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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.

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.

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.

Abstract Biofilm-associated candidiasis poses a significant challenge in clinical settings due to the limited effectiveness of existing antifungal treatments. The challenges include increased pathogen virulence, multi-drug resistance, and inadequate penetration of antimicrobials into biofilm structures. One potential solution to this problem involves the development of novel drugs that can modulate fungal virulence and biofilm formation, which is essential for pathogenesis. Resistance in Candida albicans is initiated by morphological changes from yeast to hyphal form. This transition triggers a series of events such as cell wall elongation, increased adhesion, invasion of host tissues, pathogenicity, biofilm formation, and the initiation of an immune response. The cell wall is a critical interface for interactions with host cells, primarily through various cell wall proteins, particularly mannoproteins. Thus, cell wall proteins and enzymes are considered potential antifungal targets. In this regard, we explored α-glucosidase as our potential target which plays a crucial role in processing mannoproteins. Previous studies have shown that inhibition of α-glucosidase leads to defects in cell wall integrity, reduced adhesion, diminished secretion of hydrolytic enzymes, alterations in immune recognition, and reduced pathogenicity. Since α-glucosidase, primarily converts carbohydrates, our study focuses on FDA-approved carbohydrate mimic drugs (Glycomimetics) with well-documented applications in various biological contexts. Through virtual screening of 114 FDA-approved carbohydrate-based drugs, a pseudo-sugar Acarbose, emerged as a top hit. Acarbose is known for its pharmacological potential in managing type 2 diabetes mellitus by targeting α-glucosidase. Our preliminary investigations indicate that Acarbose effectively inhibits C. albicans biofilm formation, reduces virulence, impairs morphological switching, and hinders the adhesion and invasion of host cells, all at very low concentrations in the nanomolar range. Furthermore, transcriptomic analysis reveals the mechanism of action of Acarbose, highlighting its role in targeting α-glucosidase.

Diabetes According to WHO (2016) is a serious chronic disease that occurs when the pancreas does not produce enough insulin or when the body cannot effectively use the insulin it produces. The high cost of treating DM patients is reaching USD 1,500 to 9,000 in developing countries. The difference in costs for oral antidiabetics and the high cost analysis method. This study aims to determine the minimum cost between metformin 500 mg and acarbose 100 mg drugs in Sultan Suriansyah Banjarmasin in adult patients. This research was conducted using a cross-sectional design based on medical records and detail of patient costs in January-December 2022. The number of sample in this study were 39 patients. The statistic analysis used in study is the Mann-Whitney test and the Independent T-Test. The result of the analysis of cost minimization based on the average total cost of therapy are Rp 419,560 for metformin 500ng and Rp 680,922 for acarbose 100 mg with a probability value > 0.05 for the cost of co morbidities which means that there is no significant difference between the two drugs. Probability value < 0.05 for antidiabetic oral drug costs, lab costs and total therapy costs which means the there is a significant difference between the two drugs. Conclusion in this study is aral antidiabetic therapy for minimal diabetes mellitus is metformin compared to acarbose.

The aim of the present study was to investigate the inhibition of enzymes alpha-amylase and glucoamylase by methanol extract of the plant Fagonia indica Burm.f. responsible for hypoglycemic activity. This study was performed for phytochemical investigation of this plant using the standard methods. Both qualitative and quantitative analysis of methanol extract of the plant was done for the analysis and estimation of phytochemical constituents. Alpha-amylase and glucoamylase inhibition by this extract was assessed for the evaluation of hypoglycemic activity. Gas chromatographic-mass spectrometric (GC-MS) analysis of hypoglycemic methanol extract was done to identify the compounds responsible for this activity. Phytochemical analysis exhibited the presence of various phytoconstituents in methanol extract. The maximum %age of enzymes inhibition of this extract was 49.1 ± 2.4% (IC50 values of 104.2 ± 8.7 μg/ml) and 31.7 ± 2.9% (IC50 values of 273.7 ± 54.6 μg/ml) for alpha amylase and glucoamylase enzymes respectively at 100 μg/ml concentration. The standard acarbose showed 68.91±3.0% (IC50=52.9±4.8 μg/ml) and 57.3±0.4% (IC50=70.2±3.4 μg/ml) inhibition of these enzymes respectively at the same concentration. GC-MS analysis identified 15 compounds in this extract. This finding confirms traditional use of this plant in managing diabetes.

Abstract Background Type 2 diabetes mellitus (T2DM) is widely prevalent worldwide, and respiratory tract infections (RTIs) have become the primary cause of death for T2DM patients who develop concurrent infections. Among these, Pseudomonas aeruginosa infection has been found to exhibit a high mortality rate and poor prognosis and is frequently observed in bacterial infections that are concurrent with COVID-19. Studies have suggested that acarbose can be used to treat T2DM and reduce inflammation. Our objective was to explore the effect of acarbose on P. aeruginosa RTI in T2DM individuals and elucidate its underlying mechanism. Methods High-fat diet (HFD) induction and P. aeruginosa inhalation were used to establish a RTI model in T2DM mice. The effect and mechanism of acarbose administered by gavage on P. aeruginosa RTI were investigated in T2DM and nondiabetic mice using survival curves, pathological examination, and transcriptomics. Results We found that P. aeruginosa RTI was more severe in T2DM mice than in nondiabetic individuals, which could be attributed to the activation of the NF-κB and TREM-1 signaling pathways. When acarbose alleviated P. aeruginosa RTI in T2DM mice, both HIF-1α and NF-κB signaling pathways were inhibited. Furthermore, inhibition of the calcium ion signaling pathway and NF-κB signaling pathway contributed to the attenuation of P. aeruginosa RTI by acarbose in nondiabetic mice. Conclusions This study confirmed the attenuating effect of acarbose on P. aeruginosa RTIs in T2DM and nondiabetic mice and investigated its mechanism, providing novel support for its clinical application in related diseases.

ABSTRACTS. sesban is mainly used as economical purpose and S. grandiflora is known for medicinal as well as economical. Chemical characterization and antidiabetic activity of seed extracts were not explored yet. Seeds of S. sesban and S. grandiflora were separated in seed coat, germ, and endosperm by domestic grinder mixer. Successive soxhlet extraction of separated parts of Sesbania seed were carried out. Chemical profiling of methanolic extract was carried out by GC-MS, HPLC, and in vitro alpha amylase inhibitory assay. D-pinitol was found to be maximum (48.39%) in seed coat and minimum in seed (8.35%) of methanolic extracts of Sesbania seed. Alpha-amylase inhibitory activity of methanolic extracts of different parts were also studied in which DSSh, DSSp, & DSSe showed similar IC50 to acarbose, antidiabetic drugs. The result showed that S. sesban and S. grandiflora seed and endosperm is rich in health promoting mineral like Na (241 mg/100 gm and 238 mg/100 gm), K (103.1 mg/100 gm) and (60.2 mg/100 gm), Ca (525 mg/100 gm) and (500 mg/100 gm) and Fe (67.5 and 91.9 mg/100 gm). Hence, it is similar to some edible legumes which possess bioactive compound with therapeutic value and can be efficiently explored for the development of new functional or nutraceutically valued food products.

