Tenuigenin exhibits anti-inflammatory activity via inhibiting MAPK and NF-κB and inducing Nrf2/HO-1 signaling in macrophages.
Tenuigenin (TNG), isolated from the root of the Chinese herb Polygala tenuifolia, possesses various biological and pharmacological activities, including anti-oxidation and anti-inflammation activities. In this study, we aimed to further investigate whether its anti-inflammatory activity is associated with the inhibition of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Our results showed that TNG treatment dramatically reduced prostaglandin E2 (PGE2) and NO production, decreased iNOS and COX-2 gene expression, inhibited JNK1/2, ERK1/2, p38 and NF-κB (p65) phosphorylation, and blocked IκBα phosphorylation and degradation. Further studies revealed that TNG dramatically up-regulated heme oxygenase (HO)-1 and nuclear factor erythroid 2-related factor 2 (Nrf2) expression, which was related to the induction of Nrf2 nuclear translocation and decreased Keap1 protein expression. Additionally, treatment with JNK1/2, ERK1/2 or p38 inhibitors had no effect on the TNG-induced HO-1 protein expression. Furthermore, the LPS-induced iNOS and COX-2 expression levels were inhibited by TNG, which was partially reversed by the HO-1-siRNA and HO-1 inhibitors. Together, these results showed that TNG's anti-inflammatory activity is related to the inhibition of iNOS and COX-2 expression via down-regulation of the MAPK and NF-κB, and up-regulation of the Nrf2/HO-1 signaling pathways.
College of Veterinary Medicine, Jilin University, Changchun 130062, PR China. yipengfei1982@126.com.
Hongming
H
Lv
College of Animal sciences, Jilin University, Changchun 130062, PR China.
Wenzhi
W
Ren
College of Veterinary Medicine, Jilin University, Changchun 130062, PR China. yipengfei1982@126.com.
Yuwei
Y
Zheng
College of Animal sciences, Jilin University, Changchun 130062, PR China.
Lidong
L
Wang
College of Veterinary Medicine, Jilin University, Changchun 130062, PR China. yipengfei1982@126.com.
Gejin
G
Lu
College of Veterinary Medicine, Jilin University, Changchun 130062, PR China. yipengfei1982@126.com.
Pengfei
P
Yi
College of Veterinary Medicine, Jilin University, Changchun 130062, PR China. yipengfei1982@126.com and Institutes of Translational Medicine, the First Hospital, Jilin University, Changchun, 130001, PR China. xinxinci@aliyun.com.
Xinxin
X
Ci
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents; D051546:Cyclooxygenase 2; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism*; D000072019:Kelch-Like ECH-Associated Protein 1; D008070:Lipopolysaccharides / Q000633:toxicity; D008264:Macrophages / Q000187:drug effects*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008665:Metalloporphyrins; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics / Q000378:metabolism*; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D031801:Polygala / Q000737:chemistry; D011524:Protoporphyrins; D000067996:RAW 264.7 Cells; D034741:RNA, Small Interfering; D015398:Signal Transduction
D048868:Adaptor Proteins, Signal Transducing; D000893:Anti-Inflammatory Agents; D003598:Cytoskeletal Proteins; D004365:Drugs, Chinese Herbal; C117301:Keap1 protein, mouse; D000072019:Kelch-Like ECH-Associated Protein 1; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D008665:Metalloporphyrins; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495636:Nfe2l2 protein, mouse; D011524:Protoporphyrins; D034741:RNA, Small Interfering; C493220:tenuigenin; C032628:tin protoporphyrin IX; D052247:Nitric Oxide Synthase Type II; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D020929:Mitogen-Activated Protein Kinase Kinases