羊栖菜组分多糖对α-葡萄糖苷酶的抑制作用

为高效利用羊栖菜组分多糖(SFPSⅠ),以SFPSⅠ为原料,α-葡萄糖苷酶作为靶标,研究SFPSⅠ对α-葡萄糖苷酶的抑制作用及其结构的影响,建立具有α-葡萄糖苷酶活性的Caco-2细胞模型,并对Caco-2细胞模型上α-葡萄糖苷酶活性的抑制效果进行研究。结果表明,SFPSⅠ对α-葡萄糖苷酶有明显的抑制作用,使得α-葡萄糖苷酶活力下降一半时的抑制剂浓度,即半抑制(IC₅₀)为0.31 mg·mL^-1。SFPSⅠ对α-葡萄糖苷酶的抑制作用是一个可逆过程,抑制类型为混合型抑制。动力学分析结果表明,SFPSⅠ对α-葡萄糖苷酶的抑制常数(K_i)为0.143μmol·L^-1。荧光测定结果表明,SFPSⅠ结合会引起α-葡萄糖苷酶三级结构的明显变化。随着SFPSⅠ浓度的升高,其对Caco-2细胞模型上α-葡萄糖苷酶抑制效果越好。本研究结果为进一步探讨和设计新型α-葡萄糖苷酶抑制剂奠定了科学基础,同时也为开发具有降血糖功能的功能性药品与保健品提供了新资源。     

Cellular uptake and efflux of trans-piceid and its aglycone trans-resveratrol on the apical membrane of human intestinal Caco-2 cells

Two stilbenes (trans-piceid and its aglycone trans-resveratrol) were investigated in the uptake across the apical membrane of the human intestinal cell line Caco-2 in order to determine their mechanisms of transport. The uptake was quantified using a reverse phase high-performance liquid chromatography method with fluorescence detection. The rate of cellular accumulation in the cells was found to be higher for trans-resveratrol than for trans-piceid. In addition, trans-resveratrol uses passive transport to cross the apical membrane of the cells, whereas the transport of trans-piceid is likely active. With regard to the mechanisms of transport, the involvement of the active transporter SGLT1 in the absorption of trans-piceid was deduced using various inhibitors directly or indirectly exploiting the activity of this transporter (glucose, phlorizin, and ouabain). Moreover, we investigated the involvement of the multidrug-related protein 2 (MRP2), an efflux pump present on the apical membrane, in stilbene efflux by Caco-2 cells. The effect of MK-571 (an MRP inhibitor) seems to implicate MRP2 as responsible for apical efflux of trans-piceid and trans-resveratrol.     

Effect of ginsenosides on glucose uptake in human Caco-2 cells is mediated through altered Na+/glucose cotransporter 1 expression

In this study, we measured the effect of ginsenosides on glucose uptake using the Caco-2 cell system. At submicromolar concentrations, these compounds exhibited marked effects on the rate of glucose transport across the differentiated Caco-2 cell monolayer. Compound K (CK), the main intestinal bacterial metabolite of the protopanaxadiol ginsenosides, significantly enhanced the steady-state glucose transport rate to about 50% of the control sample rate (from 1.54 +/- 0.09 to 2.25 +/- 0.15 nmol/min). Conversely, the protopanaxatriol ginsenoside Rg1 inhibited glucose transport to about 70% of the original rate (from 1.54 +/- 0.09 to 1.02 +/- 0.05 nmol/min). Consistent with the effect on glucose uptake rate, CK and Rg1 conferred a significant and paralleled alteration on both the protein and mRNA expression levels of the Na+/glucose cotransporter 1 (SGLT1) gene. Unlike SGLT1, there is no significant alteration on the protein or mRNA levels of GLUTs in CK- or Rg1-treated cells. Taken together, our results demonstrate that ginsenosides CK and Rg1 elicited potent enhancing and suppressing effects, respectively, on glucose uptake across human intestinal Caco-2 monolayer through modulation of SGLT1 expression.     

