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Beneficial Effects of Phyllanthus amarus Against High Fructose Diet Induced Insulin Resistance and Hepatic Oxidative Stress in Male Wistar Rats

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Abstract

Insulin resistance (IR) is a characteristic feature of obesity, type 2 diabetes mellitus, and cardiovascular diseases. Emerging evidence suggests that the high-fructose consumption is a potential and important factor responsible for the rising incidence of IR. The present study investigates the beneficial effects of aqueous extract of Phyllanthus amarus (PAAE) on IR and oxidative stress in high-fructose (HF) fed male Wistar rats. HF diet (66% of fructose) and PAAE (200 mg/kg body weight/day) were given concurrently to the rats for a period of 60 days. Fructose-fed rats showed weight gain, hyperglycemia, hyperinsulinemia, impaired glucose tolerance, impaired insulin sensitivity, dyslipidemia, hyperleptinemia, and hypoadiponectinemia (P < 0.05) after 60 days. Co-administration of PAAE along with HF diet significantly ameliorated all these alterations. Regarding hepatic antioxidant status, higher lipid peroxidation and protein oxidation, lower reduced glutathione levels and lower activities of enzymatic antioxidants, and the histopathological changes like mild to severe distortion of the normal architecture as well as the prominence and widening of the liver sinusoids observed in the HF diet-fed rats were significantly prevented by PAAE treatment. These findings indicate that PAAE is beneficial in improving insulin sensitivity and attenuating metabolic syndrome and hepatic oxidative stress in fructose-fed rats.

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Abbreviations

AI:

Atherogenic index

AUG:

Areas under the curve

CAT:

Catalase

CVD:

Cardiovascular disease

DMRT:

Duncan multiple range test

GI index:

Glucose–insulin index

GPx:

Glutathione peroxidase

GR:

Glutathione reductase

GSH:

Reduced glutathione

GST:

Glutathione-S-transferase

H&E:

Hematoxilin and eosin

HDL-C:

High-density lipoprotein cholesterol

HF:

High fructose

HOMA:

Homeostasis model assessment

IR:

Insulin resistance

LDL-C:

Low-density lipoprotein cholesterol

LPO:

Lipid peroxidation

MDA:

Malondialdehyde

MS:

Metabolic syndrome

NAFLD:

Non-alcoholic fatty liver disease

OGTT:

Oral glucose tolerance test

PAAE:

Aqueous extract of Phyllanthus amarus

PC:

Protein carbonyl

Pio:

Pioglitazone

PO:

Protein oxidation

ROS:

Reactive oxygen species

SOD:

Superoxide dismutase

T2DM:

Type 2 diabetes mellitus

TBARS:

Thiobarbituric acid reactive substances

TC:

Total cholesterol

TG:

Triglycerides

VLDL-C:

Very-low-density lipoprotein cholesterol

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Acknowledgements

This work was supported by grants from the University Grant Commission, New Delhi, India (F.4-3/2007 (BSR)/11-59/2007 (BSR). Thanks are also due to Dr. Ch. Appa Rao and Mr. K. Vinay Kumar, Sri Venkateswara University, Tirupati, AP, India, and Prof. B. Sashidhar Rao and Dr. G. Kavitha, Osmania University, Hyderabad, AP, India, for providing lab facility, Mr. R. Rajendran, Green Chem Herbal Extract and Formulations, Bangalore, for HPLC analysis, Prof. P. Md. Akthar, Department of Statistics, S.K. University for statistical analysis, and Prof. P.B.B.N. Charyulu, Department of Microbiology (Rtd), S.K. University Anantapuramu, AP, India, for proofreading of this article.

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Putakala, M., Gujjala, S., Nukala, S. et al. Beneficial Effects of Phyllanthus amarus Against High Fructose Diet Induced Insulin Resistance and Hepatic Oxidative Stress in Male Wistar Rats. Appl Biochem Biotechnol 183, 744–764 (2017). https://doi.org/10.1007/s12010-017-2461-0

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