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.

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.

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.

Zebrafish is a developing vertebrate model with several advantages, including its small size, and high experimental efficiency. Malaysia exhibit one of the highest diabetes rates in the Western Pacific and incurring an annual cost of 600 million US dollars. The objective of the study is to determine the antidiabetic properties of green honey (GH) using a zebrafish model. Adult zebrafish, aged 3–4 months, were subjected to overfeeding and treated with streptozotocin (STZ) through intraperitoneal injection (IP) on days 7 and 9. The study assessed the oral sucrose tolerance test (OSTT) and the anti-diabetic effects of green honey. The evaluation was conducted at three time points: 30, 60, and 120 min after treatment and sucrose administration. The study utilised a model with a sample size of 5. The study was performed in six groups. These groups are (1) Normal control (non-diabetic, no intervention), (2) Normal control + GH (non-diabetic, supplemented with GH 3 μl), (3) DM control (diabetic, no intervention), (4) DM Gp1 (diabetic, 3 μL GH), (5) DM Gp2 (diabetic, 6 μ L GH), (6) DM Acarbose (diabetic, treated with acarbose). Fasting blood glucose levels for non-diabetic (non-DM) and diabetic (DM) groups were evaluated before and after the 10 days of diabetic induction. DM groups (excess of food and two injections of STZ) have caused a significant increment in the fasting blood glucose to 11.55 mmol/l (p

Abstract Background The Acarbose Cardiovascular Evaluation (ACE) trial (ISRCTN91899513) evaluated the alpha‐glucosidase inhibitor acarbose, compared with placebo, in 6522 patients with coronary heart disease and impaired glucose tolerance in China and showed a reduced incidence of diabetes. We assessed the within‐trial medical resource use and costs, and quality‐adjusted life years (QALYs). Methods Resource use data were collected prospectively within the ACE trial. Hospitalizations, medications, and outpatient visits were valued using Chinese unit costs. Medication use was measured in drug days, with cardiovascular and diabetes drugs summed across the trial by participant. Health‐related quality of life was captured using the EuroQol‐5 Dimension‐3 Level questionnaire. Regression analyses were used to compare resource use, costs, and QALYs, accounting for regional variation. Costs and QALYs were discounted at 3% yearly. Results Hospitalizations were 6% higher in the acarbose arm during the trial (rate ratio 1.06, p = .009), but there were no significant differences in total inpatient days (rate ratio 1.04, p = .30). Total costs per participant, including study drug, were significantly higher for acarbose (¥ [Yuan] 56 480, £6213), compared with placebo (¥48 079, £5289; mean ratio 1.18, p

The conventional approach of drug development, which focused on inhibiting a single target, has been superseded by a more advanced strategy known as multi-target design. In this study, we describe the synthesis of new N-adamantyl-2-(2-(phenyl)hydrazone)-3-oxobutanamide (6a-k). These compounds were designed with the intention of serving as prospective drug like candidates that can target both alpha glucosidase and urease enzymes. For this purpose, both in-vitro and in-silico investigations were performed after synthesis and characterization. The density functional theory calculations were employed to calculate optimized geometries, global reactivity descriptors and frontier molecular orbital (FMO) analysis. All compounds were found reactive and compounds 6b, 6c, 6d and 6e were found the most stable. The synthesized compounds were also tested for their ability to inhibit the enzyme activities of urease and α-glucosidase. The compound 6c exhibited strong inhibition of urease enzyme, with IC50 value of 13.10 ± 0.55 µM, in comparison to the IC50 value of the standard inhibitor thiourea i.e., 16.4 ± 1.02 µM. In addition to this, compounds 6d and 6e demonstrated a significant α-glucosidase inhibition with IC50 values of 17.16 ± 0.91 µM but found less potent as compared to the standard inhibitor Acarbose, i.e. 9.80 ± 0.20 μM. The structure–activity relationship (SAR) was established and the in-vitro results were further supported by the molecular docking investigations and molecular dynamic simulation studies. The in-vitro and in-silico results demonstrated a strong correlation in assessing the drug-like characteristics of all synthesized compounds (6a-k). The in silico investigation confirmed the findings in the search for inhibitors against the listed enzymes by elucidating the binding relationship between most of the active compounds and the active site of urease and α-glucosidase.

The increasing prevalence of diabetes mellitus, together with the limited access of many patients to conventional antidiabetic drugs and the side effects resulting from their use, are the reason for the ever-increasing need for new agents. One of the most important strategies used in the therapy of this disease is to reduce the postprandial blood glucose level by inhibiting the carbohydrate-degrading enzymes α-amylase and α-glucosidase. The purpose of the present study was to provide in vitro evidence for the potential hypoglycemic effect of leaf and inflorescence aqueous extracts of Bulgarian endemic species Betonica bulgarica Degen and Neič. Total phenolic and flavonoid contents and antioxidant activities were determined by spectrophotometric methods. Qualitative and quantitative determinations of principal phenolic acids and flavonoids were performed using HPLC with a dual absorbance detector. The plant extracts were able to retard the enzymatic breakdown of starch to glucose with 50% inhibiting concentrations of 1.86 mg/mL and 1.54 mg/mL respectively for leaf and flower extract. Some of the plant constituents are proven inhibitors of α-amylase and/or α-glucosidase, but their adsorption on starch seems to be one additional mechanism for the inhibition of glucose release. Combination index analysis carried out with binary mixtures of acarbose and plant extracts showed a tendency toward synergism with an increase in concentrations and level of inhibition.

Acarbose is an α-glucosidase inhibitor that slows the digestion of carbohydrates and can prevent sharp increases in blood sugar levels after meals (spikes). Excessive postprandial blood glucose spikes have been associated with chronic conditions, increase all-cause mortality, and may contribute to aging. Therefore, the prevention of glucose spikes may contribute to the preservation of human healthspan. Indeed, acarbose has been associated with increased lifespan in animal models. However, its tolerability profile has limited acarbose use in healthy individuals. We hypothesized that using low-dose acarbose right before the occasional high-carbohydrate meal may prevent glucose spikes in healthy individuals. We performed a prospective clinical study to evaluate the tolerability and efficacy of acarbose in healthy individuals. Participants were randomized into two arms, each performing two control tests and two treatment tests. Continuous glucose monitor (CGM) measurements were collected for 2 h after high carbohydrate meals with or without pre-meal 50 mg acarbose intake. Tolerability was assessed using questionnaires. Twelve patients had evaluable results. Acarbose pretreatment resulted in reductions in CGM glucose measurements, with a significant decrease in glucose levels at the start, after 15 min, and at peak glucose levels. Few participants reported acarbose adverse events, and these included flatulence, bloating, nausea, abdominal pain, and stomach aches. No statistical difference in tolerability was detected between periods with and without acarbose. In conclusion, treatment with 50 mg of acarbose before meals was found to be well tolerated and efficacious in blunting the postprandial glucose spike by over 17% in healthy individuals.

