Antimicrobial DNA-binding Photosensitizers from the Common Rush, Juncus effusus¶

Abstract

Our continuing survey of phototoxins from higher plants has led to the isolation and identification from the common rush, Juncus effusus L., of the phenanthrene, dehydroeffusol (1), and the dihydrophenanthrene, juncusol (2), compounds that display enhanced antimicrobial activities in light. The antimicrobial activities (minimum inhibitory concentrations) for these compounds against methicillin‐resistant and ‐sensitive Staphylococcus aureus and Candida albicans were increased 16‐ and two‐fold, respectively, by irradiation with ultraviolet A (UVA). Photosensitized DNA‐binding activities (as possible covalent bond formation) of these compounds were determined by using restriction enzymes and a specially prepared 1.5 kb DNA fragment. Under UVA irradiation, dehydroeffusol strongly inhibited all the restriction enzymes (KpnI, XbaI, PmeI, DraI, PacI and BciVI) that have at least one 5′‐TpA sequence in their recognition sites. Weak inhibitions were found for the restriction enzymes EcoRI, SacI, BamHI, SalI, PstI and HindIII, which do not possess a 5′‐TpA sequence at their restriction sites and the restriction site sequences of which consist of all bases, A, T, G and C. Trace or no inhibition was found for AscI and SmaI, the restriction site sequences of which are composed of only C and G. The results indicate the necessity of thymine (adenine) for the photosensitized DNA‐binding activity of dehydroeffusol. A strong inhibition against SphI, which does not have a 5′‐TpA sequence in the restriction sequence, indicates that there are possibly other binding sequence(s) for dehydroeffusol. With juncusol and UVA, strong inhibitions for KpnI and BciVI and trace inhibitions for PacI, XbaI, PmeI and DraI were found. This result also showed a preference of juncusol for 5′‐TpA, but the preference could be more selective than that of dehydroeffusol depending on the surrounding sequences of 5′‐TpA in the respective restriction sites. A strong inhibition of SphI by juncusol with UVA also indicated the existence of an unknown binding sequence for this compound. Generally, the DNA‐binding activity of this compound was weaker than that of dehydroeffusol.

Family Juncaceae: promising source of biologically active natural phenanthrenes

“…Gentamicin (MIC values were 0.6 lg/mL for each bacteria, in both condition), methicillin (MIC values 1.6 lg/mL for MSSA, 500.0 lg/mL for MRSA, and 31.25 lg/mL for B. subtilis, in both conditions) and nystatin [MIC values [ 10.0 (UV) and 2.5 lg/mL (dark), in case of C. albicans] were used as positive controls. Photosensitized DNA-binding activities of these compounds were also determined by using restriction enzymes and a specially prepared 1.5 kb DNA fragment (Hanawa et al 2002).…”

“…The whole herb of J. effusus and its medulla (Medulla Junci TCM) are also used for treatment of diseases including pharyngitis, aphtha, and traumatic bleeding (Ma et al 2016). This drug was recorded to be used in traditional medicine as an antipyretic, antiphlogistic and as a sedative agent in Japan and China (Miles et al 1977;Shima et al1991;Hanawa et al 2002). The seeds of J. rigidus are consumed in Egypt in order to treat diarrhoea and diuretic disorders (Mahmoud and Gairola 2013).…”

