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Background Aims and Methods Results Conclusions Dumping syndrome is a complex of gastrointestinal symptoms originally studied in peptic ulcer surgery patients. At present, it is most prevalent in patients who underwent bariatric, upper gastrointestinal cancer or anti‐reflux surgery. The symptom pattern comprises early and late dumping symptoms. Several management options have been reported including nutritional, pharmacological and surgical approaches.In this study, we aimed to review the current evidence on dumping syndrome definition, diagnosis and treatment, including preliminary data from newer pharmacological studies.Current pathophysiological concepts and analyses of provocative tests has led to a clear definition of dumping syndrome, including both early and late dumping symptoms. The term postbariatric hypoglycemia represents a limited focus on late dumping only. The diagnosis relies on recognition of symptoms and signs in a patient with appropriate surgical history; and can be confirmed by provocative testing or registration of spontaneous hypoglycemia. The initial treatment focuses on dietary intervention, to which meal viscosity enhancers and/or the glycosidase inhibitor acarbose can be added. The most effective therapy is the use of short‐ or long‐acting somatostatin analogues, which is however expensive and entails side effect issues. In case of refractory hypoglycemia, diazoxide or SGLT2 inhibitors can be considered, based on limited evidence. In refractory patients, continuous enteral feeding or (rarely) surgical reinterventions have been advocated, although not supported by solid evidence. Therapies under current evaluation include the broad‐spectrum somatostatin analogue pasireotide, GLP‐1 receptor antagonists, GLP‐1 receptor agonists and administration of stable forms of glucagon are currently under study.Dumping syndrome is a well‐defined but probably under‐diagnosed complication of upper gastrointestinal, especially bariatric, and surgeries. Diagnosis is confirmed by a provocative test and incremental therapies starting with diet, adding meal viscosity enhancers or glycosidase inhibitors and adding somatostatin analogues in refractory cases. A number of emerging therapies targeting intestinal propulsion, peptide hormone effects and hypoglycemic events are under evaluation. [ABSTRACT FROM AUTHOR]

Astragalus membranaceus is a traditional Chinese medicine with multiple pharmacological activities. Modern pharmacological research has found that Astragalus membranaceus extract has an inhibitory effect on α-glucosidase, however, which component can inhibit the activity of α-glucosidase and its degree of inhibition are unknown. To address this issue, this study used affinity ultrafiltration screening combined with UPLC-ESI-Orbitrap-MS technology to screen α-glucosidase inhibitors in Astragalus membranaceus. Using affinity ultrafiltration technology, we obtained the active components, and using UPLC-ESI-Orbitrap-MS technology, we quickly analyzed and identified them. As a result, a total of 8 ingredients were selected as α-glucosidase inhibitors. [ABSTRACT FROM AUTHOR]

Summary: α‐Glycosidase, a critical therapeutic target in type 2 diabetes mellitus (T2DM), can be modulated by inhibitors to reduce postprandial blood glucose levels. This study investigated the inhibitory effects of vine tea (Ampelopsis grossedentata) and its key compounds on α‐glycosidase. The results demonstrated that fifteen varieties of vine tea extracts inhibited α‐glycosidase in a dose‐dependent manner, with IC50 values ranging from 5.25 to 35.8 μg mL−1. HPLC analysis revealed dihydromyricetin (DHM) as the main compound in vine tea, with an IC50 value of 262.50 μM. Notably, the synergistic combination of DHM and the antidiabetic drug acarbose (ABS) significantly enhanced inhibitory effectiveness, with the optimal ratio (1:125) yielding a potentiation index (CI) of 0.09. Fluorescence and molecular docking analyses supported the hypothesis that DHM enhanced ABS's inhibitory effect through complex formation and specific interactions, offering a promising option for safer and more effective diabetes therapy. [ABSTRACT FROM AUTHOR]

This study aimed to develop and evaluate a niosomal formulation loaded with Plumbago zeylanica extract (PZE). The solvent evaporation method was used to prepare niosomes and optimized using the Box–Behnken design. The optimized formulation (PZE-Ns-Opt) was characterized for drug release, DPPH assay, α-amylase inhibition assay, α-glucosidase inhibition assay, and confocal laser scanning microscopy (CLSM) study. PZE-Ns-Opt showed a vesicle size of 253.6 nm, PDI of 0.108, entrapment efficiency of 62.4%, and drug release of 84.01%. The CLSM image of the rat's intestine suggested that the rhodamine red B-loaded PZE-Ns-Opts showed superior penetration compared to the control. Further, the antioxidant activity of the prepared formulation was exhibited as 89.46%±0.016 as compared to PZE (78.10%±0.005). In addition to this, α- amylase activity was inhibited by 95.11%±4.62, 85.88%±2.56, and 89.87%±3.65 by acarbose, PZE, and PZE-Ns-Opt, respectively. In comparison, the α-glucosidase activity was inhibited by 88.47%±1.04, 81.07%±0.50 and 85.78%±0.71 by acarbose, PZE, and PZE-Ns-Opt, respectively. To conclude, the development of PZE-Ns-Opt formulation and its characterization showed the establishment's authenticity. The in vitro antidiabetic, antioxidant studies expressed the protective effect from oxidative stress, CLSM of rat's intestine ability to penetrate to great extent and could be a promising candidate for the management of diabetes mellitus. [ABSTRACT FROM AUTHOR]

In this work, a series of pyrazole‐linked 1,2,4‐triazole‐3‐thiol derivatives (3a–i) were prepared and identified by 13C NMR, 1H NMR, and mass spectrometry (ESI‐MS) data. The newly synthesized molecules were also evaluated in vitro for their α‐amylase and α‐glucosidase inhibitory potential. All newly synthesized compounds exhibited potent α‐glucosidase inhibition activity with IC50 in the range of 1.016 ± 0.70 to 24.40 ± 0.02 µM and good α‐amylase inhibitory with IC50 in the range of 49.91 ± 0.32 to 500 µM, as compared to acarbose. The most potent compound among this series is derivative 3e, with IC50 value of 1.016 ± 0.70 µM, which is many folds more than that of acarbose. In addition, in docking studies, both compounds exhibited good interactions at the active region of target proteins. Therefore, this study may lead via structural modifications to the discovery of new potent α‐amylase and α‐glucosidase inhibitors useful in the diabetes treatment. [ABSTRACT FROM AUTHOR]

The carbazole-3-carbaldehyde 2, produced by N-ethyl carbazole via Vilsmeier-Haack reaction, was subjected to Dakin type oxidation with H2O2 and H2SO4 in methanol to produce the carbazole-3-ol 3. The reaction of 3 with a range of commercially available α-haloketones 4a–f in the presence of Al2O3 as catalyst in xylene led to their regio-selective cyclization to afford the furo[2,3-c]carbazoles 5a–f. Identification of the furo[2,3-c]carbazoles 5a–f were performed through 1H NMR,13C NMR, FT-IR and high resolution mass spectrometry. Single crystal X-ray diffraction analysis was employed to further confirm the structures of the some of the targeted compounds. In vitro antidiabetic activities of the newly synthesized furocarbazoles 5a–e were investigated utilizing α-glucosidase and α-amylase enzymes. The biological evaluation revealed the obvious efficiencies of the targeted molecules toward the α-glucosidase enzyme inhibition with the potent IC50 values compared to the standard acarbose. In the case of α-glucosidase inhibition, the furo[2,3-c]carbazoles chloro substituted 5c and nitro substituted 5f were found to be more potent than acarbose with the values of 215.0 and 162.70 μM, respectively. On the other hand, the compound 5f was found to be only promising candidate for α-amylase enzyme but not as effective as the standard acarbose. [ABSTRACT FROM AUTHOR]

