Wild Bitter Melon Leaf Extract Inhibits Porphyromonas gingivalis-Induced Inflammation: Identification of Active Compounds through Bioassay-Guided Isolation

• Published in: Molecules (Basel, Switzerland) Vol. 21; no. 4; p. 454
• Main Authors: Tsai, Tzung-Hsun, Huang, Wen-Cheng, Ying, How-Ting, Kuo, Yueh-Hsiung, Shen, Chien-Chang, Lin, Yin-Ku, Tsai, Po-Jung
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 06.04.2016; MDPI
• Subjects: Animals; anti-inflammation; Bioassays; Cell Line; cucurbitane triterpenoid; Cytokines; Cytotoxicity; Ethanol; Glycosides - administration & dosage; Glycosides - chemistry; Glycosides - isolation & purification; Gum disease; Hospitals; Humans; Inflammation - drug therapy; Inflammation - microbiology; Kinases; Mice; Momordica charantia; Momordica charantia - chemistry; Pathogenesis; Periodontium; Plant Extracts - administration & dosage; Plant Extracts - chemistry; Plant Leaves - chemistry; Porphyromonas gingivalis; Porphyromonas gingivalis - drug effects; Porphyromonas gingivalis - pathogenicity; Triterpenes - administration & dosage; Triterpenes - chemistry; Triterpenes - isolation & purification; Tumor necrosis factor-TNF; wild bitter melon; Taiwan; Porphyromonas gingivalis; anti-inflammation; wild bitter melon; cucurbitane triterpenoid
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules21040454

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.