The Phytochemistry of Cherokee Aromatic Medicinal Plants

“…[238] Rhizomes: alkaloids (berberine, canadaline, canadine, β-hydrastine, and isocorypalmine) [239] Rhizomes: alkaloids (hydrastinine, hydrastine, canadaline, berberine, canadine) [240] Leaves Hyperic-aceae St. John s wort root poultice used for stakebite root [15] Aerial parts: acyl-phloroglucinols (saroaspidin A, uliginosin A, hyperbrasilol C) [243] Aerial parts: acyl-phloroglucinols (3 -prenyl-phlorisobutyrophenone, saroaspidin A, uliginosin A, hyperbrasilol C) [244] Aerial parts: chlorogenic acid, hyperoside, isoquercitrin, quercitrin, quercetin, at least 9 acyl-phloroglucinols (not identified). The acyl-phloroglucinols fraction reduced prostaglandin E2 synthesis in mammalian macrophages [245] Underground parts: phenanthrenes (dehydroeffusol, juncusol); compounds showed UVA light-enhanced antimicrobial activities due to DNA binding [259] Plant: phenanthrenes (4-ethenyl-9,10-dihydro-1,8-dimethyl-2,7-phenanthrenediol, 4-ethenyl-9,10-dihydro-7-methoxy-1,8-dimethyl-2-phenanthrenol, 4-ethenyl-9,10-dihydro-3,8-dimethyl-1,7-phenanthrenediol, 4-ethenyl-9,10-dihydro-7-methoxy-3,8-dimethyl-1-phenanthrenol, 4-ethenyl-9,10-dihydro-7-hydroxy-8-methyl-2-phenanthrenecarboxylic acid) [260] Plant: phenanthrenes (junceunin F 2-methyl ether, 4-formyl-9,10-dihydro-3,7-dihydroxy-2,8-dimethylphenanthrene, 5-ethenyl-9,10-dihydro-1,7-dimethyl-2,3-phenanthrenediol, 9,10-dihydro-1,7-dihydroxy-4-(1-hydroxyethyl)-2,8-dimethylphenanthrene, 9,10-dihydro-6,6-dihydroxy-5-(1-hydroxyethyl)-1,7-dimethylphenanthrene, 9,10-dihydro-2,6-dihydroxy-5-(1-methoxyethyl)-1,7-dimethylphenanthrene, 4-ethenyl-9,10-dihydro-7-hydroxy-8-methyl-1-phenanthrenecarboxylic acid) [261] Plant: phenanthrenes (2-hydroxy-7-(hydroxymethyl)-1-methyl-5-vinyl-9,10-dihydrophenanthrene, 2-hydroxy-6-(hydroxymethyl)-1-methyl-5-vinyl-9,10-dihydrophenanthrene, 2-hydroxy-5-(hydroxymethyl)-1,7-dimethyl-9,10-dihydrophenanthrene, 2,7-dihydroxy-5-(hydroxymethyl)-1,8-dimethyl-9,10dihydrophenanthrene, 2-hydroxy-5-(hydroxymethyl)-7-methoxy-1,8-dimethyl-9,10dihydrophenanthrene, 5-(1-ethoxy)-2,7-dihydroxy-1,8-dimethyl-9,10-dihydrophenanthrene, 2-hydroxy-1,7-dimethyl-9,10 -dihydrophenanthro-[5,6-b]-4 ,5 -dihydro-4 ,5 -dihydroxyfuran) [262] Plant: phenanthrene glucosides (Effusides I-V) [263] Aerial parts: phenanthrenes (7-carboxy-2-hydroxy-1-methyl-5-vinyl-phenanthrene, 2,7-dihydroxy-1-methyl-5-aldehyde-9,10-dihydrophenanthrene, dehydroeffusol, dehydrojuncusol, 7-carboxy-2-hydroxy-1-methyl-5-vinyl-9,10-dihydrophenanthrene, 8-carboxy-2-hydroxy-1-methyl-5-vinyl-9,10-dihydrophenanthrene, effusol, and juncusol; effusol and juncusol showed anxiolytic and sedative activities) [264] Medullae: diterpenoid effusenone A, phenanthrene 5-(hydroxymethyl)-1-methylphenanthrene-2,7-diol, pyrenes 1-methylpyrene-2,7-diol and 7-methoxy-8-methylpyren-2-ol [265] Medullae: phenanthrenes (effusol, dehydroeffusol, dehydroeffusal) [266] Medullae: phenanthrenes (effusol, dehydroeffusol, juncusol, dehydrojuncusol, ju...…”

Dehydroeffusol inhibits hypoxia-induced epithelial–mesenchymal transition in non-small cell lung cancer cells through the inactivation of Wnt/β-catenin pathway

“…Dehydroeffusol (DHE) is a phenanthrene compound isolated from the Traditional Chinese Medicine (TCM) Juncus effusus. In vitro and in vivo biological evaluation reveal that DHE is a bioactive phytochemical with broad activities, including antimicrobial [10,11], anxiolytic and sedative [12] and anti-spasmogenic [13]. In recent years, DHE has been demonstrated to possess anticancer effects through several cancer-associated signaling pathways, such as NF-κB, β-catenin, and endoplasmic reticulum stress [14][15][16][17].…”