Alpha-amylase Inhibitor Research Articles

Recent Advances in the Development of Alpha-Glucosidase and Alpha-Amylase Inhibitors in Type 2 Diabetes Management: Insights from In silico to In vitro Studies.

Diabetes is a metabolic disorder caused by high glucose levels, leading to serious threats such as diabetic neuropathy and cardiovascular diseases. One of the most reliable measures for controlling postprandial hyperglycemia is to reduce the glucose level by inhibiting enzymes in the digestive system, such as Alpha-Glucosidase and Alpha-Amylase. Here, we have investigated the use of inhibitors to inhibit carbohydrate metabolism in order to restrict glucose levels in diabetic patients. Acarbose, Voglibose, and Miglitol are three inhibitors approved by the FDA that efficiently inhibit these two enzymes and thereby minimising hyperglycemia but are al-so significantly helpful in reducing the risk of cardiovascular effects. We also provide insight into the other known inhibitors currently available in the market. The adverse effects associated with other inhibitors emphasise the demand for the latest in silico screening and in vitro validation in the development of potent inhibitors with greater efficacy and safety for the treatment of Type 2 diabetes. The recent findings suggest that Alpha-Glucosidase and Alpha-Amylase play a major role in carbohydrate metabolism and triggering the increase in glucose levels. This review pro-vides the latest scientific literature findings related to these two enzymes as well as the role of primary and secondary inhibitors as potential candidates. Moreover, this review elaborates the framework on the mechanism of action, different plant sources of extraction of these enzymes, as well as kinetic assay of inhibitors and their interaction that can be used in future prospects to de-velop potential leads to combat Type 2 diabetes.

Evaluations of the in vitro and in vivo antidiabetic activity of 70 % ethanolic fruit extracts of Rosa abyssinica

BackgroundDiabetes mellitus is becoming major health challenge with continually increasing burden. High costs of conventional medicines and numerous side effects associated with them, on the other hand, easy availability and accessibility of traditional herbal medicines calls upon experimental investigations to validate their effect on lowering blood glucose level. MethodsThe dried fruit of Rosa abyssinica was macerated with 70 % ethanol and the extract's in vitro antidiabetic activity was investigated using dinitrosalisylic acid method for alpha amylase inhibitory activity. Furthermore, the in vivo hypoglycemic and Antihyperglycemic effects of various doses of the extract (100, 200 and 400 mg/kg) was determined on normoglycemic, glucose loaded (1500 mg/kg) and Streptozotocine (180 mg/kg)-induced diabetic mice models. ResultsThe acute oral toxicity study revealed the plant showed no toxic effect on swiss albino mice at 2000 mg/kg. The in vitro alpha amylase inhibitory activity study showed that the extract has comparable IC50 value of 21.37 ± 4.252 μg/ml with the standard drug acarbose (IC50 value of 26.72 ± 3.59 μg/ml). On the other hand, in normal mice, none of the dose levels except at 400 mg/kg significantly reduces blood glucose level. This is in contrast to the oral glucose tolerance test, which the extract produced significant reduction at 60, 90 and 120 min following glucose challenge. The 70 % ethanolic fruit extracts of Rosa abyssinica also experienced profound antidiabetic activity in streptozotocin-induced diabetic model. In the single-dose study, both RAFE200 and RAFE400 demonstrated a significant (P˂0.05) reduction in blood glucose levels at 1, 2, 3, and 4 h. Similarly, in the repeated-dose study, RAFE200 and RAFE400 not only significantly reduced blood glucose levels but also produced a notable improvement in animal body weight. ConclusionThe 70 % ethanolic fruit extracts of Rosa abyssinica have shown significant in vitro alpha amylase inhibition effect and an in vivo blood glucose level lowering effects in diabetic mice.Therefore, this study supports the traditional use of Rosa abyssinica in the management of diabetes mellitus.

Phytochemical profiling of wastes from the processing of shea butter (Vitellaria paradoxa) and pharmacological potentials within the paradigm of circular bioeconomy: Emphasizing antioxidant and antidiabetic applications

