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采用整合分子生物学和代谢组学的方法来理解玉米须汤降低胰岛素抵抗的作用机制。

Integrated molecular biology and metabonomics approach to understand the mechanism underlying reduction of insulin resistance by corn silk decoction.

机构信息

College of Pharmacy, Harbin University of Commerce, No.138, Tongda Street, Daoli District, Harbin, Heilongjiang, China; Institute of Chinese Materia Medica, Heilongjiang Academy of Chinese Medicine Sciences, No.72 Xiang'an Street, Xiangfang District, Harbin, Heilongjiang, China.

Institute of Chinese Materia Medica, Heilongjiang Academy of Chinese Medicine Sciences, No.72 Xiang'an Street, Xiangfang District, Harbin, Heilongjiang, China.

出版信息

J Ethnopharmacol. 2022 Feb 10;284:114756. doi: 10.1016/j.jep.2021.114756. Epub 2021 Oct 16.

DOI:10.1016/j.jep.2021.114756
PMID:34666141
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Corn silk is composed of the style and stigma of Zea mays L. Its medical value was first reported in "Southern Yunnan Materia Medica" in the Ming Dynasty. It was considered to be a heat-clearing and diuretic drug. In "Zhejiang Folk Herbal Medicine," the following has been reported: "Corn silk needs one liang. Decoction in water can cure diabetes." Recent studies have shown that corn silk can lower blood sugar levels; however, to date, corn silk has undergone simple pharmacodynamic evaluations, with both its degree and mechanism of action remaining unclear.

AIM OF THE STUDY

This study aimed to investigate the mechanism of action of corn silk, with respect to having antioxidative ability, reducing insulin resistance, and having a hypoglycemic effect.

MATERIALS AND METHODS

In this study, a type 2 diabetes mellitus (T2DM) rat model was established via a high sugar and high fat diet combined with streptozotocin (35 mg/kg) administration. Wistar rats were administered corn silk decoction and metformin via gavage for four weeks, and the fasting blood glucose (FBG) and body weight were measured every two weeks. After the experiment, the insulin level, insulin index, and glycogen content were determined. Hematoxylin-eosin staining was used to observe the morphological changes of the skeletal muscle tissue in rats. The levels of malondialdehyde and superoxide dismutase in the serum and skeletal muscle were detected, and the mRNA content and protein levels of key proteins in the JNK-IRS-GLUT4 signaling pathway were determined using real-time quantitative polymerase chain reaction and western blotting. Then, ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry, combined with multiple statistical analyses, was used to identify potential biomarkers in the serum of T2DM rats, for determining the key metabolic pathways responsible for the action of corn silk.

RESULTS

The results showed that corn silk could reduce FBG, insulin level, and glycogen content in T2DM rats; reduce the level of oxidative stress in serum and skeletal muscle; restore the pathological structure of skeletal muscle; inhibit the phosphorylation of c-Jun N-terminal kinase (JNK) and insulin receptor substrate (IRS) in skeletal muscle; and upregulate the expression of glucose transporter type 4 (GLUT4) for transport of glucose and to reduce insulin resistance. Moreover, metabonomic analysis elucidated that corn silk could significantly affect 26 biomarkers (such as pentosidine, palmitic acid, lysoPC, and p-Cresol sulfate) and metabolic pathways (such as phenylalanine metabolism, phospholipid metabolism, bile acid metabolism, and biosynthesis of unsaturated fatty acids).

CONCLUSION

The interaction between endogenous metabolites and proteins in signaling pathways was analyzed using metabonomics and molecular biology methods. Corn silk inhibited JNK-IRS-GLUT4 signal transduction in skeletal muscle via antioxidative effects, by increasing the sensitivity of peripheral tissue to insulin, by reducing insulin resistance, and through hypoglycemic effects.

摘要

民族药理学相关性

玉米须由玉米的花柱和柱头组成。其药用价值最早在明代的《云南南部本草》中有所记载,被认为是一种清热利尿药。《浙江民间草药》中记载:“玉米须一两。水煎服,可治糖尿病。”最近的研究表明,玉米须可以降低血糖水平;然而,迄今为止,玉米须仅经过了简单的药效评估,其作用程度和作用机制仍不清楚。

研究目的

本研究旨在探讨玉米须通过抗氧化、降低胰岛素抵抗和降血糖作用的作用机制。

材料和方法

本研究通过高糖高脂饮食联合链脲佐菌素(35mg/kg)注射建立 2 型糖尿病(T2DM)大鼠模型。给予 Wistar 大鼠玉米须煎剂和二甲双胍灌胃 4 周,每两周测量一次空腹血糖(FBG)和体重。实验结束后,测定胰岛素水平、胰岛素指数和糖原含量。苏木精-伊红染色观察大鼠骨骼肌组织的形态变化。检测血清和骨骼肌中丙二醛和超氧化物歧化酶的水平,并采用实时定量聚合酶链反应和蛋白质印迹法测定 JNK-IRS-GLUT4 信号通路关键蛋白的 mRNA 含量和蛋白水平。然后,采用超高效液相色谱-四极杆飞行时间质谱联用技术,并结合多种统计分析方法,鉴定 T2DM 大鼠血清中的潜在生物标志物,以确定玉米须作用的关键代谢途径。

结果

结果表明,玉米须可降低 T2DM 大鼠的 FBG、胰岛素水平和糖原含量;降低血清和骨骼肌中氧化应激水平;恢复骨骼肌的病理结构;抑制骨骼肌中 c-Jun N-末端激酶(JNK)和胰岛素受体底物(IRS)的磷酸化;上调葡萄糖转运蛋白 4(GLUT4)的表达,促进葡萄糖转运,降低胰岛素抵抗。此外,代谢组学分析表明,玉米须可显著影响 26 种生物标志物(如戊糖素、棕榈酸、溶血磷脂酰胆碱和 p-对甲酚硫酸盐)和代谢途径(如苯丙氨酸代谢、磷脂代谢、胆汁酸代谢和不饱和脂肪酸的生物合成)。

结论

采用代谢组学和分子生物学方法分析内源性代谢物与信号通路中蛋白质的相互作用。玉米须通过抗氧化作用抑制骨骼肌中 JNK-IRS-GLUT4 信号转导,增加外周组织对胰岛素的敏感性,降低胰岛素抵抗,从而发挥降血糖作用。

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