Intestinal disaccharidases in five species of phyllostomoid bats.

1. Intestinal disaccharidases were studied in nectarivorous (Leptonycteris curasoae and Glossophaga soricina), frugivorous (Artibeus jamaicensis and Sturnira lilium), and insectivorous (Pteronotus personatus) adult bats. 2. Adult bats lacked measurable lactase activity. With the exception of trehalase activity, which was present only in P. personatus, nectar- and fruit-eating bats exhibited higher disaccharidase activities standardized by intestinal nominal area than insect-eating P. personatus. 3. Maltase and sucrase activities were significantly linearly correlated. 4. Apparent affinity of sucrase varied almost 5-fold among species. This variation may reflect unstirred layer effects resulting from sucrase being a membrane bound enzyme rather than differences in the "true" affinity of sucrase in solution. 5. Passerine birds showed higher maltase activity per unit of sucrase activity than bats and hummingbirds. Maximal sucrase and maltase activities standardized per intestinal nominal area are 1.5-2 times higher in hummingbirds than in nectar-feeding bats.     

Test of the adaptive modulation hypothesis in rodents: dietary flexibility and enzyme plasticity.

The phenotypic response of digestive enzymes was assessed in two species of rodents with different foods habits. Species were Phyllotis darwini (omnivorous) and Octodon degus (herbivorous). The activity of sucrase, maltase and aminopeptidase-N were determined in vitro in animals feeding two contrasting diets. No effect of dietary chemistry on sucrase and maltase activities was observed. Nevertheless, aminopeptidase-N showed a reversible response to diet in P. darwini but not in O. degus. Through Principal Component Analysis we separated the specific and non-specific modulation of the enzymes. The analysis showed that aminopeptidase-N activity is up-regulated by dietary protein in P. darwini. Differences in the phenotypic response of this species apparently reflect the historic levels of specific substrates of the natural diets for this enzyme, linking dietary flexibility and digestive plasticity in an evolutionary context.     

Dietary modulation of intestinal enzymes of the house sparrow (Passer domesticus): testing an adaptive hypothesis

Insectivorous/frugivorous passerine species studied so far lack the ability to modulate intestinal maltase activity, in contrast to galliformes. We tested for dietary modulation of small intestine (SI) enzymes including maltase in house sparrows to understand whether the difference between the galliformes on the one hand, and the passerines on the other, reflects a phylogenetic pattern (maltase modulated in galliformes but not passerines), a dietary pattern (maltase modulated in granivores but not insectivore/frugivores), some other pattern, or chance. We also tested the prediction that intestinal peptidase activity would be increased on a high protein (HP) diet. Birds were fed three diets high in starch, protein, or lipid for 10 days. For birds on the HP diet (60.3% protein) we observed the predicted upward modulation of aminopeptidase-N activity, as compared with the lower-protein, high starch (HS) (12.8% protein) diet. In contrast, birds eating the HS diet had similar maltase and sucrase activities, and only slightly higher isomaltase activity, compared with birds eating the high protein (HP), starch-free diet. Birds eating high lipid (HL) diet had low activities of both carbohydrases and peptidase. Considering that the statistical power of our tests was adequate, we conclude that house sparrows show little or no increase in carbohydrases in response to elevated dietary carbohydrate. We cannot reject the hypothesis that maltase lability among avian species has a phylogenetic component, or that high dietary fat has a depressing effect on both carbohydrase and peptidase activities.     