In connection with our interest in the phytochemical investigation of Elaeocarpus hainanensis Oliv. (Elaeocarpaceae) growing in Vietnam, two new sulphated oleanane triterpenes were obtained herein and structurally identified. Based on the combination of the extensive 1D-, 2D NMR and HR ESI MS spectroscopic data analysis, their chemical structures have been elucidated as 1α,3β-dihydroxy-olean-18-ene 1-sulphate (1) and 1α,3β-dihydroxy-olean-12-ene 1-sulphate (2). Notably, compounds 1 and 2 are corroborating the proposition that triterpenoid sulphates serve as chemosystematic markers of the Elaeocarpus genus. Additionally, all these two new compounds 1 and 2 strongly inhibited α-glucosidase in vitro with the respective IC50 values of 3.81 ± 0.33 µM and 21.27 ± 0.48 µM, which were significantly better than that obtained from positive control, acarbose (IC50 247.73 ± 11.85 µM). [ABSTRACT FROM AUTHOR]

Aging is a primary risk factor for cognitive impairment and exacerbates multiple biological processes in the brain, including but not limited to nutrient sensing, insulin signaling, and histone deacetylation activity. Therefore, a pharmaceutical intervention of aging that targets distinct but overlapping pathways provides a basis for testing combinations of drugs as a cocktail. Our previous study showed that middle-aged mice treated with a cocktail of rapamycin, acarbose, and phenylbutyrate for 3 months had increased resilience to age-related cognitive decline. This finding provided the rationale to investigate the transcriptomic and molecular changes within the brains of mice that received this cocktail treatment or control treatment. Transcriptomic profiles were generated through ribonucleic acid (RNA) sequencing, and pathway analysis was performed by gene set enrichment analysis to evaluate the overall RNA message effect of the drug cocktail. Molecular endpoints representing aging pathways were measured using immunohistochemistry to further validate the attenuation of brain aging in the hippocampus of mice that received the cocktail treatment, each individual drug or control. Results showed that biological processes that enhance aging were suppressed, with an increased trend of autophagy in the brains of mice given the drug cocktail. The molecular endpoint assessments indicated that treatment with the drug cocktail was overall more effective than any of the individual drugs for relieving cognitive impairment by targeting multiple aging pathways. [ABSTRACT FROM AUTHOR]

One undescribed benzofuran derivative (illiciumphenolicacid A, 1) and one new phenolic glycoside (illiciumphenolicacid B, 2), together with six known compounds (3–8) were isolated from the leaves of Illicium dunnianum Tutcher. Their structures were elucidated by detailed spectroscopic data (UV, IR, HR-ESI-MS, 1D and 2D NMR). In addition, we determined the α-glucosidase inhibitory activity of the isolates in vitro using spectrophotometric methods. Compared with the positive control acarbose (IC50 306.2 ± 4.1 μM), compounds 1–8 were shown to be moderate potential α-glucosidase inhibitory activity with IC50 values in the range 380–655 μM. [ABSTRACT FROM AUTHOR]

A new pregnane steroid, jasminanthoside (1), together with three known compounds, telosmoside A7 (2), syringaresinol (3), and methyl 6–deoxy–3–O–methyl–β–D–allopyranosyl–(1→4)–β–D–oleandropyranoside (4) were isolated from the ethyl acetate extract of Jasminanthes tuyetanhiae roots collected in Vietnam. Their chemical structures were elucidated by NMR and MS spectroscopic data analysis along with the comparison of their data with the published ones in the literature. Although 4 was a known compound, its full NMR data were reported for the first time. All isolated compounds, evaluated for their α-glucosidase inhibition, showed activities stronger than the positive control acarbose. Among them, 1 was the best with the IC50 value of 7.41 ± 0.59 µM. [ABSTRACT FROM AUTHOR]

This study involved the synthesis, characterization, and assessment of fourteen pyridazine analogs (designated as 1–14) to investigate their efficacy in inhibiting the α‐amylase enzyme for potential diabetes treatment using an in vitro approach. Additionally, in silico molecular docking and molecular dynamic (MD) simulations were conducted to assess the inhibitory properties of these analogs. Physicochemical and pharmacokinetic properties of the fourteen pyridazine analogs were predicted using the DataWarrior tool. Results indicated that all tested compounds demonstrated significant α‐amylase inhibitory activity, with IC50 values ranging from 81.28±0.00 to 1623.54±2.67 μM compared to the standard drug acarbose (IC50=220.42±36.40 μM). Notably, compounds 8 and 12 exhibited the most potent α‐amylase inhibitory activity, with IC50 values of 81.28±0.00 μM and 200.60±34.65 μM, respectively. Molecular docking analysis revealed binding energies ranging from −7.53 to −5.77 kcal/mol and inhibition constants ranging from 3.00 to 58.96 μM, with compounds 9, 7, 8, 5, and 3 demonstrating the best binding energies. Subsequent MD simulation analyses indicated that all five compound formed stable complexes after 100 ns MD simulation. Consequently, these compounds hold promise as potential α‐amylase inhibitors pending successful clinical validation. [ABSTRACT FROM AUTHOR]

One new 3-O-glycoside of betulinic acid, named heptaelliptoic acid A (1), together with one known betulinic acid analogue (2), and four other compounds (3-6) were separated by combinatively chromatographic techniques. For the first time, all of the purified compounds (1-6) were reported from the H. ellipticum species. Their structures were obviously elucidated basing exhaustive and pervasive UV-VIS, FT-IR, HR-MS-ESI, and NMR experiment data. Compounds 2-4 were significantly displayed the in vitro α-glucosidase inhibition (IC50 values of 11.53, 28.75, and 10.90 µM, respectively) better than the acarbose positive drug (IC50 value of 214.50 µM). [ABSTRACT FROM AUTHOR]

The elaboration of a new family of tetrapodal molecules L1–L3 bearing two pyrazole–tetrazole units is presented. The structure assigned to such molecules was verified by various techniques, including FTIR, NMR, HRMS and elemental analysis. The ability of these tetrapods to inhibit the growth of four fungal strains was examined, and the obtained results showed that they have some antifungal potency in the range of 12–16 mm. The alpha-amylase inhibition activity of these molecules was also evaluated. The obtained IC50 values (1.34 × 10−1–1.2 × 10−2 mg/mL) demonstrated that all compounds are potent enough to inhibit this enzyme much better than the positive control acarbose (2.6 × 10−1 mg/mL). A docking study on the porcine alpha-amylase was performed, and the results were in good correlation with the experimental results. [ABSTRACT FROM AUTHOR]

