|کد مقاله||کد نشریه||سال انتشار||مقاله انگلیسی||ترجمه فارسی||نسخه تمام متن|
|2579777||1561583||2016||10 صفحه PDF||سفارش دهید||دانلود رایگان|
• ATMs treated rats or restraint stressed rats exhibit dysregulated gut microbiota.
• Fecal β-d-glucosidase activity was changed in ATMs treated or restraint stressed rats.
• Dysregulated fecal β-d-glucosidase leads to changed systemic exposure of ginsenoside Rb1 and its metabolites.
Ginsenoside Rb1, an active ingredient in Panax ginseng, was widely used for its various biological activities. To clarify the role of the gut microbiota in pharmacokinetics and metabolism of Rb1, a comprehensive and comparative study of colonic deglycosylation metabolism and systemic exposure of ginsenoside Rb1 in normal rats, antimicrobials (ATMs) treated rats, and restraint stressed rats was conducted. ATMs treated rats received oral administration of non-absorbable antimicrobial mixtures for 7 consecutive days. Restraint stressed rats were subjected to repeated restraint stress for a period of 2 h once daily for 7 days. Plasma concentration dynamics, urine and fecal excretion of Rb1 and its deglycosylation metabolites (Rd, F2, and C-K) were studied. Moreover, the in vitro metabolism of Rb1 in fecal suspension and the fecal β-d-glucosidase activity were profiled. Systemic exposure of the deglycosylation metabolites of ginsenoside Rb1 (F2, C-K) were significantly higher in restraint stressed rats, but ATMs treated rats exhibited a decreased plasma levels of F2 and C-K, compared with normal rats. Further studies illustrated that altered systemic Rb1 and its deglycosylation metabolites exposure in restraint-stressed rats and ATMs treated rats may be partially attributed to alternations in cumulative fecal excretion. The distinguishing fecal β-d-glucosidase, in vitro elimination of Rb1, and formation of these deglycosylation metabolites afforded further evidence for the in vivo data. In conclusion, the dys-regulated fecal β-d-glucosidase activity and deglycosylation metabolism may contribute to the altered pharmacokinetic of ginsenoside Rb1 and its hydrolysis metabolites after ATMs treatment or restraint stress exposure. Our results may offer valuable insights into the pharmacological changes of bioactive ginsenosides in dys-regulated gut microbiota statue.
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Journal: Chemico-Biological Interactions - Volume 258, 25 October 2016, Pages 187–196