Occurrence of orally administered mulberry 1-deoxynojirimycin in rat plasma

1-deoxynojirimycin (DNJ), a potent glucosidase inhibitor, is a characteristic constituent of the mulberry leaf. Dietary mulberry DNJ may be beneficial for the suppression of abnormally high blood glucose levels, thereby preventing diabetes mellitus. Although there is considerable interest in the effects of mulberry DNJ, the intestinal absorption and pharmacokinetic profile of orally administered mulberry DNJ have never been characterized. In this study, we developed a method for determining the level of plasma DNJ by hydrophilic interaction chromatography coupled to a mass spectrometric detector (HILIC-MS) to investigate the absorption and metabolism of orally administered mulberry DNJ in rats. DNJ was separated from plasma extract on a TSK gel Amide-80 column, a representative column for HILIC. At postcolumn, DNJ was concurrently detected and identified by MS. The plasma DNJ concentration in fasted rats was below the detection limit [<1 microg (6 nmol)/mL]; however, the concentration reached a maximum [15 microg (92 nmol)/mL] 30 min after the administration of mulberry DNJ (110 mg/kg of body weight), and the DNJ concentration decreased rapidly thereafter. When the rats received different amounts of mulberry DNJ (1.1, 11, and 110 mg/kg of body weight), dose-dependent incorporation of DNJ into the plasma was confirmed. We did not detect any DNJ metabolites in the plasma. These findings indicate that orally administered mulberry DNJ is absorbed as an intact form from the alimentary tract and then is quickly excreted from the body. The developed HILIC-MS method could be applied in determining levels of DNJ in urine and tissues, and therefore, the method would be a powerful tool for studying the metabolic fate of mulberry DNJ as well as its bioavailability.     

Antiobesity effects and improvement of insulin sensitivity by 1-deoxynojirimycin in animal models

The alpha-glucosidase inhibitor 1-deoxynojirimycin (DNJ) is one of the simplest naturally occurring carbohydrate mimics, with promising biological activity in vivo. Although there is considerable interest in the pharmacological effects of DNJ, the antidiabetic effects of DNJ in type 2 diabetes mellitus have received little attention. In this work, DNJ was isolated from the silkworm (Bombyx mori), and its antidiabetic effects were evaluated in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an established animal model of human type 2 diabetes mellitus, and in control Long-Evans Tokushima Otsuka (LETO) rats. DNJ treatment showed significant antidiabetic effects in OLETF rats, with significant improvements in fasting blood glucose levels and glucose tolerance and, especially, increased insulin sensitivity. Furthermore, there was significant loss of body weight in both groups. DNJ also showed significant antihyperglycemic effects in streptozotocin- and high-fat-diet-induced hyperglycemic rats. Its efficacy and dose profiles were better than those of acarbose, a typical alpha-glucosidase inhibitor in clinical use. Furthermore, a substantial fraction of DNJ was absorbed into the bloodstream within a few minutes of oral administration. DNJ was also detected in the urine. These findings suggest that its postprandial hypoglycemic effect in the gastrointestinal tract is a possible but insufficient mechanism of action underlying the antidiabetic effects of DNJ. Its antiobesity effect and improvement of insulin sensitivity are other possible antidiabetic effects of DNJ.     

Assessment of carotenoid bioavailability of whole foods using a Caco-2 cell culture model coupled with an in vitro digestion

Epidemiological studies have shown that consumption of carotenoid-rich fruits and vegetables is associated with a reduced risk of developing chronic diseases. beta-Carotene, alpha-carotene, and beta-cryptoxanthin are precursors of vitamin A, a nutrient essential for human health. However, little is known about the bioavailability of carotenoids from whole foods. This study characterized the intestinal uptake performance of carotenoids using monolayers of differentiated Caco-2 human intestinal cells and mimicked human digestion to assess carotenoid absorption from carrots and corn. Results showed that Caco-2 cellular uptake of beta-carotene and zeaxanthin was higher than that of lutein. Uptake performances of pure carotenoids and carotenoids from whole foods by Caco-2 cells were both curvilinear, reaching saturated levels after 4 h of incubation. The time kinetics and dose response of carotenoid uptake presented a similar pattern in Caco-2 cells after plating for 2 and 14 days. Furthermore, the applicability of this new model was verified with whole grain corn, showing that cooked corn grain significantly enhanced carotenoid bioavailability. These results support the feasibility of the in vitro digestion cell model for assessing carotenoid absorption from whole foods as a suitable and cost-effective physiological alternative to current methodologies.     