Key Clinical Message: High‐dose acarbose may increase the risk of diabetic ketosis/diabetic ketoacidosis in Asian patients on sodium‐glucose cotransporter‐2 inhibitors. Healthcare providers and patients should be cautious to avoid this combination. Low‐calorie diets should be avoided in patients receiving sodium‐glucose cotransporter‐2 (SGLT‐2) inhibitors to decrease the risk of diabetic ketoacidosis (DKA). High‐dose acarbose can decelerate carbohydrate absorption. We detail three cases of diabetic ketosis (DK) following concurrent SGLT‐2 inhibitor and high‐dose acarbose therapy (acarbose 300 mg/day and dapagliflozin 10 mg/day). Patients, aged 38–63 years with 3–10 years of type 2 diabetes mellitus (T2DM), developed DK, indicated by moderate urinary ketones and high glucose (urine ketone 2+ to 3+ and glucose 3+ to 4+) without acidosis, within 4 days to 1 month post‐therapy initiation. Serum glucose was 172.8–253.8 mg/dL; HbA1c was 9.97%–10.80%. The combination therapy was halted, and DK was managed with low‐dose intravenous insulin and fluids, followed by intensive insulin therapy. High‐dose acarbose with SGLT‐2 inhibitors may increase the risk of DK/DKA in Asian patients. [ABSTRACT FROM AUTHOR]

Pistacia species (P. spp) have been used as a treatment for various diseases, including diabetes and inflammation. This study aimed to identify the main components of flavonoids in Pistacia species and evaluate the effect of aqueous extracts of P. spp on pancreatic enzymes and on cancer cells associated with obesity in colon and rectum. HPLC was used to identify the major components of flavonoids. The potent inhibitory effect of Pistacia species against pancreatic α-amylase, α-glucosidase and lipase was examined. The antiproliferative efficacy of the plant extract against several colorectal cancer cell lines were then measured. The main flavonoids component found in Pistacia species are quercetin-3-β-D-glucoside, rutin, kaempferol and vitexin. The starch blockade IC50 (µg/mL) of Pistacia species in a descending order were: P. lentiscus leaves: 1.09±0.01; P. atlantica leaves: 0.96±0.09 and P. atlantica fruits: 0.48±0.02. Pistacia species exerted promising inhibition effect for pancreatic lipase (PL). Besides the aglycones of P. atlantica leaves, all the tested aqueous extracts exerted appreciably novel antiproliferative activity against the tested colorectal cancer cell lines. This study provides useful indication for the Pistacia species as a potential novel therapeutic agent against diabesity and cancer. [ABSTRACT FROM AUTHOR]

A more efficient and environmentally friendly approach has been developed for synthesizing phosphonates through the Michaelis-Arbuzov reaction, catalyzed by nano-ZnO in a solvent-free environment, utilizing microwave irradiation. Before synthesis, each compound underwent in silico ADMET analysis and molecular docking to assess drug-like characteristics and their potential to inhibit α-amylase. The structure of the newly synthesized compounds was validated using spectroscopic analysis, and their in vitro inhibitory effects on α-amylase were assessed. Among the compounds, dimethyl 2-(anthracen-10-yl)-4-oxo-4H-chromen-6-yl-6-phosphonate (6j), dimethyl 2-(naphthalen-1-yl)-4-oxo-4H-chromen-6-yl-6-phosphonate (6h), and dimethyl 2-(1-methyl-1H-indol-3-yl)-4-oxo-4H-chromen-6-yl-6-phosphonate (6e) displayed the highest inhibitory activity compared to the reference substance, acarbose. Additionally, compounds dimethyl 2-(benzo[d][1,3]dioxol-4-yl)-4-oxo-4H-chromen-6-yl-6-phosphonate (6i), dimethyl 4-oxo-2-phenyl-4H-chromen-6-yl-6-phosphonate (6a), and dimethyl 2-(1H-indol-5-yl)-4-oxo-4H-chromen-6-yl-6-phosphonate (6g) exhibited nearly equivalent effective inhibitory activity when compared to the standard. The remaining compounds demonstrated moderate to good enzyme inhibition. [ABSTRACT FROM AUTHOR]

• PCOS is a complex disorder depicted by metabolic, endocrinologic, dermatologic, gynaecologic and reproductive anomalies. • Acarbose is known to exert reproductive effectiveness over the recent years with potential safety and tolerability in the carb consuming south asian population. • The use of combinational dual therapy is postulated to possess synergistic effect with better effectiveness, safety and treatment compliance on PCOS women in the long run. PCOS, beyond being characterized by reproductive disturbances, is a complicated rapid expanding metabolic and endocrinologic disorder of the recent times. Nearly 70% PCOS women show resistance to insulin. AIM: The aim of the study is to determine and compare the effectiveness of acarbose plus metformin and acarbose plus myo-inositol combination therapy in alleviating the metabolic and endocrinologic complications of PCOS. An open labelled RCT was conducted on 168 PCOS women attending the gynaecology clinic at SRM MCH & RC, Chengalpattu and the trial was registered in CTRI (No. CTRI/2022/04/041877). Group A (n = 56) received metformin 500 mg/TID alone; group B (n = 54) received (acarbose 25 mg/TID for 4 weeks then 50 mg/TID for other 20 weeks) along with metformin 500 mg/TID and group C (n = 54) received (acarbose 25 mg/TID for 4 weeks then 50 mg/TID for other 20 weeks) along with myoinositol 1000 mg/BD. All parameters were measured at baseline and at the end of 6 months. Significant reduction of LH, LH: FSH, TT, HOMA-IR was observed in all the groups. FSH increased only in metformin group. Increase in serum progesterone and reduction in FI, TGL, LDL were significant only in acarbose plus myo-inositol group. SHBG and HDL increased significantly only in acarbose plus metformin group. No changes in BMI, TC and VLDL were observed in any group. Therefore, decrease in FI, HOMA-IR, TGL, LDL seen in acarbose plus myo-inositol group indirectly contributes to cardio-metabolic safety in PCOS. Similarly, a significant increase in SHBG levels with acarbose plus metformin group shows correction of the excess androgen and restoration of ovulation. [ABSTRACT FROM AUTHOR]

Background: Several epidemiologic studies have revealed a higher risk of cancer in patients with diabetes mellitus (DM) relative to the general population. To investigate whether the use of acarbose was associated with higher/lower risk of new‐onset cancers. Method: We conducted a retrospective cohort study, using a population‐based National Health Insurance Research Database of Taiwan. Both inpatients and outpatients with newly onset DM diagnosed between 2000 and 2012 were collected. The Adapted Diabetes Complications Severity Index (aDCSI) was used to adjust the severity of DM. The Cox proportional hazards regression model was used to estimate the hazard ratio (HR) of disease. Results: A total of 22 502 patients with newly diagnosed DM were enrolled. The Cox proportional hazards regression model indicating acarbose was neutral for risk for gastroenterological malignancies, when compared to the acarbose non‐acarbose users group. However, when gastric cancer was focused, acarbose‐user group had significantly lowered HR than non‐acarbose users group (p = 0.003). After adjusted for age, sex, cancer‐related comorbidity, severity of DM, and co‐administered drugs, the HR of gastric cancer risk was 0.43 (95% CI = 0.25–0.74) for acarbose‐user patients. Conclusion: This long‐term population‐based study demonstrated that acarbose might be associated with lowered risk of new‐onset gastric cancer in diabetic patients after adjusting the severity of DM. [ABSTRACT FROM AUTHOR]