Shea butter is a natural fat that is extracted from the kernels of the shea butter tree, and it is widely used in food preparation, cosmetics, and therapeutic practices. Shea trees are prevalent across Africa, and the traditional extraction methods produce significant wastes. However, there is dearth of information on the phytochemical profiling of these wastes and their potential biomedical values. Thus, this study conducted a thorough phytochemical investigation of the shea butter wastes from different processing stages, including brown and black shea cakes (SNC1 and SNC2), shea nut shells (SNS), and shea nut wastewater (SNWW). By using gas chromatography-mass spectrometry (GC–MS), the bioactive chemicals in these wastes were identified and quantified. Furthermore, the antioxidant and antidiabetic activities of the wastes were investigated for their potential pharmacological applications. The maximum antioxidant activities obtained at 60 mg/ml revealed DPPH radical scavenging of 62.34 % for SNC1, ferric reducing power of 68.13 % for SNC2, H2O2 radical scavenging of 38.46 % for SNS, and nitric oxide scavenging of 35.13 % for SNWW indicating their potentials in combating oxidative stress. Additionally, the promising anti-diabetic activity, with alpha-amylase inhibition reaching 84.74 % for SNS at 60 mg/ml highlights their potential in diabetes management. This study provides a holistic understanding of shea butter wastes, unraveling their chemical complexity and exploring their pharmacological potentials. It not only expands our knowledge of shea butter wastes, but also unlocks new avenues for utilization of the wastes in various industries, thereby contributing to waste management and sustainable exploitation of shea resources.

Formulation and evaluation of phytosomes containing bioactive from Carica papaya seeds

Background: Papaya seeds are a rich source of proteins, fat, fibers, vitamins, minerals, monounsaturated fatty acids, polyphenols, and powerful antioxidants like flavonoids. Low solubility limits the absorption and bioavailability of herbal constituents. Hence, phytosomes of Papaya seed extract were formulated to enhance its solubility and bioavailability. Methodology: Papaya seeds were extracted using ethanol as solvent, and all the phytoconstituents present in the extract were assessed during the phytochemical screening and LC-MS analysis. In-vitro antidiabetic activity pure extract was determined by alpha-amylase and alpha-glucosidase enzyme inhibitory assay. The phytosomes of extract were formulated using the lipid thin film formation method and Soya lecithin and Cholesterol as lipids. The formulated phytosomes were analyzed for parameters such as particle size, zeta potential, encapsulation efficiency, percent drug content, and In-vitro dissolution study. The chemical nature of the formulation was studied using FTIR analysis and powder X-ray diffractometry. Thermal stability of phytosomes analyzed with the help of Differential Scanning calorimetry. Results: LC-MS identified 16 phytoconstituents. In-vitro antidiabetic activity showed 59.97% and 51.17% inhibition of enzymes alpha-amylase and alpha-glucosidase, respectively. The encapsulation efficiency of the optimized formulation was 88.41±0.91% with a particle size of 188.0±53.7nm. TEM images of formulation confirm the formation of phytosomes. FTIR, DSC, and Powder X-ray diffractometry showed no unwanted peaks. The in vitro dissolution study showed 89.26±1.05% CDR of phytosome, while the extract showed 47.78±0.59% CDR. Conclusion: Evaluation results of phytosomes suggest that this formulation can be used as an effective herbal antidiabetic formulation

Evaluation of antidiabetic activity of Ocimum sanctum (Tulsi) through inhibition of alpha-amylase and alpha-glucosidase: an in vitro study

Evaluation of antidiabetic activity of Ocimum sanctum (Tulsi) through inhibition of alpha-amylase and alpha-glucosidase: an in vitro study

Evaluation of Proximate, Phytochemicals, Antioxidant Capacity, Enzymatic Inhibition, and Anti-Inflammatory Properties of Avocado Seed Meal as Potential Feed Additive

This study examined the proximate composition, phytochemical profile, antioxidant capacity, enzymatic inhibition, and anti-inflammatory properties of avocado seed meal. The proximate analysis revealed that avocado seed meal is rich in protein (17.32%), fat (15.33%), and carbohydrates (48.73%), with moderate levels of moisture (10.26%), ash (2.39%), and crude fiber (5.97%). Phytochemical analysis indicated high contents of phenols (111.56 mg/g), saponins (96.94 mg/g) and flavonoids (66.66 mg/g), but lower levels of alkaloids (14.60 mg/g), tannins (1.17 mg/g), and steroids (0.89 mg/g). The antioxidant properties assessed showed significant DPPH (50.05%) and FRAP (63.04%) free radical scavenging activities, though lower inhibition of lipid peroxidation (34.88%) and vitamin C content (0.03 mg/g). Enzymatic inhibition assays demonstrated alpha-lipase, alpha-glucosidase, and alpha-amylase inhibition rates of 31.46%, 27.56%, and 50.88%, respectively. Anti-inflammatory properties were also notable, with 24.02% albumin denaturation inhibition and 37.99% antiprotease activity. These findings suggest that avocado seed meal holds considerable potential for nutritional and therapeutic applications as natural feed supplement for livestock and humans.

