Chemical structures and induction of cell death via heat shock protein inhibition of the prenylated phloroglucinol derivatives isolated from Hypericum erectum.

Four new prenylated phloroglucinol derivatives (+)-erectumol I (1a), (-)-erectumol I (1b), (-)-erectumol II (2a), and (+)-erectumol II (2b) were isolated from the methanol extracts of the whole plants of Hypericum erectum. These new compounds were isolated as a pair of enantiomers, respectively. The planar chemical structures and relative configurations of the new compounds were suggested by Cu-Kα X-ray diffraction analysis and been confirmed by high-resolution mass and 1D and 2D NMR spectroscopic data. The absolute configuration of the four new compounds were established by comparing the experimental and predicted electronic circular dichroism data. Isolated compounds 1b and 2b induced death of Adriamycin-treated HeLa cells. Their enantiomers 1a and 2a did not. In addition, the apparent mechanism of cell death of 1b was the inhibited expression of heat shock protein 105.

Uliginosin B presents antinociceptive effect mediated by dopaminergic and opioid systems in mice.

Previous studies have shown that uliginosin B inhibits dopamine reuptake in rat brain. This compound occurs in Hypericum polyanthemum and H. caprifoliatum for which was reported to have antinociceptive effect sensitive to naloxone. The aim of this study was to assess the antinociceptive effect of uliginosin B and to evaluate the involvement of opioid and dopaminergic receptors activation. Uliginosin B presented antinociceptive effect in hot-plate and abdominal writhing tests, in mice, at doses that did not impair the motor coordination (15 mg/kg, i.p.). Uliginosin B in high dose (90 mg/kg, i.p.) presented ataxic effect in the rotarod apparatus. These effects seem to be mediated by distinct receptors since the effect on the hot-plate was completely abolished by naloxone and sulpiride, but it was unaffected by SCH 23390. On the other hand, the motor impairment induced by uliginosin B was completely prevented by naloxone and partially prevented by sulpiride and SCH 23390. However, the receptors' activation appears to be indirect since uliginosin B did not bind to opioid and dopaminergic receptors. Thus, uliginosin B effects probably are due to its ability to inhibit monoamine reuptake with consequent activation of dopamine receptors and indirect stimulation of opioid system.

Uliginosin B, a phloroglucinol derivative from Hypericum polyanthemum: a promising new molecular pattern for the development of antidepressant drugs.

In this study we have demonstrated that cyclohexane extract of Hypericum polyanthemum (POL) and its main phloroglucinol derivative uliginosin B (ULI) present antidepressant-like activity in rodent forced swimming test (FST). The involvement of monoaminergic neurotransmission on the antidepressant-like activity of ULI was evaluated in vivo and in vitro. POL 90 mg/kg (p.o.) and ULI 10 mg/kg (p.o.) reduced the immobility time in the mice FST without altering locomotion activity in the open-field test. The combination of sub-effective doses of POL (45 mg/kg, p.o.) and ULI (5 mg/kg, p.o.) with sub-effective doses of imipramine (10 mg/kg, p.o.), bupropion (3 mg/kg, p.o.) and fluoxetine (15 mg/kg, p.o.) induced a significant reduction on immobility time in FST. The pretreatment with SCH 23390 (15 µg/kg, s.c., dopamine D1 receptor antagonist), sulpiride (50 mg/kg, i.p., dopamine D2 receptor antagonist), prazosin (1mg/kg, i.p., α1-adrenoceptor antagonist), yohimbine (1mg/kg, i.p., α2-adrenoceptor antagonist) and pCPA (100 mg/kg/day, i.p., p-chlorophenilalanine methyl ester, inhibitor of serotonin synthesis, for four consecutive days) before ULI administration (10 mg/kg, p.o.) significantly prevented the anti-immobility effect in FST. ULI was able to inhibit synaptosomal uptake of dopamine (IC50 = 90 ± 38 nM), serotonin (IC50 = 252 ± 13 nM) and noradrenaline (280 ± 48 nM), but it did not bind to any of the monoamine transporters. These data firstly demonstrated the antidepressant-like effect of POL and ULI, which depends on the activation of the monoaminergic neurotransmission in a different manner from the most antidepressants.

Influence of mineral amendment on disease suppressive activity of Pseudomonas fluorescens to Fusarium wilt of chickpea.

Fusarium wilt caused by Fusarium oxysporum f. sp. ciceri causes considerable yield loss of chickpea. Pseudomonas fluorescens4-92 (Pf4-92) strain can suppress the disease. Amendment of zinc EDTA and copper EDTA could not suppress the disease significantly when used alone; however, they significantly suppressed the disease in presence of Pf4-92. In vitro observation showed that at 40, 30 and 20microgml(-1) concentrations of these minerals, i.e. Zn, Cu and Zn plus Cu, respectively, completely repressed the production of the phytotoxin, fusaric acid (FA). FA concentration (0.5microgml(-1)) has been shown to suppress the production of 2,4-diacetylphloroglucinol (DAPG) by Pf4-92, and DAPG, salicylic acid, pyochelin and pyoluteorin production was enhanced by these mineral amendments. In rockwool bioassays, Zn, Cu and Zn plus Cu amendments reduced FA production and enhanced DAPG production. This study demonstrates that Zn and Cu enhance biocontrol activity by reducing FA produced by the pathogen, F. oxysporum f. sp. ciceri.

Hyperforin--a key constituent of St. John's wort specifically activates TRPC6 channels.

Hyperforin, a bicyclic polyprenylated acylphloroglucinol derivative, is the main active principle of St. John's wort extract responsible for its antidepressive profile. Hyperforin inhibits the neuronal serotonin and norepinephrine uptake comparable to synthetic antidepressants. In contrast to synthetic antidepressants directly blocking neuronal amine uptake, hyperforin increases synaptic serotonin and norepinephrine concentrations by an indirect and yet unknown mechanism. Our attempts to identify the molecular target of hyperforin resulted in the identification of TRPC6. Hyperforin induced sodium and calcium entry as well as currents in TRPC6-expressing cells. Sodium currents and the subsequent breakdown of the membrane sodium gradients may be the rationale for the inhibition of neuronal amine uptake. The hyperforin-induced cation entry was highly specific and related to TRPC6 and was suppressed in cells expressing a dominant negative mutant of TRPC6, whereas phylogenetically related channels, i.e., TRPC3 remained unaffected. Furthermore, hyperforin induces neuronal axonal sprouting like nerve growth factor in a TRPC6-dependent manner. These findings support the role of TRPC channels in neurite extension and identify hyperforin as the first selective pharmacological tool to study TRPC6 function. Hyperforin integrates inhibition of neurotransmitter uptake and neurotrophic property by specific activation of TRPC6 and represents an interesting lead-structure for a new class of antidepressants.

Pseudomonas for biocontrol of phytopathogens: from functional genomics to commercial exploitation.

Pseudomonas spp. that can colonise the roots of crop plants and produce antifungal metabolites represent a real alternative to the application of chemical fungicides. Presently, much research is aimed at understanding, at the molecular level, the mechanisms that enable Pseudomonas strains to act as efficient biological control agents. This approach is facilitating the development of novel strains with modified traits for enhanced biocontrol efficacy. However, without solving some inherent problems associated with the effective delivery of microbial inoculants to seeds and without knowledge on the biosafety aspects of novel biocontrol agents, the commercial potential of Pseudomonas spp. for plant disease control will not be realised.