Lina Shibib,1 Mo Al-Qaisi,1 Nicola Guess,2 Alexander D Miras,3 Steve E Greenwald,4 Marc Pelling,1 Ahmed Ahmed1 1Department of Surgery and Cancer, Imperial College London, London, UK; 2Nuffield Department of Primary Care Health Sciences, Oxford University, Oxford, UK; 3School of Medicine, Ulster University, Coleraine, UK; 4Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UKCorrespondence: Mo Al-Qaisi, Email mrcgp74@yahoo.co.ukAbstract: This review paper explores post-prandial glycemia in type 2 diabetes. Post-prandial glycemia is defined as the period of blood glucose excursion from immediately after the ingestion of food or drink to 4 to 6 hours after the end of the meal. Post-prandial hyperglycemia is an independent risk factor for cardiovascular disease with glucose “excursions” being more strongly associated with markers of oxidative stress than the fasting or pre-prandial glucose level. High blood glucose is a major promoter of enhanced free radical production and is associated with the onset and progression of type 2 diabetes. Oxidative stress impairs insulin action creating a vicious cycle where repeated post-prandial glucose spikes are key drivers in the pathogenesis of the vascular complications of type 2 diabetes, both microvascular and macrovascular. Some authors suggest post-prandial hyperglycemia is the major cause of death in type 2 diabetes. Proper management of post-prandial hyperglycemia could yield up to a 35% cut in overall cardiovascular events, and a 64% cut in myocardial infarction. The benefits of managing post-prandial hyperglycemia are similar in magnitude to those seen in type 2 diabetes patients receiving secondary prevention with statins – prevention which today is regarded as fundamental by all practitioners. Given all the evidence surrounding the impact of post-prandial glycemia on overall outcome, it is imperative that any considered strategy for the management of type 2 diabetes should include optimum dietary, pharma, and lifestyle interventions that address glucose excursion. Achieving a low post-prandial glucose response is key to prevention and progression of type 2 diabetes and cardiometabolic diseases. Further, such therapeutic interventions should be sustainable and must benefit patients in the short and long term with the minimum of intrusion and side effects. This paper reviews the current literature around dietary manipulation of post-prandial hyperglycemia, including novel approaches. A great deal of further work is required to optimize and standardize the dietary management of post-prandial glycemia in type 2 diabetes, including consideration of novel approaches that show great promise.Keywords: glycemic response, post-prandial, hyperglycemia, diabetes, acarbose, GLP-1, metformin, plant fibre, whey protein, gastric emptying, intestinal absorption, glycemic index, glucose excursion

Summary: Background: Based on available data, acarbose may have an effect on body weight reduction. Nevertheless, the results were inconsistent and inconclusive. Therefore, the purpose of this review and meta-analysis of randomized placebo-controlled trials (RCTs) was to assess the existing data as thoroughly as possible. Methods: The relevant keywords were used to search the online databases to identify RCTs that examined the effect of acarbose on body weight, body mass index (BMI), and waist circumference (WC) up to April 2023. A random-effects model was applied to examine the weighted mean difference (WMD) and 95% confidence interval (CI). Results: Seventy-one RCTs with 73 effect sizes were included in this meta-analytic work. The effect sizes for body weight, BMI, and WC were 45, 47, and 9, respectively. The pooled analysis demonstrated significant decrease in body weight (WMD = −1.21 kg; 95%CI, −1.67, −0.75; p

Tea tree essential oil (TEO) Rosemary Essential Oil (REO) and Guggul essential oil (GEO) (EOs) are a priceless essential oil that has been linked to several biological activities, including antibacterial, antifungal, immunomodulatory, anticancer, and anti-inflammatory effects. α-amylase inhibition is a hopeful curative target against type-2 diabetes as it can downgrade fierce digestion and absorption of carbohydrates into absorbable monosaccharides. The purpose of the study is in silico molecular docking of principal component of TEO, REO and GEO followed by and in vitro validation of inhibition of α-amylase activity. For docking Cb-dock2 tool was utilized. Ligand-Protein 2-D interactions were also studied. From the perspective of human health, in-silico ADMET pharmacoinformatic features (Physicochemical, Lipophilicity, Medicinal Chemistry, Druglikeness, Absorption, Water Solubility, Distribution, Metabolism, Pharmacokinetics, Excretion) have prospected. Using α-amylase, wet lab validation was carried out. 2, 2-Diphenyl-1-picryl hydrazyl (DPPH) radical inhibition assay was conducted to ascertain antioxidant role of all EO’s. Docking investigation demonstrated the effective binding of all the ligands with the α-amylase. The interaction results imply that the enzyme-ligand complexes form hydrogen, hydrophobic, and other interactions. In-silico ADMET examination disclosed that all the ligand molecules have no toxic effect and acceptable absorption as well. Further, TEO, REO and GEO has dose-dependent inhibitory action against α-amylase. All EO’s depicted good antioxidant potential. Kinetic analysis revealed that TEO, REO and GEO competitively inhibited α-amylase. It was concluded that these substances can function as model molecules for the synthesis of novel anti-diabetic substances.

Aim: The alpha-glucosidase inhibitor acarbose is approved for the treatment of type 2 diabetes (T2D). It acts in the lumen of the gut by reducing intestinal hydrolysis and absorption of ingested carbohydrates. This reduces postprandial blood glucose concentration and increases the content of carbohydrates in the distal parts of the intestine potentially influencing gut microbiome (GM) composition and possibly impacting the gut microbiome (GM) dysbiosis associated with T2D. Here, we investigated the effect of acarbose on GM composition in patients with T2D. Methods: Faecal samples were collected in a previously conducted randomised, placebo-controlled, double-blind, crossover study in which 15 individuals with metformin-treated T2D (age 57–85 years, HbA1c 40–74 mmol/mol, BMI 23.6–34.6 kg/m2) were subjected to two 14-day treatment periods with acarbose and placebo, respectively, separated by a 6-week wash-out period. Faecal samples were collected before and by the end of each treatment period. The GM profiles were evaluated by 16S rRNA gene amplicon sequencing. Results: The GM profiles after the treatment periods with acarbose or placebo remained unaffected (P > 0.7) when compared with the GM profiles before treatment. This applied to the analysis of within-sample diversity (α-diversity) and between-sample bacterial composition diversity (β-diversity). Additionally, no dominant bacterial species differentiated the treatment groups, and only minor increases in the relative abundances of Klebsiella spp. and Escherichia coli (P < 0.05) were observed after acarbose treatment. Conclusion: In patients with metformin-treated T2D, 14 days of treatment with acarbose showed only minor effects on GM as seen in increased relative abundances of Klebsiella spp. and Escherichia coli.

Introduction: α-amylase inhibitors are an important class of second-line antihyperglycemic drugs. They slow down the breakdown and absorption of carbohydrates, reducing peak glucose concentration with meals. Recent reports have also shown other beneficial effects of α-amylase inhibitors on type 2 diabetes mellitus (T2DM). Materials and Methods: T2DM was modeled by keeping C57BL/6 mice on a high-fat diet for 21 weeks. Starting at week 18, the animals were orally administered acarbose at a dose of 24 mg/kg or the comparative drug metformin at a dose of 200 mg/kg for 4 weeks. Body weight gain, visceral fat mass, and adipocyte diameter were monitored during the period of test substances administration. At weeks 17, 19 and 21 of the study, glucose tolerance starch test and insulin resistance test were performed, and fasting blood glucose was measured. Results: Administration of acarbose for 2 and 4 weeks resulted in a significant reduction of postprandial glucose concentration in the starch test; glucose AUC was significantly lower after administration of acarbose at a dose of 24 mg/kg on the background of T2DM modeling. Acarbose at a dose of 24 mg/kg effectively reduced fasting glucose concentration after 2 and 4 weeks of daily treatment on par with metformin. Administration of acarbose at a dose of 24 mg/kg for 2 and 4 weeks resulted in a significant decrease in the glucose AUC in the insulin resistance test. Acarbose promoted a significant decrease in adipocyte diameter and body weight gain against the background of T2DM modeling. Conclusion: Long-term acarbose administration at a daily dose of 24 mg/kg is effective in reducing postprandial glucose concentration in mice with T2DM due to its α-amylase inhibitory activity. Additionally, it can alleviate insulin resistance, lower fasting glucose concentration, and prevent obesity development by stimulating GLP-1 secretion.

