Intestinal Absorption of Prenylated Isoflavones, Glyceollins, in Sprague–Dawley Rats

Abstract

Although prenylated isoflavones or glyceollins elicit physiological effects more potent than those by isoflavones, the bioavailability remains unclear. The present study aimed to clarify the intestinal absorption behavior of glyceollins in Sprague− Dawley rats. Upon oral administration of 1.0 mg/kg glyceollin I or III (daidzein as comparative compound) to the rats, no peaks corresponding to the intact forms of the compounds were detected in plasma by liquid chromatography−time-of-flight/mass spectrometry (LC−TOF/MS) analysis. In contrast, enzymatic deconjugation of plasma resulted in successful MS detection of each glyceollin; glyceollin I absorption was >10 times higher than that of daidzein, given its high log P value. The present study demonstrated for the first time that glyceollins were more absorbable than mother isoflavones due to their high hydrophobicity, and they metabolized to form sulfated, glucuronized, and methylated conjugates during the intestinal absorption process.

Tissue Distribution of Orally Administered Prenylated Isoflavones, Glyceollins, in Sprague-Dawley Rats

“…From our earlier findings, glyceollins are metabolized to form sulfated or glucuronidated conjugates in the blood during the intestinal absorption process. 2 Herein, we investigated the accumulation of each type of conjugate. After 0.5 h of administration, MS peaks corresponding to monosulfated ([Sul-glyceollin I/III − H] − , 417.065 m/z) and monoglucuronidated ([GlcA-glyceollin I/III − H] − , 513.1402 m/z) glyceollins were observed in all of the target organs and plasma (Figure 2).…”

“…The glyceollin assay in rat plasma was the same as that used in a previous study. 2 LC-TOF/MS Analysis. LC separation was performed with an Agilent 1200 series instrument (Agilent; Waldbronn, Germany) using a Cosmosil 5C 18 -MS-II column (2.0 × 150 mm, Nacalai Tesque Co., Kyoto, Japan) at 40 °C with a linear gradient elution of 0.1% FA (solvent A) to MeOH containing 0.1% FA (solvent B) over 80 min at a flow rate of 0.25 mL/min.…”

“…In addition, glyceollins were found to be rapidly (time to reach C max , T max : 0.5 h) absorbed and metabolized into methylated, sulfated, and glucuronidated conjugated forms. 2 Moreover, glyceollins exert physiological effects after intake, such as improved glucose homeostasis, by enhancing hepatic insulin sensitivity in the liver of diabetic mice. 3 The in vivo health benefits of glyceollins in organs strongly suggest that they may play a physiological role through their local accumulation.…”

“…5 In a tissue distribution study of genistein in female SD rats, the placenta was found to be one of the target organs for glucuronidated and sulfated genistein metabolites. 6 Considering the higher absorption of glyceollins compared to isoflavones, 2,7 a preferential tissue distribution of the former is highly expected after intake.…”

Effect of Berbamine Hydrochloride on Absorption Parameters of Berberine Hydrochloride Based on in Situ Single-Pass Intestinal Perfusion System in the Rat

“…Compared with the phenol red method, it only needs to determine the concentration of the drug in the perfusate, and does not involve the determination of phenol red, which makes the experimental procedure more concise and reduces the detection workload [24]. The insu ciency of the gravimetric method assumes that the density of the inlet and outlet perfusate remains constant, but various reasons such as absorption and secretion of water by the intestine, peeling of mucous membranes, and absorption of drugs can cause the density to change, which is contrary to the setting,that will bring cause errors [25].…”