aurapten and collinin

Nine terpenylated coumarins, namely 7-[(E)-3',7'-dimethyl-6'-oxo-2',7'-octadienyl]oxy-coumarin (1), schinilenol (2), schinindiol (3), collinin (4), 7-[(E)-7'-hydroxy-3',7'-dimethy-locta-2',5'-dienyloxy]-coumarin (5), 8-methoxyanisocoumarin (6), 7-(6'R-hydroxy-3',7'-dimethyl-2'E,7'-octadienyloxy)coumarin (7), (E)-4-methyl-6-(coumarin-7'-yloxy)hex-4-enal (8), and aurapten (9), along with a 4-quinolone alkaloid (10) and integrifoliodiol (11), were isolated from the leaves of Zanthoxylum schinifolium. Of the isolates, compounds 4 and 7 potentially inhibited NO production in lipopolysaccharide (LPS)-stimulated macrophage RAW264.7 cells, with IC50 values of 5.9 ± 0.8 and 18.2 ± 1.8 μM, respectively. Furthermore, compounds 4 and 7 dose-dependently reduced the LPS-induced iNOS expression. Moreover, pre-incubation of cells with 4 and 7 significantly suppressed LPS-induced COX-2 protein expression. In addition, compounds 4, 7, 8, and 10 showed strong α-glucosidase inhibitory effects, with IC50 values of 92.1 ± 0.7, 90.6 ± 0.9, 78.2 ± 0.2, and 82.4 ± 0.8 μM, respectively. Compounds 1, 5, and 11 displayed moderate effects with IC50 values of 161.6 ± 0.3, 164.4 ± 1.1, and 155.4 ± 0.9 μM, while acarbose, a positive control, possessed an IC50 value of 121.5 ± 1.0 μM. This is the first investigation on the α-glucosidase inhibitory effect of components from Zanthoxylum schinifolium. Further studies should be made on active compounds.

Topics: Alkaloids; alpha-Glucosidases; Animals; Anti-Inflammatory Agents; Coumarins; Cyclooxygenase 2; Glycoside Hydrolase Inhibitors; Imidazoles; Inflammation; Lipopolysaccharides; Macrophages; Mice; Nitric Oxide; Nitric Oxide Synthase Type II; Plant Extracts; Plant Leaves; RAW 264.7 Cells; Zanthoxylum

Dietary polyphenols are important potential chemopreventive natural agents. Other agents, such as citrus compounds, are also candidates for cancer chemopreventives. They act on multiple key elements in signal transduction pathways related to cellular proliferation, differentiation, apoptosis, inflammation, and obesity. This short review article provides our findings of preclinical studies on potential chemopreventive activities of dietary citrus compounds, auraptene, collinin, and citrus unshiu segment membrane (CUSM), using clitis- and obesity-related colon tumorigenesis models. Dietary feeding with auraptene and collinin at dose levels of 0.01% and 0.05% significantly lowered the incidence (50-60% reduction) and multiplicity (67-80% reduction) of colonic adenocarcinomas induced by azoxymetahene [AOM, single intraperitoneal injection of 10 mg/kg body weight (bw)] and dextran sodium sulfate (1% in drinking water). Anti-inflammatory potency of aurapene and collinin may contribute to the effects. Administration with CUSM at 3 doses in diet significantly inhibited development of aberrant crypts foci induced by 5 weekly subcutaneous injections of AOM (15 mg/kg bw) in male db/db mice: 53% inhibition by 0.02% CUSM, 54% inhibition by 0.1% CUSM, and 59% inhibition by 0.5% CUSM. CUSM treatment also decreased serum level of triglycerides. Our findings suggest that certain citrus materials are capable of inhibiting clitis- and obesity-related colon carcinogenesis.

Topics: Animals; Azoxymethane; Citrus; Colitis; Colonic Neoplasms; Coumarins; Cyclooxygenase 2; Interleukin-1beta; Mice; NF-kappa B; Nitric Oxide Synthase Type II; Obesity; Precancerous Conditions; Tumor Necrosis Factor-alpha