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Dihydromyricetin protects against liver ischemia/reperfusion induced apoptosis via activation of FOXO3a-mediated autophagy.
Oncotarget. 2016 11 22; 7(47):76508-76522.O

Abstract

Liver ischemia and reperfusion (I/R) injury is characterized by defective liver autophagy accompanied by alterations to the endogenous defense system. Dihydromyricetin (DHM) is a natural flavonoid that demonstrates a wide range of physiological functions, and has been implicated as a regulator of autophagy. This study investigates the protective effects of DHM pretreatment on liver injury caused by ischemia/reperfusion (I/R) and elucidates the potential mechanism of DHM-mediated protection. Mice were subjected to 60 minutes of ischemia followed by 5 hours of reperfusion. DHM (100 mg/kg bw/day) or the vehicle was administered daily by gavage 7 days before ischemia and immediately before reperfusion. In this study, DHM markedly decreased serum aminotransferase activity and inhibited liver I/R -stimulated apoptosis. Moreover, DHM exerted hepatoprotective effects by upregulating mRNA levels of various essential autophagy-related genes including ATG5, ATG12, BECN1, and LC3. Autophagy inhibitor chloroquine or Atg5 knockdown blocked DHM -mediated elevation in liver function. Specifically, DHM significantly increased FOXO3a expression, and enhanced FOXO3a nuclear translocation and Ser588 phosphorylation modification. Importantly, the inhibition of FOXO3a with FOXO3a-siRNA in mice decreased DHM-induced autophagy-related genes and diminished the protective effects of DHM against liver I/R injury. In summary, these findings identify DHM as a novel hepatoprotective small molecule by elevating FOXO3a expression and nuclear translocation, stimulating autophagy-related genes and suppressing liver I/R-induced apoptosis, suggesting FOXO3a may have therapeutic value in liver cell protection in liver I/R injury.

Authors+Show Affiliations

Department of Hepatobiliary Surgery, Fuzhou General Hospital of PLA, Fuzhou, Fujian, China. Department of Hepatobiliary Surgery, Dongfang Hospital of Xiamen University, Fuzhou, Fujian, China.Department of Hepatobiliary Surgery, Fuzhou General Hospital of PLA, Fuzhou, Fujian, China. Department of Hepatobiliary Surgery, Dongfang Hospital of Xiamen University, Fuzhou, Fujian, China.Department of Occupational Health, Third Military Medical University, Chongqing, China.The 517th Hospital of PLA, Xinzhou, Shanxi, China.Department of Hepatobiliary Surgery, Fuzhou General Hospital of Fujian Medical University, Fuzhou, Fujian, China.Department of General Surgery, Mindong Hospital of Fujian Medical University, Fuan, Fujian, China.Department of Hepatobiliary Surgery, Fuzhou General Hospital of PLA, Fuzhou, Fujian, China. Department of Hepatobiliary Surgery, Dongfang Hospital of Xiamen University, Fuzhou, Fujian, China.Department of Hepatobiliary Surgery, Fuzhou General Hospital of PLA, Fuzhou, Fujian, China. Department of Hepatobiliary Surgery, Dongfang Hospital of Xiamen University, Fuzhou, Fujian, China.Department of Hepatobiliary Surgery, Fuzhou General Hospital of PLA, Fuzhou, Fujian, China. Department of Hepatobiliary Surgery, Dongfang Hospital of Xiamen University, Fuzhou, Fujian, China.Department of Hepatobiliary Surgery, Fuzhou General Hospital of PLA, Fuzhou, Fujian, China. Department of Hepatobiliary Surgery, Dongfang Hospital of Xiamen University, Fuzhou, Fujian, China.Department of Hepatobiliary Surgery, Fuzhou General Hospital of PLA, Fuzhou, Fujian, China. Department of Hepatobiliary Surgery, Dongfang Hospital of Xiamen University, Fuzhou, Fujian, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27793014

