(10)-shogaol and shogaol

Topics: Anti-Infective Agents; Antioxidants; Catechols; Chromatography, High Pressure Liquid; Desiccation; Fatty Alcohols; Gram-Negative Bacteria; Gram-Positive Bacteria; Guaiacol; Microbial Sensitivity Tests; Oils, Volatile; Plant Extracts; Plant Oils; Zingiber officinale

Shogaols, a series of major constituents in dried ginger with the most abundant being [6]-, [8]-, and [10]-shogaols, show much higher anticancer potencies than gingerols. Previously, we reported the mercapturic acid pathway as a major metabolic route for [6]-shogaol in mice. However, it is still unclear how the side chain length affects the metabolism of shogaols and how shogaols are metabolized in humans.. We first investigate the metabolism of [10]-shogaol in mouse urine, and then investigate the biotransformation of shogaols in human urine. Our results show that eight major thiol-conjugated metabolites of [10]-shogaol were detected in mouse urine, while six major thiol-conjugated metabolites of [6]-shogaol, two thiol-conjugated metabolites of [8]-shogaol, and two thiol-conjugated metabolites of [10]-shogaol were detected in urine collected from human after drinking ginger tea, using LC/ESI-MS/MS. Our results clearly indicate the mercapturic acid pathway is a major metabolic route for [10]-shogaol in mice and for shogaols in human. Furthermore, we also investigated the regulation of glutathione (GSH) by [6]-shogaol in human colon cancer cells HCT-116. Our results show [6]-shogaol, after initially depleting glutathione levels, can subsequently restore and increase GSH levels over time.. Shogaols are metabolized extensively in mouse and human to form thiol-conjugated metabolites and GSH might play an important role in the cancer-preventive activity of ginger.

Topics: Acetylcysteine; Adult; Animals; Antineoplastic Agents, Phytogenic; Beverages; Catechols; Cell Line, Tumor; Female; Glutathione; Guaiacol; HCT116 Cells; Humans; Male; Mice; Mice, Inbred C57BL; Molecular Structure; Sulfhydryl Compounds; Tandem Mass Spectrometry; Zingiber officinale

Animal studies suggest that ginger (Zingiber officinale Roscoe) reduces anxiety. In this study, bioactivity-guided fractionation of a ginger extract identified nine compounds that interact with the human serotonin 5-HT(1A) receptor with significant to moderate binding affinities (K(i)=3-20 microM). [(35)S]-GTP gamma S assays indicated that 10-shogaol, 1-dehydro-6-gingerdione, and particularly the whole lipophilic ginger extract (K(i)=11.6 microg/ml) partially activate the 5-HT(1A) receptor (20-60% of maximal activation). In addition, the intestinal absorption of gingerols and shogaols was simulated and their interactions with P-glycoprotein were measured, suggesting a favourable pharmacokinetic profile for the 5-HT(1A) active compounds.

Topics: Anti-Anxiety Agents; Caco-2 Cells; Catechols; Cell Line; Fatty Alcohols; Humans; Molecular Structure; Serotonin 5-HT1 Receptor Agonists; Zingiber officinale

Ten shogaols were synthesized to evaluate the importance of the side-chain length in protecting cells from betaA(1-42) insult using PC12 rat pheochromocytoma and IMR-32 human neuroblastoma cells. The compounds cell protectivity against betaA insult was demonstrated using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) reduction assay. The efficacy of cell protection from betaA insult by these shogaols was shown to improve as the length of the side chain increase.

Topics: Amyloid beta-Peptides; Animals; Catechols; Cell Line, Tumor; Cell Survival; Humans; Neurons; Neuroprotective Agents; PC12 Cells; Plant Extracts; Rats; Structure-Activity Relationship