Alpha-glucosidase Inhibitor Research Articles

Quantification of the Anti-diabetic Effect of Allium cepa.

Allium cepa, or onion, boosts numerous health benefits, including anti-diabetic effects. Its rich array of antioxidants and sulfur compounds not only aids heart health by lowering cholesterol and blood pressure but also exhibits anti-inflammatory properties. Onion's antibacterial and antiviral properties help combat infections, while its compounds like quercetin show promise in cancer prevention. Additionally, Allium cepa supports respiratory health by relieving coughs and colds and aids digestion with its prebiotic properties. Incorporating onions into a balanced diet can enhance overall well-being, including managing blood sugar levels in individuals with diabetes. This study aims to determine if the ethanolic extract from the dried peel of Allium cepa holds potential as an anti-diabetic agent, with a focus on its ability to manage diabetes and reduce blood sugar levels. To prepare the ethanolic extract from dried onion peel, the peel was finely ground and soaked in ethanol. The mixture was then agitated and filtered to separate the liquid extract. Finally, the filtrate was concentrated using methods such as rotary evaporation or vacuum distillation to obtain a concentrated extract for further analysis like alpha-amylase inhibition assay and alpha-glucosidase inhibition assay. The ethanolic extracts derived from dried onion peel demonstrate inhibition of alpha-glucosidase, leading to reduced blood glucose levels. Additionally, this inhibition prompts an increase in insulin production. The study underscores that the efficacy of the ethanolic extract of dried onion peel increases with concentration. It highlights the presence of beneficial compounds like total phenolics, flavonoids, quercetin, and its derivatives in onion peel, known for their therapeutic roles in cardiovascular health, weight management, diabetes control, cancer prevention, and antimicrobial activity. These findings affirm the hypoglycemic and anti-diabetic properties of Allium cepa's ethanolic leaf extract.

Bioprospection of Potential Antidiabetic, Antioxidant, and Antimicrobial Compounds from “Secang” [Biancaea sappan (L.) Tod.

One plant in the Sulawesi region that is utilized in traditional medicine is “secang,” which is the local name of the Biancaea sappan (L.) Tod. The use of its wood is in the form of decoction to be drunk every day because it has properties for maintaining the body's immune system. Secang tree – as a valuable medicinal plant – is also known for its antioxidant, anti-inflammatory, and anticancer properties. Analysis has revealed that sappan wood harbors a variety of bioactive compounds – including brazilin, brazilein, sappan chalcone, and protosappanin. However, its use is only limited to the use of the wood. Hence, this research aims to analyze the bioprospection of the secang plant using parts of the wood, fruit, and leaves in terms of antimicrobial, antioxidant, and antidiabetic activity. The three parts of secang were extracted using ethanol solvent and then made into five concentrations – namely, 20, 40, 60, 80, and 100%. The antimicrobial activity test used five test bacteria – namely, Listeria monocytogenes, Pasteurella pestis, Escherichia coli, Salmonella thypi, and Staphylococcus aureus – using the well method. Next, the DPPH antioxidant activity test was contrasted with the vitamin C control. The antidiabetic activity test used an alpha-glucosidase inhibitor and compared with the acarbose control. The results obtained show that all samples can inhibit the growth of the five test bacteria from a concentration of 20–100%. Extracts of secang leaves and fruit have better antimicrobial and antioxidant abilities than secang stems. In the antioxidant test, the ability of the three extracts to bind free radicals increased as the concentration increased. Meanwhile, the antidiabetic test showed that the highest results were obtained from 40% secang leaf extract. Secang has shown promising medicinal properties and is an important resource in traditional medicine, hence warranting the exploration of its potential role as an important source of bioactive compounds for drug development.

Functional assessments of Psidium guajava L. and Morus alba L. leaf extracts on postprandial glucose control.

