Your browser doesn't support javascript.
loading
Epigallocatechin-3-gallate Prevents Triptolide-Induced Hepatic Injury by Restoring the Th17/Treg Balance in Mice.
Yu, Shu-Jing; Jiang, Rong; Mazzu, Ying Z; Wei, Cai-Bing; Sun, Zong-Liang; Zhang, Yu-Zhen; Zhou, Lian-Di; Zhang, Qi-Hui.
Affiliation
  • Yu SJ; * School of Chemistry and Chemical Engineering, Chongqing University, Shapingba District, Shazheng Avenue, No. 174, Chongqing 400044, P.R. China.
  • Jiang R; † College of Basic Medical, Chongqing Medical University, Yuzhong District, Yixueyuan Avenue, No. 1, Chongqing 400016, P.R. China.
  • Mazzu YZ; ‡ Department of Surgery, Memorial Sloan-Kettering Cancer Center, York Avenue, 1275, New York, NY 10065, USA.
  • Wei CB; † College of Basic Medical, Chongqing Medical University, Yuzhong District, Yixueyuan Avenue, No. 1, Chongqing 400016, P.R. China.
  • Sun ZL; * School of Chemistry and Chemical Engineering, Chongqing University, Shapingba District, Shazheng Avenue, No. 174, Chongqing 400044, P.R. China.
  • Zhang YZ; * School of Chemistry and Chemical Engineering, Chongqing University, Shapingba District, Shazheng Avenue, No. 174, Chongqing 400044, P.R. China.
  • Zhou LD; † College of Basic Medical, Chongqing Medical University, Yuzhong District, Yixueyuan Avenue, No. 1, Chongqing 400016, P.R. China.
  • Zhang QH; * School of Chemistry and Chemical Engineering, Chongqing University, Shapingba District, Shazheng Avenue, No. 174, Chongqing 400044, P.R. China.
Am J Chin Med ; 44(6): 1221-1236, 2016.
Article de En | MEDLINE | ID: mdl-27744729
Drug-induced liver injury (DILI) is the most common cause of acute liver failure. Disruption of the Th17/Treg balance can lead to hepatic inflammation, which causes the main symptoms of DILI. Here we investigate the protective mechanisms of (-)-Epigallocatechin-3-gallate (EGCG) on triptolide (TP)-induced DILI that shows the Th17/Treg imbalance. Pretreatment with EGCG (5[Formula: see text]mg/kg) for 10 days before TP (0.5[Formula: see text]mg/kg) administration in mice significantly reduced the increased alanine aminotransferase (ALT) level ([Formula: see text]) induced by TP treatment. The hepatic histology analysis further proved that EGCG protected mice from TP-induced liver injury. The imbalance of Th17/Treg was induced by TP treatment, as shown by the upregulation of TLR4 and downregulation of Tim3 expression. EGCG pretreatment can maintain the expression of TLR4 and Tim3 at normal levels to restore the Th17/Treg imbalance. In addition, EGCG can block the TP-induced expression of the downstream targets of TLR4, including MyD88, NF[Formula: see text]B, and retinoid related orphan receptor (ROR-[Formula: see text]t), while EGCG can restore the TP inhibition of forkhead/winged-helix family transcriptional repressor p3 (FoxP3) that is the downstream target of Tim3. Consequently, EGCG pretreatment can effectively inhibit the Th17-related pro-inflammatory cytokine (e.g. IL-17 and IL-6) upregulation induced by TP treatment. However, TP inhibition of Treg-related anti-inflammatory cytokine IL-10 production was restored by EGCG pretreatment. Taken together, these results suggest that EGCG possesses significant protective properties against TP-induced hepatic inflammatory injury, and that these properties are carried out via the restoration of the Th17/Treg imbalance by the inhibition of the TLR4 signaling pathway and the enhanced activation of the Tim3 signaling pathway.
Sujet(s)
Mots clés
Recherche sur Google
Collection: 01-internacional Base de données: MEDLINE Sujet principal: Phénanthrènes / Catéchine / Lymphocytes T régulateurs / Diterpènes / Lésions hépatiques dues aux substances / Cellules Th17 / Immunosuppresseurs / Phytothérapie Type d'étude: Etiology_studies Limites: Animals Langue: En Journal: Am J Chin Med Année: 2016 Type de document: Article Pays de publication: Singapour
Recherche sur Google
Collection: 01-internacional Base de données: MEDLINE Sujet principal: Phénanthrènes / Catéchine / Lymphocytes T régulateurs / Diterpènes / Lésions hépatiques dues aux substances / Cellules Th17 / Immunosuppresseurs / Phytothérapie Type d'étude: Etiology_studies Limites: Animals Langue: En Journal: Am J Chin Med Année: 2016 Type de document: Article Pays de publication: Singapour