Abstract Background Acarbose, as an alpha-glucosidase inhibitor, is widely used clinically to treat type II diabetes. In its industrial production, Actinoplanes sp. SE50/110 is used as the production strain. Lack of research on its regulatory mechanisms and unexplored gene targets are major obstacles to rational strain design. Here, transcriptome sequencing was applied to uncover more gene targets and rational genetic engineering was performed to increase acarbose production. Results In this study, with the help of transcriptome information, a TetR family regulator (TetR1) was identified and confirmed to have a positive effect on the synthesis of acarbose by promoting the expression of acbB and acbD. Some genes with low expression levels in the acarbose biosynthesis gene cluster were overexpressed and this resulted in a significant increase in acarbose yield. In addition, the regulation of metabolic pathways was performed to retain more glucose-1-phosphate for acarbose synthesis by weakening the glycogen synthesis pathway and strengthening the glycogen degradation pathway. Eventually, with a combination of multiple strategies and fed-batch fermentation, the yield of acarbose in the engineered strain increased 58% compared to the parent strain, reaching 8.04 g/L, which is the highest fermentation titer reported. Conclusions In our research, acarbose production had been effectively and steadily improved through genetic engineering based on transcriptome analysis and fed-batch culture strategy. Graphical Abstract

Abstract Background Acarbose is one of the optimal drugs for patients with the first diagnosis of type 2 diabetes mellitus (T2DM). But what kind of emerging patients has the best therapeutic response to acarbose therapy has never been reported. To this end, we investigated predictors of acarbose therapeutic efficacy in newly diagnosed T2DM patients in China. Methods A total of 346 T2DM patients received acarbose monotherapy for 48 weeks as part of participating in the Study of Acarbose in Newly Diagnosed Patients with T2DM in China (MARCH study) from November 2008 to June 2011. Change in glycated hemoglobin (ΔHbA1c) served as a dependent variable while different baseline variables including sex, age, disease duration, weight, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), HbA1c, fasting plasma glucose (FPG), 2-h postprandial blood glucose (2 h PG), fasting insulin (FINS), 2-h postprandial insulin (2 h INS), early insulin secretion index (IGI), homeostasis model assessment of insulin resistance index (HOMA-IR), homeostasis model assessment of beta cell function (HOMA-B), area under the curve (AUC) of glucagon, insulin and GLP-1 were assessed as independent predictors. Step-wise multiple linear regression was employed for statistical analysis. Results The results suggested that independent predictors of ΔHbA1c at 12 weeks included baseline body weight (β = − 0.012, P = 0.006), DBP (β = 0.010, P = 0.047), FPG (β = 0.111, P = 0.005) and 2 h PG (β = 0.042, P = 0.043). Independent predictors of ΔHbA1c at 24 weeks included disease duration (β = 0.040, P = 0.019) and FPG (β = 0.117, P = 0.001). Finally, independent predictor of ΔHbA1c at 48 weeks was disease duration (β = 0.038, P = 0.046). Conclusions Acarbose may be more effective in newly diagnosed T2DM patients with low FPG, low 2 h PG and obesity. The earlier T2DM is diagnosed and continuously treated with acarbose, the better the response to therapy.

Acarbose (ACB) seems to be an effective drug in the management of cardiovascular risk factors. However, no previous meta-analysis of randomized controlled trials (RCTs) has been done to evaluate the effects of ACB on cardiovascular risk factors on impaired glucose tolerance (IGT), type 2 diabetes mellitus (T2D), and type 1 diabetes mellitus (T1D). We comprehensively searched electronic databases including Scopus, Web of Science, and PubMed for RCTs for related keywords up to September 2022. A random-effects model was used to estimate the weighted mean difference (WMD) and 95% confidence interval (CI). The pooled analysis demonstrated that ACB treatment had a significant effect on fasting blood glucose (FBG) (WMD = −3.55 mg/dL; 95%CI: −6.29, −0.81; p = 0.011), fasting insulin (WMD = −6.73 pmoL/L; 95%CI: −10.37, −3.10; p 50 weeks, and 180 mg/day is more effective for the decrement of CRP. ACB can improve lipid profiles, glycemic indices, anthropometric indices, and inflammatory markers in T2D, T1D, and IGT patients.

Aging is a multifactorial biological process involving chronic diseases that manifest from the molecular level to the systemic level. From its inception to 31 May 2022, this study searched the PubMed, Web of Science, EBSCO, and Cochrane library databases to identify relevant research from 15,983 articles. Multiple approaches have been employed to combat aging, such as dietary restriction (DR), exercise, exchanging circulating factors, gene therapy, and anti-aging drugs. Among them, anti-aging drugs are advantageous in their ease of adherence and wide prevalence. Despite a shared functional output of aging alleviation, the current anti-aging drugs target different signal pathways that frequently cross-talk with each other. At present, six important signal pathways were identified as being critical in the aging process, including pathways for the mechanistic target of rapamycin (mTOR), AMP-activated protein kinase (AMPK), nutrient signal pathway, silent information regulator factor 2-related enzyme 1 (SIRT1), regulation of telomere length and glycogen synthase kinase-3 (GSK-3), and energy metabolism. These signal pathways could be targeted by many anti-aging drugs, with the corresponding representatives of rapamycin, metformin, acarbose, nicotinamide adenine dinucleotide (NAD+), lithium, and nonsteroidal anti-inflammatory drugs (NSAIDs), respectively. This review summarized these important aging-related signal pathways and their representative targeting drugs in attempts to obtain insights into and promote the development of mechanism-based anti-aging strategies.

Abstract Background As a traditional herbal medicine, Dracaena angustifolia Roxb has been used as an anti-inflammatory agent by the Li people in Hainan, China. In preliminary phytochemical studies conducted in our lab, its fractions were found to inhibit α-glucosidase in vitro, indicating a potential for alleviating glucose dysregulation. Methods Through in vitro enzymatic assays, the abilities of the separated components to affect α-glucosidase and α-amylase were evaluated. By establishing concentration gradients and generating Lineweaver–Burk plots, the corresponding inhibition modes together with kinetic parameters were assessed. Following the evaluation of the outcomes of their combination with acarbose, computational docking and molecular dynamic simulations were carried out to analyse the interaction mechanisms and perform virtual screening against human enzymes. Results Compared with acarbose, 7 compounds, including flavonoid derivatives, amides and aromatic derivatives, with higher α-glucosidase inhibitory efficiencies were confirmed. It was found that those competitive/mixed candidates and acarbose interacted synergistically or additively on α-glucosidase. Moreover, 3 of them were able to inhibit α-amylase in mixed mode, and additive effects were observed in combination with acarbose. Through in silico docking, it was found that the active site residues as well as adjacent residues were involved in α-glucosidase and α-amylase binding, which were mainly achieved through hydrogen bonding. Among those dual-function flavonoids, Compound 9 was predicted to be a considerable inhibitor of human enzymes, as the formation of ligand–enzyme complexes was mediated by the residues responsible for substrate recognition and catalysis, the stabilities of which were reiterated by molecular dynamics simulations. Conclusion Despite their mild effects on α-amylase, considerable α-glucosidase inhibitory efficiencies and potential synergy with acarbose were exhibited by these natural candidates. Furthermore, a stable ligand, human α-glucosidase, was predicted by the performed simulations, which provided useful information for the application of Dracaena angustifolia Roxb in diabetes treatment.