Diabetes is a leading cause of death, according to statistics published by the Department of Health, Executive Yuan of Taiwan. In modern medicine, diabetes can be controlled using various medications; however, some drugs often have undesirable side effects. It therefore became a goal to find plant-based material that can reduce glucose concentration in the blood while reducing the incidence of complications and not causing side effects. Alpha-glucosidase inhibitors (AGIs) are effective glucose-lowering medicines and are enzymes essential to carbohydrate digestion. Inhibition of α-glucosidase leads to a delayed and reduced rise in postprandial blood glucose levels. This study evaluates the inhibitory effect of mixed extracts of Psidium guajava L. and Morus alba L. leaves on α-glucosidase activity and postprandial hyperglycemia in normal and diabetic rats. The inhibition of α-glucosidase activity was assayed invitro. Half maximal inhibitory concentration (IC50) values of Psidium guajava L. and Morus alba L. were 2.25 and 0.1 mg/mL, respectively. The IC50 value of a commercial anti-hyperglycemic agent (Glucobay) is 6.41 mg/mL. The IC50 value of a mixture of extracts of Psidium guajava L. and Morus alba L. was 0.07 mg/mL. In cytotoxicity tests, survival percentages and shape did not significantly affect the murine embryonic liver cell line (BNL CL.2) when treated with varying concentrations of mixture extracts for varying periods of time. In summary, Psidium guajava L. and Morus alba L. showed positive anti-diabetes activity and suggested promising potential for alternative functional foods for diabetes mellitus (DM) patients.

A Characterization of Biological Activities and Bioactive Phenolics from the Non-Volatile Fraction of the Edible and Medicinal Halophyte Sea Fennel (Crithmum maritimum L.).

Although the biochemical composition and biological properties of the volatile fraction of the halophyte sea fennel (Crithmum maritimum L.) have been largely described, little is known about its polar constituents and bioactivities. Here, a hydromethanolic extract of Crithmum maritimum (L.) leaves was fractionated, and the fractions were evaluated in vitro for antioxidant (using DPPH, ABTS, and FRAP bioassays), anti-inflammatory (inhibition of NO production in RAW 264.7 macrophages), antidiabetic (alpha-glucosidase inhibition), neuroprotective (inhibition of acetylcholinesterase), and skin-protective (tyrosinase and melanogenesis inhibitions) activities. Polar fractions of the extract were rich in phenolics and, correlatively, displayed a strong antioxidant power. Moreover, fractions eluted with MeOH20 and MeOH80 exhibited a marked inhibition of alpha-glucosidase (IC50 = 0.02 and 0.04 mg/mL, respectively), MeOH60 fractions showed a strong capacity to reduce NO production in macrophages (IC50 = 6.4 μg/mL), and MeOH80 and MeOH100 fractions had strong anti-tyrosinase activities (630 mgKAE/gDW). NMR analyses revealed the predominance of chlorogenic acid in MeOH20 fractions, 3,5-dicaffeoylquinic acid in MeOH40 fractions, and 3-O-rutinoside, 3-O-glucoside, 3-O-galactoside, and 3-O-robinobioside derivatives of quercetin in MeOH60 fractions. These compounds likely account for the strong antidiabetic, antioxidant, and anti-inflammatory properties of sea-fennel polar extract, respectively. Overall, our results make sea fennel a valuable source of medicinal or nutraceutical agents to prevent diabetes, inflammation processes, and oxidative damage.

Real-World Assessment of Personalized Approach With Voglibose Fixed-Dose Combination in Type 2 Diabetes Mellitus.

