Tangeretin is a polymethoxyflavone concentrated in citrus peels and has several biological activities. This study examined whether tangeretin improved reproductive dysfunction in N^ω-nitro-L-arginine methyl ester hydrochloride (L-NAME)-induced hypertensive rats. Male Sprague-Dawley rats received L-NAME to induce hypertension and reproductive dysfunction for 5 w and were treated with tangeretin (15 or 30 mg/kg) or sildenafil citrate (10 mg/kg) for the final two weeks. Mean arterial pressure (MAP), intracavernosal pressure (ICP) response to cavernous nerve stimulation, endothelial nitric oxide synthase (eNOS), Angiotensin II receptor type 1 (AT₁R) and gp91^phox protein expressions and malondialdehyde (MDA) level in penile tissues were measured. Sperm concentrations and motility, seminiferous tubule morphology, serum testosterone, testicular eNOS and steroidogenic acute regulatory protein (StAR) expression were evaluated. Aortic superoxide generation, plasma and testicular MDA and plasma nitrate/nitrite levels were determined. Tangeretin reduced blood pressure and increased the maximum ICP/MAP associated with suppression of AT₁R/gp91phox and upregulation of eNOS expression in hypertensive rats (P < 0.05). Furthermore, improvement of sperm quality relevant to increased testicular eNOS and StAR expression was found in tangeretin treated rats (P < 0.05). Changes in seminiferous tubule morphology in hypertensive rats were recovered by tangeretin (P < 0.05). It increased testosterone levels and reduced oxidative stress biomarkers and raised plasma nitrate/nitrite levels in L-NAME rats (P < 0.05). In conclusion, tangeretin improved maximum ICP/MAP and testicular dysfunction and morphology in rats treated with L-NAME. The molecular mechanisms are mediated by modulations of penile eNOS and AT₁R/gp91^phox expressions and testicular eNOS and StAR expression.

Tangeretin 是一种集中在柑橘皮中的多甲氧基黄酮，具有多种生物活性。本研究检查了橘皮素是否能改善 N ^ω -硝基-L-精氨酸甲酯盐酸盐 (L-NAME) 诱导的高血压大鼠的生殖功能障碍。雄性 Sprague-Dawley 大鼠接受 L-NAME 诱导高血压和生殖功能障碍 5 周，并在最后两周用橘子 (15 或 30 mg/kg) 或枸橼酸西地那非 (10 mg/kg) 治疗。平均动脉压 (MAP)、海绵体神经刺激反应的海绵体内压 (ICP)、内皮一氧化氮合酶 (eNOS)、血管紧张素 II 受体 1 型 (AT ₁ R) 和 gp91 ^phox测量阴茎组织中的蛋白质表达和丙二醛（MDA）水平。评估了精子浓度和活力、曲细精管形态、血清睾酮、睾丸 eNOS 和类固醇急性调节蛋白 (StAR) 的表达。测定了主动脉超氧化物的产生、血浆和睾丸 MDA 以及血浆硝酸盐/亚硝酸盐水平。Tangeretin 降低血压并增加与 AT ₁ R/gp91phox 抑制和高血压大鼠 eNOS 表达上调相关的最大 ICP/MAP ( P < 0.05)。此外，在橘皮素处理的大鼠中发现与睾丸 eNOS 和 StAR 表达增加相关的精子质量改善（P< 0.05)。橘皮素可恢复高血压大鼠曲细精管形态的变化（P < 0.05）。它增加了 L-NAME 大鼠的睾酮水平，降低了氧化应激生物标志物，提高了血浆硝酸盐/亚硝酸盐水平（P < 0.05）。总之，橘皮素改善了用 L-NAME 治疗的大鼠的最大 ICP/MAP 和睾丸功能障碍和形态。分子机制是通过调节阴茎 eNOS 和 AT ₁ R/gp91 ^phox表达以及睾丸 eNOS 和 StAR 表达来介导的。