Chrysin ameliorates nonalcoholic fatty liver disease in rats

Abstract

Nonalcoholic fatty liver disease (NAFLD) is regarded as the hepatic manifestation of the metabolic syndrome. It begins with the accumulation of fat in the liver (simple steatosis), which if untreated can progress to nonalcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma. Chrysin is a flavonoid present in bee propolis and many other plants. The objective of this study was to determine if chrysin can ameliorate NAFLD induced by feeding a high fructose diet (HFD) in rats. The rats were divided into five groups: normal control, HFD control, chrysin (25, 50, and 100 mg/kg p.o. body weight). Biochemical estimations were carried out in the serum and liver of rats. The gene expressions of SREBP-1c and PPAR α were determined in the liver. The histopathology of the liver was also studied. Chrysin caused a significant decrease in the serum fasting glucose and improved the insulin resistance, dyslipidemia, and liver enzymes. It caused a significant decrease in the liver weight and hepatic free fatty acids, triglyceride, and cholesterol content. Chrysin exerted antioxidant effects, reduced carbonyl content, advanced glycation end products, collagen, TNF-α, and IL-6 concentrations in the liver. Chrysin significantly reduced the hepatic gene expression of SREBP-1c and increased that of PPAR-α. The histopathology of liver of rats treated with chrysin showed significant decrease in the steatosis, ballooning, and lobular inflammation when compared to the HFD control group. Thus, chrysin demonstrated anti-steatotic, antiglycating, antioxidant, anti-inflammatory, and antifibrotic effects and seems to be a promising molecule for the management of NAFLD.

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Abbreviations

AGE:

advanced glycation end products

ALP:

alkaline phosphatase

ALT:

alanine aminotransferase

AST:

aspartate aminotransferase

AU:

arbitrary units

C25:

chrysin 25 mg/kg body weight

C50:

chrysin 50 mg/kg body weight

C100:

chrysin100 mg/kg body weight

ELISA:

enzyme-linked immunosorbent assay

FFA:

free fatty acids

GSH:

reduced glutathione

GGT:

gamma glutamyl transferase

HDL-C:

high density lipoprotein cholesterol

HFD:

high fructose diet

HOMA-IR:

homeostasis model assessment-insulin resistance

LDL-C:

low density lipoprotein cholesterol

MDA:

malondialdehyde

NAFLD:

nonalcoholic fatty liver disease

NASH:

nonalcoholic steatohepatitis

NC:

normal control

PPAR-α:

peroxisome proliferator activated receptor alpha

SOD:

superoxide dismutase

SREBP-1c:

sterol regulatory element binding protein-1c

TC:

total cholesterol

TG:

triglycerides

VLDL-C:

very low density lipoprotein cholesterol

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Acknowledgments

The authors are grateful to Ms. Deepali Ganachari and Ms. Jaya Verma, Research Fellows at the Department of Clinical Pharmacology, T. N. Medical College and BYL Nair Charitable Hospital for their technical assistance. The authors thank Dr. Vijay Kadwad and Ms. Shripriya, Board of Radiation and Isotope Technology, Navi Mumbai for their help in performing the radioimmunoassay of insulin and Dr. Sanjay Pawar, Veterinary Pathologist for carrying out the histopathological evaluation of the rat livers.

Funding

This work was supported by a grant from the University Grants Commission, New Delhi, India (Letter no.F.25-1/2014-15 (BSR)/No. F.5-63/2007 (BSR) dated 16 February 2015).

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S.A.P. carried out the literature search and conducted the animal studies, analyzed the results, and wrote the first draft of the manuscript. R.P.M. helped in designing the study. F.H.P. and I.S.G. carried out the RT-PCR studies. A.R.J. contributed to the design of the study and overall supervision. All authors read and approved the final manuscript.

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Correspondence to Archana R. Juvekar.

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The authors declare that they have no conflict of interest.

Statement on the welfare of animals

All experimental protocols described in this paper were approved by the Institutional Animal Ethics Committee of T. N. Medical College and BYL Nair Charitable Hospital (protocol no. TNMC/IAEC/2016/8B). All institutional and national guidelines for the care and use of laboratory animals were followed.

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Pai, S.A., Munshi, R.P., Panchal, F.H. et al. Chrysin ameliorates nonalcoholic fatty liver disease in rats. Naunyn-Schmiedeberg's Arch Pharmacol 392, 1617–1628 (2019). https://doi.org/10.1007/s00210-019-01705-3

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Keywords

  • Chrysin
  • Nonalcoholic fatty liver disease
  • Nonalcoholic steatohepatitis
  • SREBP-1c
  • PPAR-α