Post-prandial hyperglycemia (PPHG) remains a complex aspect in the management of type 2 diabetes mellitus (T2DM) in the Indian population due to uncertainty in the optimal utilization of alpha-glucosidase inhibitors (AGIs) either as standalone therapy or in combination, whether initiated initially or as a sequential therapy. This was a post-approval, observational, multicentric clinical study conducted at 50 centers according to principles of the International Council for Harmonisation of Technical Requirements of Pharmaceuticals for Human Use Guideline for Good Clinical Practice (ICH-GCP) and Declaration of Helsinki and local ethics approval. Descriptive and analytical statistics were applied for conclusion and categorical variables using SPSS version 29.0.1.0 (171) (Armonk, NY: IBM Corp.). Protocol analyses of 515 cases revealed baseline demographics as follows: age 57.35±10.04 years, weight 72.86±10.92 kg, and BMI 28.33±6.07 kg/m2. Comorbidities included hypertension (N=169, 32.82%), thyroid disorders (N=99, 19.22%), and heart failure (N=92, 17.86%). Concomitant oral antidiabetics (OADs) prescribed as DPP4i (9.50%), SGLT2i (19.20%), and DPP4i+SGLT2i (7.20%). Study drug reduced glycosylated hemoglobin (HbA1c) by 13.77% (1.25% mean change, p<0.01), fasting blood glucose (FBG) by 23.69% (44.61 mg/dL mean change, p<0.01), post-prandial blood glucose (PPBG) by 24.57% (70.46 mg/dL mean change, p<0.01), and body weight by 4.43% (3.21 kg mean change, p<0.01) over 12 weeks. A total of 161 patients accomplished targeted PPBG of <180 mg/dL (119.13 mg/dL mean change, p<0.01). Regression analysis considering PPBG and HbA1c ≤7.5% showed a weak correlation between them (R-value=0.13, R-squared value=0.02), whereas between PPBG and HbA1c ≤9% yielded moderate positive correlation (R-value=0.53, R-squared value=0.28). There were no adverse events reported or analyzed during the observation period. Voglibose fixed-dose combination (FDC) demonstrates significant effectiveness at the initial dosage when started early in the management of T2DM and high PPBG levels. Moreover, it exhibits good tolerability, thereby contributing to higher compliance among Indian patients who consume a high-carbohydrate diet.

Integrative computational approaches for designing novel alpha-glucosidase inhibitors based on curculigoside A derivatives: Virtual screening, molecular docking, and molecular dynamics

Introduction: Over 422 million people worldwide suffer from diabetes, causing 1.5 million fatalities annually. The existing medications have shortcomings, including poor glucose control and adverse effects. The present study aimed to create possible alpha-glucosidase inhibitors utilizing a curculigoside A derivative ligand-based model. Methods: A pharmacophore model was constructed utilizing the structure information of curculigoside A derivatives and PharmaGist. Subsequently, virtual screening, molecular docking, and molecular dynamics were employed to simulate the hits. Results: From six training sets, eleven pharmacophore models were developed; the model with the highest score (18.0435) was chosen for further analysis. Using the verified pharmacophore model, 270 547 chemicals from the ZINC natural product database were subjected to virtual screening. Subsequently, molecular docking was performed on the top 1000 hits with AutoDock Wizard from PyRx. This analysis unveiled 434 hits with better binding energies than acarbose, the native ligand. Subsequently, second optimal docking configurations were evaluated with AutoDock 2.4; this process yielded the discovery of three prospective inhibitors (ZINC000150350051, ZINC000008382292, and ZINC000085595291) characterized by the most advantageous binding energies. To evaluate the stability and dynamics of these ligand-receptor complexes, Gromacs 2022 molecular dynamics simulations were executed for one hundred nanoseconds. Out of the three hits, ZINC000085595291 (Hit03) exhibited good energy components and interaction stability constantly during the simulation. Conclusion: The integrated computational strategy identified promising alpha-glucosidase inhibitors in curculigoside A compounds, highlighting the potential of ZINC000085595291 (Hit03) as a potential diabetes therapeutic agent.

The Role of Medicinal Plants in the Treatment and Management of Type 2 Diabetes

Abstract: Diabetes is a severe metabolic disorder characterized by hyperglycemia. Hyperglycemia is a hallmark of diabetes, a life-threatening metabolic condition. There are a variety of oral hypoglycemic drugs in the market for the treatment of diabetes mellitus, including biguanides, sulphonylurea, and alpha-glucosidase inhibitors. On the other hand, these conventional methods of treating diabetes are costly and associated with a variety of long-term issues, whereas medicinal herbs used to treat diabetes are inexpensive and have no harmful consequences or side effects. Because of the existence of different therapeutically relevant active phytochemicals such as tannins, flavonoids, alkaloids, and other compounds in medicinal plants, they can be used in treating diabetes. Various medicinal plants used to treat diabetes mellitus and their bioactive components are discussed in this review article. In this review, the prospects of these medicinal plants, as well as the challenges associated with their use, are discussed.

