2017, Verjee, Sheela, Garo, Eliane, Pelaez, Sarah, Fertig, Orlando, Hamburger, Matthias, Butterweck, Veronika

During saffron (Crocus sativus) spice production, large amounts of floral biowaste are generated. It was the aim of this study to develop a value-added product from saffron floral biowaste to be used as a natural cosmetic ingredient. HPLC-PDA-MS analysis of saffron flower extracts revealed the presence of flavonols with the highest amounts in the acetone extract. Kaempferol-3-O-sophoroside was identified as the main flavonoid in the acetone extract (saffron flower acetone extract). Saffron flower acetone extract and kaempferol-3-O-sophoroside were tested in HaCaT cells for potential effects on cell migration, proliferation, and for anti-inflammatory properties. Saffron flower acetone extract concentration dependently (50–200 µg/mL) augmented cell proliferation, as indicated by an increased BrdU-incorporation, while kaempferol-3-O-sophoroside (1–50 µM) had no effect. Furthermore, treatment of HaCaT cells with saffron flower acetone extract, but not with kaempferol-3-O-sophoroside, concentration-dependently increased vascular endothelial growth factor secretion (control 49.72 pg/mL vs. saffron flower acetone extract at 200 µg/mL 218.60 pg/mL). Cell migration was determined using time-lapse microscopy and a modification of the scratch-wound assay in which saffron flower acetone extract significantly improved wound closure compared to the untreated control. Overproduction of the proinflammatory cytokines interleukin-8 and interleukin-6 in HaCaT cells was induced by TNF-α. Kaempferol-3-O-sophoroside (10–50 µM), but not saffron flower acetone extract, inhibited TNF-α-induced IL-8 secretion. The effect was comparable to 10 µM hydrocortisone (positive control). Interestingly, saffron flower acetone extract further increased IL-6 levels in TNF-α-treated HaCaT cells in a concentration-dependent manner. In summary, the pronounced wound healing properties of saffron flower acetone extract present a promising application for the cosmetic industry.

2016, Jähne, Evelyn A., Eigenmann, Daniela E., Moradi-Afrapoli, Fahimeh, Verjee, Sheela, Butterweck, Veronika, Hebeisen, Simon, Hettich, Timm, Schlotterbeck, Götz, Smiesko, Martin, Hamburger, Matthias, Oufir, Mouhssin

Tryptanthrin and (E,​Z)​-​3-​(4-​hydroxy-​3,​5-​dimethoxybenzylidene)​indolinone (indolinone) were recently isolated from Isatis tinctoria as potent anti-​inflammatory and antiallergic alkaloids, and shown to inhibit COX-​2, 5-​LOX catalyzed leukotriene synthesis, and mast cell degranulation at low μM to nM concns. To assess their suitability for oral administration, we screened the compds. in an in vitro intestinal permeability assay using human colonic adenocarcinoma cells. For exact quantification of the compds., validated UPLC-​MS​/MS methods were used. Tryptanthrin displayed high permeability (apparent permeability coeff. > 32.0 × 10-​6 cm​/s) across the cell monolayer. The efflux ratio below 2 (< 1.12) and unchanged apparent permeability coeff. values in the presence of the P-​glycoprotein inhibitor verapamil (50 μM) indicated that tryptanthrin was not involved in P-​glycoprotein interactions. For indolinone, a low recovery was found in the human colon adenocarcinoma cell assay. High-​resoln. mass spectrometry pointed to extensive phase II metab. of indolinone (sulfation and glucuronidation)​. Possible cardiotoxic liability of the compds. was assessed in vitro by measurement of an inhibitory effect on human ether-​a-​go-​go-​related gene tail currents in stably transfected HEK 293 cells using the patch clamp technique. Low human ether-​a-​go-​go-​related gene inhibition was found for tryptanthrin (IC50 > 10 μM) and indolinone (IC50 of 24.96 μM)​. The anal. of compds. using various in silico methods confirmed favorable pharmacokinetic properties, as well as a slight inhibition of the human ether-​a-​go-​go-​related gene potassium channel at micromolar concns.