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.
Highlights
Periodontitis is a chronic inflammatory disease that compromises the integrity of the tooth-supporting tissues, which include the gingiva, periodontal ligament, and alveolar bone, and are collectively known as the periodontium
In order to begin the process of identifying the active compounds, the ethyl acetate (EE) extract was divided into five fractions, which were tested for the inhibitory effect against P. gingivalis-induced
Cells the inflammationTo elucidate the underlying anti-inflammatory mechanism,THP-1 we evaluated related signaling cascades, mitogen-activated protein kinase (MAPK) including extracellular signal-related kinase (ERK), p38-mitogenTo elucidate the underlying anti-inflammatory mechanism, we evaluated the inflammation-related activated kinase (p38), and c-Jun N-terminal kinase (JNK)
Summary
Periodontitis is a chronic inflammatory disease that compromises the integrity of the tooth-supporting tissues, which include the gingiva, periodontal ligament, and alveolar bone, and are collectively known as the periodontium. Exposure to P. gingivalis can trigger the production of pro-inflammatory mediators, such as interleukin (IL)-8, IL-6, IL-1β, and tumor necrosis factor (TNF)-α, in various cell types, including human gingival fibroblasts [4], periodontal ligament stem cells [5], macrophages, and peripheral CD4+ T helper cells [6]. These pro-inflammatory mediators may affect the activities of leukocytes, osteoblasts, and osteoclasts and promote the tissue remodeling process systemically and locally [7]. When compared with healthy individuals, a substantial subset of patients with periodontitis has elevated concentrations of pro-inflammatory cytokines in the gingival tissue [14] and serum [15]
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