Alpha-amylase and Alpha-glucosidase Inhibitory Activities of Philippine Indigenous Medicinal Plants

In the Philippines, medicinal plants still provide the first line of therapeutic remedies and their reported efficacy in traditional treatments provides an opportunity for drug discovery and development. The study aimed to evaluate in vitro commonly used Philippine medicinal plants for their alpha-amylase and alpha-glucosidase inhibitory activities as potential sources of antidiabetic agents. The study emphasised the inhibitory activities of 54 medicinal plants against α-amylase and α-glucosidase enzymes. The findings revealed 7 medicinal plants with the highest alpha-glucosidase inhibitory activity of ≥ 50% and 3 with alpha-amylase inhibitory activity of ≥ 20%. Ethyl acetate extract of Cycas sp. exhibited the highest α-glucosidase inhibitory activity with 83.87% ± 1.52 followed by the aqueous extract of cf. Calyptranthera sp. With 82.07% ± 0.14 with Acarbose as the reference standard (99.71% ± 0.63) at 10µg/mL (w/v) concentration. For the alpha-amylase inhibitory assay, the highest bioactivity was observed in ethyl acetate extract of Curcuma longa L. (39.44% ± 1.56) with Acarbose as the reference standard (51.59% ± 0.98) at 10µg/mL (w/v) concentration. These findings suggest the potential of the above-mentioned plants as sources of alpha-amylase and alpha-glucosidase inhibitors that may be used as antidiabetic agents.

Isolation, Characterization and Structure Elucidation of Antidiabetic Compound “2-({4-oxo-1H,2H,3H,4H,4aH-cyclopenta[b]pyridine-2-yl} methyl)-1H, 2H, 3H, 4H, 4aH-Cyclopenta[b]Pyridine-4-one” from the barks of Parkia timoriana (DC.) Merr.

Parkia timoriana (D.C.) Merr is a medicinal plant with long-known usage as a traditional medicine. This plant’s bark and pods have been used in medicine and food supplements. P. timoriana bark was extracted with ethyl acetate and purified using silica gel column chromatography. A pure compound, 2-({4-oxo-1H, 2H, 3H, 4H, 4aH-cyclopenta[b]pyridine-2-yl}methyl)-1H, 2H, 3H, 4H, 4Ah cyclopenta[b]pyridine-4-one (BCPP) was isolated and spectroscopic analysis was performed to determine its chemical structure. Antidiabetic studies were conducted using Bis-Cyclopenta-Pyridin (BCPP) for its enzymatic inhibition. In vitro cell culture assays, gene expression studies and in silico docking studies were done to ascertain the antidiabetic activity. P. timoriana bark was extracted using the solvents based on its polarity: hexane, ethyl acetate and methanol. At a 125 μg/ml concentration, BCPP demonstrated 75% inhibition of alpha-amylase, 74% inhibition of alpha-glucosidase and a 59% increase in glucose uptake by yeast cells (3.3 ± 0.0058 at 125 μg/ml). BCPP increased the expression of the PPARγ gene in 3T3-L1 cells by 0.23-fold. There is an increase in fold change of PPAR- γ at 25 μg/ml – 0.11-fold; at 50 μg /ml – 0.25-fold; at 75 μg /ml – 0.37-fold; 100 μg /ml – 0.73-fold; and at 125 μg/ml, there is an upregulation of 1.10-fold in 3T3-L1 cells. In silico docking studies confirmed the alpha-amylase and alpha-glucosidase inhibitory activities of BCPP. This study suggests the application of BCPP as a potential antidiabetic agent that can be used in drug design and pharmaceutics.

