Abstract
BACKGROUND: Overnutrition and unhealthy dietary habits are established risk factors for cardiovascular and renal diseases, which may lead to the development of cardiorenal syndrome (CRS). AIM: To evaluate the cardiorenal protective potential of crude ethanol extract (CEE) of green cardamom (Elettaria cardamomum L., Family Zingiberaceae). METHODS: Rats were fed a high-fat diet to induce dyslipidemia and subsequently administered cisplatin (7.5 mg/kg) to induce CRS. CEE was administered orally to CRS rats at low (100 mg/kg) and high (200 mg/kg) doses for one month. Oxidative stress, inflammatory markers, cardiovascular disease markers, cardiac indices, and renal function (in plasma and urine) were assessed. The antioxidant activity and phenolic compound profile of CEE were evaluated. Additionally, the potential interactions of CEE phenolics with components of the Hippo signaling pathway (mammalian sterile 20-like kinase 1, large tumor suppressor kinase 1, Yes-associated protein, and transcriptional coactivator with PDZ-binding motif) were investigated using molecular docking. RESULTS: Cisplatin administration combined with a high-fat diet effectively induced CRS, as evidenced by elevated oxidative stress, inflammation, and impaired cardiorenal parameters. Treatment with CEE at both doses improved these parameters, with the high dose demonstrating greater efficacy. CEE exhibited significant DPPH radical scavenging activity. Rosmarinic acid and gallic acid were identified as the major phenolic constituents. Molecular docking revealed strong binding affinities of rosmarinic acid and rutin with targets in the Hippo signaling pathway. CONCLUSION: These findings demonstrate the cardioprotective and renoprotective potential of CEE as a phenolic-rich dietary supplement. CEE mitigated inflammation and oxidative stress, key contributors to CRS pathogenesis. Furthermore, molecular docking suggests that the phenolic compounds in CEE may exert protective effects by modulating the Hippo signaling pathway. Overall, CEE shows promise as a natural therapeutic agent for the prevention and/or management of cardiorenal syndrome.