Effects of Ilex aquifolium Polyphenols on Cardiovascular, Renal and Liver Structure in a Rat Model of Metabolic Syndrome: A Biochemical and Histological Study

Metabolic syndrome (MetS) is a major driver of cardiovascular disease, renal injury, and hepatic steatosis, largely through chronic low-grade inflammation and oxidative stress. This study evaluated the cardioprotective, nephroprotective, and hepatoprotective potential of a polyphenol-rich fraction (PP) isolated from Ilex aquifolium leaves in obese Zucker (fa/fa) rats—a well-established model of MetS. Male rats (8 weeks old) were randomly assigned to receive either a standard diet (CTRL, n = 8) or the same diet supplemented with 10 mg/kg body weight/day of the polyphenol fraction (PP, n = 8) for 8 weeks. The fraction was dominated by chlorogenic acid (59.33 mg/g), neochlorogenic acid (35.39 mg/g), and rutin (9.23 mg/g). At the end of the experiment, biochemical markers of oxidative stress, inflammation, and metabolic status were assessed, together with detailed histopathological examination of the heart, kidneys, and liver. Supplementation with Ilex aquifolium polyphenols significantly increased (p < 0.01) total antioxidant status, reduced circulating IL-6 and increased MCP-1 levels. These changes were accompanied by clear cardioprotective effects. However, the intervention also produced organ-specific adverse effects. In the kidneys, polyphenol-treated rats exhibited histopathological features consistent with early-stage nephropathy. In the liver, supplementation exacerbated hepatic steatosis compared to controls. In conclusion, the polyphenol-rich fraction from Ilex aquifolium exerts potent antioxidant and anti-inflammatory effects that translate into substantial cardioprotection in obese Zucker rats. Nevertheless, its capacity to worsen renal injury and hepatic steatosis highlights the need for caution and further dose- and duration-dependent studies before considering therapeutic application in metabolic syndrome.