Abstract
Alteration in the number and composition of intestinal microbiota affects the metabolism of several xenobiotics. Gastrodin, isolated from Gastrodia elata, is prone to be hydrolyzed by intestinal microbiota. In the present study, the role of intestinal microbiota in gastrodin metabolism was investigated in vitro and in vivo. Gastrodin was incubated in an anaerobic condition with intestinal contents prepared from vehicle- and antibiotics-treated rats and the disappearance of gastrodin and formation of 4-hydroxybenzyl alcohol (4-HBA) was measured by liquid chromatography coupled to mass spectroscopy (LC-MS/MS). The results showed that almost all gastrodin incubated with control intestinal contents was metabolized to its aglycone in time- and concentration-dependent manners. In contrast, much less formation of 4-HBA was detected in intestinal contents from antibiotics-treated rats. Subsequently, in vivo pharmacokinetic study revealed that the antibiotic pretreatment of rats significantly affected the metabolism of gastrodin to 4-HBA. When administered orally, gastrodin was rapidly absorbed rapidly into plasma, metabolized to 4-HBA, and disappeared from the body within six hours. Interestingly, the pharmacokinetic parameters of 4-HBA were changed remarkably in antibiotics-treated rats, compared to control rats. The results clearly indicated that the antibiotics treatment of rats suppressed the ability of intestinal microbiota to metabolize gastrodin to 4-HBA and that, thereby, the pharmacodynamic action was significantly modulated.
Highlights
In human intestine, trillions of bacteria do play major roles in retrieving energy from carbohydrates, proteins, and fats, and synthesize or metabolize vitamins B and K and bile salts [1].In recent years, possible roles of intestinal microbiota in xenobiotic metabolism have been extensively studied [2]
The results indicate that the intestinal microbiota played a critical role in the metabolism of gastrodin to its aglycone
The results suggested that the antibiotics pretreatment of rats significantly inhibited or suppressed the intestinal microbiota, resulting in a significant change in the pharmacokinetic profiles of 4-hydroxylbenzyl alcohol (4-HBA)
Summary
Trillions of bacteria do play major roles in retrieving energy from carbohydrates, proteins, and fats, and synthesize or metabolize vitamins B and K and bile salts [1]. Because gastrodin is a Metabolites 2019, 9, 69 glycoside of 4-hydroxylbenzyl alcohol (4-HBA; Figure 1B), it is prone to be hydrolyzed into its aglycone [6] Both gastrodin and 4-HBA have wide pharmacological effects and have been used in various clinical conditions, such asand headache, migraine, and paralysis [4,5]. The clinical applications of gastrodin and its metabolites, 4-HBA, have been investigated withAlthough respect to the theirclinical pharmacokinetic characteristics of intestinal microbiota on applications of gastrodin[8,9,10], and the its effects metabolites, 4-HBA, have been gastrodin metabolism and its pharmacokinetics have not been extensively studied in vivo and in vitro. Pharmacokinetic parameters oral gastrodin between and already proven to be effective in ouroflaboratory, were were orallycompared administered to ratsvehicle-treated prior to gastrodin antibiotics-treated the in vitro studies, an anaerobic gas-generating pouch system was administration [11].rats. Formation of 4-HBA were observed by LC-MS/MS following in vitro incubation of gastrodin with intestinal contents under the anaerobic gas-generating pouch system
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