leaves: phytochemical profile and -inhibitory activity on inflammatory mediators implicated in periodontal disease.

CONTEXT

Virtually all parts of L. (Salvadoraceae) are used in traditional medicine. The twigs and leaves are used for oral health, but leaves are far less investigated.

OBJECTIVE

This study assesses the oral health-promoting potential of leaves with emphasis on anti-inflammatory and antiproliferative effects and provides an in depth-characterization of their metabolite profile.

MATERIALS AND METHODS

Hot-water and methanolic leaf extracts (1, 10, and 100 µg/mL) and their major constituents (5, 10, and 50 µM), were subjected to cellular assays on IL-8 and TNFα release in LPS-stimulated human neutrophils, NO-release in LPS/IFNγ stimulated mouse macrophages, and proliferation of HNO97 human tongue carcinoma cells. Metabolite profiling was performed by UHPLC-HRMS analysis. Major constituents were isolated and structurally elucidated.

RESULTS AND DISCUSSION

Both extracts showed pronounced anti-inflammatory activity in LPS-stimulated neutrophils. Major identified compound classes were flavonoid glycosides, the glucosinolate glucotropaeolin, phenyl- and benzylglycoside sulfates, and megastigmane glycosylsulfates, the latter ones identified for the first time in . Glucotropaeolin strongly inhibited the release of IL-8 and TNF-α (13.3 ± 2.0 and 22.7 ± 2.6% of the release of stimulated control cells at 50 µM), while some flavonoids and 3-(3'--sulfo-β-d-glucopyranosyloxy)-7,8-dihydro-β-ionone, a newly isolated megastigmane glycosylsulfate, were moderately active. Benzylisothiocyanate, which is likely formed from glucotropaeolin during traditional application of showed considerable antiproliferative activity (IC in HNO97 cells: 10.19 ± 0.72 µM) besides strongly inhibiting IL-8 and TNFα release.

CONCLUSIONS

Glucotropaeolin and benzylisothiocyanate are likely implicated in the oral health-promoting effects of leaves. The chemistry and pharmacology of the newly identified megastigmane glycosylsulfates should be further evaluated.