Transport across Caco-2 cell monolayer and sensitivity to hydrolysis of two anxiolytic peptides from αs1-casein, α-casozepine, and αs1-casein-f91-97: effect of bile salts

α-Casozepine and f91-97, peptides from α(s1)-casein, display anxiolytic activity in rats and may have to cross the intestinal epithelium to exert this central effect. We evaluated their resistance to hydrolysis by the peptidases of Caco-2 cells and their ability to cross the cell monolayer. To mimic physiological conditions, two preparations of bile salts were used in noncytotoxic concentrations: porcine bile extract and an equimolar mixture of taurocholate, cholate, and deoxycholate. The presence and composition of bile salts appeared to modulate the peptidase activities of the Caco-2 cells involved (i) in the hydrolysis of α-casozepine, leading to much higher formation of fragments f91-99, f91-98, and f91-97, and (ii) in the hydrolysis of f91-97, leading to lower degradation of this peptide. Transport of α-casozepine across Caco-2 monolayer increased significantly, in the presence of bile extract, and of fragment f91-97, in the presence of bile salts.     

Effect of dietary ligands and food matrices on zinc uptake in Caco-2 cells: implications in assessing zinc bioavailability

The kinetics, depletion/repletion of zinc, and effects of dietary ligands/food matrices on (65)Zn uptake was studied in Caco-2 cells. The uptake of zinc showed a saturable and nonsaturable component, depending upon the media zinc concentrations. Intracellular depletion increased zinc uptake, whereas zinc loading did not. Phytic acid and histidine inhibited zinc uptake, while tannic acid, tartaric acid, arginine, and methionine increased zinc uptake. Tannic acid at a 1:50 molar ratio promoted zinc uptake from wheat- and rice-based food matrices. Further, Caco-2 cells responded similarly with zinc and iron uptake when fed Indian bread prepared from low- and high-extraction wheat flour, representing low and high phytate content. However, inclusion of tea extract or red grape juice as a source of polyphenols enhanced the uptake of zinc while decreasing that of iron. These results suggest that the Caco-2 cells predict the correct direction of response to dietary ligands even from complex foods.     

Assessment of iron bioavailability in whole wheat bread by addition of phytase-producing bifidobacteria

In this study, the influence of phytase-producing Bifidobacterium strains during the breadmaking process (direct or indirect) on final bread Fe dialyzability and ferritin formation in Caco-2 cell as a measure of cell Fe uptake was assessed. The addition of bifidobacteria significantly reduced the InsP(6) + InsP(5) concentrations compared to control samples. Fe-dialyzable contents for samples with bifidobacteria were increased 2.3-5.6-fold, and dialyzability was improved by 2.6-8.6% compared to controls. However, this was not reflected in an increase of Fe uptake by Caco-2 cells as was predicted by the phytate/Fe molar ratios. The results demonstrated the usefulness of phytase-producing bifidobacteria to reduce phytate during the breadmaking process and to increase Fe accessibility, although the effects appeared to be still insufficient to improve Fe bioavailability in Caco-2 cells. Further refinement of the use of phytase-producing bifidobacterial strains and/or breadmaking technological processes is deserved for improving Fe uptake.     

Bioavailability of cadmium from in vitro digested infant food studied in Caco-2 cells

The solubility and bioavailability of cadmium (Cd) in infant foods, three cereal- and milk-based diets and two ready-to-use baby dishes, were studied after in vitro digestion and by using human intestinal Caco-2 cells. The solubility of Cd after in vitro digestion varied between diets; liver casserole had the highest solubility and was lower after infant as compared to adult digestion conditions. Generally, more Cd was soluble in infant intestinal than gastric juice in contrast to the results from the adult digestion. Caco-2 cells were incubated with supernatants of infant digests that had been equilibrated with (109)Cd during the in vitro digestion procedure, and cellular uptake and transport of (109)Cd were measured after 180 min. Statistically significant differences in both uptake and transport of Cd were detected between some of the diets and a control solution containing only digestive enzymes and (109)CdCl(2). Uptake of soluble Cd in the cells varied between diets from 4 to 6%, and the transport over the monolayers was 1-2% of the dose. We conclude that age specific digestion conditions as well as composition of diets affect both solubility and bioavailability of Cd.     

