Pneumatosis cystoides intestinalis following alpha-glucosidase inhibitor treatment:A case report and review of the literature

A 69-year-old man was diagnosed as having myasthenia gravis (MG) in September 2004,and treated with thymectomy and prednisolone. He was then diagnosed as having steroid-induced diabetes mellitus,and received sulfonylurea (SU) therapy in May 2005. An alpha-glucosidase inhibitor (αGI) was added in March 2006,resulting in good glycemic control. He experienced symptoms of abdominal distention,increased flatus,and constipation in October 2007,and was admitted into our hospital in late November with hematochezia. Plain abdominal radiography revealed small linear radiolucent clusters in the wall of the colon. Computed tomography (CT) showed intramural air in the sigmoid colon. Colonoscopy revealed multiple smooth surfaced hemispherical protrusions in the sigmoid colon. The diagnosis of pneumatosis cystoides intestinalis (PCI) was made on the basis of these findings. As the αGI voglibose was suspected as the cause of this patient's PCI,treatment was conservative,ceasing voglibose,with fasting and fluid supplementation. The patient progressed well,and was discharged 2 wk later. Recently,several reports of PCI associated with αGI therapy have been published,predominantly in Japan where αGIs are commonly used. If the use of αGIs becomes more widespread,we can expect more reports of this condition on a global scale. The possibility of PCI should be considered in diabetic patients complaining of gastrointestinal symptoms,and the gastrointestinal tract should be thoroughly investigated in these patients.

Macroalage as a source of alpha-glucosidase inhibitors

Alpha-glucosidase inhibitors were screened from organic solvent extracts of macroalgae by a spec- trophotometrical method with p-nitrophenyl-D-glucopyranosidase as the substrate. The result indicates that or- ganic crude extracts from some macroalgae such as Rhodomela confervoides (Huds.) Silva, Gracilaria textorii (Suringar) DeToni, Plocamium telfairiae Harv., Dictyopteris divaricata (Okam.) Okam, Ulval pertusa and En- teromorpha intestinalis (L.) Link et al. show strong inhibitory activity of alpha-glucosidase at concentration of 79.6 μg/ml.

Antioxidant,anti-alpha-glucosidase and pancreatic beta-cell protective effects of methanolic extract of Ensete superbum Cheesm seeds

Objective: To investigate the antioxidant, anti-a-glucosidase and pancreatic b-cell protective potential of Ensete superbum(E. superbum) seeds.Methods: A variety of in vitro assays including radical scavenging, reducing power potential, phenolic content determination, a-glucosidase assay and pancreatic b-cell(1.4E7 cells) viability were employed for assessing the effect of methanolic extract of E. superbum seeds.Results: The radical scavenging and reducing power effects comparable with the standard rutin were obtained while the enzyme inhibitory activity of the extract was 68-fold better than the standard antidiabetic drug, acarbose. The seed extract of E. superbum was packed-full of polyphenols with mean percentage gallic acid equivalent value of(38.2 ± 1.8)(n = 3). The protection of pancreatic cells from massive onslaught of hydrogen peroxide was far superior to that obtained for rutin.Conclusions: The reputed antidiabetic therapeutic uses of the seeds extract of E. superbum may be justified on the basis of inhibition of carbohydrate enzymes, antioxidant effects and pancreatic b-cell protection.

Is Alpha-Glucosidase Inhibition a Mechanism of the Antidiabetic Action of Garlic (<i>Allium sativum</i>)?

Objective: There has been a global surge in the number of diabetic cases. Many of the agents used as antidiabetic are either expensive or have side effects. Researchers are now turning their attention to phytotherapy as a viable alternative in the treatment of hyperglycemia. The aim of this study was to examine the inhibition of α-glucosidase as a possible mechanism of antidiabetic action of garlic. Method: The inhibitory effect of different concentrations of garlic was examined for alpha-glucosidase inhibitory activity in a 96-well micro plate. Saccharomyces cerevisiae was used as the source of alpha-glucosidase and the assay was analyzed with a Thermo Scientific? Multiskan Spectropho-meter at an absorbance of 400 nm. Result: The extracts of garlic exhibited a dose-dependent inhibition of alpha-glucosidase in comparison to acarbose. The IC50 of acarbose was 3.19 ± 0.42 mg/ml, for garlic, the IC50 was 16.93 mg/ml. Conclusion: In this study, garlic oil showed some promise as an antidiabetic agent with a mechanism of action similar to acarbose and miglitol that are currently used as antidiabetics. It is hoped that carrying out further research on garlic will elucidate other mechanisms of action.

