title: 3-(3-pyridylmethylidene)-2-indolinone reduces the severity of colonic injury in a murine model of experimental colitis.
abstract: Nrf2 is the key transcription factor regulating the antioxidant response which is crucial for cytoprotection against extracellular stresses. Numerous in vivo studies indicate that Nrf2 plays a protective role in anti-inflammatory response. 3-(3-Pyridylmethylidene)-2-indolinone (PMID) is a synthesized derivative of 2-indolinone compounds. Our previous study suggested that PMID induces the activation of Nrf2/ARE pathway, then protecting against oxidative stress-mediated cell death. However, little is known regarding the anti-inflammatory properties of PMID in severe inflammatory phenotypes. In the present study we determined if PMID treatment protects mice from dextran sodium sulphate- (DSS-) induced colitis. The result suggests that treatment with PMID prior to colitis induction significantly reduced body weight loss, shortened colon length, and decreased disease activity index compared to control mice. Histopathological analysis of the colon revealed attenuated inflammation in PMID pretreated animals. The levels of inflammatory markers in colon tissue and serum were reduced associated with inhibition of NF-κB activation. The expression levels of Nrf2-dependent genes such as HO-1, NQO1, and Nrf2 were increased in PMID pretreated mice. However, PMID pretreatment did not prevent DSS-induced colitis in Nrf2 knockout mice. These data indicate that PMID pretreatment in mice confers protection against DSS-induced colitis in Nrf2-dependent manner, suggesting a potential role of PMID in anti-inflammatory response.
authors: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors: Kun-Ping
authors: KP
authors: Wang
authors: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors: Chao
authors: C
authors: Zhang
authors: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors: Shou-Guo
authors: SG
authors: Zhang
authors: Anhui Medical University, Hefei 230032, China.
authors: En-Dong
authors: ED
authors: Liu
authors: Department of Anesthesiology, General Hospital of Chinese People's Armed Police Forces, Beijing 100039, China.
authors: Lan
authors: L
authors: Dong
authors: School of Chemical Engineering and Technology, Department of Pharmaceutical Engineering, Tianjin University, Tianjin 300072, China.
authors: Xiang-Zhen
authors: XZ
authors: Kong
authors: Laboratory of Cellular and Molecular Biology, Jiangsu Province Institute of Traditional Chinese Medicine, No. 100, Shizi Street, Hongshan Road, Nanjing, Jiangsu 210028, China.
authors: Peng
authors: P
authors: Cao
authors: Laboratory of Cellular and Molecular Biology, Jiangsu Province Institute of Traditional Chinese Medicine, No. 100, Shizi Street, Hongshan Road, Nanjing, Jiangsu 210028, China.
authors: Chun-Ping
authors: CP
authors: Hu
authors: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors: Ke
authors: K
authors: Zhao
authors: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors: Yi-Qun
authors: YQ
authors: Zhan
authors: School of Chemical Engineering and Technology, Department of Pharmaceutical Engineering, Tianjin University, Tianjin 300072, China.
authors: Xiao-Ming
authors: XM
authors: Dong
authors: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors: Chang-Hui
authors: CH
authors: Ge
authors: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors: Miao
authors: M
authors: Yu
authors: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors: Hui
authors: H
authors: Chen
authors: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors: Lin
authors: L
authors: Wang
authors: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China ; School of Chemical Engineering and Technology, Department of Pharmaceutical Engineering, Tianjin University, Tianjin 300072, China.
authors: Xiao-Ming
authors: XM
authors: Yang
authors: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China ; Anhui Medical University, Hefei 230032, China.
authors: Chang-Yan
authors: CY
authors: Li
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use*; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D003106:Colon / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D016207:Cytokines / Q000032:analysis / Q000235:genetics; D016264:Dextran Sulfate / Q000633:toxicity; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D007211:Indoles / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D011725:Pyridines / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use*; D012720:Severity of Illness Index
chemical_list: C000603440:3-(3-pyridylmethylidene)-2-indolinone; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D007211:Indoles; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; D011725:Pyridines; D016264:Dextran Sulfate; D051547:Heme Oxygenase-1; D016660:NAD(P)H Dehydrogenase (Quinone); C491732:Nqo1 protein, mouse