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

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.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.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.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).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.