Acylated pregnane glycosides from Caralluma sinaica.

Caralluma sinaica is sold on local markets of Saudi Arabia for various health benefits however no phytochemical study has specifically been performed on this species. NMR and UHPLC-ESI-TOF-MS profilings of the ethanolic extract of the whole plant reveal a very complex phytochemical composition dominated by pregnanes. Detailed information on its constituents was obtained after isolation. Six pregnane glycosides were obtained and characterized based on the extensive spectroscopic analysis (including IR, ¹H NMR, ¹³C NMR and MS data), in addition to ten known compounds (seven pregnanes and three flavonoids). The compounds were identified as 12ß-O-benzoyl-20-O-acetyl boucerin-3-O-6-deoxy-3-O-methyl-ß-D-glucopyranosyl-(1-->4)-ß-D-cymaropyranosyl-(1-->4)-ß-D-cymaropyranoside, 12ß-O-tigloyl-20-O-acetyl boucerin-3-O-ß-D-glucopyranosyl-(1-->4)-ß-D-cymaropyranoside, 12ß-O-benzoyl-20-O-acetyl boucerin-3-O-ß-D-glucopyranosyl-(1-->4)-ß-D-digitalopyranosyl-(1-->4)-ß-D-cymaropyranosyl-(1-->4)-ß-D-cymaropyranoside, 12ß-O-benzoyl-20-O-acetyl boucerin-3-O-ß-D-glucopyranosyl-(1-->4)-hevetopyranosyl-(1-->4)-ß-D-cymaropyranosyl-(1-->4)-ß-D-cymaropyranoside, 12ß-O-benzoyl-20-O-tigloyl boucerin-3-O-ß-D-glucopyranosyl-(1-->4)-ß-D-cymaropyranoside, 12ß-20-O-dibenzoyl boucerin-3-O-ß-D-glucopyranosyl-(1-->4)-ß-D-cymaropyranosyl-(1-->4)-ß-D-cymaropyranoside. Finally, the isolated compounds were evaluated for their quinone reductase induction.

Ginger phenylpropanoids inhibit IL-1beta and prostanoid secretion and disrupt arachidonate-phospholipid remodeling by targeting phospholipases A2.

The rhizome of ginger (Zingiber officinale) is employed in Asian traditional medicine to treat mild forms of rheumatoid arthritis and fever. We have profiled ginger constituents for robust effects on proinflammatory signaling and cytokine expression in a validated assay using human whole blood. Independent of the stimulus used (LPS, PMA, anti-CD28 Ab, anti-CD3 Ab, and thapsigargin), ginger constituents potently and specifically inhibited IL-1ß expression in monocytes/macrophages. Both the calcium-independent phospholipase A(2) (iPLA(2))-triggered maturation and the cytosolic phospholipase A(2) (cPLA(2))-dependent secretion of IL-1ß from isolated human monocytes were inhibited. In a fluorescence-coupled PLA(2) assay, most major ginger phenylpropanoids directly inhibited i/cPLA(2) from U937 macrophages, but not hog pancreas secretory phospholipase A(2). The effects of the ginger constituents were additive and the potency comparable to the mechanism-based inhibitor bromoenol lactone for iPLA(2) and methyl arachidonyl fluorophosphonate for cPLA(2), with 10-gingerol/-shogaol being most effective. Furthermore, a ginger extract (2 µg/ml) and 10-shogaol (2 µM) potently inhibited the release of PGE(2) and thromboxane B2 (>50%) and partially also leukotriene B(4) in LPS-stimulated macrophages. Intriguingly, the total cellular arachidonic acid was increased 2- to 3-fold in U937 cells under all experimental conditions. Our data show that the concurrent inhibition of iPLA(2) and prostanoid production causes an accumulation of free intracellular arachidonic acid by disrupting the phospholipid deacylation-reacylation cycle. The inhibition of i/cPLA(2), the resulting attenuation of IL-1ß secretion, and the simultaneous inhibition of prostanoid production by common ginger phenylpropanoids uncover a new anti-inflammatory molecular mechanism of dietary ginger that may be exploited therapeutically.