The protective effect of juglanin on fructose-induced hepatitis by inhibiting inflammation and apoptosis through TLR4 and JAK2/STAT3 signaling pathways in fructose-fed rats.
High fructose-feeding is an essential causative factor leading to the development and progression of hepatitis associated with high levels of endotoxin (LPS). Juglanin, as a natural compound extracted from the crude Polygonum aviculare, displayed inhibitory activity against inflammation response and cancer growth. However, researches about its role on anti-inflammation and apoptosis are far from available. Here, it is the first time that juglanin was administrated to investigate whether it inhibits fructose-feeding-induced hepatitis in rats and to elucidate the possible mechanism by which juglanin might recover it. Fructose-feeding rats were orally administrated with juglanin of 5, 10 and 20mg/kg for 6 weeks, respectively. Juglanin exerted prevention of fructose-feeding-stimulated increased LPS levels, accelerated alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP) and up-regulated inflammatory cytokines expression in serum, mainly including tumor necrosis factor-alpha (TNF-a), Interleukin 1beta (IL-1β), Interleukin 6 (IL-6) and Interleukin 18 (IL-18). Meanwhile, toll-like receptor 4 (TLR4)-modulated mitogen-activated protein kinase (MAPK)/nuclear factor kappa B (NF-κB) and apoptosis-related Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway are involved in the progression of hepatic injury and inflammation. And juglanin was found to suppress fructose-feeding-induced activation of these signaling pathways compared with the model group administrated only with fructose. These results indicate that juglanin represses inflammatory response and apoptosis via TLR4-regulated MAPK/NF-κB and JAK2/STAT3 signaling pathway respectively in rats with hepatitis induced by LPS for fructose-feeding. Treatment of juglanin might be an effective therapeutic strategy for preventing hepatitis.
Department of Infectious Disease, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China.
Guang-Yao
GY
Zhou
Department of Hepatobiliary Surgery, The Second Hospital of Nanjing, Affiliated to Southeast University, Nanjing 210003, China.
Yong-Xiang
YX
Yi
Department of Infectious Disease, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China.
Ling-Xiang
LX
Jin
Department of Infectious Disease, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China.
Wei
W
Lin
Department of Infectious Disease, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China.
Pei-Pei
PP
Fang
Department of Infectious Disease, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China.
Xiu-Zheng
XZ
Lin
Department of Infectious Disease, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China.
Yi
Y
Zheng
Department of Infectious Disease, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China. Electronic address: panchenweigrk@126.com.
Chen-Wei
CW
Pan
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D005247:Feeding Behavior; D005632:Fructose; D006027:Glycosides / Q000494:pharmacology / Q000627:therapeutic use*; D006505:Hepatitis / Q000188:drug therapy* / Q000473:pathology; D007249:Inflammation / Q000150:complications / Q000188:drug therapy*; D053614:Janus Kinase 2 / Q000378:metabolism*; D044949:Kaempferols / Q000494:pharmacology / Q000627:therapeutic use*; D008099:Liver / Q000187:drug effects / Q000293:injuries / Q000473:pathology; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use; D017207:Rats, Sprague-Dawley; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
D016207:Cytokines; D006027:Glycosides; D044949:Kaempferols; D016328:NF-kappa B; D020011:Protective Agents; D050796:STAT3 Transcription Factor; D051197:Toll-Like Receptor 4; C000590800:juglanin; D005632:Fructose; D053614:Janus Kinase 2; D020928:Mitogen-Activated Protein Kinases
Hepatitis; Inflammation; JAK2/STAT3 signaling pathway; Juglanin; TLR4