Puerarin protects against high-fat high-sucrose diet-induced non-alcoholic fatty liver disease by modulating PARP-1/PI3K/AKT signaling pathway and facilitating mitochondrial homeostasis.

Abstract

As yet, there was no effective pharmacological therapy approved for non-alcoholic fatty liver disease (NAFLD). Here, we aimed to evaluate the therapeutic potential of puerarin against NAFLD and explored the underlying mechanisms. C57BL/6J mice were fed with a high-fat high-sucrose (HFHS) diet with or without puerarin coadministration intragastrically. The levels of hepatocellular injury, steatosis, fibrosis, and mitochondrial and metabolism alteration were detected. First, puerarin ameliorated histopathologic abnormalities due to HFHS. We observed a marked increase in hepatic lipid content, inflammation, and fibrosis level, which were attenuated by puerarin. Possible mechanisms were related to puerarin-mediated activation of PI3K/AKT pathway and further improvement in fatty acid metabolism. Puerarin restored the NAD+ content and beneficially affected the hepatic mitochondrial function, which attenuated HFHS-induced steatosis and metabolic disturbances. Finally, hepatic PARP-1 was activated due to excessive fat intake. Puerarin attenuated the PARP-1 expression in HFHS-fed mice, and PJ34, the PARP inhibitor, could mimic these protections of puerarin. However, pharmacological inhibition of PI3K disabled the protection of puerarin or PJ34 toward NAD+ refilling and mitochondrial homeostasis. In conclusion, our findings indicated that puerarin could be a promising and practical therapeutic strategy in NAFLD through modulating PARP-1/PI3K/AKT signaling pathway and further facilitating mitochondrial function.

• Authors: Shuai Wang, Fa-Ji Yang, Long-Cheng Shang, Yu-Heng Zhang, Yuan Zhou, Xiao-Lei Shi
• Journal: Phytotherapy research : PTR (Phytother Res) Vol. 33 Issue 9 Pg. 2347-2359 (Sep 2019) ISSN: 1099-1573 [Electronic] England
• PMID: 31273855 (Publication Type: Journal Article)
• Copyright: © 2019 John Wiley & Sons, Ltd.

Chemical References

• Isoflavones
• Poly(ADP-ribose) Polymerase Inhibitors
• Vasodilator Agents
• Sucrose
• Proto-Oncogene Proteins c-akt
• puerarin

Topics

• Animals
• Diet, High-Fat (adverse effects)
• Humans
• Isoflavones (pharmacology, therapeutic use)
• Male
• Mice
• Mice, Inbred C57BL
• Non-alcoholic Fatty Liver Disease (drug therapy)
• Phosphatidylinositol 3-Kinases (metabolism)
• Poly(ADP-ribose) Polymerase Inhibitors (pharmacology, therapeutic use)
• Proto-Oncogene Proteins c-akt (metabolism)
• Sucrose (adverse effects)
• Vasodilator Agents (pharmacology, therapeutic use)