Gentisin

6338357

The mutagenic activities of 2 hydroxyxanthones, gentisin and isogentisin, obtained from the methanol extract of Gentianae radix (Gentianaceae) were investigated. The methanol extract of Gentianae radix, which showed mutagenicity in the Ames test in Salmonella typhimurium strain TA100 with S9 mix, was fractionated by column chromatography on Sephadex LH-20, and the fractions were purified by preparative TLC and column chromatography on polyamide. 2 mutagenic materials thus obtained, S1 and S2, each gave a single band on TLC. Identification of S1 and S2 was accomplished by comparing the analytical (mps, elementary analyses) and spectral (UV, IR, mass, NMR) results for S1 and S2 with literature data for gentisin and isogentisin. At doses below 10 micrograms, S1 (gentisin) and S2 (isogentisin) had similar specific mutagenic activities. At doses of over 10 to 50 micrograms, the mutagenic activities of S2 and S1 were 19.1 and 6.94 revertants per microgram respectively. This much lower activity of S1 than S2 may be a result of its poor solubility owing to the presence of the OMe group at C-3. The combined yield of S1 and S2 was about 76 mg (40 mg as S1 and 36 mg as S2), which accounted for 76% of the content of mutagenic compounds (100 mg) estimated roughly from the total mutagenic activity in the extract of the starting materials (100 g).

Mutagenic Activities of Gentisin and Isogentisin From Gentianae Radix (Gentianaceae)

I Morimoto, T Nozaka, F Watanabe, M Ishino, Y Hirose, T Okitsu

1983 Feb

26580586

Aberrant proliferation of vascular smooth muscle cells (VSMC) plays a major role in restenosis, the pathological renarrowing of the blood vessel lumen after surgical treatment of stenosis. Since available anti-proliferative pharmaceuticals produce unfavorable side effects, there is high demand for the identification of novel VSMC proliferation inhibitors. A natural product screening approach using a resazurin conversion assay enabled the identification of gentisin (1) from Gentiana lutea as a novel inhibitor of VSMC proliferation with an IC50 value of 7.84 µM. Aiming to identify further anti-proliferative compounds, 13 additional nonprenylated xanthones, isolated from different plant species, were also tested. While some compounds showed no or moderate activity at 30 µM, 1-hydroxy-2,3,4,5-tetramethoxyxanthone (4), swerchirin (6), and methylswertianin (7) showed IC50 values between 10.2 and 12.5 µM. The anti-proliferative effect of 1, 4, 6, and 7 was confirmed by the quantification of DNA synthesis (BrdU incorporation) in VSMC. Cell death quantification (determined by LDH release in the culture medium) revealed that the compounds are not cytotoxic in the investigated concentration range. In conclusion, nonprenylated xanthones are identified as novel, non-toxic VSMC proliferation inhibitors, which might contribute to the development of new therapeutic applications to combat restenosis.

Centaurium erythraea; Frasera caroliniensis; Gentiana lutea; Gentianaceae; atherosclerosis; bitter plants; gentisin; restenosis; vascular smooth muscle cell proliferation; xanthones..

Nonprenylated Xanthones From Gentiana Lutea, Frasera Caroliniensis, and Centaurium Erythraea as Novel Inhibitors of Vascular Smooth Muscle Cell Proliferation

Birgit Waltenberger 1 , Rongxia Liu 2 3 , Atanas G Atanasov 4 , Stefan Schwaiger 5 , Elke H Heiss 6 , Verena M Dirsch 7 , Hermann Stuppner 8

2015 Nov 13