Advanced Search

Journal of Traditional Chinese Medicine >

2023 , Vol. 43 >Issue 1: 60 - 67

DOI: https://doi.org/10.19852/j.cnki.jtcm.2023.01.007

Original articles

Astragaloside IV ameliorates insulin induced insulin resistance in HepG2 cells through reactive oxygen species mediated c-Jun N-terminal kinase pathway

  • Xiaomei YE ,
  • Xiaowei XING ,
  • Kangrui YUAN ,
  • Dongming WANG ,
  • Dudu WU ,
  • Zhi CHEN ,
  • Zhiqiang YU
Expand
  • 1 School of Pharmacy, Guangdong Medical University, Dongguan 523808, China
    2 Department of Clinical Pharmacy, SSL Central Hospital of Dongguan City (the Third People's Hospital of Dongguan City), Dongguan 523326, China
    3 School of Pharmaceutical Sciences, Guangdong Provincial Key Laboratory of New Drug Screening, Southern Medical University, Guangzhou 510515, China
    4 Department of Pharmacy, Central People's Hospital of Zhanjiang, Zhanjiang 524037, China
YU Zhiqiang, School of Pharmaceutical Sciences, Guangdong Provincial Key Laboratory of New Drug Screening, Southern Medical University, Guangzhou 510515, China. zhiqiang.yu.1@asu.edu. Telephone:+86-769-22896321; +86-769-22896560
CHEN Zhi, School of Pharmaceutical Sciences, Guangdong Provincial Key Laboratory of New Drug Screening, Southern Medical University, Guangzhou 510515, China. czwududu@126.com;

Received date: 2021-03-22

  Accepted date: 2021-06-12

  Online published: 2023-01-10

Supported by

National Natural Science Foundation of Guangdong Province(2017A030310666);National Natural Science Foundation of Guangdong Province(2018A030307003);Guangdong Medical University Nanhai Marine Biomedical Resources R&D Public Service Platform Open Fund Project(2HC18013);Guangdong Medical University Nanhai Marine Biomedical Resources R&D Public Service Platform Open Fund Project(2HC18016);“Group-type” Special Support Project for Education Talents in Universities(4SG19045G);Undergraduate Science & Technology Innovation Foundation of Guangdong Province(201810571046);Undergraduate Science & Technology Innovation Foundation of Guangdong Province(201810571073);Medical Science and Technology Development Foundation of Guangdong Province(A2016355);The Opening Project of State Key Laboratory of Polymer Materials Engineering (Sichuan University)(sklpme2018-4-23)

Fold

Abstract

OBJECTIVE: To investigate the effects and elucidate the mechanism of Astragaloside IV (AS-IV) for insulin resistance (IR) and type 2 diabet es mellitus (T2DM).
METHODS: CCK8 kit was used to detect cell viability, glucose detection kit was used to detect the concentration of glucose in cell supernatant, reactive oxygen species (ROS) detection kit and Western blot were used to explore the mechanism of Astragaloside IV (AS-IV) in improving IR. A diabetic rat model was also established by feeding high sugar and fat diet and streptozotocin (STZ) injection. After treatment with AS-IV, rosiglitazone (ROZ), or normal saline, the fasting blood glucose (FBG), C peptide (C-P), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and the glucose tolerance were assessed.
RESULTS: AS-IV could effectively reduce the content of ROS and increase the glucose uptake in high insulin-treated IR-type HepG2 cells. The results of molecular mechanisms indicated that AS-IV could improve insulin resistance by reducing JNK phosphorylation and regulating c-Jun N-terminal kinase (JNK) downstream protein expression. Additionally, AS-IV could significantly reduce the levels of FBG, TNF-α, IL-6 and the glucose tolerance in diabetic rats (P < 0.05 or < 0.01). The high and medium dose groups of AS-IV could significantly increase the C-P levels in diabetic rats (P < 0.05 or < 0.01).
CONCLUSIONS: Our results indicated that AS-IV improve liver IR through the JNK pathway and ROS, which meant a new molecular target for the treatment of diabetes. The AS-IV also helped to prevent and improved the insulin resistance of rats.

Key words： Astragaloside IV; Insulin resistance; Glucose consumption; ROS; JNK; HepG2 cells

Cite this article

Xiaomei YE , Xiaowei XING , Kangrui YUAN , Dongming WANG , Dudu WU , Zhi CHEN , Zhiqiang YU . Astragaloside IV ameliorates insulin induced insulin resistance in HepG2 cells through reactive oxygen species mediated c-Jun N-terminal kinase pathway[J]. Journal of Traditional Chinese Medicine, 2023 , 43(1) : 60 -67 . DOI: 10.19852/j.cnki.jtcm.2023.01.007

