ScopeFlavonoids are generally studied in vitro, in isolation, and as unmetabolized precursor structures. However, in the habitual diet, multiple flavonoids are consumed together and found present in the circulation as complex mixtures of metabolites. Using a unique study design, we investigated the potential for singular or additive anti‐inflammatory effects of flavonoid metabolites relative to their precursor structures.Methods and resultsSix flavonoids, 14 flavonoid metabolites, and 29 combinations of flavonoids and their metabolites (0.1–10 μM) were screened for their ability to reduce LPS‐induced tumor necrosis factor‐α (TNF‐α) secretion in THP‐1 monocytes. One micromolar peonidin‐3‐glucoside, cyanidin‐3‐glucoside, and the metabolites isovanillic acid (IVA), IVA‐glucuronide, vanillic acid‐glucuronide, protocatechuic acid‐3‐sulfate, and benzoic acid‐sulfate significantly reduced TNF‐α secretion when in isolation, while there was no effect on TNF‐α mRNA expression. Four combinations of metabolites that included 4‐hydroxybenzoic acid (4HBA) and/or protocatechuic acid also significantly reduced TNF‐α secretion to a greater extent than the precursors or metabolites alone. The effects on LPS‐induced IL‐1β and IL‐10 secretion and mRNA expression were also examined. 4HBA significantly reduced IL‐1β secretion but none of the flavonoids or metabolites significantly modified IL‐10 secretion.ConclusionThis study provides novel evidence suggesting flavonoid bioactivity results from cumulative or additive effects of circulating metabolites.

Tying the knot! The marriage of two-directional synthesis and tandem reactions allows access to twelve skeletally diverse scaffolds in just fifteen reactions. Two-directional synthesis yields a symmetrical linear “rope-like” keto-dienoate which is then subjected to twelve separate tandem reactions to “tie the rope in knots” thus creating twelve diverse natural product-like scaffolds containing useful functionality for further elaboration

Rehabilitating extensively mutilated posterior teeth after endodontic treatment still remains to be a challenge. Several treatment modalities has been established to restore the function of grossly mutilated endodontically treated teeth. Among such restorations, endocrowns are indirect monobloc crowns that engage the core space for retention. They are more conservative alternative than the use of intraradicular post as a means to increase the retention of crown to the core. In this case report, two cases are discussed in which single posterior endocrowns were fabricated after the endodontic treatment in the teeth with compromised tooth structure. One case with CAD manufacturing of lithium disilicate (IPS e.max CAD) molar endocrown and another case with the fabrication of metal ceramic molar endocrown.

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