase (XOD), the enzyme that catalyzes uric acid biosynthesis primarily in the liver, and urate transporters that reabsorb urate in the renal proximal tubules (URAT1, GLUT9, OAT4 and OAT10) and secrete urate (ABCG2, OAT1, OAT3, NPT1, and NPT4) in the renal tubules and intestine, is a major cause of hyperuricemia, along with variations in the genes encoding these proteins. The first-line therapeutic drugs used to lower serum uric acid levels include XOD inhibitors that limit uric acid biosynthesis and uricosurics that decrease urate reabsorption in the renal proximal tubules and increase urate excretion into the urine and intestine via urate transporters. However, long-term use of high doses of these drugs induces acute kidney disease, chronic kidney disease and liver toxicity. Therefore, there is an urgent need for new nephroprotective drugs with improved safety profiles and tolerance. The current systematic review summarizes the characteristics of major urate transporters, the mechanisms underlying the pathogenesis of hyperuricemia, and the regulation of uric acid biosynthesis and transport. Most importantly, this review highlights the potential mechanisms of action of some naturally occurring bioactive compounds with antihyperuricemic and nephroprotective potential isolated from various medicinal plants.

Strong inhibition of xanthine oxidase and elastase of Baccharis trimera (Less.) DC stem extract and analysis of biologically active constituents

“…Uric acid is produced as purine, a highly toxic ammonia-like by-product, is generated as protein is broken down, and uric acid is formed when this purine is detoxified and broken down in the liver. Uric acid is excreted from the body through urine, but excessive consumption of purine-containing foods can lead to excessive production of uric acid ( Yang et al, 2022 ).…”

Recent Advances in Synthetic Drugs and Natural Actives Interacting with OAT3

“…Natural medicines containing flavonoids and other functional components, particularly polyphenols, are increasingly used in clinical therapy [ 52 ]. In the elderly population with chronic diseases such as hypertension, hyperlipidemia [ 53 ], and hyperuricemia, it is common to use prescription drugs, over-the-counter drugs, and natural products simultaneously [ 47 , 54 ]. A survey showed that 78% of elderly respondents take both prescription drugs and dietary supplements, and 32.6% of them experience potential adverse drug reactions when they were taking a combination of herbs and other drugs [ 55 ].…”