ABSTRACT
In this study, a liquid chromatography-tandem multi-stage mass spectrometry (LC/MSn) method was established to characterize the metabolites of TRG in monkeys and dogs. A total of seven metabolites of TRG besides the prototype were found, which were identified as TR (M1), TRN (M2), trans-resveratrol-4'-O-glucuronide (M2'), trans-resveratrol-3-O-glucoside-4'-O-glucuronide (M3), trans-resveratrol-3-O-glucoside-5-O-glucuronide (M3'), trans-resveratrol-3-sulfate (M4) and trans-resveratrol-4'-sulfate (M4'). Additionally, the metabolic pathways of TRG in monkeys and dogs were proposed. There were also species differences of metabolism of TRG between monkeys and dogs.
Subject(s)
Glucosides , Animals , Chromatography, High Pressure Liquid , Chromatography, Liquid , Dogs , Haplorhini , Molecular Structure , StilbenesABSTRACT
Intestinal ischemia reperfusion (I/R) injury is a tissue and organ injury that frequently occurs during surgery and significantly contributes to the pathological processes of severe infection, injury, shock, cardiopulmonary insufficiency and other diseases. However, the mechanism of intestinal I/R injury remains to be elucidated. A mouse model of intestinal I/R injury was successfully established and the model mice were treated with remote ischemic postconditioning (RIPOC) and/or an ERK inhibitor (CC90003), respectively. Histopathological changes of the intestinal mucosa were determined by hematoxylin and eosin staining. In addition, the levels of highmobility group box 1 (HMGB1) and receptor for advanced glycation end products (RAGE) expression were confirmed by reverse transcriptionquantitative polymerase chain reaction, western blotting and immunohistochemistry assays. The levels of antioxidants, oxidative stress markers (8OHdG) and interleukin 1 family members were evaluated by ELISA assays and the levels of NFκB pathway proteins were analyzed by western blotting. The data demonstrated that RIPOC could attenuate the histopathological features of intestinal mucosa in the intestinal I/Rinjury mouse models via the ERK pathway. It was also revealed that HMGB1 and RAGE expression in the mouse models could be markedly reduced by RIPOC (P<0.05) and that these reductions were associated with inhibition of the ERK pathway. Furthermore, it was demonstrated that RIPOC produced significant antioxidant and antiinflammatory effects following an intestinal I/R injury and that these effects were mediated via the ERK pathway (P<0.05). In addition, RIPOC was demonstrated to suppress the NFκB (p65)/NLR family pyrin domain containing 3 (NLRP3) inflammatory pathways in the intestinal I/R injury mouse models via the ERK pathway. The findings of the present study demonstrated that RIPOC helped to protect mice with an intestinal I/R injury by downregulating the ERK pathway.
Subject(s)
Enzyme Inhibitors/pharmacology , Ischemic Postconditioning/methods , MAP Kinase Signaling System/drug effects , Reperfusion Injury/therapy , Animals , Anti-Inflammatory Agents/pharmacology , Antioxidants/pharmacology , Intestines/drug effects , Intestines/pathology , Male , Mice , Mice, Inbred C57BLABSTRACT
BACKGROUND: Trans-resveratrol-3-O-glucoside (TRG), isolated from the Chinese traditional herbal medicine Huzhang, has been shown to have a wide range of pharmacological benefits. PURPOSE: The aim of this study is to investigate the pharmacokinetics, tissue distribution and excretion of TRG and its metabolites, (TRN (trans-resveratrol-3-O-glucuronide) and TR (trans-resveratrol)), following a single intragastric (i.g.) administration of TRG in rats. STUDY DESIGN: To evaluate the pharmacokinetic properties of TRG, TRN and TR, groups of rats were administrated a single i.g. dose of either 75, 150 or 300â¯mg/kg TRG. The absolute bioavailability of TRG was estimated from the ratios of AUC0-∞ values for oral and intravenous administration. Tissue distributions of TRG, TRN and TR in rats were investigated following a single i.g. administration to four groups at 150â¯mg/kg dosage of TRG. For urinary, fecal and biliary excretion study, TRG, TRN and TR excretions were recovered from a group of rats administered a single i.g. dose of 150â¯mg/kg TRG. METHODS: The levels of TRG, TRN and TR in plasma, tissues, bile, urine and feces were measured by a rapid and sensitive LC-UV method. The precision was below 10.0%, and the accuracy was within ±9.9% for TRG, TRN and TR. RESULTS: The concentrations of TRN were markedly higher than those of TRG and TR in plasma, urine and bile. TRG, TRN and TR showed linear dynamics in dose range of 75-300â¯mg/kg TRG. TRG had poor absolute bioavailability in rats. The major distribution tissues of TRG, TRN, and TR in rats were in the digestive tract. TRG, TRN and TR were all eliminated from tissues quickly. TRG was mostly excreted via the renal route in the form of TRN, which accounted for 52.8% of the administered dose up to 72â¯h. CONCLUSION: Following a single i.g. administration to rats TRG was easily absorbed and rapidly converted to the metabolites TR and TRN. These metabolites were found to be mainly excreted by the kidneys.