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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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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DOI: https://doi.org/10.1007/s00210-019-01705-3