BackgroundClinically, when metformin (Met) combined with acarbose (Aca) cannot achieve the ideal hypoglycemic effect, a third drug will be usually added, such as insulin (Ins) or dipeptidyl peptidase-4 inhibitor (DPP-4i) etc., but there are few reports on the effect of triple therapy on complications related to type 2 diabetes (T2DM) .ObjectiveTo explore the risk of adverse events of DPP-4i combined with Met and Aca, Ins combined with Met and Aca in the treatment of T2DM patients, in order to provide help for the choice of drugs for clinical T2DM treatment.MethodsIn the retrospective cohort study, patients diagnosed with T2DM and treated with Met+Aca+ DPP-4i or Met+Aca+Ins in Shijiazhuang Second Hospital from November 1, 2017 to August 1, 2020 were selected as the study subject. Telephone follow-up was conducted from November 20, 2017 to August 4, 2020, the follow-up wasn't terminated until a preset outcome occurred, then that was recorded. The three prespecified outcome events were non-fatal cardiovascular disease, death from all causes, and severe hypoglycemic events. The comprehensive outcome events including all-cause death, or composite non-fatal cardiovascular events, or severe hypoglycemic events. Propensity score matching (1∶1 ratio for data matching, caliper value set to 0.02) was used, and multivariate Cox proportional hazards regression model was used to analyze the risk of comprehensive outcome events in T2DM patients after drug treatment. Stratified analysis was performed on the effect of each covariate on the risk of comprehensive outcome events in patients treated with different drugs.ResultsFinally, 1 570 patients with T2DM were enrolled, including 1 089 patients who received Met+Aca+Ins treatment (Met+Aca+Ins group) and 481 patients who received Met+Aca+DPP-4i treatment (Met+Aca+DPP-4i group) . There were 434 cases in both groups after propensity score matching. Compared with the Met+Aca+Ins group, the incidences of comprehensive outcome events (6.53/100 person-per year) , non-fatal cardiovascular disease (5.03/100 person-years) , all-cause death (0.73/100 person-per year) , and severe hypoglycemic (0.73/100 person-er year) were lower in the Met+Aca+ DPP-4i group. The multivariate Cox proportional hazards regression model analysis showed that the risk of comprehensive outcome events in the Met+Aca+DPP-4i group was 67% lower than the Met+Aca+Ins group 〔HR=0.34, 95%CI (0.23, 0.50) , P7 h/d) , non-smoking, and no family history of cardiovascular disease, Met+Aca+DPP-4i treatment reduced the incidence of comprehensive outcome events in T2DM patients compared with Met+Aca+Ins treatment (P values were 0.008, 0.031, and 0.042, respectively) .ConclusionAfter failure treatment of Met and Aca in T2DM patients, the supplementation of DPP-4i was associated with a lower risk of comprehensive outcome events, cardiovascular disease, all-cause mortality, and severe hypoglycemia compared with the Ins addition, particularly in patients with adequate sleep, no smoking, and without family history of cardiovascular disease.

Pentadecanoic acid (C15:0) is an essential odd-chain saturated fatty acid with broad activities relevant to protecting cardiometabolic, immune, and liver health. C15:0 activates AMPK and inhibits mTOR, both of which are core components of the human longevity pathway. To assess the potential for C15:0 to enhance processes associated with longevity and healthspan, we used human cell-based molecular phenotyping assays to compare C15:0 with three longevity-enhancing candidates: acarbose, metformin, and rapamycin. C15:0 (n = 36 activities in 10 of 12 cell systems) and rapamycin (n = 32 activities in 12 of 12 systems) had the most clinically relevant, dose-dependent activities. At their optimal doses, C15:0 (17 µM) and rapamycin (9 µM) shared 24 activities across 10 cell systems, including anti-inflammatory (e.g., lowered MCP-1, TNFα, IL-10, IL-17A/F), antifibrotic, and anticancer activities, which are further supported by previously published in vitro and in vivo studies. Paired with prior demonstrated abilities for C15:0 to target longevity pathways, hallmarks of aging, aging rate biomarkers, and core components of type 2 diabetes, heart disease, cancer, and nonalcoholic fatty liver disease, our results support C15:0 as an essential nutrient with activities equivalent to, or surpassing, leading longevity-enhancing candidate compounds.

A theoretical analysis of the potential inhibition of human sucrase-isomaltase (SI) by flavonoids was carried out with the aim of identifying potential candidates for an alternative treatment of type 2 diabetes. Two compounds from maize silks, maysin and luteolin, were selected to be studied with the structure-based density functional theory (DFT), molecular docking (MDock), and molecular dynamics (MD) approaches. The docking score and MD simulations suggested that the compounds maysin and luteolin presented higher binding affinities in N-terminal sucrase-isomaltase (NtSI) than in C-terminal sucrase-isomaltase (CtSI). The reactivity parameters, such as chemical hardness (η) and chemical potential (µ), of the ligands, as well as of the active site amino acids of the NtSI, were calculated by the meta-GGA M06 functional in combination with the 6-31G(d) basis set. The lower value of chemical hardness calculated for the maysin molecule indicated that this might interact more easily with the active site of NtSI, in comparison with the values of the acarbose and luteolin structures. Additionally, a possible oxidative process was proposed through the quantum chemical calculations of the electronic charge transfer values (∆N) between the active site amino acids of the NtSI and the ligands. In addition, maysin displayed a higher ability to generate more oxidative damage in the NtSI active site. Our results suggest that maysin and luteolin can be used to develop novel α-glucosidase inhibitors via NtSI inhibition.

Abstract Background Rapamycin (Rapa), acarbose (ACA), and 17α-estradiol (17aE2, males only) have health benefits that increase lifespan of mice. Little is known about how these three agents alter the network of pathways downstream of insulin/IGF1 signals as well as inflammatory/stress responses. Results ACA, Rapa, and 17aE2 (in males, but not in females) oppose age-related increases in the MEK1- ERK1/2-MNK1/2 cascade, and thus reduce phosphorylation of eIF4E, a key component of cap-dependent translation. In parallel, these treatments (in both sexes) reduce age-related increases in the MEK3-p38MAPK-MK2 pathway, to decrease levels of the acute phase response proteins involved in inflammation. Conclusion Each of three drugs converges on the regulation of both the ERK1/2 signaling pathway and the p38-MAPK pathway. The changes induced by treatments in ERK1/2 signaling are seen in both sexes, but the 17aE2 effects are male-specific, consistent with the effects on lifespan. However, the inhibition of age-dependent p38MAPK pathways and acute phase responses is triggered in both sexes by all three drugs, suggesting new approaches to prevention or reversal of age-related inflammatory changes in a clinical setting independent of lifespan effects.

