naphthoquinones and aethiopinone

Transcriptional activation of genes belonging to the plastidial MEP-derived isoprenoid pathway by elicitation with methyl jasmonate and coronatine enhanced the content of bioactive abietane diterpenes in Salvia sclarea hairy roots. We have shown that aethiopinone, an abietane diterpene synthesized in Salvia sclarea roots is cytotoxic and induces apoptosis in human melanoma cells. To develop a production platform for this compound and other abietane diterpenes, hairy root technology was combined with the elicitation of methyl jasmonate (MeJA) or the phytotoxin coronatine (Cor). Both MeJA and Cor induced a significant accumulation of aethiopinone, but prolonged exposure to MeJA irremediably caused inhibition of hairy root growth, which was unaffected by Cor treatment. Considering together the fold increase in aethiopinone content and the final hairy root biomass, the best combination was a Cor treatment for 28 days, which allowed to obtain up to 105.34 ± 2.30 mg L

Topics: Abietanes; Acetates; Amino Acids; Biomass; Cyclopentanes; Gene Expression Profiling; Gene Expression Regulation, Plant; Indenes; Naphthoquinones; Oxylipins; Plant Roots; RNA, Messenger; Salvia; Transcription, Genetic

Amoebae from the genus Acanthamoeba are known agents leading to various diseases such as granulomatous amoebic encephalitis (GAE), a chronic progressive disease of the central nervous system, amoebic keratitis (AK), chronic eye infection, amoebic pneumitis (AP), chronic lung infection, and skin infections. It is known that various synthetic anti-Acanthamoeba substances are ineffective. Therefore, other substances, e.g., natural plant compounds, are the focus of biological investigations regarding anti-parasite activity. In this work, the ability of four abietane diterpenoids (ferruginol, salvipisone, aethiopinone, and 1-oxo-aethiopinone) to inhibit Acanthamoeba growth is reported. All investigated compounds were active against Acanthamoeba growing in vitro. Among them, ferruginol demonstrated the highest activity against Acanthamoeba. This compound inhibited Acanthamoeba growth by about 72% in a 3-day exposure period (IC50 17.45 μM), while aethiopinone and 1-oxo-aethiopinone demonstrated this activity at the level of 55-56%. Salvipisone reduced the growth of Acanthamoeba in vitro culture by 39%. For this compound, the value of IC50 was 701.94 μM after 72 h of exposure.

Topics: Abietanes; Acanthamoeba; Amebicides; Diterpenes; Naphthoquinones; Plant Extracts; Plant Roots; Salvia

Two diterpenoids, salvipisone (Salv) and aethiopinone (Aeth), isolated from hairy roots of Salvia sclarea, were tested with respect to their activity against methicillin-resistant Staphylococcus aureus (MRSA) and S. epidermidis (MRSE) strains, cultured as planktonic cells or as adherent biofilms. The standard CLSI method, MTT reduction assay or confocal laser scanning microscopy (CLSM) were used for this purpose and also applied for testing the susceptibility to oxacillin, vancomycin, linezolid and their potential synergy with diterpenoids (evaluated as a fractional inhibitory concentration (FIC) index). Salv and Aeth were shown to be bactericidal or bacteriostatic against S. aureus and S. epidermidis planktonic cultures. Both diterpenoids, at the concentrations of 1/2 MIC, showed synergy with antibiotics representing the beta-lactam, glycopeptide and oxazolidinone groups. None of the antibiotics used at a high concentration killed the staphylococcal biofilms. On the contrary, Salv and Aeth decreased the number of live biofilm cells by 45.7 - 77.1% and slightly reduced the biofilm inhibitory concentration of oxacillin. Diterpenoids also changed the parameters of biofilm morphology, as shown by the CLSM image processing package (PHLIP). It was concluded that salvipisone and aethiopinone (relatively highly lipophilic, log P respectively = 3.4; 4.8) synergized the action of beta-lactam antibiotics towards MRSA and MRSE probably by alteration of cell surface hydrophobicity and cell wall/membrane permeability, but not by changing penicillin-binding protein, PBP2a expression and penicillinase production or by direct binding to the cell wall peptidoglycan and teichoic acids.

