Pyranocoumarins from Root Extracts of Peucedanum praeruptorum Dunn with Multidrug Resistance Reversal and Anti-Inflammatory Activities

• Published in: Molecules (Basel, Switzerland) Vol. 20; no. 12; pp. 20967 - 20978
• Main Authors: Lee, Jun, Lee, You Jin, Kim, Jinhee, Bang, Ok-Sun
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 25.11.2015; MDPI
• Subjects: Animals; anti-inflammation; Anti-Inflammatory Agents - chemistry; Anti-Inflammatory Agents - pharmacology; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Apiaceae - chemistry; Cells, Cultured; Cytokines - metabolism; Drug resistance; Drug Resistance, Multiple - drug effects; Drug Resistance, Neoplasm - drug effects; Efflux; Female; Furanocoumarins; Humans; Inflammation; Ionization; Ions; Lipopolysaccharides; Lipopolysaccharides - pharmacology; Macrophages - cytology; Macrophages - drug effects; Mass spectrometry; Mass spectroscopy; Mice; Molecular Structure; MRP protein; Multidrug resistance; Multidrug resistant organisms; Nitric oxide; Nitric Oxide - metabolism; NMR; Nuclear magnetic resonance; Peucedanum; Peucedanum praeruptorum; Plant Extracts - pharmacology; Plant Roots - chemistry; Polyacetylene; Proteins; pyranocoumarin; Pyranocoumarins - chemistry; Pyranocoumarins - pharmacology; Sarcoma; Sarcoma - drug therapy; Sarcoma - pathology; Umbelliferae; Uterine Neoplasms - drug therapy; Uterine Neoplasms - pathology; multidrug resistance; pyranocoumarin; anti-inflammation; Umbelliferae; Peucedanum praeruptorum
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules201219738

In the search for novel herbal-based anticancer agents, we isolated a new angular-type pyranocoumarin, (+)-cis-(3'S,4'S)-3'-angeloyl-4'-tigloylkhellactone (1) along with 12 pyranocoumarins (2-13), two furanocoumarins (14, 15), and a polyacetylene (16) were isolated from the roots of Peucedanum praeruptorum using chromatographic separation methods. The structures of the compounds were determined using spectroscopic analysis with nuclear magnetic resonance (NMR) and high-resolution-electrospray ionization-mass spectrometry (HR-ESI-MS). The multidrug-resistance (MDR) reversal and anti-inflammatory effects of all the isolated compounds were evaluated in human sarcoma MES-SA/Dx5 and lipopolysaccharide (LPS)-induced RAW 264.7 cells. Among the 16 tested compounds, two (2 and 16) downregulated nitric oxide (NO) production and five (1, 7, 8, 11, and 13) inhibited the efflux of drugs by MDR protein, indicating the reversal of MDR. Therefore, these compounds may be potential candidates for the development of effective agents against MDR forms of cancer.