Xu Lijiao, Chen Rongchang, Zhang Xu, Zhu Yue, Ma Xiaoyu, Sun Guibo, Sun Xiaobo
Institute of Medicinal Plant Development, Chinese Academy of Medical Science, Peking Union Medical College, Beijing, China.
School of Life and Environment Sciences, Harbin University of Commerce, Harbin, China.
Ann Palliat Med. 2021 Mar;10(3):2481-2493. doi: 10.21037/apm-19-516. Epub 2021 Feb 2.
Scutellarin (Scu) shows both anti-inflammatory and antioxidant activities. The study investigates cardioprotective effects of Scu in mice with type 1 diabetes and the underlying molecular mechanism.
Streptozotocin (STZ) was used to induce diabetic cardiomyopathy (DCM) in C57BL/6 mice by intraperitoneal injection (i.p.). Normal and diabetic mice were divided into 6 groups: control, diabetic model group (DM), DM + Scu (5 mg/kg), DM + Scu (10 mg/kg), DM + Scu (20 mg/kg), DM + pioglitazone (Pio) (10 mg/kg). Scu was administered to the mice intraperitoneally and Pio was administrated by oral. Mice in control and DM groups were simply treated normal saline. Four weeks later, myocardial function, myocardial fibrosis, the levels inflammatory factors and oxidative stress were detected.
Scu improved cardiac function and reduced heart injury in diabetic mice, which was indicated by increasing Left ventricular (LV) end-diastolic volume (LVVd), fractional shortening (FS), and ejection fraction (EF) levels and decreased pathological changes of heart. Scu inhibited the level of myocardial fibrosis by reducing the release of inflammatory cytokines and increasing activities of antioxidant enzymes. Further study showed that Scu inhibited the activation of nucleotide-binding oligomerization domain-like receptor with a pyrin domain 3 (NLRP3) and nuclear factor-kappa B (NF-κB) and activated phospho-protein kinase B (p-AKT), nuclear factor E2-related factor 2 (Nrf2), and heme oxygenase (HO-1).
Scu protects against DCM in STZ-induced diabetic mice by inhibiting oxidative stress and inflammatory responses and might be a potential therapeutic agent to treat DCM.
灯盏花素（Scu）具有抗炎和抗氧化活性。本研究探讨Scu对1型糖尿病小鼠的心脏保护作用及其潜在的分子机制。
采用链脲佐菌素（STZ）腹腔注射诱导C57BL/6小鼠发生糖尿病性心肌病（DCM）。将正常小鼠和糖尿病小鼠分为6组：对照组、糖尿病模型组（DM）、DM + Scu（5 mg/kg）组、DM + Scu（10 mg/kg）组、DM + Scu（20 mg/kg）组、DM + 吡格列酮（Pio）（10 mg/kg）组。Scu腹腔注射给药，Pio口服给药。对照组和DM组小鼠仅给予生理盐水。4周后，检测心肌功能、心肌纤维化、炎症因子水平和氧化应激情况。
Scu改善了糖尿病小鼠的心脏功能，减轻了心脏损伤，表现为左心室舒张末期容积（LVVd）、缩短分数（FS）和射血分数（EF）水平升高，心脏病理变化减轻。Scu通过减少炎症细胞因子的释放和增加抗氧化酶的活性来抑制心肌纤维化水平。进一步研究表明，Scu抑制含吡咯结构域的核苷酸结合寡聚化结构域样受体3（NLRP3）和核因子κB（NF-κB）的激活，并激活磷酸化蛋白激酶B（p-AKT）、核因子E2相关因子2（Nrf2）和血红素加氧酶（HO-1）。
Scu通过抑制氧化应激和炎症反应对STZ诱导的糖尿病小鼠的DCM具有保护作用，可能是治疗DCM的潜在治疗药物。