Enhanced Enzyme Inhibitory Effects of the Nanohybrid Eggplant Extract: An Unusual Pharmaceutical Form for Medicinal Plant

Objective: Recently, biosynthesis/synthesis of nanoflowers has become very attractive for chemical and pharmaceutical sciences, and enhanced enzyme activities. Various plant extracts and their active compounds are effectively used as organic component for novel nanoflowers synthesis. Solanum melongena L., commonly known as eggplant in English, a vegetable and medicinal plant belongs to Solanaceae family has several advantages in materials synthesis due to cheap and obtained easily. The aim of this study is to compare the enzyme ((alpha-glucosidase (AGase), alpha-amylase (AAase), tyrosinase (Tyr), acetylcholinesterase (AChE) and butyryl cholinesterase (BChE)) inhibitory effects of the eggplant’ calyx extract and its Solanum-inorganic hybrid nanoflower (Sm-ihNFs) via in vitro experimental methods. &#x0D; Methods: The hybrid nanoflower was formed (NF) with organic molecules, eggplant extract (Sm), and inorganic compounds, copper to enhance the catalytic activities. The inhibition capacities of the eggplant extract, and its hybrid nanoflower were evaluated on selected enzymes (AGase, AAase, Tyr, AChE and BChE) which play significant roles physiologically by in vitro tests in this study. &#x0D; Results: According to inhibition percentages and IC50 values, Sm-ihNFs showed higher inhibitory activities on enzymes other than ache than the plain crude plant extract. Among all the enzymes that were studied, Sm-ihNFs demonstrated significantly higher alpha-glucosidase and alpha-amylase inhibition activities compared to acarbose. And when compared to galanthamine hydrobromide Sm-ihNFs showed higher enzyme inhibition and significant IC50 value. &#x0D; Conclusion: It was thought that Sm-ihNFs prepared from eggplant extract may have promising potential for antidiabetic drug formulations in the future. The hybrid nanoflowers will be promising and guide for the future work in terms of pharmaceutical and cosmeceutical industry.

Synthesis of Competitive and Noncompetitive Inhibitors of Alpha-Glucosidase and Anticancer Agents.

Imidazoles and phenylthiazoles are an important class of heterocycles that demonstrate a wide range of biological activities against various types of cancers, diabetes mellitus and pathogenic microorganisms. The heterocyclic structure having oxothiazolidine moiety is an important scaffold present in various drugs, with potential for enzyme inhibition. In an effort to discover new heterocyclic compounds, we synthesized 26 new 4,5-diphenyl-1H-imidazole, phenylthiazole, and oxothiazolidine heterocyclic analogues that demonstrated potent α-glucosidase inhibition and anticancer activities. Majority of the compounds noncompetitively inhibited α-glucosidase except for two that exhibited competitive inhibition of the enzyme. Docking results suggested that the noncompetitive inhibitors bind to an apparent allosteric site on the enzyme located in the vicinity of the active site. Additionally, the analogues also exhibited significant activity against various types of cancers including non-small lung cancer. Since tubulin protein plays an important role in the pathogenesis of non-small lung cancer, molecular docking with one of the target compounds provided important clues to its binding mode. The current work on imidazoles and phenylthiazole derivatives bears importance for designing of new antidiabetic and anticancer drugs.

Unlocking potential diabetes therapeutics: Insights into alpha-glucosidase inhibition

