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ARS Home » Plains Area » Houston, Texas » Children's Nutrition Research Center » Research » Publications at this Location » Publication #356249
Title: Honokiol protects hepatocytes from oxidative injury through mitochondrial deacetylase SIRT3

Author
item LIU, JING-XIN - UNIVERSITY OF MACAU
item SHEN, SHENG-NAN - UNIVERSITY OF MACAU
item TONG, QIANG - CHILDREN'S NUTRITION RESEARCH CENTER (CNRC)
item WANG, YI-TAO - UNIVERSITY OF MACAU
item LIN, LI-GEN - UNIVERSITY OF MACAU

Submitted to: European Journal of Pharmacology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/19/2018
Publication Date: 7/20/2018
Citation: Liu, J., Shen, S., Tong, Q., Wang, Y., Lin, L. 2018. Honokiol protects hepatocytes from oxidative injury through mitochondrial deacetylase SIRT3. European Journal of Pharmacology. 834:176-187. http://doi.org/10.1007/s00018-018-2847-3.
DOI: https://doi.org/10.1007/s00018-018-2847-3

Interpretive Summary: Honokiol is a natural molecule from Magnolia plants. It exhibits potent anti-oxidant property. This study evaluates honokiol protection against oxidative injury to liver induced by chemicals such as t-BHP and CCl4. The results showed honokiol protects t-BHP-injured liver cells and CCl4-induced liver damage in mice by activating SIRT3, which plays a key role in anti-oxidant defense in cellular power plant mitochondria. Honokiol enhances the anti-oxidant capacity of superoxide dismutase 2. Honokiol also increases PGC1a level to increase the numbers of mitochondria. Moreover, honokiol attenuates t-BHP-induced mitochondrial fragmentation. These results suggest that honokiol can ameliorate oxidative damage in liver cells by activating SIRT3. Therefore, honokiol might be used for the treatment of liver cell damage.

Technical Abstract: Oxidative stress contributes to the initiation and progression of liver damage. SIRT3 is a member of nicotinamide adenine dinucleotide-dependent deacetylases that plays a key role in anti-oxidative defense and mitochondrial function in the liver. Honokiol is a natural lignan from the plants of Magnolia genus that exhibits potent anti-oxidative property. This study aims to evaluate the hepatoprotective potential of honokiol against oxidative injury in tert-butyl hydroperoxide (t-BHP)-injured AML12 hepatocytes in vitro and carbon tetrachloride (CCl4)-stimulated liver damaged mice in vivo and to determine whether or not this effect occurs by activating SIRT3. The results showed honokiol protects t-BHP-injured AML12 hepatocytes and CCl4-stimulated liver damage in mice by activating SIRT3. Honokiol reduces the acetylation level of superoxide dismutase 2 to enhance its anti-oxidative capacity, which decreases reactive oxygen species accumulation in AML12 cells. Honokiol increases the deacetylated peroxisome proliferator-activated receptor y coactivator 1-a level to promote mitochondrial biogenesis. Moreover, honokiol attenuates t-BHP induced mitochondrial fragmentation through Ku70-dynamin-related protein 1 axis. These results suggest that honokiol can ameliorate oxidative damage in hepatocytes by activating SIRT3, which might be a potential therapeutic agent for liver oxidative injury.