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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
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 o...
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Published in: | Phytotherapy research 2019-09, Vol.33 (9), p.2347-2359 |
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Main Authors: | , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | 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. |
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ISSN: | 0951-418X 1099-1573 |
DOI: | 10.1002/ptr.6417 |