Diabetes mellitus (DM) stands as a significant global health challenge, ranking third among causes of mortality worldwide. Despite extensive endeavors, effective treatments for diabetes remain elusive. Alpha-glucosidase, a pivotal enzyme in glycoprotein metabolism regulation, emerges as a promising therapeutic target for mitigating postprandial hyperglycemia, a hallmark of diabetes. In this study, we employed advanced computational methodologies to identify inhibitors of lysosomal α-glucosidase. Leveraging pharmacophore-based virtual screening of a vast library of drug-like molecules, we unearthed 161 potential inhibitors capable of binding within the enzyme's active pocket. Subsequent molecular docking simulations yielded five lead molecules exhibiting robust binding affinities and favorable interaction profiles with critical catalytic residues. Further analysis through molecular dynamics simulations provided crucial insights into the stability and conformational dynamics of the inhibitor-enzyme complexes. Notably, certain residues emerged as pivotal for the retention of inhibitors within the active site. Our findings underscore the potential of LIG1-LIG5 as promising inhibitors against lysosomal α-glucosidase, presenting novel avenues for the development of effective diabetes therapeutics. This research enriches our understanding of the molecular underpinnings of diabetes treatment, facilitating targeted drug development strategies in the quest for improved patient outcomes.

Benzothiazole based sulfonamide scaffolds as active inhibitors of alpha-Amylase and alpha-glucosidase; synthesis, structure confirmation, In Silico molecular docking and ADME analysis

In the current research study, benzothiazole based sulfonamide scaffolds were designed and synthesized having promising efficacy as dual inhibitors of alpha-Amylase & alpha-Glucosidase with a purpose to cure one of the chronic diseases, Diabetes Mellitus. Synthetic confirmation of all the derivatives was accomplished through different spectroscopic techniques, 13C NMR, 1H NMR and HREI-MS. For the evaluation of drug potency of the newly synthesized ligands, biological activity was conducted using the standard drug acarbose (IC50 = 5.40 ± 0.30 µM for α-amylase and 5.70 ± 0.50 µM for α-glucosidase). A wide span of inhibitory potentials were shown by the analogs of current series covering a range of IC50 = 20.70 ± 0.20 µM and 2.10 ± 0.70 µM for α-amylase and 21.40 ± 0.20 µM and 2.40 ± 0.10 µM for α-glucosidase. Potency of the analogs is mainly dependent on the attached substituent moieties, their nature, number and position on the phenyl ring. Based on these protocols, analog-4 with an IC50 = 2.10 ± 0.70 µM for α-amylase and 2.40 ± 0.10 µM for α-glucosidase was found to be the top ranking scaffold with excellent inhibition against the target enzymes in the series. In analog-4, the trifluoromethyl moiety at the para position of the ring, capable to interact through hydrogen bond with active site of the enzyme, is the contributing factor to the efficacy of the analog. Binding insight of the protein-ligand interaction of all the potent analogs was gained through molecular docking study. Furthermore, the drug likeness attributes of the potent derivatives were explored through ADME analysis.

SCREENING OF ALPHA-GLUCOSIDASE INHIBITORY ACTIVITY FROM TWO PRODUCTS OF THE CAPSULIZED JAMU CINNAMON EXTRACT (CINNMOMUM BURMANNII)

&#x0D; Cinnamon (Cinnamomim burmannii) found in the markets, comes in many forms with one of them being a type of jamu which the cinnamon dust is capsulized. The capsulized jamu is claimed to be beneficial on treating diabetes melitus. The effects of antidiabetics on some products of the capsulized jamu is suspected to work through the alpha-glucosidase enzyme inhibition activites contained in them. The aim of this research is to verify the activities of some capsulized cinnamon dust extract in jamu (C. burmannii) found in the markets on its effect to inhibit alpha-glucosidase activity and to know its IC50 value. Experiment is done by using analytic experiments using two different products (product A and product B) and by using acarbose 50mg as a positive control factor. Enzyme activity are then calculated using UV-Vis spectrophotometer on a 410 nm wavelength. The result of this research is alpha-glucosidase enzyme inhibition activity found in product A and B are 155,104 µg/mL and 6.795,893 µg/mL, wherease the acarbose as a positive control are 47,466 µg/mL. The conclusion of this research is alpha-glucosidase enzyme inhibition activity found on the products as IC50 shows that product A has a better alpha-glucosidase enzyme inhibition activity than product B. However, when compared to the acarbose as the positive control, product A has a lesser alpha glucosidase enzyme inhibition activity.&#x0D; Kata kunci : Cinnamomum burmannii, diabetes mellitus, alpha glucosidase inhibition.&#x0D; &#x0D;