Developmental changes in digestive physiology of nestling house sparrows, Passer domesticus

Six decades of studies have speculated that digestive capacity might limit avian growth rate or that developmental changes in the gut might determine developmental changes in digestive efficiency. However, there are no studies on digestive enzymes during avian development, except for studies on mainly domestic birds that exhibit the precocial mode of development. We studied alimentary organ masses, intestinal enzyme activities (sucrase, maltase, isomaltase, aminopeptidase-N), and pancreatic enzyme activities (amylase, trypsin, chymotrypsin) during development of a wild passerine bird exhibiting the altricial mode of development. Wild nestling house sparrows were studied immediately after removal from the nest (days 0, 3, 6 of age; day 0=hatch), whereas captives were raised in the laboratory beginning day 3 on a formulated casein/starch-based diet until fledging age (after day 12). Digestive biochemistry was dynamic. Tissue-specific activities of some digestive enzymes continued to increase through fledging, by >10 times in some cases (e.g., sucrase and maltase in midintestine). Total pancreatic amylase activity increased 100 times between hatch and day 12 through a combination of increases in tissue-specific activity and pancreas mass. House sparrows differ from poultry, in whom after about 2 wk of age the specific activity of intestinal and pancreatic digestive enzymes is generally constant or declines during development. The data on intestinal and pancreatic enzymes help explain why digestive efficiency of nestling house sparrows improves with age, and the data seem consistent with the idea that digestive capacity might limit feeding rate and hence growth rate.     

Ontogenesis of intestine morphology and intestinal disaccharidases in chickens (Gallus gallus) fed contrasting purified diets

Two groups of growing posthatching Cornish x Rock cross chickens were fed with either a carbohydrate-containing (52.5%) or a carbohydrate-free diet. At 36 days after hatching some of the chicks in each group were shifted to the opposite diet. Chickens fed on a carbohydrate-containing diet grew faster and achieved higher asymptotic masses than chickens fed on a carbohydrate-free diet. Chickens fed on a carbohydrate-free diet had longer intestines and larger intestinal areas than chickens of the same mass fed on a carbohydrate-containing diet. In both groups sucrase and maltase activity (standardized by either intestinal area or mass) increased from day 1 to approximately day 17. After day 17, chickens fed on a carbohydrate-containing diet exhibited 1.8 and 1.9 times higher sucrase and maltase activities per unit intestinal area, respectively, than chickens fed on a carbohydrate-free diet. Analysis of covariance was used to estimate the contribution of sucrase and the sucrase-independent maltases to maltase activity, and to estimate the effect of diet on the sucrase-independent maltases. Sucrase contributed 80% and 75% of the maltase activity in carbohydrate and carbohydrate-free fed chickens, respectively. Chickens shifted from a carbohydrate-free to a carbohydrate diet converged in gross intestinal morphology and intestinal sucrase and maltase levels with carbohydrate-fed chickens within 8 days. Chickens shifted from carbohydrate to carbohydrate-free diets, in contrast, did not show appreciable changes in intestinal length and after 8 days had not reduced levels of sucrase and maltase to those of chickens fed on the carbohydrate-free diet. A comparison of integrated maltase intestinal activity with published data on glucose uptake showed that the ratio of maltose hydrolysis to glucose uptake seemed to be about 7 and to remain relatively invariant during ontogeny. Because so little is known about the interaction between hydrolysis and uptake in vivo, it is difficult to determine if this relatively high ratio represents excess hydrolytic capacity or if it is needed to provide high lumenal glucose concentrations that maximize uptake.Abbreviations m body mass - K _m Michaelis constant - K _m ^* apparent Michaelis constant - GI gastro-intestinal     

Understanding the early ontogenetic stages of Mugil liza (Mugilidae): Morphological traits and digestive/metabolic profile of pre-juveniles after recruitment