Topics: Anti-Bacterial Agents; Biofilms; Diterpenes; Humans; Methicillin Resistance; Microbial Sensitivity Tests; Naphthoquinones; Phytotherapy; Plant Roots; Salvia; Staphylococcus aureus; Staphylococcus epidermidis

From the roots of Salvia eriophora (Lamiaceae), a new compound, 4,14-dihydroxysaprorthoquinone, was isolated in addition to ten known diterpenoids. The structure of the new compound was established by spectroscopic analysis. The crude extract of the plant and the isolated diterpenoids were tested for their cardiovascular activities using Wistar Albino rats. Activity was demonstrated in the crude extract and in 4,14-dihydroxysaprorthoquinone, aethiopinone, ferruginol, 4,12-dihydroxysapriparaquinone, and 6,7-dehydroroyleanone.

Topics: Abietanes; Animals; Blood Pressure; Diterpenes; Heart Rate; Magnetic Resonance Spectroscopy; Male; Molecular Structure; Naphthoquinones; Plant Extracts; Plant Roots; Quinones; Rats; Rats, Wistar; Salvia

We have investigated the mechanisms of action of aethiopinone, an anti-inflammatory compound from Salvia aethiopis L. roots.. Human neutrophils from healthy volunteers and murine peritoneal macrophages. Swiss mice were randomly divided into groups of six animals.. Test compounds were applied topically in the mouse ear oedema test. In the air pouch, mice received aethiopinone (0.001-0.5 pmol/pouch or 12.5-50 mg/kg p.o.).. LTB4 production was assayed in human neutrophils and COX-2 and iNOS activities in murine macrophages. Air pouches were induced subcutaneously in mice and injected with zymosan on the day six. Mouse ear oedema was induced by arachidonic acid. Dunnett's t-test was employed for statistical analysis.. We have observed potent inhibitory effects on human neutrophil LTB4 production without effects on COX or NOS activities. Aethiopinone is an in vitro inhibitor of 5-LO from human neutrophils (IC50 = 0.11 microM). In addition, aethiopinone reduced leukocyte accumulation and showed in vivo inhibitory activity on this enzyme.. Our results indicate that inhibition of 5-LO could participate in the anti-inflammatory properties of this natural product.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arachidonic Acid; Cyclooxygenase 1; Cyclooxygenase 2; Dinoprostone; Ear; Edema; Humans; Inflammation; Isoenzymes; Leukotriene B4; Lipoxygenase Inhibitors; Macrophages, Peritoneal; Membrane Proteins; Mice; Naphthoquinones; Neutrophils; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Phospholipases A; Prostaglandin-Endoperoxide Synthases

Aethiopinone (1), an o-naphthoquinone diterpene from Salvia aethiopis L. roots and two hemisynthetic derivatives 2 and 3 have been evaluated for toxicity, anti-inflammatory, analgesic, antipyretic, and haemostatic activities. The compounds tested showed low toxicity and a pharmacological profile similar to other NSAI substances on reducing the edema induced by carrageenan and contractions induced by phenyl-p-quinone; the most active compounds were 1 and 2. In the same way and as expected with these types of substances, the bleeding time increased. In the TPA-induced ear inflammation model, the three compounds showed a moderate reduction of edema, and 1 produced a significant increase in the reaction time against thermal painful stimuli in the tail immersion test. The results demonstrated strong anti-inflammatory, peripheral and central analgesic properties for 1, as well as antiedematose topical action and peripheral analgesic properties for 2 and 3.

Topics: Analgesics; Analgesics, Non-Narcotic; Animals; Anti-Inflammatory Agents, Non-Steroidal; Coagulants; Female; Male; Mice; Naphthoquinones; Plant Roots; Rats; Rats, Wistar