Chiral flavanones from Amygdalus lycioides Spach: structural elucidation and identification of TNFalpha inhibitors by bioactivity-guided fractionation

Abstract

Phytochemical investigation on the Amygdalus lycioides Spach branchelets resulted in the isolation of four chiral flavanones: (2R,3R)-Taxifolin, (2R,3R)-aromadendrin, (S)-5,7,3',5'-tetrahydroxyflavanone and (S)-naringenin. The flavanones were isolated by semi-preparative HPLC, their structures elucidated based on spectroscopic data and their absolute configuration assigned. As a part of our ethnobotanical-directed search for novel TNFα inhibitors, the bioassay-guided fractionation of the n-hexane-acetone (n-Hex-Ac, 1:1 v/v) Amygdalus lycioides Spach branchelets extract was performed. In this way, (S)-naringenin was identified as the constituent responsible for the TNFα blocking effect, being effective in vitro and in vivo after oral administration. This is the first investigation on bioactive secondary metabolites of Amygdalus lycioides Spach branchelets.

Figure 1

HPLC-UV/PAD/CD chromatogram (290 nm) of Amygdalus lycioides extract. A: UV trace (with UV spectra of each principal peak); B: CD trace.

Figure 2

Structures of compounds 1–4.

Figure 3

CD spectra and Δε data of 3 and 4.

Figure 4

TNFα inhibitory activity of the MASE extract and the chloroform fraction.

Figure 5

In vivo TNFα inhibitory activity of the MASE extract and the chloroform fraction; *** p < 0.0001 compared with LPS-treated mice.