This study was carried out to investigate the effect of acarbose or combination of acarbose and Oleuropein (OLEU) on glycemic index and antioxidant status of male rats exposed to high fructose(40%) and 0.05% hydrogen peroxide H2O2 Thirty-two adult male rats were randomly divided into four equal groups: control group (CC); T1( HFr-H2O2) group were exposed to high fructose (40%) in drinking water and given orally 0.05% H2O2; T2: 30mg/kg of acarbose were given orally to HF-H2O2 treated rats, while combination of acarbose and Oleuropein (50mg/kg. B.W) were given orally to (HFr-H2O2) treated rats in group T3. Blood samples were taken at zero time and after two months of the experiment for measuring some parameters related to glycemic index and antioxidant status. The results declared an elevation in the glycemic index (insulin and glucose concentrations and insulin resistance (IR)) and malondialdehyde (MDA) and depression in glutathione (GSH) concentrations in T1 group at the end of experiment comparing to other treated groups. Antioxidant status and glycemic index were restored after acarbose or combination of acarbose and Oleuropein treatment characterized by significant depression of serum glucose, insulin concentrations and IR, and alleviation of oxidative stress clarified by depression of serum MDA with elevation in serum GSH concentration in groups T2 and T3. On conclusion, the current study documented the oxidative and hyperglycemic effect of fructose and H2O2 that can be ameliorating by oral administration of acarbose. Besides, combination of OLUE supplement with acarbose possessed additive effects.

Background: Excipients are used in the formulation of pharmaceutical dosage forms, but mayinteract with active pharmaceutical ingredients (APIs). Some of these interactions could alterthe physicochemical properties of the APIs which can affect the therapeutic efficacy and safety.Acarbose is an anti-diabetic drug used in this study as an API to investigate its compatibility withcommon excipients in order to development of pharmaceutical controlled release formulations. Methods: For this purpose, 15 different excipients were selected. Binary mixtures of drug witheach of the excipients (1:1 mass ratio) were prepared. Mixtures were analyzed immediately aftermixing and also after incubation at stress conditions (adding 20% water and incubated at 40°Cfor 2 months). The thermal analytical investigation like differential scanning calorimetry (DSC),Fourier transform infra-red spectroscopy (FTIR) and high-performance liquid chromatography(HPLC) were employed for physicochemical evaluations of the possible incompatibility.Photodiode-array (PDA) and mass studies were performed to ensure the peak purity of theHPLC peaks of API in stressed samples. Results: Incompatible excipients with acarbose were determined as EC (ethyl cellulose),Carbopol 934, Hydroxypropyl cellulose, PEG2000 (Polyethylene Glycol 2000), Mg Stearate, NaAlginate and Poloxamer. Conclusion: Results of this study would be used for the development of controlled releaseformulation of acarbose. It is recommended to avoid the use of incompatible excipients.

Insects rely on carbohydrates such as starch and glycogen as an energy supply for growth of larvae and for longevity. In this sense α-amylases have essential roles under extreme conditions, e.g., during nutritional or temperature stress, thereby contributing to survival of the insect. This makes them interesting targets for combating insect pests. Drosophila melanogaster α-amylase, DMA, which belongs to the glycoside hydrolase family 13, sub family 15, has been studied from an evolutionary, biochemical, and structural point of view. Our studies revealed that the DMA enzyme is active over a broad temperature and pH range, which is in agreement with the fluctuating environmental changes with which the insect is confronted. Crystal structures disclosed a new nearly fully solvated metal ion, only coordinated to the protein via Gln263. This residue is only conserved in the subgroup of D. melanogaster and may thus contribute to the enzyme adaptive response to large temperature variations. Studies of the effect of plant inhibitors and the pseudo-tetrasaccharide inhibitor acarbose on DMA activity, allowed us to underline the important role of the so-called flexible loop on activity/inhibition, but also to suggest that the inhibition modes of the wheat inhibitors WI-1 and WI-3 on DMA, are likely different.

Abstract Currently, available therapies for diabetes could not achieve normal sugar values in a high percentage of treated patients. In this research project, a series of 17 benzodioxole derivatives were evaluated as antidiabetic agents; that belong to three different groups were evaluated against lipase and alpha-amylase (α-amylase) enzymes. The results showed that 14 compounds have potent inhibitory activities against α-amylase with IC50 values below 10 µg/ml. Among these compounds, 4f was the most potent compound with an IC50 value of 1.11 µg/ml compared to the anti-glycemic agent acarbose (IC50 6.47 µg/ml). On the contrary, these compounds showed weak or negligible activities against lipase enzyme. However, compound 6a showed the best inhibitory anti-lipase activity with IC50 44.1 µg/ml. Moreover, all the synthesized compounds were undergone Molinspiration calculation, and the result showed that all compounds obeyed Lipinski’s rule of five. Molecular docking studies were performed to illustrate the binding interactions between the benzodioxole derivatives and α-amylase enzyme pocket. Related to the obtained results it was clear that the carboxylic acid, benzodioxole ring, halogen or methoxy substituted aryl are important for the anti-amylase activities. The potent inhibitory results of some of the synthesized compounds suggest that these molecules should go further in vivo evaluation. It also suggests the benzodioxole derivatives as lead compounds for developing new drug candidates.

Carbohydrate digestibility is a key determinant for elevated postprandial hyperglycemia (PPHG). Apart from dietary restrictions, one of the strategies to reduce PPHG is to limit the activity of carbohydrate digestive enzymes within the gastrointestinal tract in order to reduce monosaccharide absorption rates. The present work aimed to assess the inhibitory capabilities of digestive enzymes (e.g., α-glucosidase and α-amylase) by anthoxanthins when used independently, in combination with acarbose, or with a different anthoxanthin. Our results showed that quercetin, myricetin, and luteolin presented lower IC50 values than acarbose and inhibited α-glucosidase through mixed-type inhibition. On the other hand, acarbose when compared with these anthoxanthins, remained the most potent inhibitor of α-amylase. Combinatorial treatment (i) acarbose-quercetin and (ii) myricetin-luteolin showed synergistic activity (CI value less than 0.9) in α-glucosidase inhibition. An additive effect (CI value between 0.9 and 1.1) in α-glucosidase inhibition was observed when acarbose-myricetin, acarbose-luteolin or when a combination of two different anthoxanthins (quercetin-myricetin and quercetin-luteolin) was used. This study suggests the potential use of anthoxanthins as functional food ingredients to mitigate PPHG towards the management of T2DM.

