秦皮乙素通过改善脂肪组织重塑和激活 IRS1/PI3K/AKT/GLUT4 通路来改善肥胖诱导的胰岛素抵抗。
Esculin ameliorates obesity-induced insulin resistance by improving adipose tissue remodeling and activating the IRS1/PI3K/AKT/GLUT4 pathway.
机构信息
Department of Pharmacy, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China; Hunan Provincial Engineering Research Central of Translational Medical and Innovative Drug, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
Department of Geriatrics, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
出版信息
J Ethnopharmacol. 2024 Jan 30;319(Pt 2):117251. doi: 10.1016/j.jep.2023.117251. Epub 2023 Sep 29.
ETHNOPHARMACOLOGICAL RELEVANCE
Cortex fraxini (also known as qinpi)-the bark of Fraxinus rhynchophylla Hance (Oleaceae)-is widely used as a Chinese traditional medicinal for its anti-inflammatory and anti-hyperuricemic activities.
AIM OF THE STUDY
Obesity-induced insulin resistance (IR) is driving the rising incidence of type 2 diabetes mellitus and is related to pathological adipose tissue remodeling. Esculin, a major active component of Cortex fraxini, has anti-diabetic effects. However, whether esculin improves obesity-induced IR by regulating adipose tissue remodeling is unclear. The aims of the present study were to assess the effects of esculin on obesity-induced IR and to explore the underlying mechanisms.
MATERIALS AND METHODS
Obese IR C57BL/6J mice were treated with esculin (40 or 80 mg/kg/day) for 4 weeks. Oral glucose tolerance tests were used to assess insulin sensitivity. Histological analyses were performed to analyze the number and size distribution of adipocytes. Glucose uptake was assessed using 2-NBDG.
RESULTS
Esculin had no effect on body weight gain but reduced fasting blood glucose, improved oral glucose tolerance, and increased insulin sensitivity. Esculin reduced adipocyte size and the expression levels of collagen 4A1 and tumor necrosis factor α and increased the number of adipocytes and the expression of vascular endothelial growth factor A. Esculin promoted the differentiation of 3T3-L1 cells and upregulated the mRNA expression of CCAAT/enhancer-binding protein α and peroxisome proliferator-activated receptor-γ, activated the insulin receptor substrate 1 (IRS1)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway, and enhanced the translocation of glucose transporter type 4 (GLUT4) and glucose uptake in adipocytes treated with palmitic acid.
CONCLUSIONS
These data suggest that esculin increases insulin sensitivity by improving adipose tissue remodeling and activating the IRS1/PI3K/AKT/GLUT4 pathway.
植物亲缘学相关性
秦皮（又称芩皮）- 是由白蜡树属 Fraxinus rhynchophylla Hance（木犀科）的树皮制成，因其具有抗炎和抗高尿酸血症的活性，在中国传统医学中被广泛用作药物。
研究目的
肥胖引起的胰岛素抵抗（IR）是导致 2 型糖尿病发病率上升的原因，并且与病理性脂肪组织重塑有关。秦皮中的主要活性成分七叶灵具有抗糖尿病作用。然而，七叶灵是否通过调节脂肪组织重塑来改善肥胖引起的 IR 尚不清楚。本研究旨在评估七叶灵对肥胖引起的 IR 的影响，并探讨其潜在机制。
材料和方法
采用 40 或 80mg/kg/天的七叶灵处理肥胖 IR C57BL/6J 小鼠 4 周。采用口服葡萄糖耐量试验评估胰岛素敏感性。进行组织学分析以分析脂肪细胞的数量和大小分布。使用 2-NBDG 评估葡萄糖摄取。
结果
七叶灵对体重增加没有影响，但能降低空腹血糖，改善口服葡萄糖耐量，提高胰岛素敏感性。七叶灵降低了脂肪细胞的大小以及胶原 4A1 和肿瘤坏死因子 α 的表达水平，增加了脂肪细胞的数量和血管内皮生长因子 A 的表达。七叶灵促进了 3T3-L1 细胞的分化，并上调了 CCAAT/增强子结合蛋白-α和过氧化物酶体增殖物激活受体-γ 的 mRNA 表达，激活了胰岛素受体底物 1（IRS1）/磷酸肌醇 3-激酶（PI3K）/蛋白激酶 B（AKT）信号通路，并增强了经棕榈酸处理的脂肪细胞中葡萄糖转运蛋白 4（GLUT4）的转位和葡萄糖摄取。
结论
这些数据表明，七叶灵通过改善脂肪组织重塑和激活 IRS1/PI3K/AKT/GLUT4 通路来提高胰岛素敏感性。
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