title: Catalpol suppresses advanced glycation end-products-induced inflammatory responses through inhibition of reactive oxygen species in human monocytic THP-1 cells.
abstract: Advanced glycation end-products (AGEs) play a pivotal role in the development of diabetic complications by inducing inflammation. We previously reported that the fresh roots of Rehmannia glutinosa Libosch., which have been used for the treatment of diabetes in traditional Korean medicine, also have the potential to suppress AGE-mediated inflammatory response in THP-1 cells. In the present study, we isolated catalpol from R. glutinosa, and examined whether it has anti-inflammatory effects on AGE-stimulated THP-1 cells. Catalpol reduced the expression of pro-inflammatory mediates, such as monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), inducible NO synthase (iNOS), and receptor for AGE (RAGE). Promoter and electromobility shift assays showed that transcriptional activation of NF-κB was significantly reduced by catalpol treatment, while AP-1 was not. Catalpol also suppressed AGE-induced phosphorylation of mitogen activated protein (MAP) kinases, degradation of IκBα and the nuclear localization of NF-κB. Moreover, the production of intracellular reactive oxygen species (ROS) elicited by AGE was also suppressed by catalpol treatment, through dual action of reducing ROS itself and inhibiting NADPH oxidase activity. Our findings indicate that catalpol suppresses AGE-mediated inflammation by inhibiting ROS production and NF-κB activity. We suggest that catalpol, a major constituent of the fresh roots of R. glutinosa, contributes to the prevention of AGE-mediated diabetic complications.
authors: Division of Applied Medicine, School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam 626-870, Republic of Korea.
authors: Hee-Jung
authors: HJ
authors: Choi
authors: Hye-Jin
authors: HJ
authors: Jang
authors: Tae-Wook
authors: TW
authors: Chung
authors: Seung-Il
authors: SI
authors: Jeong
authors: Jaeho
authors: J
authors: Cha
authors: Jun-Young
authors: JY
authors: Choi
authors: Chang Woo
authors: CW
authors: Han
authors: Yong-Suk
authors: YS
authors: Jang
authors: Myungsoo
authors: M
authors: Joo
authors: Han-Sol
authors: HS
authors: Jeong
authors: Ki-Tae
authors: KT
authors: Ha
mesh_terms: D001692:Biological Transport; D002460:Cell Line; D048909:Diabetes Complications / Q000188:drug therapy / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D057888:Iridoid Glucosides / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D008517:Phytotherapy; D018517:Plant Roots; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors* / Q000378:metabolism; D032267:Rehmannia / Q000737:chemistry*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects
chemical_list: D004365:Drugs, Chinese Herbal; D017127:Glycation End Products, Advanced; D020672:I-kappa B Proteins; D018836:Inflammation Mediators; D057888:Iridoid Glucosides; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D017382:Reactive Oxygen Species; D018808:Transcription Factor AP-1; D000072000:NF-KappaB Inhibitor alpha; C078040:catalpol; D019255:NADPH Oxidases; D020928:Mitogen-Activated Protein Kinases