The pseudo-tetrasaccharide acarbose, produced by Actinoplanes sp. SE50/110, is a α-glucosidase inhibitor used for treatment of type 2 diabetes patients. In industrial production of acarbose, by-products play a relevant role that complicates the purification of the product and reduce yields. Here, we report that the acarbose 4-α-glucanotransferase AcbQ modifies acarbose and the phosphorylated version acarbose 7-phosphate. Elongated acarviosyl metabolites (α-acarviosyl-(1,4)-maltooligosaccharides) with one to four additional glucose molecules were identified performing in vitro assays with acarbose or acarbose 7-phosphate and short α-1,4-glucans (maltose, maltotriose and maltotetraose). High functional similarities to the 4-α-glucanotransferase MalQ, which is essential in the maltodextrin pathway, are revealed. However, maltotriose is a preferred donor and acarbose and acarbose 7-phosphate, respectively, serve as specific acceptors for AcbQ. This study displays the specific intracellular assembly of longer acarviosyl metabolites catalyzed by AcbQ, indicating that AcbQ is directly involved in the formation of acarbose by-products of Actinoplanes sp. SE50/110.

Abstract Background African star apple (Chrysophyllum albidum) is a traditonal fruit, which is predominant in tropical regions with the fruit parts consumed by the populace and used in folklore to manage diabetes. However, the likely activity mechanism is still undetermined. The current study examined and compared the inhibitory abilities of African star apple fruit parts on selected key enzymes related to diabetes mellitus in the pancreas tissue of rat. Methods Inhibitory effect of aqueous extract (1:10 w/v) of African star apple fruit parts (pulp, cotyledon, seed coat and pulp coat) on the activities of α-amylase, α-glucosidase, as well as their starch composition, phenolic constituents, estimated glycemic index, and antioxidant properties were assessed. Results The fruit parts showed low sugar, eGI, amylose, and amylopectin contents. The analysis also showed that the fruit parts inhibited α-glucosidase and α-amylase activities and exhibited antioxidant properties. Furthermore, the fruit parts contain high concentrations of beta-amyrin acetate, eleagine, epicatechin, epigallocatechin, skatole, stigmasterol and tetrahydro − 2- methylharman as revealed by HPLC-DAD. Conclusion The fruit part low estimated glycemic indices, strong antioxidant properties, inhibition of α-amylase and α-glucosidase activities exhibited might be related to the bioactive compounds contained in the extract. This could also be a potential mechanism for the use in the prevention and management of type-2 diabetes. Nevertheless, the African star apple pulp coat displayed the highest property in comparison to other parts of the fruit.

Introduction: Gestational diabetes (GD) is one of the most common medical complications of pregnancy, associated with increased incidence of pre-eclampsia, macrosomia, and cesarean delivery. Insulin therapy is the cornerstone treatment in those individuals with inadequate glycemic control by diet alone. The burden of insulin treatment includes the need for multiple injections, intensive blood glucose monitoring, risk of hypoglycemia, and emotional distress. Alternatives to insulin treatment have been studied in the past but there is limited previous experience with acarbose. Objective: To compare acarbose to insulin therapy and evaluate the proportion of subjects requiring rescue therapy with insulin due to inadequate glycemic control; as a secondary objective, pregnancy outcomes were assessed. Materials and Methods: Pregnant patients diagnosed with GD who failed glycemic control on dietetic treatment, were randomized to receive standard insulin therapy or acarbose. If the oral drug was not tolerated or glycemic goals were not met, standard insulin therapy was initiated. Results: A total of 104 patients were randomized (acarbose n = 40). Two patients in the acarbose group and six in the insulin group withdrew their consent before any study intervention due to personal preferences. In the acarbose group, 27/38 subjects (71%) achieved and maintained glycemic targets until delivery, while 11/38 (29%) received rescue insulin therapy and discontinued the study drug. No differences were found in birth weight, gestational age at birth, or Apgar score. Three patients in the acarbose and five in the insulin group presented perinatal complications. Conclusion: In this study, acarbose was found to be a safe and effective alternative to insulin therapy. Insulin therapy and its burden were avoided in over 70% of the GD patients failing nutritional therapy. Studies with a larger sample size and long-term follow-up are needed.

Abstract Aims/Introduction This secondary analysis of the 24‐week SMART study examined the efficacy of add‐on saxagliptin or acarbose to metformin across different patient subgroups with type 2 diabetes mellitus, based on baseline characteristics. Materials and Methods Randomized patients (n = 481) were classified into subgroups based on their baseline age (9%. The effect of acarbose on postprandial glucose was also variable (+0.23 to −3.38 mmol/L). Conclusions As add‐on to metformin, both saxagliptin and acarbose reduced HbA1c regardless of baseline HbA1c, age, body mass index and renal function; however, only saxagliptin was effective at a stable glycemic control (FPG and PPG). The efficacy of acarbose on FPG and PPG was significantly attenuated in patients with higher baseline HbA1c (≥8%).

Background & Objective: Polycystic ovary syndrome (PCO) is one of the most common causes of infertility due to anovulatory in women. The use of insulin-sensitizing agents was one of the treatments for this syndrome. The main purpose of this study was to evaluate the effects of Metformin, Pioglitazone, Ripaglinide and Acarbose on histomorphological changes of polycystic ovaries. Materials & Methods: In this study, Polycystic ovaries were induced by injection of testosterone enanthate (TE) in immature female mice, for four weeks, then they had been divided into five groups; the control, Metformin, Pioglitazone, Repaglinide and Acarbose groups. Body weight, the ratio of ovary-to-animal weight, ovarian diameter, histomorphological changes of ovaries and characteristics of ovarian tissues were studied. Tukey test was used to calculate these parameters (P≤0.05). Results:TE significantly increased the percentage of cystic Follicular and decreased follicular growth compared to treatment groups. The body weight, the ratio of ovary-to-animal weight and ovarian diameter, in all groups showed a significant decrease compared to the control group (p

ObjectiveGut microbial dysbiosis is associated with high heterogeneity of polycystic ovary syndrome (PCOS); however, studies about gut microbiota targeted clinical intervention in PCOS are limited. Our study aimed to evaluate the effects of high-fiber diet or combined with acarbose on the clinical phenotypes of PCOS, focusing on the possible influence of gut microbiota in this process.MethodsTwenty-five patients with PCOS were recruited and randomly divided into two groups, W group (n = 14) received the WTP diet (a high-fiber diet composed of whole grains, traditional Chinese medicinal foods, and prebiotics), and A group (n = 11) received the WTP diet combined with acarbose. The follow-up time was 12 weeks. The sex hormonal and glycolipid metabolic parameters, inflammatory factors, brain–gut peptides, and alteration of gut microbiota were evaluated.ResultsThe PCOS clinical phenotypes, inflammatory state, and brain–gut peptides secretion were all alleviated in both groups, while the hyperandrogenism, insulin resistance, and brain–gut peptides secretion were better improved in the A group. Alpha and beta diversities were altered more significantly in the A group. Amplicon sequence variants (ASVs) were clustered into 14 co-abundant groups (CAGs) as potential functional groups that may respond to the intervention. The CAGs predominantly comprised of Bifidobacterium and Lactobacillus were more enriched, while the CAGs predominantly comprised of Bacteroides vulgatus, Alistipes, Blautia, Lachnospira, and Roseburia were more inhibited in the A group than in W group. Moreover, the CAGs enriched in the A group had a stronger negative correlation with the luteinizing hormone (LH)/follicle-stimulating hormone (FSH) ratio, testosterone, homeostasis model assessment-insulin resistance (HOMA-IR), α-1-acid glycoprotein (α-AGP), and leptin, and positive correlation with adiponectin and spexin, while the CAGs inhibited showed an opposite trend.ConclusionsHigh-fiber diet could alleviate the chronic metabolic inflammation, reproductive function, and brain–gut peptides secretion of patients with PCOS, and high-fiber diet combined with acarbose could better improve the PCOS clinical phenotypes. The remodeling of gut microbiota by our intervention may play an important role in these improvements.Clinical Trial Registrationhttp://www.chictr.org.cn/showproj.aspx?proj=4500, ChiCTR-TRC-14005075

