芒果苷降糖活性及其体内药代动力学研究

Study on hypoglycemic activity of mangiferin and its pharmacokinetics in vivo

摘要:

目的：探究芒果苷对小鼠成肌细胞（C2C12）葡萄糖的吸收影响及其在SD大鼠体内的药代动力学特征。方法：C2C12分化成成熟的肌管后分为正常细胞（normal C2C12 cells，Nor-C2C12）和胰岛素抵抗细胞（insulin resistance C2C12 cells，IR-C2C12）（棕榈酸造模），不同浓度芒果苷干预后分别观察各组细胞葡萄糖吸收情况。6只SD大鼠灌胃20 mg/kg芒果苷，液质联用法检测不同时间段大鼠体内血药浓度，分析其药代动力学参数。结果：IR-C2C12葡萄糖吸收明显低于Nor-C2C12（P＜0.01）。且无论是Nor-C2C12还是IR-C2C12，芒果苷在较高剂量（1 000、500、250 μg/mL）下均可以明显提高细胞的葡萄糖吸收（P＜0.01）。药代动力学结果显示，芒果苷的HL_Lambda_z=1.34 h；Tmax=1.75 h；Cmax=90.65 ng/mL；AUClast=318.40 h·ng/mL；AUCINF_pred=327.10 h·ng/mL；MRTlast=2.47 h；Vz_F_pred=136.42 L/kg；Cl_F_pred=67.48 L/（h·kg）。结论：芒果苷具有增加C2C12细胞葡萄糖吸收、改善细胞胰岛素抵抗状态的活性。该药物发挥作用相对较快，生物利用度较高，具有开发成良好降糖药物或保健品的潜质。

Abstract:

Objective：To investigate the effect of mangiferin on glucose uptake in mouse myoblasts（C2C12） and its pharmacokinetic features in SD rats. Methods：After C2C12 differentiated into mature myotubes，it was divided into normal C2C12 cells（Nor-C2C12） and insulin resistance C2C12 cells（IR-C2C12） （palmitic acid modeling）. The glucose uptake of cells was observed after intervention with different concentrations of mangiferin. Then we administered 20 mg/kg mangiferin by gavage to 6 SD rats，and detected the blood concentration of mangiferin in the rats at different times by LC-MS，and analyzed its pharmacokinetic parameters. Results：The glucose uptake of IR-C2C12 was significantly lower than that of Nor-C2C12（P<0.01）. And whether it was normal cells or IR cells，mangiferin at higher doses（1 000，500，250 μg/mL） could significantly increase the glucose uptake of cells（P<0.01）. Pharmacokinetic study results showed：mangiferin HL_Lambda_z=1.34 h；Tmax=1.75 h；Cmax=90.65 ng/mL；AUClast=318.40 h·ng/mL；AUCINF_pred=327.10 h·ng/mL；MRTlast=2.47 h；Vz_F_pred=136.42 L/kg；Cl_F_pred=67.48 L/（h·kg）. Conclusion：Mangiferin has the activity of increasing the glucose uptake of C2C12 cells and alleviating the IR state of cells. This drug acts relatively quickly and has high bioavailability，which has the poten－tial to be developed into a good hypoglycemic drug or health care product.