The family Mugilidae consists mainly of diadromous species, whose reproduction occurs in offshore waters. Pre-juveniles shift their diet in the surf zone (zooplanktophagous to iliophagous). Later, during their recruitment into estuaries, huge changes take place in their digestive system. However, digestive and metabolic characteristics and some morphological traits at recruitment are unknown for Mugilidae. We performed comparative studies on early and late pre-juveniles of Mugil liza recruited in Mar Chiquita Coastal Lagoon (37°32′–37°45′S, 57°19′–57°26′W, Argentina). We determined digestive enzyme activities (intestine), energy reserves (liver/muscle), total/standard length, total weight, intestinal coefficient, hepatosomatic index and retroperitoneal fat. Pre-juveniles exhibited amylase, maltase, sucrase, lipase, trypsin and aminopeptidase-N (APN) activities, which were maintained over a wide range of pH and temperature, and exhibited Michaelis–Menten kinetics. In late pre-juveniles, amylase (422 ± 131 μmol maltose min⁻¹ mgprot⁻¹), sucrase (86 ± 14 mg glucose min⁻¹ mgprot⁻¹), trypsin (84 ± 9 μmoles min⁻¹ mgprot⁻¹) and APN (0.58 ± 0.08 μmoles min⁻¹ mgprot⁻¹) activities were higher (42%, 28%, 35% and 28%, respectively) than in the early stage. Also, the intestinal coefficient was higher in late (3.04) compared to early (2.06) pre-juveniles. Moreover, the liver appeared to be a main site of glycogen and triglyceride storage in late pre-juveniles, muscle being the site of storage in early pre-juveniles, exhibiting higher glycogen, free glucose and protein concentrations (92%, 82%, 32%, respectively). The results suggest that pre-juveniles of M. liza exhibit an adequate digestive battery to perform complete hydrolysis of various dietary substrates, availability of energy reserves and morphological characteristics to support their feeding habit and growth after recruitment. Our results represent an important contribution to knowledge of the ecology and digestive physiology of pre-juveniles of Mugilidae in the wild.     

The synthesis and biological evaluation of 1-C-alkyl-L-arabinoiminofuranoses, a novel class of α-glucosidase inhibitors

The asymmetric synthesis of 1-C-alkyl-l-arabinoiminofuranoses 1 was achieved by asymmetric allylic alkylation (AAA), ring closing metathesis (RCM), and Negishi cross coupling as key reactions. Some of the prepared compounds showed potent inhibitory activities towards intestinal maltase, with IC₅₀ values comparable to those of commercial drugs such as acarbose, voglibose, and miglitol, which are used in the treatment of type 2 diabetes. Among them, the inhibitory activity (IC₅₀ = 0.032 μM) towards intestinal sucrase of 1c was quite strong compared to the above commercial drugs.     

小鼠小肠四种消化酶活力的胎后发育模式

为明确晚成型小鼠胎后发育肠道消化酶活力的建立过程和发育模式,探讨其与适应性调节假说的关系,测定了从出生后至27日龄小鼠小肠前、中、后段的乳糖酶、蔗糖酶、麦芽糖酶和氨基肽酶的酶活力。结果发现单位组织酶活力方面,乳糖酶活力先增后降,小肠前段在9日龄而中后段在12日龄达到最高,至27日龄时仅中段有微弱的酶活力;蔗糖酶活力12日龄始出现,前段和后段自15日龄迅速升高,至18日龄达最高,但随后显著降低,而中段在15日龄后持续升高至21日龄达到最高,此后维持在较高水平;麦芽糖酶出生时已具有活力,但在15日龄前维持较低水平,此后迅速升高,前后段在18日龄,中段在21日龄达到峰值,此后下降;小肠前段的氨基肽酶活力出生后至27日龄持续下降,而后段和中段从出生到断乳前则持续升高,断乳后略有下降。除乳糖酶总酶活力先增后降,在15日龄达峰值外,其余3种酶的总酶活力均持续增加。在小肠不同位置4种酶活力的分布具有显著差异,且日龄对不同位置酶活力的影响趋势不同。总之,小鼠小肠4种消化酶的酶活力随时间的变化能够与其食物转变的消化需求相匹配,部分地支持适应性调节假说。     

Adaptation of intestinal cell membrane enzymes to low temperatures in the Antarctic teleost Pagothenia bernacchii

