Polyphenols and ADPKD: A Further Aid from Nature?

Treating autosomal dominant polycystic kidney disease (ADPKD) has always been a challenge because the disease is too complex for single-target drugs, which are often held back by side effects. This narrative review explores a different strategy: using plant-derived polyphenols to target multiple disease pathways at the same time. Looking at research from 2005 to 2026, we break down how key compounds like resveratrol, curcumin, naringenin, quercetin, and epigallocatechin-3-gallate (EGCG) actually work. Preclinical studies show these molecules can slow down cyst growth by tackling inflammation, rapid cell division, and tissue scarring all at once, while also resetting the skewed energy metabolism of cystic cells. Some mechanisms are strikingly specific, such as naringenin's direct interaction with polycystin-2 and quercetin's ability to clear senescent cells. Yet, the real-world hurdle is poor absorption; a recent clinical trial with standard curcumin fell short simply because the compound could not reach the kidneys in high enough concentrations. Moving forward, the field needs to focus on testing these compounds in realistic animal models, designing smart nanoformulations to improve bioavailability, and exploring combinations that could safely complement current therapies like tolvaptan.