Colon cancer is the most common cancer and the third leading cause of cancer mortality in humans. Using mass spectrometry-based metabolomics, the current study revealed the accumulation of four uremic toxins (cresol sulfate, cresol glucuronide, indoxyl sulfate, and phenyl sulfate) in the serum of mice harboring adenomatous polyposis coli (APC) gene mutation-induced colon cancer. These uremic toxins, likely generated from the gut microbiota, were associated with an increase in the expression of the proinflammatory cytokine IL-6 and a disorder of lipid metabolism. Nutmeg, which exhibits antimicrobial activity, attenuated the levels of uremic toxins and decreased intestinal tumorigenesis in Apc(min/+) mice. Nutmeg-treated Apc(min/+) mice had decreased IL-6 levels and normalized dysregulated lipid metabolism, suggesting that uremic toxins are responsible, in part, for the metabolic disorders that occur during tumorigenesis. These studies demonstrate a potential biochemical link among gut microbial metabolism, inflammation, and metabolic disorders and suggest that modulation of gut microbiota and lipid metabolism using dietary intervention or drugs may be effective in colon cancer chemoprevention strategies.
A rapid, sensitive, and accurate ultra-performance liquid chromatography-UV detection method was developed and validated for simultaneous determination of seven active alkaloids, berberine, palmatine, coptisine, jatrorrhizine, epiberberine, evodiamine, and rutaecarpine, in the Coptis-Evodia herb couple and the Zuojin pill preparation. The original validated method had a total time of about 11 min, which was reduced to 4.7 min by further optimization of gradient elution conditions with eluent A comprising water/methanol/formic acid (v/v/v, 90:10:0.1) and eluent B ACN. An accelerated solvent extraction method was used for the rapid extraction of herb products and pill preparations. Linear behavior over the investigated concentration ranges was observed, with values of r(2) greater than 0.9987 for all analytes. Experiment results were satisfactory for both intra-day and inter-day precision, and method accuracy. Method recovery ranged from 95.7 to 103.5% based on pure reference standards. The validated method was successfully applied to determine amounts of bioactive alkaloid compounds in five samples, in the Coptis-Evodia herb couple, and the commercial Zuojin pill products. The developed method achieved baseline resolution for all seven main basic compounds and is suitable for use as a routine procedure for the rapid identification and quantification of basic compounds in the Coptis-Evodia herb couple and related products.
A new dammarane-type triterpene monoglucoside, named isoginsenoside-Rh(3), has been isolated from the fruits of Panax ginseng C. A. Mey, together with eight known analogs, ginsenoside-Rb(1), -Rb(2), -Rc, -Rd, -Re, -Rg(1), -Rh(1), -Rh(2). On the basis of chemical and physicochemical evidence, the structure of isoginsenoside-Rh(3) has been elucidated as 3-O-beta--glucopyranosyl-dammarane-(E)-20(22),24-diene-3beta,12beta-diol (1).
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