The enzymatic activity (expressed as milliunits per milligram total proteins) of three intestinal brush-border membrane enzymes, leucine aminopeptidase, alkaline phosphatase and maltase, measured over a range of temperatures between 1.5 and 37 °C, has been found to be much higher in the Antarctic fish Pagothenia bernacchii than in the temperate fish Anguilla anguilla. To explain this experimental observation the apparent Michaelis-Menten constant, the maximal velocity, the activation energy values and the thermal stability of these three enzymes were measured. The apparent Michaelis-Menten constant values of leucine amino peptidase and alkaline phosphatase were different in the intestine mucosal homogenate of the two fish at each measured temperature (from a minimum of 2.5 to a maximum of 37 °C). However, the values found at 2.5 °C for the Antarctic species and 15 °C for the eel where comparable. Furthermore, its value was unchanged in eel intestine apical membranes, both in the presence and without enzyme lipid microenvironment. While the maximal enzymatic activities of the leucine aminopeptidase and maltase did not decrease without their enzyme lipid microenvironment, produced by treatment with Triton X-100, the impairment of alkaline phosphatase maximal activity cannot be significantly differentiated from a non-specific inhibitory effect of the detergent. The activation energy values of leucine amino peptidase, alkaline phosphatase and maltase were lower in the Antarctic fish (11.7, 5.6 and 11.8 kcal·mol^-1, respectively) than in the eel (13.6, 7.6 and 13.1 kcal·mol^-1, respectively). The thermal stability of alkaline phosphatase and maltase is different in Pagothenia bernacchii and Anguilla anguilla intestinal homogenate.Abbreviations BBM brush border membrane - E _a activation energy - EGTA ethyleneglycol-bis-(-amino ethylether)N, N-tetraacetic acid - HEPES 2-[4-(2-hydroxyethyl)-1-piperazinyl]-ethane sulphonic acid - Km_app apparent Michaelis-Menten constant - PMSF phenylmethyl-sulphonyl fluoride - TRIS TRIS (hydroxymethyl)-aminomethane     

A series of cinnamic acid derivatives and their inhibitory activity on intestinal α-glucosidase

Inhibition of α-glucosidase and α-amylase delays the digestion of starch and disaccharides to absorbable monosaccharides, resulting in a reduction of postprandial hyperglycemia. Finding effective mammalian α-glucosidase inhibitors from natural sources can be beneficial in the prevention and treatment of diabetes mellitus. We investigated the inhibitory activity of cinnamic acid derivatives against rat intestinal α-glucosidase and porcine pancreatic α-amylase in vitro. Among 11 cinnamic acid derivatives, caffeic acid, ferulic acid, and isoferulic acid were the most potent inhibitors against intestinal maltase with IC₅₀ values of 0.74?±?0.01, 0.79?±?0.04, and 0.76?±?0.03?mM, respectively, whereas ferulic acid (IC₅₀?=?0.45?±?0.01?mM) and isoferulic acid (IC₅₀?=?0.45?±?0.01?mM) were effective intestinal sucrase inhibitors. However, all cinnamic acid derivatives were found to be inactive in pancreatic α-amylase inhibition. Kinetic analysis revealed that intestinal maltase was inhibited by caffeic acid, ferulic acid, and isoferulic acid in a mixed-inhibition manner. In addition, ferulic acid and isoferulic acid inhibited intestinal sucrase in a mixed type manner, whereas caffeic acid was a non-competitive inhibitor. The combination of isoferulic acid and acarbose showed an additive inhibition on intestinal sucrase. This study could provide a new insight into naturally occurring intestinal α-glucosidase inhibitors that could be useful for treatment of diabetes and its complications.     