Antioxidant Activity, Alpha-Glucosidase Inhibitors Ethanol Extract of Vernonia amygdalina Del. and Nutraceutical Potential

Vernonia amygdalina Del is a shrub that is very well known in African continent and usually grows in tropical climates, including in Indonesia. In this research, we tested the The ethanol extract's anti-oxidant properties of Vernonia amygdalina Del leaves and the inhibitory activity of alpha-glucosidase. Vernonia amygdalina Del leaves ethanol extract was obtained using Ultrasound Assisted Extraction (UAE) method by variation of time and amplitude. Antioxidant activity of Vernonia amygdalina Del leaves ethanol extract was tested using DPPH and CUPRAC methods. Based on the research, IC50 of Vernonia amygdalina Del leaves ethanol extract was obtained by DPPH method respectively that is A (111.72±0.10)mg/L, B (154.08±0.02)mg/L, C (191.22±0.04) mg/L and D (190.99±0.08) mg/L. While IC50 of the Vernonia amygdalina Del leaves ethanol extract by CUPRAC method are A (26.71±4.85), B (78.57±5.04), C (43.50±4.62) and D (76.60±1.79). In this study, an alpha-glucosidase inhibition test was carried out where the greatest inhibitory activity was obtained by the Vernonia amygdalina Del leaves ethanol extract with variation A (30 minute extraction time with a 0.60 m amplitude) and IC50 is (0.69±0.13)mg/L. Based on this study, it can be concluded that Vernonia amygdalina Del has potential as an antidiabetic and nutraceutical drug.

Integrative Approach for Designing Novel Triazole Derivatives as α-Glucosidase Inhibitors: QSAR, Molecular Docking, ADMET, and Molecular Dynamics Investigations.

In response to the increasing prevalence of diabetes mellitus and the limitations associated with the current treatments, there is a growing need to develop novel medications for this disease. This study is focused on creating new compounds that exhibit a strong inhibition of alpha-glucosidase, which is a pivotal enzyme in diabetes control. A set of 33 triazole derivatives underwent an extensive QSAR analysis, aiming to identify the key factors influencing their inhibitory activity against α-glucosidase. Using the multiple linear regression (MLR) model, seven promising compounds were designed as potential drugs. Molecular docking and dynamics simulations were employed to shed light on the mode of interaction between the ligands and the target, and the stability of the obtained complexes. Furthermore, the pharmacokinetic properties of the designed compounds were assessed to predict their behavior in the human body. The binding free energy was also calculated using MMGBSA method and revealed favorable thermodynamic properties. The results highlighted three novel compounds with high biological activity, strong binding affinity to the target enzyme, and suitability for oral administration. These results offer interesting prospects for the development of effective and well-tolerated medications against diabetes mellitus.

Associations Between Thiazolidinediones Use and Incidence of Rheumatoid Arthritis: A Retrospective Population-Based Cohort Study.

Preclinical studies suggest that thiazolidinediones (TZDs) may have a protective effect on rheumatoid arthritis (RA), but evidence from population-based studies is scarce. This study aimed to assess the association between use of TZDs and incidence of RA in a retrospective cohort of patients with type 2 diabetes mellitus (T2DM). A retrospective cohort of patients with T2DM who were new users of TZDs or alpha glucosidase inhibitors (AGIs) was assembled. We applied the inverse probability of treatment weighted Cox model to estimate the hazard ratio (HR) of RA incidence associated with the use of TZDs compared with AGIs. The final analysis included 56,796 new users of AGIs and 14,892 new users of TZDs. The incidence of RA was 187.4 and 135.2 per 100,000 person-years in AGI users and TZD users, respectively. Compared with use of AGIs, TZD use was associated with a reduction in RA incidence, with an HR of 0.72 (95% confidence interval [95% CI] 0.59-0.89). HRs for cumulative use of TZDs for 0.51 to 4.0 years and more than 4 years with incidence of RA were 0.55 (95% CI 0.35-0.88) and 0.74 (95% CI 0.57-0.98), respectively. Various subgroup analyses and sensitivity analyses were consistent with the primary analysis. Use of TZDs is associated with a decreased risk of incident RA in patients with T2DM.