Grape Seed-Derived Procyanidins Decrease Dipeptidyl-peptidase 4 Activity and Expression

Dipeptidyl-peptidase 4 (DPP4) inhibitors are among the newest treatments against type 2 diabetes. Since some flavonoids modulate DPP4 activity, we evaluated whether grape seed-derived procyanidins (GSPEs), which are antihyperglycemic, modulate DPP4 activity and/or expression. In vitro inhibition assays showed that GSPEs inhibit pure DPP4. Chronic GSPE treatments in intestinal human cells (Caco-2) showed a decrease of DPP4 activity and gene expression. GSPE was also assayed in vivo. Intestinal but not plasmatic DPP4 activity and gene expression were decreased by GSPE in healthy and diet-induced obese animals. Healthy rats also showed glycemia improvement after oral glucose consumption but not after an intraperitoneal glucose challenge. In genetically obese rats, only DPP4 gene expression was down-regulated. Thus, procyanidin inhibition of intestinal DPP4 activity, either directly and/or via gene expression down-regulation, could be responsible for some of their effects in glucose homeostasis.     

Food-grade mulberry powder enriched with 1-deoxynojirimycin suppresses the elevation of postprandial blood glucose in humans

Mulberry 1-deoxynojirimycin (DNJ), a potent glucosidase inhibitor, has been hypothesized to be beneficial for the suppression of abnormally high blood glucose levels and thereby prevention of diabetes mellitus. However, DNJ contents in commercial mulberry products were as low as about 0.1% (100 mg/100 g of dry product), implying that the bioavailability of DNJ might not be expected. We carried out studies in two directions: (1) production of food-grade mulberry powder containing a maximally high DNJ content; (2) determination of the optimal dose of the DNJ-enriched powder for the suppression of the postprandial blood glucose through clinical trials. The following method was used: (1) DNJ concentrations in mulberry leaves from different cultivars, harvest seasons, and leaf locations were determined using hydrophilic interaction chromatography with evaporative light scattering detection. (2) Healthy volunteers received 0, 0.4, 0.8, and 1.2 g of DNJ-enriched powder (corresponding to 0, 6, 12, and 18 mg of DNJ, respectively), followed by 50 g of sucrose. Before and 30-180 min after the DNJ/sucrose administration, plasma glucose and insulin were determined. The following results were obtained: (1) Young mulberry leaves taken from the top part of the branches in summer contained the highest amount of DNJ. After optimization of the harvesting and drying processes for young mulberry leaves (Morus alba L. var. Shin ichinose), DNJ-enriched powder (1.5%) was produced. (2) A human study indicated that the single oral administration of 0.8 and 1.2 g of DNJ-enriched powder significantly suppressed the elevation of postprandial blood glucose and secretion of insulin, revealing the physiological impact of mulberry DNJ (effective dose and efficacy in humans). This study suggests that the newly developed DNJ-enriched powder can be used as a dietary supplement for preventing diabetes mellitus.     

Inhibition of iron uptake from iron salts and chelates by divalent metal cations in intestinal epithelial cells

Iron chelates, namely, ferrous bisglycinate and ferric EDTA, are promising alternatives to iron salts for food fortification. The objectives of this study were to compare iron uptake from radiolabeled ferrous sulfate, ferrous ascorbate, ferrous bisglycinate, ferric chloride, ferric citrate, and ferric EDTA by Caco-2 cells with different iron status and in the presence of divalent metal cations. Iron-loaded Caco-2 cells, with reduced DMT-1 and elevated HFE mRNA levels, down-regulated uptake from ferrous ascorbate and bisglycinate but not from ferric compounds. Nevertheless, iron uptake from all compounds was markedly inhibited in the presence of 100-fold molar excess of Co2+ and Mn2+ cations, with ferrous compounds showing a greater percent reduction. Our results suggest that ferrous iron is the predominant form of iron taken up by intestinal epithelial cells and the DMT-1 pathway is the major pathway for uptake. Iron uptake from chelates appears to follow the same pathway as uptake from salts.     

Impact of the stage of ripening and dietary fat on in vitro bioaccessibility of beta-carotene in 'Ataulfo' mango

Pulp from "slightly ripe", "moderately ripe", or "fully ripe" mangoes was digested in vitro in the absence and presence of processed chicken as a source of exogenous fat and protein to examine the impact of stage of ripening of mango on micellarization during digestion and intestinal cell uptake (i.e., bioaccessibility) of beta-carotene. The quantity of beta-carotene transferred to the micelle fraction during simulated digestion significantly increased as the fruit ripened and when chicken was mixed with mango before digestion. Qualitative and quantitative changes that occur in pectin from mango pulp during the ripening process influenced the efficiency of micellarization of beta-carotene. Finally, the uptake of beta-carotene in micelles generated during simulated digestion by Caco-2 human intestinal cells confirmed the bioaccessibility of the provitamin A carotenoid in mango.     