Digestive organ sizes and enzyme activities of refueling western sandpipers (Calidris mauri): contrasting effects of season and age

We examined seasonal and age-related variation in digestive organ sizes and enzyme activities in female western sandpipers (Calidris mauri) refueling at a coastal stopover site in southern British Columbia. Adult sandpipers exhibited seasonal variation in pancreatic and intestinal enzyme activities but not in digestive system or organ sizes. Spring migrants had 22% higher total and 67% higher standardized pancreatic lipase activities but 37% lower total pancreatic amylase activity than fall migrants, which suggests that the spring diet was enriched with lipids but low in glycogen. Spring migrants also had 47% higher total intestinal maltase activity as well as 56% higher standardized maltase and 13% higher standardized aminopeptidase-N activities. Spring migrants had higher total enzymic capacity than fall migrants, due primarily to higher total lipase and maltase activities. During fall migration, the juvenile's digestive system was 10% larger than the adult's, and it was composed differently: juveniles had a 16% larger small intestine but a 27% smaller proventriculus. The juvenile's larger digestive system was associated with lower total enzymic capacity than the adult's due to 20% lower total chitinase and 23% lower total lipase activities. These results suggest that juvenile western sandpipers may process food differently from adults and/or have a lower-quality diet.     

Using the Noninvasive 13C-Sucrose Breath Test to Measure Intestinal Sucrase Activity in Swine

The sucrose breath test (SBT) is a simple noninvasive technique used currently to determine intestinal absorptive function in humans and rodents. However, to date, the test has not been adapted for use in swine. During weaning, intestinal sucrase activity in piglets temporarily declines in response to stressors and is commonly used as a marker of the intestinal response to weaning. Here we assessed the sucrose dose needed for using the SBT in piglets. Six randomly allocated piglets were orogastrically gavaged with ¹³C-labeled sucrose at a dose of 2 g/kg; breath samples were collected for measurement of ¹³CO₂ on days 0 (approximately 17 h after weaning), 5, and 10 after weaning. The resultant SBT value (cumulative dose at 90 min) was decreased by 46% on day 5 after weaning relative to baseline levels, consistent with temporal changes in gastrointestinal sucrase activity associated with weaning. We conclude that a sucrose dose of 2 g/kg is satisfactory to conduct SBT studies in piglets. With further development, the SBT may provide a new tool to noninvasively monitor digestive function in weaned piglets, to assess the effects of nutritional strategies on intestinal health, and as an indicator of gut integrity and function in swine models of human gastrointestinal disease.Abbreviations: SBT, sucrose breath testThe activity of the digestive brush border enzymes, specifically sucrase, develops gradually in the small intestine as piglets mature.^3,9 Sucrase activity is absent in the newborn piglet, with levels increasing slowly during the first 4 d postnatally.^3,7,9 Sucrase activity is measurable in all segments of the small intestine by 7 d of age^9,16 and continues to increase thereafter, reaching a plateau at approximately 14 d of age.⁷ However, this pattern of sucrase activity is adversely affected by the weaning process, with the abrupt weaning typical of commercial pig production resulting in decreased villus height, increased crypt depth, and significantly reduced intestinal sucrase activity.¹³Studies in rats^{1,2,6,11,22,23} and humans²¹ have demonstrated that total intestinal sucrase activity can be determined accurately and noninvasively by using the recently developed sucrose breath test (SBT). The release of ¹³CO₂ from ¹³C-labeled substrates forms the basis for several noninvasive gut function tests, including those to assess gastric emptying,¹⁷ and gastrointestinal transit.⁸ The SBT relies on the detection of ¹³CO₂ in expired breath after oral ingestion of an appropriate substrate. For the SBT, the substrate used is sucrose, which is metabolized to glucose and fructose by sucrase. After transit through the hepatic and respiratory systems, ¹³CO₂ is released. The expression of sucrase decreases in a proximal-to-distal gradient along the small intestine.¹⁵ Therefore, the SBT provides an integrated index of the total activity of sucrase throughout the small intestine.The SBT quantifies ¹³CO₂ in the expired breath after oral ingestion of ¹³C-sucrose to provide a marker of total intestinal sucrase activity.^2,20 This technique has demonstrated diagnostic application in humans to monitor the development of chemotherapy-induced intestinal mucositis.²¹ Moreover, the SBT has been used in rats to determine the potential of diverse nutraceutical agents^1,22,23 and probiotics¹⁹ to modify small intestinal absorption. Pigs are an excellent omnivore model on which to base relevant nutritional models to investigate the mechanisms underlying chronic human gastrointestinal diseases.¹⁴ However, to date, the SBT has not been adapted for use in pigs, in which it might become a valuable tool to assess longitudinal changes in intestinal sucrase activity in response to weaning, dietary manipulations, and disease processes. This technique therefore might be applied in the biomedical field in addition to the animal production research environment. In the current study, we sought to establish the experimental conditions required to conduct the SBT in piglets and noninvasively determine total intestinal sucrase activity at 3 time points after weaning.     