Homology Modeling of Human Alpha-Glucosidase Catalytic Domains and SAR Study of Salacinol Derivatives

Maltase-glucoamylase (MGAM) and sucrase-isomaltase (SI) belong to human intestinal alpha-glucosidase and their N-terminal side catalytic domains are called NtMGAM and NtSI, and their C-terminal side catalytic domains are called CtMGAM and CtSI. As an antidiabetic, alpha-glucosidase inhibitor is required to bind to all of these domains to inhibit disaccharides hydrolysis. Salacinol and kotalanol isolated from Salacia reticulata are novel seed compounds for al-pha-glucosidase inhibitor. Even though the complex structures of NtMGAM or NtSI have been determined experimen-tally, those of CtMGAM and CtSI have not been revealed. Thus, homology modeling for CtMGAM and CtSI has been performed to predict the binding mode of salacinol and its derivatives for each domain. The binding affinities for these compounds were also calculated to explain the experimental structure-activity relationships (SARs). After a docking study of the derivatives to each catalytic domain, the MM/PBSA method has been applied to predict the binding affinities. The predicted binding affinities were almost consistent with the experimental SARs. The comparison of the complex structures and binding affinities provided insights for designing novel compounds, which inhibit all catalytic domains.

Computational Study on the Comparative Differences in the Activity of Inhibitors of Human versus Rat Alpha-Glucosidase

Differences between the inhibitory activities of specific compounds on analogous enzymes isolated from different animal species are one of the critical issues to evaluate when exploring structure-activity relationships. The activity of acarbose is about ten times stronger in rat than in human, and that of neosalacinol is similar in both species. Binding affinities of acarbose and neosalacinol to four catalytic domains of alpha-glucosidases in human and rat were compared to investigate the cause of activity differences among species. Species difference was brought about complicatedly by the balance of interaction with four domains, and the result was indicated that larger ligand would show larger species difference in activity.

Effect of experimental varicocele on structure and function of epididymis in adolescent rats

<abstract>Aim: To study the effect of experimental left varicocele (ELV) on epididymal structure and function in adolescent Sprague-Dawley rats. Methods: ELV was induced by partial ligation of the left renal vein. Sham-operated animals served as the controls. Four and 8 weeks after the operation, the histological, ultrastructural and biochemical (alpha-glucosidase activity and carnitine content) changes in different segments of the epididymis were observed. Results: In the treated animals, there were degeneration of the epididymal epithelium and edema of the interstitial tissue; numerous shedding cells, residual bodies, deformed sperm and macrophages appeared in the epididymal lumen. Morphometric measurement indicated a significant reduction in the epididymal tubular diameter (P<0.05) and a significant increase in the epididymal interstitial area (P<0.05) compared with the controls. Ultrastructural study showed sparse microvilli of the columnar epithelium, increased and enlarged lysosomes in the principal cells with defected organelles and the presence of large cytoplasmic vacuoles. The protein and carnitine contents and the alpha-glucosidase activity in the caput, corpus and cauda epididymis of the ELV rats were lower than those of the controls (P< 0.05). Conclusion: There were structural and functional changes in the epididymis of adolescent ELV rats, which may contribute to the infertility caused by varicocele.

In vitro inhibition activity of polyphenol-rich extracts from Syzygium aromaticum(L.)Merr.& Perry(Clove)buds against carbohydrate hydrolyzing enzymes linked to type 2 diabetes and Fe^(2+)-induced lipid peroxidation in rat pancreas

To investigate and compare the inhibitory properties of free and bound phenolic extracts of clove bud against carbohydrate hydrolyzing enzymes (alpha-amylase & alpha-glucosidase) and Fe2+-induced lipid peroxidation in rat pancreas in vitro. Methods: The free phenolics were extracted with 80% (v/v) acetone, while bound phenolics were extracted from the alkaline and acid hydrolyzed residue with ethyl acetate. Then, the interaction of the extracts with alpha-amylase and alpha-glucosidase was subsequently assessed. Thereafter, the total phenolic contents and antioxidant activities of the extracts were determined. Results: The result revealed that both extracts inhibited alpha-amylase and alpha-glucosidase in a dose-dependent manner. However, the alpha-glucosidase inhibitory activity of the extracts were significantly (P<0.05) higher than their alpha-amylase inhibitory activity. The free phenolics (31.67 mg/g) and flavonoid (17.28 mg/g) contents were significantly (P<0.05) higher than bound phenolic (23.52 mg/g) and flavonoid (13.70 mg/g) contents. Both extracts also exhibited high antioxidant activities as typified by their high reducing power, 1,1 diphenyl-2- picrylhydrazyl (DPPH) and 2, 2-azinobis-3-ethylbenzo-thiazoline-6-sulfonate (ABTS) radical scavenging abilities, as well as inhibition of Fe2+-induced lipid peroxidation in rat pancreas in vitro. Conclusions: This study provides a biochemical rationale by which clove elicits therapeutic effect on type 2 diabetes.