Assessment of degradation and intestinal cell uptake of carotenoids and chlorophyll derivatives from spinach puree using an in vitro digestion and Caco-2 human cell model

Although numerous studies have demonstrated the health benefits of chlorophyll derivatives, information regarding the digestion, absorption, and metabolism of these phytochemicals is quite limited. To better understand the digestion of these pigments, green vegetables including fresh spinach puree (FSP), heat- and acid-treated spinach puree (HASP), and ZnCl(2)-treated spinach puree (ZnSP) were subjected to an in vitro digestion method which simulates both the gastric and small intestinal phases of the process. Native chlorophylls were converted to Mg-free pheophytin derivatives during digestion. Conversely, Zn-pheophytins were completely stable during the digestive process. Transfer of lipophilic chlorophyll derivatives, as well as the carotenoids lutein and beta-carotene, into the aqueous micellar fraction from the food matrix was quantified. Micellarization of total chlorophyll derivatives differed significantly (p < 0.05) for FSP (37.6%), HASP (17.2%), and ZnSP (8.7%). Micellarization of chlorophyll a derivatives was determined to be significantly more efficient than chlorophyll b derivatives in FSP and HASP (p < 0.01), but not in ZnSP (p > 0.05). Intestinal cell uptake of micellarized pigments was investigated using HTB-37 (parent) and clonal TC7 lines of human Caco-2 cells. Medium containing the pigment-enriched fraction generated during digestion was added to the apical surface of fully differentiated monolayers for 4 h. Pigments were then extracted from cells and analyzed by C18 HPLC with photodiode array detection. Both Caco-2 HTB-37 and TC7 clone cells accumulated 20-40% and 5-10% of micellarized carotenoid and chlorophyll derivatives, respectively. These results are the first to demonstrate uptake of chlorophyll derivatives by human intestinal cells and to support the potential importance of chlorophylls as health-promoting phytochemicals.     

A high-throughput assay for quantification of starch hydrolase inhibition based on turbidity measurement

A high-throughput method for rapid determination of starch hydrolase inhibition was developed using a 96-well microplate UV-vis reader to monitor the turbidity decrease over time. The area under the curve of turbidity measured over time was used to quantify the inhibitory effect of polyphenolic compounds on porcine pancreatic amylase, rat intestine α-glucosidase, and fungal amyloglucosidase. Acarbose equivalence (AE) was introduced for the first time and defined as IC50 of acarbose divided by the IC50 of the sample measured under the same 96-well plate. This way, the run-to-run variations are canceled out. Among the plant extracts tested, grape seed extracts (1,440 μmolAE/g) and cinnamon bark extracts (1600 μmolAE/g) are the most active in inhibiting rat intestine α-glucosidase. For porcine α-amylase inhibition, grape seed extracts (5710 μmol AE/g) are close to four times more active (equal weight basis) than acarbose (1550 μmolAE/g).     

Sodium copper chlorophyllin: in vitro digestive stability and accumulation by Caco-2 human intestinal cells

Sodium copper chlorophyllin (SCC), a mixture of water-soluble chlorophyll derivatives, is used as both a food colorant and a common dietary supplement. Although the potential antimutagenic and antioxidant properties of this commercial preparation have been demonstrated, limited information is available on its digestion and absorption by humans. Stability of SCC was examined during simulated gastric and small intestinal digestion. Three preparations were subjected to in vitro digestion: SCC in water, SCC in water + 10% corn oil, and SCC in applesauce. SCC components from raw material preparations and in digested samples were analyzed by C(18) HPLC with photodiode array detection. Cu(II)chlorin e(4), the major chlorin component of SCC, was relatively stable during simulated digestion. In contrast, greater than 90% of Cu(II)chlorin e(6) was degraded to undetermined products during digestion. Recovery of Cu(II)chlorin e(6) after digestion was increased by incorporation of SCC into applesauce, suggesting a protective role of the inclusion matrix for stabilization of labile SCC components. Accumulation of SCC derivatives was investigated by using differentiated cultures of the TC7 clone of the Caco-2 human intestinal cell line. Cellular accumulation from media containing 0.5 to 60 ppm SCC was linear with intracellular content ranging between 0.2 and 29.6 microg of total SCC per mg of cellular protein. Uptake of SCC by Caco-2 cells was significantly (p < 0.01) lower in cultures incubated at 4 degrees C than in those incubated at 37 degrees C. Although intracellular SCC was transported into both apical and basolateral compartments when Caco-2 cells were grown on inserts, apical efflux was significantly greater (p < 0.01) than basolateral efflux. Stability of Cu(II)chlorin e(4) during in vitro digestion and effective uptake by Caco-2 enterocyte-like cells support the likelihood that a portion of this SCC component or its metabolites is absorbed from the human intestine.     

