title: Amomum tsao-ko fruit extract suppresses lipopolysaccharide-induced inducible nitric oxide synthase by inducing heme oxygenase-1 in macrophages and in septic mice.
abstract: Amomum tsao-ko Crevost et Lemarié (Zingiberaceae) has traditionally been used to treat inflammatory and infectious diseases, such as throat infections, malaria, abdominal pain and diarrhoea. This study was designed to assess the anti-inflammatory effects and the molecular mechanisms of the methanol extract of A. tsao-ko (AOM) in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages and in a murine model of sepsis. In LPS-induced RAW 264.7 macrophages, AOM reduced the production of nitric oxide (NO) by inhibiting inducible nitric oxide synthase (iNOS) expression, and increased heme oxygenase-1 (HO-1) expression at the protein and mRNA levels. Pretreatment with SnPP (a selective inhibitor of HO-1) and silencing HO-1 using siRNA prevented the AOM-mediated inhibition of NO production and iNOS expression. Furthermore, AOM increased the expression and nuclear accumulation of NF-E2-related factor 2 (Nrf2), which enhanced Nrf2 binding to antioxidant response element (ARE). In addition, AOM induced the phosphorylation of extracellular regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) and generated reactive oxygen species (ROS). Furthermore, pretreatment with N-acetyl-l-cysteine (NAC; a ROS scavenger) diminished the AOM-induced phosphorylation of ERK and JNK and AOM-induced HO-1 expression, suggesting that ERK and JNK are downstream mediators of ROS during the AOM-induced signalling of HO-1 expression. In LPS-induced endotoxaemic mice, pretreatment with AOM reduced NO serum levels and liver iNOS expression and increased HO-1 expression and survival rates. These results indicate that AOM strongly inhibits LPS-induced NO production by activating the ROS/MAPKs/Nrf2-mediated HO-1 signalling pathway, and supports its pharmacological effects on inflammatory diseases.
authors: Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, Seoul, Korea.|Reactive Oxygen Species Medical Research Center, School of Medicine, Kyung Hee University, Seoul, Korea.|Department of Physiology, School of Medicine, Kyung Hee University, Seoul, Korea.
authors: Ji-Sun
authors: JS
authors: Shin
authors: Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, Seoul, Korea.|Department of Biomedical Science, College of Medical Science, Kyung Hee University, Hoegi-Dong, Seoul, Korea.
authors: Suran
authors: S
authors: Ryu
authors: Department of Life and Nanopharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul, Korea.
authors: Dae Sik
authors: DS
authors: Jang
authors: Reactive Oxygen Species Medical Research Center, School of Medicine, Kyung Hee University, Seoul, Korea.|Department of Physiology, School of Medicine, Kyung Hee University, Seoul, Korea.
authors: Young-Wuk
authors: YW
authors: Cho
authors: Department of Pharmacy, College of Pharmacy, Kyung Hee University, Seoul, Korea.
authors: Eun Kyung
authors: EK
authors: Chung
authors: Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, Seoul, Korea.|Department of Life and Nanopharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul, Korea.
authors: Kyung-Tae
authors: KT
authors: Lee
mesh_terms: D035801:Amomum / Q000737:chemistry; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005638:Fruit; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis* / Q000235:genetics; D008517:Phytotherapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal; D000067996:RAW 264.7 Cells; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis; D017382:Reactive Oxygen Species / Q000378:metabolism; D018805:Sepsis / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014162:Transfection
chemical_list: D000893:Anti-Inflammatory Agents; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D010936:Plant Extracts; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases
keywords: Amomum tsao-ko; HO-1; NO; Nrf2; ROS; sepsis