References

1 Riddy DM, Delerive P, Summers RJ, Sexton PM, Langmead CJ. G Protein-Coupled Receptors Targeting Insulin Resistance, Obesity, and Type 2 Diabetes Mellitus. Pharmacol Rev 2018; 70: 39-67.
2 Farrokhian A, Bahmani F, Taghizadeh M, et al. Selenium supplementation affects insulin resistance and serum hs-CRP in patients with type 2 diabetes and coronary heart disease. Horm Metab Res 2016; 48: 263-8.
3 Motiani P, Virtanen KA, Motiani KK, et al. Decreased insulin-stimulated brown adipose tissue glucose uptake after short-term exercise training in healthy middle-aged men. Diabetes Obes Metab 2017; 19: 1379-88.
4 Keane KN, Cruzat VF, Carlessi R, de Bittencourt PIH, Newsholme P. Molecular events linking oxidative stress and inflammation to insulin resistance and β-cell dysfunction. Oxid Med Cell Longev 2015; 181643.
5 Bonnard C, Durand A, Peyrol S, et al. Mitochondrial dysfunction results from oxidative stress in the skeletal muscle of diet-induced insulin-resistant mice. J Clin Invest 2008; 118: 789-800.
6 Rehman K, Akash MSH. Mechanism of generation of oxidative stress and pathophysiology of type 2 diabetes mellitus: how are they interlinked? J Cell Biochem 2017; 118: 3577-85.
7 Badeau RM, Honka M-J, Lautam?ki R, et al. Systemic metabolic markers and myocardial glucose uptake in type 2 diabetic and coronary artery disease patients treated for 16 weeks with rosiglitazone, a PPARγ agonist. Ann Med 2014; 46: 18-23.
8 Zhang J, Liu X, Xie XB, Cheng XC, Wang RL. Multitargeted bioactive ligands for PPARs discovered in the last decade. Chem Biol Drug Des 2016; 88: 635-63.
9 Meijun L, Zhicheng L, Bin X, Wei Z, Jianwei C. Review of systematic reviews and Meta-analyses investigating Traditional Chinese Medicine treatment for type 2 diabetes mellitus. J Tradit Chin Med 2016; 36: 555-63.
10 Li L, Hou X, Xu R, Liu C, Tu M. Research review on the pharmacological effects of astragaloside IV. Fund Clin Pharmacol 2017; 31: 17-36.
11 Lv L, Wu SY, Wang GF, et al. Effect of astragaloside IV on hepatic glucose-regulating enzymes in diabetic mice induced by a high-fat diet and streptozotocin. Phytother Res 2010; 24: 219-24.
12 Yin Y, Qi F, Song Z, Zhang B, Teng J. Ferulic acid combined with astragaloside IV protects against vascular endothelial dysfunction in diabetic rats. BioSci Trends 2014; 8: 217-26.
13 Ji TJ, Wang ZY, Zhu YF, et al. Effect of astragaloside Ⅳ in regulating PI3K/Akt/FoxO1 pathway and inhibiting hepatic gluconeogenesis in diabetic rats. Zhong Guo Shi Yan Fang Ji Xue Za Zhi 2020; 26: 78-86.
14 Wang LN, Fang XM, Hu JP, Jia XF, Zhu GQ, Li YJ. Effect of Qidi Xiaoke prescription on C-peptide, tumor necrosis factor-α, interleukin-6, and histopathological changes of the spleen in rats with type 2 diabetes with deficiency of both Qi and Yin. J Anhui Univ Chin Med 2017; 36: 72-5.
15 Li M, Yang CY, Fu CH, Xiong YG, Ling Y. Study of purslane/ licorice/dandelion compound on insulin resistance in type 2 diabetic rats. Acta Lab Anim Sci Sin 2020: 1-10.
16 Liu P, Shi L, Cang X, et al. CtBP2 ameliorates palmitate-induced insulin resistance in HepG2 cells through ROS mediated JNK pathway. Gen and Comp Endocr 2017; 247: 66-73.
17 Lee BC, Lee J. Cellular and molecular players in adipose tissue inflammation in the development of obesity-induced insulin resistance. BBA - Mol Basis Dis 2014; 1842: 446-62.
18 Dai B, Wu Q, Zeng C, et al. The effect of Liuwei Dihuang decoction on PI3K/Akt signaling pathway in liver of type 2 diabetes mellitus (T2DM) rats with insulin resistance. J Ethnopharmacol 2016; 192: 382-9.
19 Zhang H, Ge Z, Tang S, Meng R, Bi Y, Zhu D. Erythropoietin ameliorates PA-induced insulin resistance through the IRS/AKT/ FOXO1 and GSK-3β signaling pathway, and inhibits the inflammatory response in HepG2 cells. Mol Med Rep 2017; 16: 2295-301.
20 Gao W, Du X, Lei L, et al. NEFA-induced ROS impaired insulin signalling through the JNK and p38MAPK pathways in non-alcoholic steatohepatitis. J Cell Mol Med 2018; 22: 3408.
21 Dong Y, Gao G, Fan H, Li S, Li X, Liu W. Activation of the liver X receptor by agonist TO901317 improves hepatic insulin resistance via suppressing reactive oxygen species and JNK Pathway. PLoS One 2015; 10: e0124778.
22 Yang Y, Li W, Li Y, Wang Q, Gao L, Zhao J. Dietary Lycium barbarum polysaccharide induces Nrf2/ARE pathway and ameliorates insulin resistance induced by high-fat via activation of PI3K/AKT sSignaling. Oxid Med Cell Longev 2014; 145641.
23 He S, Peng WB, Zhou HL. Combination treatment of deep sea water and fucoidan attenuates high glucose-induced insulin-resistance in HepG2 hepatocytes. Mar Drugs 2018; 16: 48.
24 Cordero-Herrera I, Martín Má, Goya L, Ramos S. Cocoa flavonoids attenuate high glucose-induced insulin signalling blockade and modulate glucose uptake and production in human HepG2 cells. Food Chem Toxicol 2014; 64: 10-9.
25 Song R, Wang X, Mao Y, et al. Resistin disrupts glycogen synthesis under high insulin and high glucose levels by down-regulating the hepatic levels of GSK3β. Gene 2013; 529: 50-6.
Options
Outlines

/

〈 〉