Peptides isolated from in vitro digests of milk enhance iron uptake by caco-2 cells

Milk proteins, during digestion, produce a range of biologically active peptides. Among those are peptides that may enhance iron absorption. The objective of this project was to investigate the effect of isolated milk peptides on iron uptake. Cow's milk, 0% fat, was subjected to a modified in vitro digestion process. The milk digest was further fractionated by gel filtration. All eluted fractions as well as beta-casein synthetic peptides (a tripeptide and a hexapeptide) were subsequently tested for effects on iron uptake with Caco-2 cell monolayers. Fractions of milk digests obtained through Sephadex G-25 gel filtration had a significant enhancing effect on iron uptake in Caco-2 cells compared to nonfractionated milk digests. Two fractions (P = 0) and the hexapeptide (P < 0.0001) enhanced iron uptake by up to 3-fold, whereas others and the tripeptide had no effect. These results suggest that selected peptides produced during the in vitro digestion of milk may enhance iron absorption; however, it remains to be demonstrated whether this effect may be nutritionally significant.     

Zinc transport in Caco-2 cells and zinc balance in rats: influence of the heat treatment of a casein-glucose-fructose mixture

The effects of the heat treatment of casein in the presence of glucose-fructose on Zn bioavailability were studied. Changes in Zn speciation were compared after in vitro digestion of heated (HC) and unheated mixture (C) alone and as part of the diet. The uptake and transport of digested soluble Zn was investigated in Caco-2 cells grown in bicameral chambers; balance studies were done in rats fed diets containing the different samples. After in vitro digestion, the precipitated Zn was significantly higher in HC than in C. In assays with Caco-2 cells, the amount of Zn transferred from the apical to the basolateral chamber was significantly greater when the culture medium contained raw or heated casein. However, because a larger proportion of Zn was precipitated by in vitro digestion, Zn utilization was less efficient in the presence of casein. In biological experiments, food efficiency of the heated casein-glucose-fructose diet was lower, and feeding this diet increased the urinary Zn excretion and lowered Zn absorption and retention. The effects of browning products generated during food processing should be taken into account, especially in diets containing marginally adequate levels of Zn, to prevent possible deficiency.     

In vitro pharmacokinetic characterization of mulberroside A, the main polyhydroxylated stilbene in mulberry (Morus alba L.), and its bacterial metabolite oxyresveratrol in traditional oral use

Mulberroside A (MulA) is one of the main bioactive constituents in mulberry (Morus alba L.). This study examined the determining factors for previously reported oral pharmacokinetic profiles of MulA and its bacterial metabolite oxyresveratrol (OXY) on in vitro models. When incubated anaerobically with intestinal bacteria, MulA underwent rapid deglycosylation and generated two monoglucosides and its aglycone OXY sequentially. MulA exhibited a poor permeability and predominantly traversed Caco-2 cells via passive diffusion; yet, the permeation of OXY across Caco-2 cells was much more rapid and involved efflux (both p-glycoprotein and MRPs)-mediated mechanisms. Moreover, OXY underwent extensive hepatic glucuronidation; yet, the parent MulA was kept intact in liver subcellular preparations. There was insignificant species difference in intestinal bacterial conversion of MulA and the extent of OXY hepatic glucuronidation between humans and rats, while OXY exhibited a distinct positional preference of glucuronidation in the two species. Overall, these findings revealed a key role of intestinal bacterial conversion in absorption and systemic exposure of MulA and its resultant bacterial metabolite OXY in oral route in humans and rats and warranted further investigational emphasis on OXY and its hepatic metabolites for understanding the benefits of mulberry.