Abstract Aims Type 2 diabetes mellitus (T2DM) is a strong risk factor for complications of coronavirus disease 2019 (COVID‐19). The effect of T2DM medications on COVID‐19 outcomes remains unclear. In a retrospective analysis of a cohort of 131 patients with T2DM hospitalized for COVID‐19 in Wuhan, we have previously found that metformin use prior to hospitalization is associated with reduced mortality. The current study aims to investigate the effects of inpatient use of T2DM medications, including metformin, acarbose, insulin and sulfonylureas, on the mortality of COVID‐19 patients with T2DM during hospitalization. Methods We continue to carry out a retrospective analysis of a cohort of 131 patients with T2DM hospitalized for COVID‐19 and treated with different combinations of diabetes medications. Results We found that patients using metformin (p = .02) and acarbose (p = .04), alone or both together (p = .03), after admission were significantly more likely to survive than those who did not use either metformin or acarbose. 37 patients continued to take metformin after admission and 35 (94.6%) survived. Among the 57 patients who used acarbose after admission, 52 survived (91.2%). A total of 20 patients used both metformin and acarbose, while 57 used neither. Of the 20 dual‐use patients, 19 (95.0%) survived. Conclusion Our analyses suggest that inpatient use of metformin and acarbose together or alone during hospitalization should be studied in randomized trials.

Abstract Background Insulin autoimmune syndrome (IAS) is a rare cause of hypoglycemia and is characterized by the presence of insulin autoantibodies. Patients with IAS usually complain of hypoglycemia without any previous insulin received. Glucocorticoids and immunosuppressants are used to treat IAS. Case presentation We report four patients with diabetes who were diagnosed with non-classical IAS and describe the treatment of these patients. Moreover, the differential diagnosis with hyperinsulinism is discussed. Conclusion High levels of insulin autoantibodies, as well as hyperinsulinemic hypoglycemia, are found in patients with diabetes mellitus and prior exogenous insulin exposure. This situation that we classified as non-classical IAS should be attached importance to.

Diabetic nephropathy (DN) exacerbates renal tissue damage and is a major cause of end-stage renal disease. Reactive oxygen species play a vital role in hyperglycemia-induced renal injury. This study examined whether the oral hypoglycemic drug acarbose (Ab) could attenuate the progression of DN in type 2 diabetes mellitus mice. In this study, 50 mg/kg body weight of Ab was administered to high-fat diet (HFD)-fed db/db mice. Their body weight was recorded every week, and the serum glucose concentration was monitored every 2 weeks. Following their euthanasia, the kidneys of mice were analyzed through hematoxylin and eosin, periodic acid Schiff, Masson’s trichrome, and immunohistochemistry (IHC) staining. The results revealed that Ab stabilized the plasma glucose and indirectly improved the insulin sensitivity and renal functional biomarkers in diabetic mice. In addition, diabetes-induced glomerular hypertrophy, the saccharide accumulation, and formation of collagen fiber were reduced in diabetic mice receiving Ab. Although the dosages of Ab cannot decrease the blood sugar in db/db mice, our results indicate that Ab alleviates glucolipotoxicity-induced DN by inhibiting kidney fibrosis-related proteins through the Ras/ERK pathway.

Dan Mo,1 Songfang Liu,1 Hong Ma,1 Haoming Tian,1 Honglin Yu,2 Xiangxun Zhang,2 Nanwei Tong,2 Jiayu Liao,3,4 Yan Ren11Division of Endocrinology and Metabolism, West China Hospital of Sichuan University, Chengdu 610041, People’s Republic of China; 2Laboratory of Endocrinology and Metabolism, West China Hospital of Sichuan University, Chengdu 610041, People’s Republic of China; 3Department of Bioengineering, Bourns College of Engineering, University of California, Riverside, CA 92521, USA; 4West China Hospital-California Multiomics Research Center, Key Laboratory of Transplant Engineering and Immunology, National Health Commission of PRC, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of ChinaObjective: This study aimed to investigate the changes in inflammatory biomarkers between newly diagnosed type 2 diabetes (T2DM) patients under one-year acarbose treatments and those under metformin managements.Methods: Seventy patients with newly diagnosed T2DM and 32 volunteers with normal glucose tolerance (normal controls, NCs) were enrolled. Seventy patients with T2DM were randomly assigned to two subgroups and treated with acarbose (n=34) or metformin (n=36) for 1 year. Blood glucose, insulin, glycosylated hemoglobin (A1C), triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and inflammatory biomarker levels (interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-2 (IL-2), and ferritin) were detected at 0, 6 and 12 months.Results: After adjusting for sex, the waist-to-hip ratio (WHR) and body mass index (BMI), higher fasting plasma glucose (FPG), standard meal test 1/2 hr and 2 hr glucose, TG, TC, LDL-C, IL-6, TNF-α, IL-2 and ferritin levels were observed in T2DM group than in NCs (P

Abstract Background Postprandial hypotension (PPH) occurs frequently in the elderly and patients with type 2 diabetes, and lacks a satisfactory treatment. Gastric distension and the α-glucosidase inhibitor, acarbose, may attenuate the postprandial fall in blood pressure (BP) by complementary mechanisms. We aimed to determine whether gastric distension and acarbose have additive effects to attenuate the fall in BP induced by oral sucrose. Methods Ten healthy older adults (74.0 ± 1.4 yr) had measurements of BP and superior mesenteric artery (SMA) blood flow for 120 min after receiving either (i) the ‘study drink’ of 100 g sucrose in 300 mL of water (control treatment), (ii) a 300 mL water ‘preload’ 15 min before the ‘study drink’ (distension treatment), (iii) 100 mg acarbose dissolved in the ‘study drink’ (acarbose treatment) or (iv) a 300 ml water ‘preload’ 15 min before 100 mg acarbose dissolved in the ‘study drink’ (acarbose and distension treatment). Results The area under the curve (AUC)0–120min for mean arterial pressure (MAP) was greater (P = 0.005) and the maximum fall in MAP was less (P = 0.006) during treatments with acarbose. Gastric distension did not affect the MAP-AUC0–120min response to acarbose (P = 0.44) and there was no effect of gastric distension alone (P = 0.68). Both acarbose treatments attenuated the rise in SMA blood flow (P = 0.003), whereas gastric distension had no effect. Conclusions In healthy older adults, acarbose (100 mg), but not gastric distension, attenuates the fall in BP and rise in SMA blood flow after oral sucrose. The observations support the use of acarbose, but not gastric distension, to attenuate a postprandial fall in BP. Trial registration The study was retrospectively registered at (ACTRN12618000152224) on February 02nd 2018.