Objective: Diabetic individuals have a higher probability of suffering from illness and death due to small blood vessel-related problems such as retinopathy, neuropathy, nephropathy, and stroke than other complications. There are many synthetic anti-diabetic agents available, but these can be expensive and have undesirable pathological effects. The enzyme α-amylase (hydrolase), catalyzes the hydrolysis of starch to maltose and glucose via the cleavage of α-1,4-glucosidic linkages. Diabetes mellitus patients may benefit from a therapeutic strategy that involves slowing the hydrolysis of starch by inhibiting the activity of α-amylase. Thus, looking for cost-effective, natural, and safe antidiabetic agents is essential. This study aims to screen phytoconstituents and evaluate the in-vitro and in-silico α-amylase inhibitory activity of the ethanolic extract of Adhatoda vasica leaves. Methods: The extraction of Adhatoda vasica leaves was performed using ethanol via the Soxhlet extraction process. Different concentrations (100 μg/mL to 1000 μg/mL) of ethanolic extract, Acarbose, and Sitagliptin, were prepared and evaluated for α-amylase inhibitory activity using the spectrophotometric method. Molecular docking (AutodockVina 1.2.0) and toxicity profiling (SToPToX web server) studies were performed. Results: The ethanolic extract of Adhatoda vasica leaves showed the highest percentage inhibition against α-amylase (56.763 ± 0.0035) at a concentration of 1000 μg/mL. The in-silico study supported this inhibitory activity. Vasicoline (C5) and Quercetin (C9), the active constitute of Adhatoda vasica, showed the best binding energies of −8.3 and −8.0 Kcal/mol, respectively against α-amylase enzyme (PDBID: 4W93). A toxicity study revealed the safety profile of the plant extract. Conclusion: It was concluded that Adhatoda vasica leaves possess some bioactive compounds that are responsible for controlling blood glucose levels, and their identification, purification, and isolation may lead to the development of new therapeutic agents with fewer side effects than the available drugs. [ABSTRACT FROM AUTHOR]

Reactions with allyl-, acetyl-, and phenylisothiocyanate have been studied on the basis of 3-amino-4,6-dimethylpyridine-2(1H)-one, 3-amino-4-phenylpyridine-2-one, and 3-amino-4-(thiophene-2-yl)pyridine-2(1H)-one (benzoyl-)isothiocyanates, and the corresponding thioureide derivatives 8-11a-c were obtained. Twelve thiourea derivatives were obtained and studied for their anti-diabetic activity against the enzyme α-glucosidase in comparison with the standard drug acarbose. The comparison drug acarbose inhibits the activity of α-glucosidase at a concentration of 15 mM by 46.1% (IC50 for acarbose is 11.96 mM). According to the results of the conducted studies, it was shown that alkyl and phenyl thiourea derivatives 8,9a-c, in contrast to their acetyl–(benzoyl) derivatives and 10,11a-c, show high antidiabetic activity. Thus, 1-(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)-3-phenylthiourea 9a has the highest inhibitory activity against the enzyme α-glucosidase, exceeding the activity of the comparison drug acarbose, which inhibits the activity of α-glucosidase by 56.6% at a concentration of 15 mm (IC50 = 9,77 mM). 1-(6-methyl-2-oxo 4-(thiophen-2-yl)-1,2-dihydropyridin-3-yl)-3-phenylthiourea 9c has inhibitory activity against the enzyme α-glucosidase, comparable to the comparison drug acarbose, inhibiting the activity of α-glucosidase at a concentration of 15 mm per 41.2% (IC50 = 12,94 mM). Compounds 8a, 8b, and 9b showed inhibitory activity against the enzyme α-glucosidase, with a lower activity compared to acarbose, inhibiting the activity of α-glucosidase at a concentration of 15 mM by 23.3%, 26.9%, and 35.2%, respectively. The IC50 against α-glucosidase for compounds 8a, 8b, and 9b was found to be 16.64 mM, 19.79 mM, and 21.79 mM, respectively. The other compounds 8c, 10a, 10b, 10c, 11a, 11b, and 11c did not show inhibitory activity against α-glucosidase. Thus, the newly synthesized derivatives of thiourea based on 3-aminopyridine-2(1H)-ones are promising candidates for the further modification and study of their potential anti-diabetic activity. These positive bioanalytical results will stimulate further in-depth studies, including in vivo models. [ABSTRACT FROM AUTHOR]

From the EtOAc extract of the wood of the stems of Taxotrophis ilicifolius (Moraceae), two new secondary metabolites, named taxotrophises A (1) and B (2), were isolated, together with five known compounds (3–7). Their chemical structures have been elucidated by extensive NMR spectroscopic analysis. All isolated compounds have been evaluated for α-glucosidase inhibitory activity. In the present work, compounds 1 and 4 showed the strongest α-glucosidase inhibitory activity with IC50 values of 6.5 and 1.5 μM, respectively, and stronger than that of a positive control, acarbose (IC50; 214.5 μM). [ABSTRACT FROM AUTHOR]

The current study was aimed to synthesize a series of adamantane-linked aminothiazole derivatives (6a-) and to assess their enzyme inhibitory activities. These derivatives were synthesized based on the structural features of known enzyme inhibitors, and their structures were characterized using various spectroscopic techniques, including FTIR, 1H NMR, 13C NMR, and mass spectrometry. The synthesized compounds were further evaluated for their inhibitory activities against the enzymes urease, α-glucosidase and carbonic anhydrase. The results of the enzyme inhibitory activity showed that compounds 6c, 6g and 6k possessed an excellent urease inhibitory activities, with IC50 values of 18.07 ± 0.11, 13.05 ± 0.2 and 17.12 ± 0.1 µM, respectively. These values were significantly lower than the IC50 value of the standard inhibitor thiourea (21,021 ± 0.02 µM). Additionally, compound 6c and 6e showed good α-glucosidase inhibitory activities. Therefore, compound 6c and 6e has excellent activity of IC50 value as 18.4 ± 0.11 and 58.01 ± 0.8 µM against α-glucosidase enzyme, respectively, and considerable relative potency compared with the known α-glucosidase inhibitor i.e., acarbose having an IC50 value of 883.93 ± 2.18 µM. The inhibitory effect of the compound 6f, 6k, 6j was considerably high against carbonic anhydrase, with their IC50 values of 3.02 ± 0.31 µM, 4.5 ± 0.041 µM and 2.7 ± 0.004 µM, respectively, as compared to acetazolamide with an IC50 value of IC50 0.12 ± 0.03 µM. The molecular docking of the active compounds docked in the active site of urease, α-glucosidase enzyme and carbonic anhydrase and depicted a good-binding score for all active derivatives. The present results indicate the significance of the structure–activity relationship in the development of potent enzyme inhibitors. Hence, the results obtained from the current study may be useful for designing further studies on related compounds with potential medicinal importance. [ABSTRACT FROM AUTHOR]

