Oxygenated compounds from the bioconversion of isostevic acid and their inhibition of TNF-α and COX-2 expressions in LPS-stimulated RAW 264.7 cells.
Fourteen oxygenated compounds were isolated from the preparative-scale biotransformation of isostevic acid (ent-beyeran-19-oic acid). Incubation of it with Aspergillus niger BCRC 32720 produced eight metabolites, four with Bacillus megaterium ATCC 14581, and another four with Mortierella isabellina ATCC 38063. In addition to their structural elucidation by NMR spectroscopy and HRMS, structures of four of these were further confirmed by X-ray diffraction studies. Real-time reverse transcription PCR analysis found that 15 of these compounds displayed significant in vitro anti-inflammatory activity in lipopolysaccharide-stimulated RAW 264.7 macrophages by reducing the levels of both TNF-α and COX-2 mRNA relative to control cells stimulated by LPS alone. The activity of one metabolite was similar to that of dexamethasone in inhibiting the expression of TNF-α mRNA, while all test compounds except two of them were more potent than dexamethasone in inhibiting the expression of the COX-2 mRNA.
Department of Medicinal Chemistry, College of Pharmacy, Taipei Medical University, Taipei 110, Taiwan.
Li-Ming
LM
Yang
Shwu-Fen
SF
Chang
Wen-Kuang
WK
Lin
Bo-Hon
BH
Chou
Li-Hsuan
LH
Wang
Pan-Chun
PC
Liu
Shwu-Jiuan
SJ
Lin
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D004224:Diterpenes / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000235:genetics
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D004224:Diterpenes; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C572286:isostevic acid; D051546:Cyclooxygenase 2