Citation

Chen, Yongbiao, et al. "Dihydromyricetin Protects Against Liver Ischemia/reperfusion Induced Apoptosis Via Activation of FOXO3a-mediated Autophagy." Oncotarget, vol. 7, no. 47, 2016, pp. 76508-76522.
Chen Y, Lv L, Pi H, et al. Dihydromyricetin protects against liver ischemia/reperfusion induced apoptosis via activation of FOXO3a-mediated autophagy. Oncotarget. 2016;7(47):76508-76522.
Chen, Y., Lv, L., Pi, H., Qin, W., Chen, J., Guo, D., Lin, J., Chi, X., Jiang, Z., Yang, H., & Jiang, Y. (2016). Dihydromyricetin protects against liver ischemia/reperfusion induced apoptosis via activation of FOXO3a-mediated autophagy. Oncotarget, 7(47), 76508-76522. https://doi.org/10.18632/oncotarget.12894
Chen Y, et al. Dihydromyricetin Protects Against Liver Ischemia/reperfusion Induced Apoptosis Via Activation of FOXO3a-mediated Autophagy. Oncotarget. 2016 11 22;7(47):76508-76522. PubMed PMID: 27793014.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dihydromyricetin protects against liver ischemia/reperfusion induced apoptosis via activation of FOXO3a-mediated autophagy. AU - Chen,Yongbiao, AU - Lv,Lizhi, AU - Pi,Huifeng, AU - Qin,Weijia, AU - Chen,Jianwei, AU - Guo,Dengfang, AU - Lin,Jianyu, AU - Chi,Xiaobing, AU - Jiang,Zhelong, AU - Yang,Hejun, AU - Jiang,Yi, PY - 2016/08/08/received PY - 2016/10/15/accepted PY - 2016/10/30/pubmed PY - 2018/2/27/medline PY - 2016/10/30/entrez KW - FOXO3a KW - dihydromyricetin KW - liver ischemia/reperfusion KW - Autophagy SP - 76508 EP - 76522 JF - Oncotarget JO - Oncotarget VL - 7 IS - 47 N2 - Liver ischemia and reperfusion (I/R) injury is characterized by defective liver autophagy accompanied by alterations to the endogenous defense system. Dihydromyricetin (DHM) is a natural flavonoid that demonstrates a wide range of physiological functions, and has been implicated as a regulator of autophagy. This study investigates the protective effects of DHM pretreatment on liver injury caused by ischemia/reperfusion (I/R) and elucidates the potential mechanism of DHM-mediated protection. Mice were subjected to 60 minutes of ischemia followed by 5 hours of reperfusion. DHM (100 mg/kg bw/day) or the vehicle was administered daily by gavage 7 days before ischemia and immediately before reperfusion. In this study, DHM markedly decreased serum aminotransferase activity and inhibited liver I/R -stimulated apoptosis. Moreover, DHM exerted hepatoprotective effects by upregulating mRNA levels of various essential autophagy-related genes including ATG5, ATG12, BECN1, and LC3. Autophagy inhibitor chloroquine or Atg5 knockdown blocked DHM -mediated elevation in liver function. Specifically, DHM significantly increased FOXO3a expression, and enhanced FOXO3a nuclear translocation and Ser588 phosphorylation modification. Importantly, the inhibition of FOXO3a with FOXO3a-siRNA in mice decreased DHM-induced autophagy-related genes and diminished the protective effects of DHM against liver I/R injury. In summary, these findings identify DHM as a novel hepatoprotective small molecule by elevating FOXO3a expression and nuclear translocation, stimulating autophagy-related genes and suppressing liver I/R-induced apoptosis, suggesting FOXO3a may have therapeutic value in liver cell protection in liver I/R injury. SN - 1949-2553 UR - https://www.unboundmedicine.com/medline/citation/27793014/Dihydromyricetin_protects_against_liver_ischemia/reperfusion_induced_apoptosis_via_activation_of_FOXO3a_mediated_autophagy_ L2 - http://www.impactjournals.com/oncotarget/misc/linkedout.php?pii=12894 DB - PRIME DP - Unbound Medicine ER -