Phytochemical study on the roots of Achyranthes bidentata Blume led to the isolation of sixteen compounds including three new ones (1–3). Their chemical structures were determined as oleanolic acid 28-O-β-D-glucopyranoside-3-O-[β-D-glucopyranosyl-(1→3)-β-D-galactopyranoside) (1), methyl (8Z,11Z)-5,6,7-trihydroxytetradeca-8,11-dienoate (2), methyl (6E,11Z)-5,8,9-trihydroxytetradeca-6,11-dienoate (3), fulgidic acid (4), (9E,11E)-13-oxooctadeca-9,11-dienoic acid (5), (9Z,11E,15Z)-13-hydroxyoctadeca-9,11,15-trienoic acid (6), oleanolic acid 28-O-β-D-glucopyranoside-3-O-α-L-rhamnopyranosyl-(1→4)-β-D-glucuronopyranoside (7), oleanolic acid 28-O-β-D-glucopyranoside-3-O-β-D-glucopyranosyl-(1→2)-[α-L-rhamnopyranosyl-(1→3)]-β-D-glucuronopyranoside (8), oleanolic acid 3-O-β-D-glucopyranosyl-(1→2)-[α-L-rhamnopyranosyl-(1→3)]-β-D-glucuronopyranoside (9), oleanolic acid 3-O-α-L-rhamnopyranosyl-(1→3)-β-D-glucuronopyranoside (10), blumenol C glucoside (11), citroside A (12), 6S,9S-roseoside (13), ginsenoside Rg1 (14), 20-hydroxyecdysone (15), and benzyl α-L-rhamnopyranosyl-(1→6)]-β-D-glucopyranoside (16) by spectroscopic analysis. Compounds 1, 7 and 11–16 inhibited NO production in LPS-activated RAW264.7 cells with IC50 values in the range from 28.03 to 54.23 µM (positive control, L-NMMA: IC50 = 35.52 µM). Compounds 14 and 15 showed anti α-glucosidase activity with IC50 values of 176.24 and 156.92 µM, respectively, compared with the positive control, acarbose, IC50 = 160.99 μM. [ABSTRACT FROM AUTHOR]

Polycystic ovarian syndrome is a perplexed condition addressing endocrinal, cardiometabolic and gynaecological issues. It affects women of adolescent age and is drastically increasing in the Indo-Asian ethnicity over the recent years. According to Rotterdam criteria, PCOS is characterized by clinical or biochemical excess androgen and polycystic ovarian morphology; however, it has been established in the recent years that PCOS exacerbates to further serious metabolic conditions on the long term. This is a narrative literature review and not systematic review and is based on PubMed searches with relevant keywords "Polycystic ovarian syndrome AND acarbose OR metformin OR myoinositol; PCOS AND metabolic syndrome OR cardiovascular disease OR menstrual irregularity OR infertility OR chronic anovulation OR clinical hyperandrogenism" used in the title and are limited to articles published in English language with no time limits. A prominent aspect of PCOS is hyperandrogenaemia and hyperinsulinemia. About 50-70% of afflicted women have compensatory hyperinsulinemia and close to one tierce suffer from anovulation and infertility. Insulin resistance leads to metabolic complications and works with luteinizing hormone in increasing the ovarian androgen production. This excess androgen leads to clinical manifestations, irregular menstrual cycles and infertility. There isn't an entire cure, only the symptomatic clinical factors are considered rather than focusing on the underlying long-term complications. Therefore, the article focuses on a potent alpha glucosidase inhibitor, acarbose which suppresses the post meal glucose and insulin by delaying the absorption of complex carbs. It exhibits cardio-metabolic and hormonal benefits and is well tolerable in the south asian population. This review highlights the safety, effectiveness of acarbose in ameliorating the long-term complications of PCOS. [ABSTRACT FROM AUTHOR]

A novel series of imidazole appended quinoline derivatives (6a–j) have been synthesized using the one-pot three-component reaction that occurred between the starting materials of substituted 2-phenoxyquinolin-3-carbaldehydes (3a-j), benzil (4), and ammonium acetate (5) by taking equimolar ratio. The newly synthesized imidazole-appended quinolines were subjected to probable inhibition against the anti-diabetic drug target maltase enzyme. The efficacy was tested using in-silico molecular docking analysis and molecular dynamics simulation. The studies revealed that the test 6f ligand (3-(4,5-diphenyl-1H-imidazol-2-yl)-2-phenoxy quinoline) is a strong inhibitor of the target protein maltase when compared with the known inhibitor acarbose and sheds new light on the medicinal chemistry research for the application of the synthesized 6f ligand in the pharmaceutical industry. [ABSTRACT FROM AUTHOR]

Previous research has demonstrated that complex carbohydrates (maltodextrins) can be perceived in the oral cavity. However, little research has been conducted to thoroughly investigate complex carbohydrate taste perception and contributing factors. This study explored the effects of the degree of polymerization and the concentration of complex carbohydrates on taste perception. Additionally, the impact of lactisole and acarbose on carbohydrate taste perception was investigated. Using a blinded, Latin Square design, participants (n = 40) received samples (control) or samples with acarbose (5 mM) or lactisole (1.4 mM). Per visit, participants received solutions: (1) short chain maltodextrin (average DP 6) (SCM), (2) long chain maltodextrin (average DP 24) (LCM), (3) maltose, and (4) glucose. Samples were evaluated in duplicate, both at low concentration and high concentration. Participants tasted the samples and rated sweetness, starchiness, and viscosity (mouthfeel) perceived on a 10 cm continuous line scale and perceived intensity on a Labelled Magnitude Scale. There was a significant effect of degree of polymerisation on sweetness (p = 0.001) and intensity (p = 0.001). For low concentration samples, no significant differences were found between LCM and acarbose LCM or SCM and acarbose SCM for sweetness, starchiness, or mouthfeel (all p > 0.05). Significant differences were observed between LCM and lactisole LCM for sweetness (1.1 ± 0.1 vs. 2.5 ± 0.3, p = 0.001), starchiness (1.4 ± 0.2 vs. 2.3 ± 0.3, p = 0.005), and mouthfeel (1.4 ± 0.2 vs. 2.3 ± 0.3, p = 0.013). In conclusion, the taste perception of maltodextrins is influenced by the degree of polymerisation. Furthermore, for this study, the sweet taste receptor was not involved in maltodextrin taste perception. While salivary α-amylase did not appear to influence taste perception with low concentration maltodextrins, further investigation is necessary. [ABSTRACT FROM AUTHOR]

