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Vitexin isolated from Acanthus ilicifolius L. leaf enhances GLUT-4 translocation in experimental diabetic rats

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Abstract

Acanthus ilicifolius L. leaf is extensively used in the Indian and Chinese medicine systems to treat diabetes mellitus. In this study, the antidiabetic effect of vitexin isolated from A. ilicifolius leaf extract and their effect on glucose transporter protein type-4 (GLUT-4) translocation and peroxisome proliferator-activated receptor gamma (PPAR-γ) expression was evaluated in high-fat diet-streptozotocin (HFD-STZ) induced rats. In vitro antidiabetic effect of vitexin was investigated through glucose uptake activity in L6 (rat skeletal muscle) cell lines. Vitexin (10 and 20 mg/kg BW) was administered orally to HFD-STZ-induced diabetic rats for 48 days. The effect of vitexin on body weight, fasting blood glucose, serum insulin, total protein, urea, creatinine, and liver enzymes was examined. GLUT-4 translocation and PPAR-γ expression were studied in the skeletal muscle and adipocytes of experimental rats. The interaction of vitexin with GLUT-4 and PPAR-γ was validated by molecular docking analysis. Vitexin significantly lowered the blood glucose and also normalized other biochemical parameters. Furthermore, the treatment with vitexin up-regulates the mRNA expression of GLUT-4 and PPAR-γ in diabetic rats. In silico analysis also supports the promising interactions between vitexin and target proteins. These results explained that vitexin up-regulates the mRNA expression of GLUT-4 and PPAR-γ and enhanced the translocation of GLUT-4 which maintains glucose homeostasis. Thus, vitexin can serve as a novel antidiabetic drug in future.

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Abbreviations

A. ilicifolius :

Acanthus ilicifolius

ALT:

Alanine transaminase

ALP:

Alkaline phosphatase

AST:

Aspartate aminotransferase

ANOVA:

Analysis of variance

ACE:

Atomic contact energy

BW:

Body weight

13C NMR:

Carbon-13 nuclear magnetic resonance

cDNA:

Complementary DNA

DM:

Diabetes mellitus

DEPC:

Diethyl pyrocarbonate

DMSO:

Dimethyl sulfoxide

ELISA:

Enzyme-linked immunosorbent assay

EDTA:

Ethylene diamine tetraacetic acid

FBG:

Fasting blood glucose

FSI:

Fasting serum insulin

FTIR:

Fourier transform infrared

GC:

Gas chromatography

GLUT-4:

Glucose transporter protein type-4

HbA1c:

Glycated hemoglobin

HSQC:

Heteronuclear single quantum coherence

HDL:

High-density lipoprotein cholesterol

HFD:

High-fat diet

HFD-STZ:

High-fat diet-streptozotocin

HOMA-IR:

Homeostasis of model assessment-insulin resistance

1H NMR:

Hydrogen-1 nuclear magnetic resonance

IR:

Infrared

λmax :

Lambda max

LD50 :

lethal dose, 50%

LC-MS:

Liquid chromatography-mass spectrometry

LDL:

Low-density lipoprotein

NTC:

Negative temperature coefficient

NMR:

Nuclear magnetic resonance

OECD:

Organisation for Economic Co-operation and Development

PPAR-γ:

Peroxisome proliferator-activated receptor gamma

PCR:

Polymerase chain reaction

PDB:

Protein Data Bank

RBC:

Red blood cell

RT-PCR:

Real-time polymerase chain reaction

Rf :

Retention factor

RNA:

Ribonucleic acid

RNAse:

Ribonuclease

NaOH:

Sodium hydroxide

STZ:

Streptozotocin

TLC:

Thin-layer chromatography

TC:

Total cholesterol

TP:

Total protein

TG:

Triglycerides

2D COSY:

Two-dimensional correlation spectroscopy

VLDL:

Very low-density lipoproteins

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Acknowledgements

The authors would like to thank the management of Vellore Institute of Technology for supporting the study.

Funding

This study was supported by the management of Vellore Institute of Technology.

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Authors and Affiliations

  1. Department of Bio-Medical Sciences, School of Bio Sciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, 632014, India

    G. A. Gayathri, P. Kavya, D. Ashwini, Eshika Chakraborty & Gayathri Mahalingam

  2. Arcot Sri Mahalakshmi Women’s College, Villapakkam, Ranipet district, Tamil Nadu, 632521, India

    G. A. Gayathri

  3. Department of Biotechnology, Faculty of Applied Science, Lincoln University College, Petaling Jaya, Selangor, 47301, Malaysia

    Idris Adewale Ahmed

  4. Centre for Natural Products Research and Drug Discovery (CENAR), Level 3, Research Management & Innovation Complex, University Malaya, Kuala Lumpur, 50603, Malaysia

    Idris Adewale Ahmed

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Contributions

Study conception and design, material preparation, data collection, analysis, and writing of the first draft of the manuscript (Gayathri GA). Data analysis, manuscript writing, revision, and edition (Kavya P). Manuscript revision (Ashwini D, Eshika Chakraborty, and Idris Adewale Ahmed). Research work design and supervision, supervision of manuscript writing, revision, editing, and approval of the final version of the manuscript (Gayathri M). All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Gayathri Mahalingam.

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The study was conducted after obtaining the approval from Institutional Animal Ethical Committee (VIT/IEAC/9th/july26th/18). All the protocols on animal experiments were performed as per the guidelines of OECD.

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Gayathri, G.A., Kavya, P., Ashwini, D. et al. Vitexin isolated from Acanthus ilicifolius L. leaf enhances GLUT-4 translocation in experimental diabetic rats. Aquacult Int 31, 3159–3187 (2023). https://doi.org/10.1007/s10499-023-01235-z

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