title: 3-Methoxy-catalposide inhibits inflammatory effects in lipopolysaccharide-stimulated RAW264.7 macrophages.
abstract: Pseudolysimachion rotundum var. subintegrum is utilized as a traditional herbal remedy to treat cough, bronchitis, and asthma in Korea, Russia, China, and Europe. Here, we show that 3-methoxy-catalposide, a novel iridoide glycoside isolated from P. rotundum var. subintegrum has the anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated macrophages. The chemical structure of 3-methoxy-catalposide was determined by NMR, optical rotation and HRESIMS. In in vitro experiment, RAW264.7 cells were treated with 3-methoxy-catalposide for 2h before exposure to LPS for different times. Inflammatory gene and protein expressions were assayed using RT-PCR and ELISA. Activities of signal proteins were examined using western analysis. Our results demonstrated that 3-methoxy-catalposide significantly inhibits the expression of cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) in RAW264.7 cells stimulated by LPS, thereby suppressing the release of prostaglandin E2 (PGE2) and nitric oxide (NO). Moreover, 3-methoxy-catalposide markedly reduced the LPS-induced expression of pro-inflammatory genes, such as interleukin (IL)-6, IL-1β, and TNF-α. Further, 3-methoxy-catalposide inhibited both LPS-induced activation of three MAP kinases (ERK 1/2, JNK, and p38) and the nuclear translocation of NF-κB and AP-1. These results support that 3-methoxy-catalposide may be a promising candidate for inflammation treatment.
authors.affiliation: Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang, Cheongju, Chungbuk 28116, Republic of Korea.
authors.forename: Hyung Won
authors.initials: HW
authors.lastname: Ryu
authors.affiliation: Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang, Cheongju, Chungbuk 28116, Republic of Korea.
authors.forename: Su Ui
authors.initials: SU
authors.lastname: Lee
authors.affiliation: Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang, Cheongju, Chungbuk 28116, Republic of Korea; College of Bioscience and Biotechnology, Chungnam National University, Daejeon 34134, Republic of Korea.
authors.forename: Seoghyun
authors.initials: S
authors.lastname: Lee
authors.affiliation: R&D Team, Agency for Korea National Food Cluster (AnFC), 460 Iksan-daero, Iksan, Jeonbuk 507-749, Republic of Korea.
authors.forename: Hyuk-Hwan
authors.initials: HH
authors.lastname: Song
authors.affiliation: Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang, Cheongju, Chungbuk 28116, Republic of Korea; College of Pharmacy, Chungbuk National University, Cheongju 28644, Republic of Korea.
authors.forename: Tae Hyun
authors.initials: TH
authors.lastname: Son
authors.affiliation: Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang, Cheongju, Chungbuk 28116, Republic of Korea.
authors.forename: Yeah-Un
authors.initials: YU
authors.lastname: Kim
authors.affiliation: Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang, Cheongju, Chungbuk 28116, Republic of Korea.
authors.forename: Heung Joo
authors.initials: HJ
authors.lastname: Yuk
authors.affiliation: College of Bioscience and Biotechnology, Chungnam National University, Daejeon 34134, Republic of Korea.
authors.forename: Hyunju
authors.initials: H
authors.lastname: Ro
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju 28644, Republic of Korea.
authors.forename: Chong-Kil
authors.initials: CK
authors.lastname: Lee
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science & Technology, 291 Daehak-ro, Yuseong, Daejeon 34141, Republic of Korea. Electronic address: mogwai@kaist.ac.kr.
authors.forename: Sung-Tae
authors.initials: ST
authors.lastname: Hong
authors.affiliation: Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang, Cheongju, Chungbuk 28116, Republic of Korea. Electronic address: seiryang@kribb.re.kr.
authors.forename: Sei-Ryang
authors.initials: SR
authors.lastname: Oh
mesh_terms: D000818:Animals; D048049:Extracellular Signal-Regulated MAP Kinases / Q000276:immunology*; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D057888:Iridoid Glucosides / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008264:Macrophages / Q000276:immunology* / Q000473:pathology; D051379:Mice; D015846:Monokines / Q000276:immunology*; D016328:NF-kappa B / Q000276:immunology; D000067996:RAW 264.7 Cells; D018808:Transcription Factor AP-1 / Q000276:immunology
chemical_list: D057888:Iridoid Glucosides; D008070:Lipopolysaccharides; D015846:Monokines; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: 3-Methoxy-catalposide; AP-1; MAP kinase; NF-κB; NO; PGE(2)