Background: Metabolic surgery is the foremost treatment for obesity and its associated medical conditions. Nonetheless, post-bariatric hypoglycemia (PBH) emerges as a prevalent complication. PBH pathophysiology implicates heightened insulin and glucagon-like peptide 1 (GLP-1) levels, with bile acids (BA) contributing to GLP-1 release. A plausible association exists between cholecystectomy and PBH, which is attributed to alterations in BA metabolism and ensuing hormonal responses. The objective of this retrospective cohort study was to evaluate the impact of cholecystectomy on PBH pharmacological treatment, diagnostic timelines and metabolic parameters. Materials and methods: Patients diagnosed with PBH after bariatric surgery were evaluated based on their history of cholecystectomy. Demographic, anthropometric and clinical data were collected. Mixed meal tolerance tests (MMTT) results were compiled to assess metabolic responses. Results: Of the 131 patients with PBH included in the study, 29 had prior cholecystectomy. The time to PBH diagnosis was similar across groups. Patients with prior cholecystectomy required higher doses of acarbose (p = 0.046), compared to those without prior cholecystectomy. Additionally, MMTT revealed higher insulin (t = 60 min: p = 0.010 and t = 90 min: p = 0.034) and c-peptide levels (t = 60 min: p = 0.008) and greater glycemic variability in patients with prior cholecystectomy (p = 0.049), highlighting the impact of cholecystectomy on glucose metabolism. Conclusion: Our study offers novel insights into PBH pharmacotherapy, indicating that PBH patients with a history of cholecystectomy require elevated doses of acarbose for symptom control than PBH patients without such surgical history. Furthermore, our findings underscore the pivotal role of hyperinsulinism in PBH aetiology, emphasizing the significance of the BA-GLP-1-insulin axis. [ABSTRACT FROM AUTHOR]

Rehmannia glutinosa was extensively used to control blood sugar in diabetes treatment in tradition Chinese medicine. In the present study, three new compounds, including an iridoid rehmannia A (1) and two ionone rehmannias B-C (7-8), together with fourteen known compounds (2-6 and 9-17), were isolated from the roots of R. glutinosa. The structures of these compounds were determined by physicochemical constants and spectral analysis (1D, 2D-NMR and MS). The effect of 1-17 on α-glucosidase activity was tested in vitro. Compounds 9, 10, and 11 (IC50: 5.0, 3.1, and 6.3 mM) showed moderate activity to suppress α-glucosidase relative to acarbose (IC50 = 3.0 mM). The findings provided some new insights to understand the hypoglycemic effect of R. glutinosa and the development towards the α-glucosidase inhibitor drugs. [ABSTRACT FROM AUTHOR]

Psidium guajava is a plant of the Myrtaceae with various pharmacological activity. In this study, the water extract and the isolated compounds from guava leaves were evaluated for in vitro α-glucosidase inhibition using spectrophotometric method. Ellagic acid, quercetin, quercetin-3-O-glucuronide, avicularin, isoquercitrin, and quercetin-3-galactoside showed α-glucosidase inhibitory activity, and their IC50 value were 25.0, 41.0, 53.5, 46.9, 60.0 and 72.1 μg/mL, respectively compared with the positive control acarbose (IC50 49.2 μg/mL). This study could provide a theoretical basis for the application of Psidium guajava in the treatment of hyperglycemia. [ABSTRACT FROM AUTHOR]

The research aimed to investigate the efficacy of fermented Mamasa honey with Lacticaseibacillus casei strain NC1 as a potential treatment for diabetes mellitus, considering the high prevalence rate of 10.8 million patients in Indonesia and the challenges posed by expensive and less effective diabetes treatments. Methodologically, the study involved fermenting honey with L. casei strain NC1 and evaluating its antidiabetic properties and antioxidant activity. Encouragingly, the results of this study revealed notable outcomes -- the fermented honey exhibited significant antidiabetic activity, particularly evident at an optical density (OD) of 0.75 after 72 h of incubation, hence surpassing the efficacy of the positive control (acarbose). Additionally, the antioxidant testing demonstrated strong antioxidant potential, with the highest activity observed in black honey at the same OD and incubation period. The fermented honey demonstrated significant antidiabetic activity, with the highest effectiveness observed at an OD of 0.75 after 72 h of incubation. The antidiabetic activity reached 20006.3%, hence surpassing the efficacy of the positive control (acarbose), which only achieved 639.8%. The antioxidant testing of the fermented honey also yielded positive results, with the highest activity observed in black honey at OD 0.75 after 72 h of incubation. The antioxidant activity was recorded at 199.1%, hence indicating strong antioxidant potential. In the organoleptic test, white honey produced after a 48-h incubation period was preferred by the respondents. [ABSTRACT FROM AUTHOR]

Acarbose is a potent glycosidase inhibitor widely used in the clinical treatment of type 2 diabetes mellitus (T2DM). Various acarbose analogs have been identified while exploring compounds with improved pharmacological properties. In this study, we found that AcbE from Actinoplanes sp. SE50/110 catalyzes the production of acarbose analogs that exhibit significantly improved inhibitory activity towards α-amylase than acarbose. Recombinant AcbE mainly catalyzed the formation of two new compounds, namely acarstatins A and B, using acarbose as substrate. Using high-resolution mass spectrometry, nuclear magnetic resonance, and glycosidase hydrolysis, we elucidated their chemical structures as O-α-D-maltosyl-(1 → 4)-acarbose and O-α-D-maltotriosyl-(1 → 4)-acarbose, respectively. Acarstatins A and B exhibited 1584- and 1478-fold greater inhibitory activity towards human salivary α-amylase than acarbose. Furthermore, both acarstatins A and B exhibited complete resistance to microbiome-derived acarbose kinase 1-mediated phosphorylation and partial resistance to acarbose-preferred glucosidase-mediated hydrolysis. Therefore, acarstatins A and B have great potential as candidate therapeutic agents for T2DM. [ABSTRACT FROM AUTHOR]

Introduction: Post‐bariatric hypoglycaemia (PBH) is a rare yet disabling clinical condition, mostly reported after Roux‐en‐Y gastric bypass (RYGB) surgery. RYGB is one of the most widely used and effective bariatric procedures. The pathophysiology of PBH remains unclear, and treatment options are limited in effectiveness and/or carry significant side effects. Acarbose slows carbohydrates digestion and absorption and is generally considered first‐line pharmacological treatment for PBH but its gastrointestinal side effects limit patient compliance. Canagliflozin inhibits intestinal and renal sodium‐dependent glucose absorption and reduces postprandial excursions of glucose, insulin and incretins after RYGB – effects that could be beneficial in ameliorating PBH. Aims: The trial aims to investigate how blood glucose levels are affected during daily living in subjects with PBH during treatment with canagliflozin or acarbose compared with placebo, and to study the meal‐induced entero‐endocrine mechanisms implied in the treatment responses. Methods: In a double‐blinded, randomized, crossover clinical trial, HypoBar I will investigate the effectiveness in reducing the risk of PBH, safety, ambulatory glucose profile and entero‐endocrine responses when PBH is treated with canagliflozin 300 mg twice daily during a 4‐week intervention period, compared with acarbose 50 mg thrice daily or placebo. Ethics and Dissemination: HypoBar I is approved by the Local regulatory entities. Results will be published in peer‐reviewed journals. Conclusion: If effective, well‐tolerated and safe, canagliflozin could be a novel treatment for people with PBH. HypoBar I might also unravel new mechanisms underlying PBH, potentially identifying new treatment targets. Trial Registration: EudraCT number 2022–000157‐87. [ABSTRACT FROM AUTHOR]

