Dada Anelize, Vilhena da Silva Rita de Cássia, Zanovello Mariana, Macarini Anelise Felício, Boeing Thaise, Cechinel Filho Valdir, de Souza Priscila
Programa de Pós-Graduação em Ciências Farmacêuticas (PPGCF), Universidade do Vale do Itajaí (Univali), Itajaí 88302-901, Brazil.
Pharmaceuticals (Basel). 2025 Jun 12;18(6):873. doi: 10.3390/ph18060873.
: Systemic arterial hypertension is one of the leading global health concerns, significantly increasing the risk of cardiovascular and kidney diseases, including nephrolithiasis. The treatment, still far from ideal, is constantly undergoing new alternatives. In this context, medicinal plants rich in flavonoids, such as naringenin-a compound found in citrus fruits-have gained attention for their potential diuretic, nephroprotective, and blood pressure-lowering effects. : This study aimed to evaluate the effects of naringenin (100 mg/kg, orally) over nine days on blood pressure, renal function, and calcium oxalate crystal formation in normotensive Wistar (NTR) and spontaneously hypertensive male rats (SHR). : Key assessments included blood pressure and heart rate measurements in vivo, urine volume and electrolyte excretion in vivo, in vitro calcium oxalate crystallization, and in silico molecular docking analyses to investigate molecular interactions. : Naringenin treatment significantly reduced blood pressure and increased diuresis in both NTR and SHR groups, while a notable natriuretic effect was observed specifically in NTR. In vitro, naringenin reduced the formation of calcium oxalate crystals in urines from NTR. Molecular docking studies suggested that these effects may be mediated by interactions with SGLT1 and SGLT2 transporters, potentially explaining the diuretic and natriuretic outcomes. Additionally, interactions with MMP-9 and β2-adrenergic receptors may contribute to the reduction in crystal formation. : Collectively, these findings indicate that repeated administration of naringenin exerts beneficial effects on both cardiovascular and renal parameters, and point to promising molecular targets that may underlie its protective actions.
全身性动脉高血压是全球主要的健康问题之一，显著增加了心血管疾病和肾脏疾病（包括肾结石）的风险。其治疗方法仍远非理想，且不断有新的替代方案出现。在此背景下，富含黄酮类化合物的药用植物，如柑橘类水果中含有的柚皮素，因其潜在的利尿、肾保护和降血压作用而受到关注。本研究旨在评估连续九天口服100mg/kg柚皮素对正常血压的Wistar大鼠（NTR）和自发性高血压雄性大鼠（SHR）的血压、肾功能以及草酸钙晶体形成的影响。主要评估指标包括体内血压和心率测量、体内尿量和电解质排泄、体外草酸钙结晶以及计算机模拟分子对接分析以研究分子相互作用。柚皮素治疗显著降低了NTR组和SHR组的血压并增加了尿量，而在NTR组中特别观察到显著的利钠作用。在体外，柚皮素减少了NTR大鼠尿液中草酸钙晶体的形成。分子对接研究表明，这些作用可能是通过与SGLT1和SGLT2转运蛋白的相互作用介导的，这可能解释了利尿和利钠的结果。此外，与MMP-9和β2-肾上腺素能受体的相互作用可能有助于减少晶体形成。总体而言，这些发现表明重复给予柚皮素对心血管和肾脏参数均有有益作用，并指出了可能是其保护作用基础的有前景的分子靶点。
