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

CONTEXT: Virtually all parts of Salvadora persica 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 S. persica 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 S. persica leaf extracts (1, 10, and 100 microg/mL) and their major constituents (5, 10, and 50 microM), were subjected to cellular assays on IL-8 and TNFalpha release in LPS-stimulated human neutrophils, NO-release in LPS/IFNgamma 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 S. persica. Glucotropaeolin strongly inhibited the release of IL-8 and TNF-alpha (13.3 +/- 2.0 and 22.7 +/- 2.6% of the release of stimulated control cells at 50 microM), while some flavonoids and 3-(3'-O-sulfo-beta-d-glucopyranosyloxy)-7,8-dihydro-beta-ionone, a newly isolated megastigmane glycosylsulfate, were moderately active. Benzylisothiocyanate, which is likely formed from glucotropaeolin during traditional application of S. persica, showed considerable antiproliferative activity (IC(50) in HNO97 cells: 10.19 +/- 0.72 microM) besides strongly inhibiting IL-8 and TNFalpha release. CONCLUSIONS: Glucotropaeolin and benzylisothiocyanate are likely implicated in the oral health-promoting effects of S. persica leaves. The chemistry and pharmacology of the newly identified megastigmane glycosylsulfates should be further evaluated.