Hypoglycemic activity of the antioxidant saponarin,characterized as α-glucosidase inhibitor present in Tinospora cordifolia

Tinospora cordifolia, used in anti-diabetic herbal drug preparations, was reported [12] to contain an α-glucosidase inhibitor, characterized as saponarin (apigenin-6-C-glucosyl-7-O-glucoside). The leaf extract had appreciable antioxidant and hydroxyl radical scavenging activities and contained the flavonoid in the range of 32.1 ± 1.5–45.5 ± 3.5 mg/g of dry solid. Saponarin showed mixed competitive inhibition on activities of α-glucosidase and sucrase of different origins. IC₅₀, Ki and ki′ values determined were 48 μM, 8 μM and 19.5 μM respectively for intestinal maltase and 35 μM, 6 μM and 13 μM respectively for intestinal sucrase. When given orally to maltose-fed rat, saponarin showed hypoglycemic activity in the range of 20–80 mg/kg compared to 100–200 mg/kg for acarbose as reported [27].     

Reproductive biology of the melon cactus, Melocactus curvispinus (Cactaceae)

We examined the reproductive biology of Melocactus curvispinus Pfeiffer (Cereeae, Cactoideae) in xeric areas of northern Venezuela. Floral traits correspond to a classic hummingbird-pollination syndrome; however, pollination is shared between hummingbirds, Leucippus fallax (Bourcier 1843), and anthophorid bees, Ceratina sp. Reproduction occurs during most of the year. Anthesis and nectar secretion occur between noon and sunset. Average daily nectar production per flower was 163.1 l, nectar sugar concentration between 29.1 and 30.2% (w/w). Hummingbirds promoted inter-plant pollen movement and were relatively more reliable floral visitors than anthophorid bees, but these insects had a higher frequency of floral visits (28.75/day) than hummingbirds (4.96/day). M. curvispinus is self-compatible and autogamous. By combining extended reproductive activity, frequent animal-mediated pollination, and selfing capabilities, this cactus possesses a mating strategy that guarantees reproduction under variable environmental conditions. We argue that based on its reproductive biology, M. curvispinus should be considered an example of evolutionary transition towards selfing within tribe Cereeae.     

Membrane-bound intestinal enzymes of passerine birds: dietary and phylogenetic correlates

Bird species exhibit great diversity in digestive tract morphology and enzymatic activity that is partly correlated with the chemical composition of their natural diets. However, no studies have assessed whether the activities of digestive enzymes of the enterocytes correlate with dietary chemical composition data analyzed as a continuous variable at an evolutionary scale. We used a phylogenetically explicit approach to examine the effect of diet on the hydrolytic activity of three digestive enzymes (maltase, sucrase, and aminopeptidase-N) in 16 species of songbirds (Order Passeriformes) from Central Chile. The total activities (μmol/min) of these enzymes were positively associated with body mass using both conventional least squares regressions and phylogenetically independent contrasts. After removing mass effects, we found a significant negative correlation between the ratio of aminopeptidase-N and maltase to the proportion of seeds found in the gizzard, but this relationship was no longer significant after controlling for phylogeny. When we analyzed the specific nutritional content of the diet, we found that the percentage of nitrogen in diet was negatively correlated with residual maltase activity and positively correlated with the ratio aminopeptidase-N/maltase. Given the large interspecific differences in biochemical capacity, we conclude that these differences reflect genetically determined evolutionary changes associated with the nutrient contents of each species’ natural diet.     

