Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, BS-10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow, 226031, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, U.P., India.
Division of Biochemistry & Structural Biology, CSIR-Central Drug Research Institute, BS-10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow, 226031, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, U.P., India.
Phytochemistry. 2022 Sep;201:113286. doi: 10.1016/j.phytochem.2022.113286. Epub 2022 Jun 23.
Bioactivity guided phytochemical investigation led to isolation of six undescribed furostanol saponins, furoasparoside A-F along with five known compounds, gallic acid, methyl gallate, quercetin-3-O-β-glucopyranoside, liquiritigenin 4-O-β-apiofuranosyl-(1 → 2)-β-glucopyranoside and β-glucogallin for the first time from the roots of Asparagus racemosus. Isolated saponins were screened for their antidiabetic potential in L6-GLUT4myc myotubes in vitro followed by an in vivo evaluation in streptozocin-induced diabetic rats and db/db mice. Furoasparoside E produced a notable decrease in the postprandial blood glucose profile, in leptin receptor-deficient db/db mice, type 2 diabetes model. The effect of furoasparoside E on GLUT4 translocation was found to be mediated by the AMPK-dependent signaling pathway in L6-GLUT4myc myotubes. Moreover, it emerged as a stable plant metabolite with higher bioavailability and efficacy in in vivo pharmacokinetic studies. Therefore, these studies indicated that furoasparoside E may serve as a propitious lead for the management of type 2 diabetes and its secondary complications from natural source.
生物活性导向的植物化学研究导致分离出六种未描述的呋甾烷醇皂苷,即呋罗 asparoside A-F,以及五种已知化合物,没食子酸、甲基没食子酸、槲皮素-3-O-β-吡喃葡萄糖苷、甘草素 4-O-β-阿魏酰-(1→2)-β-吡喃葡萄糖苷和β-葡萄糖没食子酸酯,这是首次从天门冬属植物的根部分离出来的。分离出的皂苷在体外 L6-GLUT4myc 肌管中进行了抗糖尿病潜力的筛选,然后在链脲佐菌素诱导的糖尿病大鼠和 db/db 小鼠中进行了体内评价。在瘦素受体缺陷型 db/db 小鼠(2 型糖尿病模型)中,呋罗 asparoside E 可显著降低餐后血糖谱。在 L6-GLUT4myc 肌管中,发现呋罗 asparoside E 对 GLUT4 易位的作用是通过 AMPK 依赖性信号通路介导的。此外,它作为一种稳定的植物代谢物,在体内药代动力学研究中具有更高的生物利用度和疗效。因此,这些研究表明,呋罗 asparoside E 可能成为从天然来源管理 2 型糖尿病及其继发性并发症的有利先导化合物。