Antioxidant and anti-inflammatory activities of the major phenolics from Zygophyllum simplex L

Abstract

Ethnopharmacological relevance: Zygophyllum simplex L. is a halophyte plant that follows Zygophyllaceae. The plant is growing in arid and semiarid regions. It has been used traditionally in Arabic region to treat gout, asthma and inflammation.

Aim of study: Although ant-inflammatory activity has been reported for this plant, this study aimed to isolate and identify the major constituents of Zygophyllum simplex L., as well as assessing their antioxidant and anti-inflammatory activities in-vitro. In this study, the mechanism of anti-inflammatory activity of the isolated compounds was assessed.

Materials and methods: Defatted fraction of the total methanol extract of the aerial parts of Z. simplex was repeatedly chromatographed on Diaion HP-20, polyamide, and RP₁₈ columns to give five major phenolic compounds. The identity of the purified compounds was established by NMR experiments and comparing with previously known analogs. Moreover, the antioxidant and anti-inflammatory activities of the purified phenolics were investigated in-vitro through measuring of NFκB, PGE₂, IL-6, IL-1β and TNF-α levels in human peripheral blood mononuclear cells (PBMC) stimulated with phytohaemagglutinin (PHA).

Results: Phytochemical investigation of the flowering aerial parts of Z. simplex resulted in isolation of five major metabolites identified as isorhamnetin-3-O-β-D-rutinoside (1), myricitrin (2), luteolin-7- O-β-D-glucoside (3), isorhamnetin-3-O-β-D-glucoside(4), and isorhamnetin (5). It is noteworthy to report that compounds 1-3 were isolated from the plant for the first time. It was reported that NFκB represents an important linkage between oxidative stress and inflammation. Compounds 2 and 3 have exhibited the highest antioxidant activity and showed the most efficient in decreasing NFκB p65 at the lowest concentration (1µM). Moreover; at 1µM concentrations, only compounds 2 and 3 significantly decreased IL-6, IL-1β and TNF-α levels from PHA treatment. Nevertheless, at 100µM, all isolated metabolites significantly decreased IL-6 compared to PHA treatment.

Conclusion: Five major phenolic compounds were isolated from Z. simplex. Anti-inflammatory activity exhibited by the isolated compounds augment the traditional use of this plant as anti-inflammatory. The effect was mediated via inhibition of NFκB through antioxidant mechanism and subsequent inhibition to other inflammatory mediators like TNF-α, IL-1β and IL-6.

Keywords: Anti-inflammatory; Anti-oxidant; Flavonoids; Zygophyllum simplex.