PMID- 34666141 OWN - NLM STAT- MEDLINE DCOM- 20220216 LR - 20220216 IS - 1872-7573 (Electronic) IS - 0378-8741 (Linking) VI - 284 DP - 2022 Feb 10 TI - Integrated molecular biology and metabonomics approach to understand the mechanism underlying reduction of insulin resistance by corn silk decoction. PG - 114756 LID - S0378-8741(21)00985-5 [pii] LID - 10.1016/j.jep.2021.114756 [doi] AB - 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. CI - Copyright (c) 2021 Elsevier B.V. All rights reserved. FAU - Dong, Wenting AU - Dong W AD - 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. Electronic address: dongjiang20161103@163.com. FAU - Zhao, Yuanyuan AU - Zhao Y AD - Institute of Chinese Materia Medica, Heilongjiang Academy of Chinese Medicine Sciences, No.72 Xiang'an Street, Xiangfang District, Harbin, Heilongjiang, China. Electronic address: 634149407@qq.com. FAU - Hao, Yiming AU - Hao Y AD - Marine Engineering College, Dalian Maritime University, Dalian, 116026, Liaoning, China. Electronic address: hym1346010402@163.com. FAU - Sun, Guodong AU - Sun G AD - Institute of Chinese Materia Medica, Heilongjiang Academy of Chinese Medicine Sciences, No.72 Xiang'an Street, Xiangfang District, Harbin, Heilongjiang, China. Electronic address: xiaoqijulian@163.com. FAU - Huo, Jinhai AU - Huo J AD - Institute of Chinese Materia Medica, Heilongjiang Academy of Chinese Medicine Sciences, No.72 Xiang'an Street, Xiangfang District, Harbin, Heilongjiang, China. Electronic address: jinhaihuo@126.com. FAU - Wang, Weiming AU - Wang W AD - 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. Electronic address: zyyjy@163.com. LA - eng PT - Journal Article DEP - 20211016 PL - Ireland TA - J Ethnopharmacol JT - Journal of ethnopharmacology JID - 7903310 RN - 0 (Antioxidants) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - 0 (Plant Extracts) RN - 5W494URQ81 (Streptozocin) SB - IM MH - Animals MH - Antioxidants/isolation & purification/pharmacology MH - Diabetes Mellitus, Experimental/*drug therapy MH - Diabetes Mellitus, Type 2/drug therapy MH - Diet, High-Fat MH - Hypoglycemic Agents/isolation & purification/*pharmacology MH - Insulin/metabolism MH - Insulin Resistance MH - Male MH - Metabolomics MH - Molecular Biology MH - Plant Extracts/*pharmacology MH - Rats MH - Rats, Wistar MH - Signal Transduction/drug effects MH - Streptozocin MH - Zea mays/*chemistry OTO - NOTNLM OT - Corn silk OT - Insulin resistance OT - JNK signal pathway OT - Metabonomics OT - Oxidative stress OT - Type 2 diabetes mellitus EDAT- 2021/10/20 06:00 MHDA- 2022/02/17 06:00 CRDT- 2021/10/19 20:14 PHST- 2021/08/09 00:00 [received] PHST- 2021/10/02 00:00 [revised] PHST- 2021/10/15 00:00 [accepted] PHST- 2021/10/20 06:00 [pubmed] PHST- 2022/02/17 06:00 [medline] PHST- 2021/10/19 20:14 [entrez] AID - S0378-8741(21)00985-5 [pii] AID - 10.1016/j.jep.2021.114756 [doi] PST - ppublish SO - J Ethnopharmacol. 2022 Feb 10;284:114756. doi: 10.1016/j.jep.2021.114756. Epub 2021 Oct 16.