A Review on Antidiabetic Potential of Genus Ferula (Apiaceae)

Background: One of the most important metabolic disorders in the current century is diabetes, which can negatively affect the physiology of many body parts. Unfortunately, this disease is not limited to a specific part of the body and causes destructive effects on the nervous system, cardiovascular system, kidneys and many other parts of the body. The high costs and increasing prevalence of this disease have made scientists look for natural compounds to prevent and treat diabetes. Medicinal plants are a huge source of unknown compounds that can alleviate many human diseases. Objective: One of the oldest plant families that have been used medicinally is the Apiaceae family. One of the most important genera of this family is Ferula, which has 170 different species and is distributed in hot and dry regions of the earth and has various therapeutic properties. The purpose of this article is to review the anti-diabetic effects of the Ferula genus on diabetes. Methods: In this review article, key science databases, including Science Direct, PubMed, and Google Scholar, were searched to find information on Ferula genus using a combination of different keywords, including diabetes, hyperglycemia, and alpha-glucosidase inhibition. Results: A total of 9 types of Ferula have been reported in the articles that have anti-diabetic properties. Conclusion: The review of the conducted research shows that the genus Ferula has a high potential in reducing blood sugar and other aspects of diabetes, and additional research should be performed in this field.

Antidiabetic and Anti-inflammatory activity of Green Solvent Extracts of Heterospathe elata fruits

Background: Plants are the prime source of phytoconstituents that can act as potent agents for the prevention and treatment of various diseases. Heterospathe elata is a plant belonging to the Arecaceae family having numerous medicinal properties. The present study aimed to investigate the antidiabetic and anti-inflammatory activities of green solvent extracts of Heterospathe elata fruit. Method: The extraction was carried out with green solvents like isopropyl alcohol, hydro alcohol, and water with increasing order of polarity. In-vitro antidiabetic activity was evaluated by alpha-amylase and alpha-glucosidase inhibition assays. Anti-inflammatory activity was evaluated by the Bovin denaturation method and HRBC membrane stabilization. Result: Our results revealed that out of three green extracts hydro alcohol extract of Heterospathe elata fruit had the highest antidiabetic and anti-inflammatory activity. Conclusion: The results suggest that the fruit of Heterospathe elata is a potential source of antidiabetic and anti-inflammatory properties.

In Vitro Evaluation of Alpha Amylase and Alpha Glucosidase Inhibitory Activity of Kamadhenu Ark extracts of Climate Smart Crop Millets

Diabetes Mellitus is characterized by abnormal Metabolism of glucose. The maintenance of glucose levels in blood without any side effects is still challenging in the medication of this disease. Various medical approaches like Allopathy, Homeopathy, Ayurveda, Unani etc are striving a lot for success in this field of medication. Present study is aimed to evaluate the Antidiabetic activity of Millets in combination with Kamadhenu Ark as solvent for the probable alpha Amylase and alpha Glucosidase inhibitory activities to reduce hyperglycemia. The Millets namely Paspalum scrobiculatum, Panicum miliaceum, Panicum sumatrense were selected for the study. The Kamadhenu Ark Extracts were prepared by Maceration method. The extracts were used for the estimation of alpha amylase and alpha-glucosidase inhibition activity. Extract of Panicum miliaceum exhibited highest α amylase and α glucosidase inhibitory potential with IC50 values of 0.239 and 1.526 mg/ml, respectively, which was comparable with acarbose (0.258 and 1.985 mg/ml). Extracts of Paspalum scrobiculatum and Panicum sumatrense have shown low activity. Present study paves a new path revealing the effective inhibition of α amylase and α glucosidase by Kamadhenu Ark extract of Panicum miliaceum (Proso Millet KPM).