Evaluation of antiparasitic,anticancer,antimicrobial and hypoglycemic properties of organic extracts from Panamanian mangrove plants

Objective: To investigate 33 organic extracts of mangrove plants for: antiparasitic, anticancer, and antibacterial activities, as well as their ability to inhibit the activity of the α-glucosidase enzyme. Methods: Leaves from all different plant mangrove species located in five mangrove zones of the Pacific coast of Panama were collected according to standard procedures. Qualitative phytochemical analysis of the organic extracts was performed by thin layer chromatography. The antiparasitic activity against Plasmodium falciparum, Trypanosoma cruzi and Leishmania donovani, toxicity against Artemia salina, anticancer activity in MCF-7 cell line, and antibacterial activity against Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa of all organic extract were investigated according protocols stablished in our institution. Finally, the ability to inhibit the enzymatic activity of α-glucosidase was evaluated by monitoring the hydrolysis of p-nitrophenyl α-Dglucopyranoside. Results: Thirty-three different samples belonging to nine different species of vascular plants with seeds of true mangroves were collected. Triterpenoids, phenolics, and tannins were the main groups of compounds found in the sampled mangroves. Saponins, quinones, and coumarins were found in less than 50%of the samples. Laguncularia racemosa showed moderate activity against Plasmodium falciparum. None of the extracts presented anticancer activity. Rhizophora mangle exhibited potent activity against Staphylococcus aureus and Bacillus subtilis [(90.41 ±7.33)% and(96.02±6.14)% of inhibition]; Avicennia germinans and Conocarpus erectus had activity against Escherichia coli[(71.17±6.15)% and(60.60±5. 13)% of inhibition,respectively]. About 60% of the mangroves showed α-glucosidase inhibitory activity. In particular, extracts from Laguncularia racemosa, Pelliciera rhizophorae, Conocarpus erectus, Mora oleifera, and Tabebuia palustris species showed α-glucosidase inhibitory potential, with IC_(50) values of(29.45±0.29),(20.60±0.70),(730.06±3.74),(25.59±0.37), and(853.39±5.30) μg/mL, respectively. Conclusions: Panamanian mangroves are mainly a promising potential source of hypoglycemic compounds, specifically α-glucosidase inhibitors.These results highlight the therapeutic virtues of extracts from American mangrove plants.

Identification of Seven Novel Mutations in the Acid Alpha-glucosidase Gene in Five Chinese Patients with Late-onset Pompe Disease

Background： Pompe disease is a rare lysosomal glycogen storage disorder linked to the acid alpha-glucosidase gene （GAA）. A wide clinical and genetic variability exists between patients from different ethnic populations, and the genotype-phenotype correlations are still not well understood. The aim of this study was to report the clinicopathological and genetic characteristics of five Chinese patients with late-onset Pompe disease （LOPD） who carried novel GAA gene mutations. Methods： Clinical and pathological data of patients diagnosed with glycogen storage disease at our institution from April 1986 to August 2017 were collected, and next-generation sequencing of frozen muscle specimens was conducted. Results： Of the five patients included in the study, the median disease onset age was 13 years, with a median 5 years delay in diagnosis. The patients mainly manifested as progressive weakness in the proximal and axial muscles, while one patient developed respiratory insufficiency that required artificial ventilation. In muscle biopsies, vacuoles with variable sizes and shapes appeared inside muscle fibers, and they stained positive for both periodic acid-Schiff and acid phosphatase staining. Ten GAA gene mutations, including seven novel ones （c.796C〉A, c. 1057C〉T, c. 1201C〉A, c. 1780C〉T, c. 1799G〉C, c.2051C〉A, c.2235dupG）, were identified by genetic tests. Conclusions： The seven novel GAA gene mutations revealed in this study broaden the genetic spectrum of LOPD and highlight the genetic heterogeneity in Chinese LOPD patients.

Inhibitive efficacy of Nymphoides indica rhizome extract onα-glucosidase, and cross-link formation of advanced glycation end products

OBJECTIVE: To investigate the inhibitive efficacy of Nymphoides Indica(L.) Kuntze rhizome extract onα-glucosidase and on cross-link formation of advanced glycation end products(AGEs).METHODS: The plant extracts were prepared by cold maceration and fractionated in solvents of diverse polarity. The in vitro α-glucosidase inhibition assay, fluorescence spectrometry and SDS-PAGE analysis was performed for antiglycation assays.RESULTS: During α-glucosidase inhibition assay significant inhibition by chloroform(0.43 mg/mL)and methanol fractions(0.66 mg/mL) was noticed.During the AGEs inhibition assay, both oxidative(BSA-MGO) and non-oxidative(BSA-glucose)modes were employed. The inhibition of AGEs by total extract was considered moderate(IC_(50)0.10 mg/mL) as a result of non-oxidative mode, whereas in case of oxidative mode(BASA-MGO) no activity was recorded. Among fractions the methanolic fraction presented significant results both in oxidative(IC_(50)0.01 mg/mL) and non-oxidative modes(IC_(50) 0.3 mg/mL). Likewise the ethyl acetate fraction was more active in non-oxidative mode(IC_(50)0.04 mg/mL) compared to oxidative mode(IC_(50)0.32 mg/mL).During assay for inhibition of cross-link formation,the chloroform fraction significantly inhibited cross-link formation in a dose dependent mode.CONCLUSION: It was finally concluded that N. Indica rhizome extract possesses significant properties that inhibit α-glucosidase, and AGEs cross-link formation.