Phenotypic flexibility in the intestinal enzymes of the African clawed frog Xenopus laevis

The intestinal plasticity of digestive enzymes of amphibian species is poorly known. The goal of this study was to characterize digestive enzyme profiles along the small intestine of adult frogs, Xenopus laevis, in response to an experimental diet. We acclimated adult X. laevis for 30 days either to carbohydrate-rich or protein-rich diets, and determined the morphology and digestive enzymes of the small intestine. We found a significant difference of aminopeptidase-N activity between carbohydrate-rich and protein-rich acclimated animals. We also found a little variation in the expression of maltase activity, which contrast with the proposed hypothesis about the existence of digestive tradeoff in vertebrates. This finding supports the adaptive modulation hypothesis and suggests that caution is called for when analyzing physiological data regarding assumed discrete trophic category of species.     

Antioxidant and antiviral activities ofEuphorbia thymifolia L.

The antioxidant and antiviral activities ofEuphorbia thymifolia L. (Euphorbiaceae) were investigated in this study. The results showed that all of the fractions (MeOH, CHCl₃, EtOAc, n-butanol and water) and pure compounds (3-O-galloyl-4,6-(S)-HHDP-D-glucose, rugosin B and 1,3,4,6-tetra-O-galloyl-K--D-glucose)tested possessed antioxidant activities, with the exception of the organic aqueous fraction in the anti-lipid and anti-super-oxide formation assays. The range of IC₅₀ of anti-lipid formation, anti-superoxide formation and free radical scavenging assays for all fractions and pure compounds were 2.81–7.63, 0.03–2.18 and 0.013–2.878 mg/ml, respectively. Electron spin resonance studies showed that water extract and pure compounds ofE. thymifolia exhibited superoxide radical and hydroxyl radical scavenging activities. Besides antioxidant activities, 3-O-galloyl-4,6-(S)-HHDP-D-glucose and EtOAc fraction also showed anti-HSV-2 activity. Thus,E. thymifolia was concluded to possess antioxidant and anti-HSV-2 activities.     

Furofuran lignans as a new series of antidiabetic agents exerting α-glucosidase inhibition and radical scarvenging: Semisynthesis,kinetic study and molecular modeling

A new series of furofuran lignans containing catechol moiety were prepared from the reactions between lignans and a variety of phenolics. All 22 products obtained were evaluated against three different α-glucosidases (maltase, sucrase and Baker’s yeast glucosidase) and DPPH radical. Of furofuran lignans evaluated, β-14, having two catechol moieties and one acetoxy group, was the most potent inhibitor against Baker’s yeast, maltase, and sucrase with IC₅₀ values of 5.3, 25.7, and 12.9 µM, respectively. Of interest, its inhibitory potency toward Baker’s yeast was 28 times greater than standard drug, acarbose and its DPPH radical scavenging (SC₅₀ 11.2 µM) was 130 times higher than commercial antioxidant BHT. Subsequent investigation on mechanism underlying the inhibitory effect of β-14 revealed that it blocked Baker’s yeast and sucrase functions by mixed-type inhibition while it exerted non-competitive inhibition toward maltase. Molecular dynamics simulation of the most potent furofuran lignans (4, α-8b, α-14, and β-14) with the homology rat intestinal maltase at the binding site revealed that the hydrogen bond interactions from catechol, acetoxy, and quinone moieties of furofuran lignans were the key interaction to bind tightly to α-glucosidase. The results indicated that β-14 possessed promising antidiabetic activity through simultaneously inhibiting α-glucosidases and free radicals.