BackgroundWe evaluated the efficacy and safety of acarbose add-on therapy in Korean patients with type 2 diabetes mellitus (T2DM) who are inadequately controlled with metformin and sitagliptin.MethodsA total of 165 subjects were randomized to metformin and sitagliptin (Met+Sita, n=65), metformin, sitagliptin, and acarbose (Met+Sita+Acarb, n=66) and sitagliptin and acarbose (Sita+Acarb, exploratory assessment, n=34) therapy in five institutions in Korea. After 16 weeks of acarbose add-on or metformin-switch therapy, a triple combination therapy was maintained from week 16 to 24.ResultsThe add-on of acarbose (Met+Sita+Acarb group) demonstrated a 0.44%±0.08% (P

Abstract Background Actinoplanes sp. SE50/110 is a natural producer of acarbose. It has been extensively studied in the last decades, which has led to the comprehensive analysis of the whole genome, transcriptome and proteome. First genetic and microbial techniques have been successfully established allowing targeted genome editing by CRISPR/Cas9 and conjugal transfer. Still, a suitable system for the overexpression of singular genes does not exist for Actinoplanes sp. SE50/110. Here, we discuss, test and analyze different strategies by the example of the acarbose biosynthesis gene acbC. Results The integrative φC31-based vector pSET152 was chosen for the development of an expression system, as for the replicative pSG5-based vector pKC1139 unwanted vector integration by homologous recombination was observed. Since simple gene duplication by pSET152 integration under control of native promoters appeared to be insufficient for overexpression, a promoter screening experiment was carried out. We analyzed promoter strengths of five native and seven heterologous promoters using transcriptional fusion with the gusA gene and glucuronidase assays as well as reverse transcription quantitative PCR (RT-qPCR). Additionally, we mapped transcription starts and identified the promoter sequence motifs by 5′-RNAseq experiments. Promoters with medium to strong expression were included into the pSET152-system, leading to an overexpression of the acbC gene. AcbC catalyzes the first step of acarbose biosynthesis and connects primary to secondary metabolism. By overexpression, the acarbose formation was not enhanced, but slightly reduced in case of strongest overexpression. We assume either disturbance of substrate channeling or a negative feed-back inhibition by one of the intermediates, which accumulates in the acbC-overexpression mutant. According to LC–MS-analysis, we conclude, that this intermediate is valienol-7P. This points to a bottleneck in later steps of acarbose biosynthesis. Conclusion Development of an overexpression system for Actinoplanes sp. SE50/110 is an important step for future metabolic engineering. This system will help altering transcript amounts of singular genes, that can be used to unclench metabolic bottlenecks and to redirect metabolic resources. Furthermore, an essential tool is provided, that can be transferred to other subspecies of Actinoplanes and industrially relevant derivatives.

Objectives: The objective of this study was to evaluate antidiabetic activity of Chaturmukha rasa based on streptozotocin induced diabetes model, alpha amylase inhibitory activity, alpha Glucosidase inhibitory activity and inhibition of sucrase. Methods: Chaturmukha rasa was prepared as per Ayurvedic formulary. Antidiabetic activity was measured in experimentally streptozotocin induced rats. The dose was taken as 45 mg/kg, i.p. The antidiabetic activity of Chaturmukha rasa was compared Triphala Kwatha, a marketed formulation. Further In vitro ά- Amylase Inhibitory Assay, In vitro salivary amylase Inhibitory Assay, In vitro α-Glucosidase Inhibitory Assay and In vitro Sucrase Inhibitory Assay was performed with respect to Chaturmukha rasa . The IC50 value was calculated for all the above activity. Results: Streptozotocin with Acarbose showed significant decrease in blood glucose level whereas streptozotocin with Triphala kwatha showed more decrease in blood glucose level than Streptozotocin with Acarbose. The combination of Streptozotocin + Triphala kwatha + Chaturmukha rasa showed a significant decrease in blood glucose level on 21st day. In vitro ά- Amylase Inhibitory Assay the Chaturmukha rasa showed IC50 value 495.94 μl when compared with Acarbose 427.33 μl, respectively. In the α-Glucosidase Inhibitory Assay Chaturmukha rasa showed IC50 value 70.93 μl when compared with Acarbose 102.28 μl, respectively. In vitro Sucrase Inhibitory Assay Chaturmukha rasa showed IC50 value 415.4 μl when compared with Acarbose 371.43 μl, respectively. Conclusion: This study supports that Chaturmukha rasa may inhibit diabetes by inhibition of salivary amylase or alpha Glucosidase or sucrase. This may be the mechanism by which Chaturmukha rasa inhibits diabetes. Further this study supports the usage of Chatur mukha rasa for the management of diabetes.

Abstract Background Annona muricata has been used in folklore in the management of diabetes. A major strategy in decreasing postprandial hyperglycemia in diabetes involves the inhibition of carbohydrate-hydrolyzing enzymes - α-amylase and α-glucosidase. Thus, this study evaluated the in vivo and in vitro inhibitory potentials of the different parts (fruit-pulp, leaf, stem-bark and root-bark) of Annona muricata. Methods A total of 120 Wistar rats were treated with methanol extracts for 28 days after which blood and tissue samples were collected for α-amylase assay. In vitro inhibitory properties of methanol, ethyl acetate and dichloromethane extracts of the various parts of the plant on α-amylase and α-glucosidase activities were performed using standard procedures. The mode and mechanism of interactions between the enzymes and extracts (and isolated acetogenin) were determined using various kinetic interpolations and in silico experiments. Result The fruit-pulp and root-bark methanolic extracts better -inhibited plasma and tissue amylase in vivo. The in vitro studies revealed that the stem-bark methanolic, fruit-pulp ethyl acetate, and leaf dichloromethane extracts, better inhibited α-amylase activity compared with the standard acarbose. Also, the leaf methanol, fruit-pulp ethyl acetate, and root-bark dichloromethane extract better inhibited α-glucosidase activity. These observations were corroborated with their higher Bmax and Vmax and lower Kd values. All the extracts exhibited an “uncompetitive” type of inhibition pattern. Also, the isolated acetogenin (15-acetyl guanacone) from the fruit-pulp showed a better binding affinity compared to the standard drug, Metformin. Conclusion Better natural remedy for diabetics can be obtained from Annona muricata with minimal or no adverse side effects.