Department of Pharmacology, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, Jiangsu Province, China.
Food Funct. 2019 Feb 20;10(2):1179-1190. doi: 10.1039/c8fo01663a.
Stevioside, a natural glycoside compound, has many beneficial biological activities, but its protective effect on myocardial fibrosis has not been reported yet. This study aimed to investigate the effect of stevioside. The isoproterenol-induced model mice were orally given stevioside 75-300 mg kg-1 for 40 days. The results showed that after the administration of stevioside, the myocardial hydroxyproline, collagen accumulation, and protein expressions of collagen I/III, α-smooth muscle actin, transforming growth factor-β1 (TGF-β1), nuclear factor kappa B p65 (NF-κB p65), Smad2/3, and P-Smad2/3 were decreased, while the glutathione peroxidase and superoxide dismutase levels in serum and myocardial tissues and protein expressions of myocardial peroxisome proliferator-activated receptor γ (PPARγ) and Smad7 were increased. After the preincubation of isoproterenol-stimulated cardiac fibroblasts with the PPARγ antagonist GW9662, stevioside-reduced protein expressions were decreased, but stevioside-induced Smad7 was not affected. These findings demonstrated that stevioside could exert a protective effect on mouse myocardial fibrosis, and its mechanisms were associated with the increments of antioxidant ability, PPARγ activation, and Smad7 expression, which caused a synergistic inhibition of the NF-κB/TGF-β1/Smad signaling pathway.
甜菊糖苷是一种天然糖苷化合物，具有许多有益的生物活性，但它对心肌纤维化的保护作用尚未被报道。本研究旨在探讨甜菊糖苷的作用。通过给异丙肾上腺素诱导的模型小鼠灌胃 75-300mg/kg 的甜菊糖苷 40 天。结果表明，甜菊糖苷给药后，心肌羟脯氨酸、胶原积累以及胶原 I/III、α-平滑肌肌动蛋白、转化生长因子-β1（TGF-β1）、核因子 kappa B p65（NF-κB p65）、Smad2/3 和 P-Smad2/3 的蛋白表达降低，而血清和心肌组织中的谷胱甘肽过氧化物酶和超氧化物歧化酶水平以及心肌过氧化物酶体增殖物激活受体 γ（PPARγ）和 Smad7 的蛋白表达增加。用 PPARγ 拮抗剂 GW9662 孵育异丙肾上腺素刺激的心肌成纤维细胞后，甜菊糖苷降低的蛋白表达减少，但甜菊糖苷诱导的 Smad7 不受影响。这些发现表明，甜菊糖苷可对小鼠心肌纤维化发挥保护作用，其机制与抗氧化能力的增加、PPARγ 激活和 Smad7 表达有关，从而协同抑制 NF-κB/TGF-β1/Smad 信号通路。
