title: Wild Bitter Melon Leaf Extract Inhibits Porphyromonas gingivalis-Induced Inflammation: Identification of Active Compounds through Bioassay-Guided Isolation.
abstract: Porphyromonas gingivalis has been identified as one of the major periodontal pathogens. Activity-directed fractionation and purification processes were employed to identify the anti-inflammatory active compounds using heat-killed P. gingivalis-stimulated human monocytic THP-1 cells in vitro. Five major fractions were collected from the ethanol/ethyl acetate extract of wild bitter melon (Momordica charantia Linn. var. abbreviata Ser.) leaves and evaluated for their anti-inflammatory activity against P. gingivalis. Among the test fractions, Fraction 5 effectively decreased heat-killed P. gingivalis-induced interleukin (IL)-8 and was subjected to separation and purification by using chromatographic techniques. Two cucurbitane triterpenoids were isolated from the active fraction and identified as 5β,19-epoxycucurbita-6,23-diene-3β,19,25-triol (1) and 3β,7β,25-trihydroxycucurbita-5,23-dien-19-al (2) by comparing spectral data. Treatments of both compounds in vitro potently suppressed P. gingivalis-induced IL-8, IL-6, and IL-1β levels and the activation of mitogen-activated protein kinase (MAPK) in THP-1 cells. Both compounds effectively inhibited the mRNA levels of IL-6, tumor necrosis factor (TNF)-α, and cyclooxygenase (COX)-2 in P. gingivalis-stimulated gingival tissue of mice. These findings imply that 5β,19-epoxycucurbita-6,23-diene-3β,19,25-triol and 3β,7β,25-trihydroxycucurbita-5,23-dien-19-al could be used for the development of novel therapeutic approaches against P. gingivalis infections.
authors.affiliation: Department of Dentistry, Keelung Chang-Gung Memorial Hospital, Keelung 204, Taiwan. tts1725@gmail.com.
authors.forename: Tzung-Hsun
authors.initials: TH
authors.lastname: Tsai
authors.affiliation: Department of Pediatrics, Taipei Tzu-Chi Hospital, The Buddhist Tzuchi Medical Foundation, New Taipei City 231, Taiwan. tim810481@yahoo.com.tw.|Department of Human Development and Family Studies, National Taiwan Normal University, Taipei 106, Taiwan. tim810481@yahoo.com.tw.
authors.forename: Wen-Cheng
authors.initials: WC
authors.lastname: Huang
authors.affiliation: Department of Human Development and Family Studies, National Taiwan Normal University, Taipei 106, Taiwan. rhutuyghk11@yahoo.com.tw.
authors.forename: How-Ting
authors.initials: HT
authors.lastname: Ying
authors.affiliation: Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung 404, Taiwan. kuoyh@mail.cmu.edu.tw.|Department of Biotechnology, Asia University, Taichung 413, Taiwan. kuoyh@mail.cmu.edu.tw.
authors.forename: Yueh-Hsiung
authors.initials: YH
authors.lastname: Kuo
authors.affiliation: National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Peitou, Taipei 112, Taiwan. ccshen@nricm.edu.tw.
authors.forename: Chien-Chang
authors.initials: CC
authors.lastname: Shen
authors.affiliation: Department of Chinese Internal Medicine, Keelung Chang-Gung Memorial Hospital, Keelung 204, Taiwan. lin1266@cgmh.org.tw.
authors.forename: Yin-Ku
authors.initials: YK
authors.lastname: Lin
authors.affiliation: Department of Human Development and Family Studies, National Taiwan Normal University, Taipei 106, Taiwan. pjtsai@ntnu.edu.tw.
authors.forename: Po-Jung
authors.initials: PJ
authors.lastname: Tsai
mesh_terms: D000818:Animals; D002460:Cell Line; D006027:Glycosides / Q000008:administration & dosage* / Q000737:chemistry / Q000302:isolation & purification; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000382:microbiology; D051379:Mice; D029777:Momordica charantia / Q000737:chemistry; D010936:Plant Extracts / Q000008:administration & dosage* / Q000737:chemistry; D018515:Plant Leaves / Q000737:chemistry; D016966:Porphyromonas gingivalis / Q000187:drug effects / Q000472:pathogenicity; D014315:Triterpenes / Q000008:administration & dosage* / Q000737:chemistry / Q000302:isolation & purification
chemical_list: D006027:Glycosides; D010936:Plant Extracts; D014315:Triterpenes; C514277:cucurbitane
keywords: Porphyromonas gingivalis; anti-inflammation; cucurbitane triterpenoid; wild bitter melon