The pseudotetrasaccharide acarbose, produced by Actinoplanes sp. SE50/110, is a relevant secondary metabolite used in diabetes type II medication. Although maltose plays a crucial role in acarbose biosynthesis, the understanding of the maltose/maltodextrin metabolism and its involvement in acarbose production is at an early stage. Here, we reconstructed the predicted maltose–maltodextrin pathway that involves four enzymes AmlE, MalZ, MalP, and MalQ. An investigation of enzyme activities was conducted through in vitro assays, leading to an expansion of previously postulated substrate spectra. The maltose-induced α-glucosidase AmlE is noteworthy for its high hydrolysis rate of linear α-1,4-glucans, and its capability to hydrolyze various glycosidic bonds. The predicted maltodextrin glucosidase MalZ showed slow hydrolysis activity on linear α-glucans, but it was resistant to acarbose and capable of releasing glucose from acarbose. AmlE compensates for the low activity of MalZ to ensure glucose supply. We determined the enzyme activity of MalP and its dual function as maltodextrin and glycogen phosphorylase. The 4-α-glucanotransferase MalQ plays a central role in the maltose/maltodextrin metabolism, alongside MalP. This study confirmed the simultaneous degradation and synthesis of long-chain α-glucans. The product distribution showed that with an increasing number of glycosidic bonds, less glucose is formed. We found that MalQ, like its sequence homolog AcbQ from the acarbose biosynthetic gene cluster, is involved in the formation of elongated acarviosyl metabolites. However, MalQ does not participate in the elongation of acarbose 7-phosphate, which is likely the more readily available acceptor molecule in vivo. Accordingly, MalQ is not involved in the formation of acarviosyl impurities in Actinoplanes sp. SE50/110. [ABSTRACT FROM AUTHOR]

Sigma factors are transcriptional regulators that are part of complex regulatory networks for major cellular processes, as well as for growth phase-dependent regulation and stress response. Actinoplanes sp. SE50/110 is the natural producer of acarbose, an α-glucosidase inhibitor that is used in diabetes type 2 treatment. Acarbose biosynthesis is dependent on growth, making sigma factor engineering a promising tool for metabolic engineering. ACSP50_0507 is a homolog of the developmental and osmotic-stress-regulating Streptomyces coelicolor σHSc. Therefore, the protein encoded by ACSP50_0507 was named σHAs. Here, an Actinoplanes sp. SE50/110 expression strain for the alternative sigma factor gene ACSP50_0507 (sigHAs) achieved a two-fold increased acarbose yield with acarbose production extending into the stationary growth phase. Transcriptome sequencing revealed upregulation of acarbose biosynthesis genes during growth and at the late stationary growth phase. Genes that are transcriptionally activated by σHAs frequently code for secreted or membrane-associated proteins. This is also mirrored by the severely affected cell morphology, with hyperbranching, deformed and compartmentalized hyphae. The dehydrated cell morphology and upregulation of further genes point to a putative involvement in osmotic stress response, similar to its S. coelicolor homolog. The DNA-binding motif of σHAs was determined based on transcriptome sequencing data and shows high motif similarity to that of its homolog. The motif was confirmed by in vitro binding of recombinantly expressed σHAs to the upstream sequence of a strongly upregulated gene. Autoregulation of σHAs was observed, and binding to its own gene promoter region was also confirmed. [ABSTRACT FROM AUTHOR]

Key Clinical Message High‐dose acarbose may increase the risk of diabetic ketosis/diabetic ketoacidosis in Asian patients on sodium‐glucose cotransporter‐2 inhibitors. Healthcare providers and patients should be cautious to avoid this combination. Abstract Low‐calorie diets should be avoided in patients receiving sodium‐glucose cotransporter‐2 (SGLT‐2) inhibitors to decrease the risk of diabetic ketoacidosis (DKA). High‐dose acarbose can decelerate carbohydrate absorption. We detail three cases of diabetic ketosis (DK) following concurrent SGLT‐2 inhibitor and high‐dose acarbose therapy (acarbose 300 mg/day and dapagliflozin 10 mg/day). Patients, aged 38–63 years with 3–10 years of type 2 diabetes mellitus (T2DM), developed DK, indicated by moderate urinary ketones and high glucose (urine ketone 2+ to 3+ and glucose 3+ to 4+) without acidosis, within 4 days to 1 month post‐therapy initiation. Serum glucose was 172.8–253.8 mg/dL; HbA1c was 9.97%–10.80%. The combination therapy was halted, and DK was managed with low‐dose intravenous insulin and fluids, followed by intensive insulin therapy. High‐dose acarbose with SGLT‐2 inhibitors may increase the risk of DK/DKA in Asian patients.

Alpha-glucosidase inhibitors characterize a major class of Type II antidiabetic drugs and play a significant role in lowering postprandial hyperglycemia. Currently, the market offers a limited number of synthetic inhibitors, highlighting the necessity for the discovery of new and potent compounds with enhanced efficacy in this area. For this purpose, an already established library of 51 plant extracts was screened against α-glucosidase, among which Bombax ceiba extract exhibits significant α-glucosidase inhibitory activity (IC50; 1.95 ± 0.29 µg/mL) as compared to acarbose (IC50; 3.14 ± 0.49 µg/mL). Moreover, in order to investigate the specific phytochemicals responsible for this activity, a literature-based library of 78 compounds from B. ceiba were curated and subsequently screened against α-glucosidase using molecular docking. The selection of hit compounds was evaluated on the base of computational tools. Out of these 78 compounds, nine potent compounds (Pelargonin, Simalin B, Linarin, Rutin, Nicotiflorin, Simalin A, Mangiferin, Quercetin and Apigenin) exhibited best binding affinities with α-glucosidase. These phytochemicals exhibited favorable binding energy, hydrogen bonding, and protein–ligand interactions as compared to acarbose. These results were further validated by in vitro α-glucosidase inhibition assay of commercially available phytochemicals. To the best of our knowledge, this report unveils B. ceiba as a highly effective inhibitor of α-glucosidase. The findings suggest that B. ceiba and its metabolites exhibit promising characteristics for the development of leading drugs in the field of anti α-glucosidase medications, which could play a crucial role in the management of diabetes.

This commentary responds to a study that evaluated the recommended bioequivalence endpoints for acarbose oral tablets by the FDA. The authors of the commentary conducted their own analysis and made recommendations for revising the FDA's guidance. They found that the recommended endpoints were able to distinguish between different doses of acarbose in one study, but not in another study due to high variability. The authors suggest using a different method for assessing the data and acknowledge the contributions of other researchers. The original data used for the analysis were obtained from a published study and additional FDA datasets were used for confirmation. [Extracted from the article]

Pharmacological treatments can extend the life span of mice. For optimal translation in humans, treatments should improve health during aging, and demonstrate efficacy when started later in life. Acarbose (ACA) and rapamycin (RAP) extend life span in mice when treatment is started early or later in life. Both drugs can also improve some indices of healthy aging, although there has been little systematic study of whether health benefits accrue differently depending on the age at which treatment is started. Here we compare the effects of early (4 months) versus late (16 months) onset ACA or RAP treatment on physical function and cardiac structure in genetically heterogeneous aged mice. ACA or RAP treatment improve rotarod acceleration and endurance capacity compared to controls, with effects that are largely similar in mice starting treatment from early or late in life. Compared to controls, cardiac hypertrophy is reduced by ACA or RAP in both sexes regardless of age at treatment onset. ACA has a greater effect on the cardiac lipidome than RAP, and the effects of early-life treatment are recapitulated by late-life treatment. These results indicate that late-life treatment with these drugs provide at least some of the benefits of life long treatment, although some of the benefits occur only in males, which could lead to sex differences in health outcomes later in life.