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鬼针草总黄酮对HepG2细胞胰岛素抵抗的影响 Δ

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庞晓军 1，2＊ ，卢琳琳 ，黎东旺 ，赵一宇 ，刘国勇（1.钦州市第二人民医院药学部，广西 钦州 535000；2.广西
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医科大学药学院，南宁 530021；3.钦州市第二人民医院康复科，广西 钦州 535000；4.钦州市第二人民医院放
射科，广西 钦州 535000）

中图分类号 R965 文献标志码 A 文章编号 1001-0408（2022）08-0968-07
DOI 10.6039/j.issn.1001-0408.2022.08.11

摘 要 目的 探究鬼针草总黄酮（TFB）对人肝癌HepG2细胞胰岛素抵抗（IR）的影响。方法 取鬼针草，用80％乙醇回流提取，制
得TFB。利用棕榈酸体外诱导HepG2细胞复制IR模型，考察低、中、高质量浓度（20、40、80 mg/L）TFB对细胞葡萄糖消耗量的影
响；以二甲双胍为阳性对照，考察低、中、高质量浓度（20、40、80 mg/L）TFB对细胞中胰岛素受体底物1（IRS-1）、c-Jun氨基端激酶
（JNK）和蛋白激酶C（PKC）表达的影响。采用分子对接技术探讨槲皮素、槲皮苷等8个TFB主要活性成分与IRS-1、JNK、PKC蛋
白的相互作用。结果 TFB低、中、高质量浓度组细胞的葡萄糖消耗量均较模型组显著升高（P＜0.05或P＜0.01）。与正常组比较，
模型组细胞中的IRS-1、JNK蛋白的表达量均显著降低，PKC蛋白的表达量显著升高（P＜0.01）；与模型组比较，TFB低、中、高质量
浓度组和二甲双胍阳性对照组能上调IRS-1、JNK蛋白的表达并下调PKC蛋白的表达（P＜0.05或P＜0.01）。TFB中的海生菊苷与
IRS-1蛋白的分子对接能量打分值为－7.9 kcal/mol（1 kcal＝4.816 kJ），海生菊苷、芦丁与JNK蛋白的分子对接能量打分值均为－9.3
kcal/mol，槲皮苷与PKC蛋白的分子对接能量打分值为－4.9 kcal/mol，成分与蛋白间的相互作用包括形成氢键、疏水键等。结论
TFB对HepG2细胞IR有显著的改善作用，其机制可能与调节IRS、JNK、PKC蛋白的表达有关；海生菊苷、芦丁和槲皮苷可能是改
善IR的潜在活性成分。
关键词 鬼针草总黄酮；人肝癌HepG2细胞；胰岛素抵抗；胰岛素受体底物1、c-Jun氨基端激酶；蛋白激酶C；分子对接

Effects of total flavonoids of Bidens pilosa on insulin resistance in HepG2 cells
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PANG Xiaojun ，LU Linlin ，LI Dongwang ，ZHAO Yiyu ，LIU Guoyong（1. Dept. of Pharmacy，the Second
People’s Hospital of Qinzhou，Guangxi Qinzhou 535000，China；2. College of Pharmacy，Guangxi Medical
University，Nanning 530021，China；3. Dept. of Rehabilitation，the Second People’s Hospital of Qinzhou，
Guangxi Qinzhou 535000，China；4. Dept. of Radiology，the Second People’s Hospital of Qinzhou，Guangxi
Qinzhou 535000，China）
ABSTRACT OBJECTIVE To explore the effects of total flavonoids of Bidens polisa L.（TFB）on insulin resistance（IR）of
HepG2 cells. METHODS B. polisa L. was refluxed and extracted with 80％ ethanol to obtain TFB. Palmitic acid was used to
induce IR mode of HepG2 cells in vitro. The effects of low-concentration，medium-concentration and high-concentration（20，40，
80 mg/L） of TFB on the consumption of glucose were investigated. Using metformin as positive control， the effects of
low-concentration，medium-concentration and high-concentration（20，40，80 mg/L）of TFB on the protein expression of insulin
receptor substrate-1（IRS-1），c-Jun N-terminal kinase（JNK）and protein kinase C（PKC）were investigated. Molecular docking
technology was used to explore the interaction between eight main active components of TFB such as quercetin，quercitrin and
IRS-1，JNK and PKC proteins. RESULTS The glucose consumption of TFB low-concentration，medium-concentration and
high-concentration groups were increased significantly （P＜0.05 or P＜0.01）. Compared with normal group，the expression of
IRS-1 and JNK protein in the model group decreased significantly，and the expression of PKC protein increased significantly（P＜
0.01）. Compared with model group，the protein expression of IRS-1 and JNK could up-regulated while the protein expression of
PKC down-regulated in TFB low-concentration，medium-concentration and high-concentration groups and metformin positive
control group（P＜0.05 or P＜0.01）. The score of molecular docking energy between maritimetin in TFB and IRS-1 protein was
－7.9 kcal/mol（1 kcal＝4.816 kJ）. The scores of molecular docking energy of maritimetin，rutin and JNK protein were －9.3 kcal/mol.
The score of molecular docking energy between quercitrin and PKC protein was －4.9 kcal/mol. Interactions between components
and proteins included forming hydrogen bonds，hydrophobic bonds and so on. CONCLUSIONS TFB can significantly improve IR
of HepG2 cells，the mechanism of which may be related to the regulation of protein expression of IRS，JNK and PKC.
Maritimetin，rutin and quercitrin may be potential active ingredients for improving IR.
KEYWORDS total flavones of Bidens polisa L.； human
Δ 基金项目：广西研究生教育创新计划项目（No.JGY2018042）；
hepatoma HepG2 cells； insulin resistance； insulin receptor
钦州市科学研究与技术开发计划项目（No.20177419）
＊主任药师，主任营养技师。研究方向：临床药学和中药药理。 substrate-1； c-Jun N-terminal kinase； protein kinase C；
电话：0771-72873282。E-mail：pangxjun@163.com molecular docking

·968 · China Pharmacy 2022 Vol. 33 No. 8 中国药房 2022年第33卷第8期