A new anti-neuroinflammation labdane diterpenoid from Salvia tricuspis.

One new labdane diterpenoid, tricuspion A (1), as well as five known triterpenoids (2-6) were isolated from Salvia tricuspis Franch (family Labiatae). The structure of tricuspion A was identified by extensive spectroscopic analysis and by comparison with previously reported data. Compounds 1-6 were evaluated for their inhibitory effects on the NO production in LPS-stimulated BV-2 microglia cells, and 1 exhibited potent inhibitory activity with IC50 value of 14.92 ± 0.51 µM. Compound 1 might exert anti-neuroinflammatory activity through inhibiting the excessive production of NO and down-regulating the protein expression of iNOS and COX-2. As such, labdane diterpenoid (tricuspion A) could provide promising anti-neuroinflammatory lead compound for further structural modification.

Structure of the N-terminal domain of ClpC1 in complex with the antituberculosis natural product ecumicin reveals unique binding interactions.

The biological processes related to protein homeostasis in Mycobacterium tuberculosis, the etiologic agent of tuberculosis, have recently been established as critical pathways for therapeutic intervention. Proteins of particular interest are ClpC1 and the ClpC1-ClpP1-ClpP2 proteasome complex. The structure of the potent antituberculosis macrocyclic depsipeptide ecumicin complexed with the N-terminal domain of ClpC1 (ClpC1-NTD) is presented here. Crystals of the ClpC1-NTD-ecumicin complex were monoclinic (unit-cell parameters a = 80.0, b = 130.0, c = 112.0 Å, ß = 90.07°; space group P21; 12 complexes per asymmetric unit) and diffracted to 2.5 Šresolution. The structure was solved by molecular replacement using the self-rotation function to resolve space-group ambiguities. The new structure of the ecumicin complex showed a unique 1:2 (target:ligand) stoichiometry exploiting the intramolecular dyad in the α-helical fold of the target N-terminal domain. The structure of the ecumicin complex unveiled extensive interactions in the uniquely extended N-terminus, a critical binding site for the known cyclopeptide complexes. This structure, in comparison with the previously reported rufomycin I complex, revealed unique features that could be relevant for understanding the mechanism of action of these potential antituberculosis drug leads. Comparison of the ecumicin complex and the ClpC1-NTD-L92S/L96P double-mutant structure with the available structures of rufomycin I and cyclomarin A complexes revealed a range of conformational changes available to this small N-terminal helical domain and the minor helical alterations involved in the antibiotic-resistance mechanism. The different modes of binding and structural alterations could be related to distinct modes of action.

Dynamics of the isoflavone metabolome of traditional preparations of Trifolium pratense L.

ETHNOPHARMACOLOGICAL RELEVANCE: The flowering tops of Trifolium pratense L., popularly known as red clover, are used in ethnic Western and Traditional Chinese medicine, in a variety of preparations, including infusions, decoctions and tinctures. Red clover has been reported to be helpful for treatment of menopausal symptoms, premenstrual syndrome, mastalgia, high cholesterol, and other conditions. AIMS OF THE STUDY: The aims were to compare the chemical dynamics between traditional preparations of infusions, decoctions, and tinctures, as well as to identify the chemical variability over time in a traditional red clover tincture. For this purpose, eight isoflavone aglycones as well as two glucosides, ononin and sissotrin, were used as marker compounds. MATERIALS AND METHODS: Quantitative NMR (qHNMR), LC-MS-MS, and UHPLC-UV methods were used to identify and quantitate the major phenolic compounds found within each extract. RESULTS: Infusions, decoctions and tinctures were shown to produce different chemical profiles. Biochanin A and formononetin were identified and quantified in infusion, decoction, and tinctures of red clover. Both infusion and decoction showed higher concentrations of isoflavonoid glucosides, such as ononin and sissotrin, than 45% ethanolic tinctures. Dynamic chemical variability ("dynamic residual complexity") of the red clover tincture was observed over time (one-month), with biochanin A and formononetin reaching peak concentrations at around six days. CONCLUSIONS: Insight was gained into why different formulation methods (infusions, decoctions, and tinctures) are traditionally used to treat different health conditions. Moreover, the outcomes show that tinctures, taken over a period of time, are dynamic medicinal formulations that allow for time-controlled release of bioactive compounds.