Unveiling the diverse bioactivity of cobalt oxide nanoparticles produced through carboxymethyl cellulose extraction

This study explores an eco-friendly method for synthesizing Cobalt oxide nanoparticles (Co3O4NPs) using extracted carboxymethyl cellulose (CMC) as a reducing and stabilizing agent. The Co3O4NPs, characterized via various analyses, demonstrated a crystalline structure with sizes ranging from 10.9 to 28.2 nm. Microscopic imaging confirmed a uniform spherical morphology with an average diameter of 27.2 nm. The biological activities of Co3O4NPs were investigated extensively, highlighting their superior antibacterial efficacy compared to amoxicillin-clavulanic acid. These nanoparticles exhibited potent antioxidant properties and demonstrated safety for potential applications based on erythrocyte viability results. Additionally, Co3O4NPs displayed significant potency against Michigan Cancer Foundation-7 (MCF-7) breast cancer cells and showed promising α-amylase enzyme inhibitory activity, highlighting their multifunctional therapeutic potential as antioxidant, antibacterial, anticancer, and alpha-amylase inhibition assay.

Evaluation of in vitro antidiabetic and anti-microbial activity of edible red seaweed Pyropia vietnamensis

IntroductionDiabetes is one of the top ten leading causes of mortality in the world with an incidence rate of 422 million. The current study aimed to investigate the antidiabetic activity of edible red seaweed Pyropia vietnamensis.Materials and methodsCrude extract was subjected to UV–visible light spectroscopy, phytochemical screening, quantification of total tannin content, DPPH free radical scavenging, alpha amylase inhibition assay, antimicrobial activity, and glucose uptake potential by yeast cell assay.ResultsThe phytochemicals study revealed the presence of alkaloids, glycosides, phenols, lignins, saponins, and further, total tannin content was estimated to be 3.86 ± 0.00378 mg/g. The methanolic extract of Pyropia vietnamensis displayed the highest DPPH free radical scavenging activity of 35.19% at 100 µg/mL. The alpha-amylase inhibition potential of the extract showed 11.5% at 400 and 13.5% at 500 µg/mL. Glucose utilization of yeast cells treated with extract with different (5, 15, and 25 mM) glucose concentrations showed a linear increase in the glucose uptake percent. The minimum inhibitory concentration (MIC) of Pyropia vietnamensis extract against E. coli MTCC-443 and S. aureus MTCC-96 was found to be 250 mg/mL and 125 mg/mL respectively. The uptake percent was 31.7, 29.5, and 38.27% for 5, 15, and 25 mM glucose concentrations respectively, exhibiting its ability to transport glucose across the yeast cell membrane. The toxicity study resulted in a more than 60% cell survival rate in all the concentrations, proving its safety for human consumption.ConclusionThe result of the study concludes that Pyropia vietnamensis could be utilized as a functional food due to its dietary source for treating diabetic conditions naturally. Further research can be done to evaluate the potential of diabetic mouse (in vivo) conditions.

Comparative Analysis of Antioxidant, Nutritional, Phytochemical and Enzyme Inhibition Properties of Justicia carnea and Alchornea cordifolia Leaf Meals

In recent years, there has been an increasing interest in plant-derived compounds for their potential health benefits and therapeutic applications. In this study, two botanical species, Alchornea cordifolia and Justicia carnea leaf meals were examined for their antioxidant characteristics, phytochemical and proximate composition, anti-proteinase properties and lipase, albumin, alpha-amylase and alpha-glucosidase inhibitory properties. A. cordifolia exhibited significantly higher levels of vitamin C, ferric ion-reducing antioxidant power, 2, 2-diphenyl-1-picrylhydrazyl hydrate scavenging activity and flavonoid content compared to J. carnea, indicating superior antioxidant potential. Conversely, J. carnea showed higher saponin and cardiac glycoside content. Notably, A. cordifolia demonstrated stronger inhibition of lipase albumin and anti-proteinase activities, as well as higher inhibition of alpha-amylase and alpha-glucosidase enzymes compared to J. carnea. Proximate composition analysis revealed differences in moisture, nitrogen-free extract, crude fat, crude fiber and crude protein contents between the two leaf meals. In conclusion, A. cordifolia emerges as a promising source of antioxidants and enzyme inhibitors, highlighting its potential as a valuable nutraceutical resource. Its superior properties to J. carnea suggest its potential application as a functional food ingredient for promoting health and preventing metabolic disorders. This study provides valuable insights into the biochemical and nutritional composition of these leaf meals, contributing to the understanding of their potential health benefits.

Evaluation of Sourdough Bread and Its Potential Use in Support of the Treatment of Chronic Non-Communicable Diseases.

Gastrointestinal disorders dysregulate the biochemical environment of the gastrointestinal tract by altering pH conditions during the gastric phase of digestion or by reducing the secretion of pancreatin during the intestinal part of the process. Ingested functional food could therefore lose some of its health-promoting potential apart from its nutritional value. In this work, we aimed to manufacture bread marked by decreased gluten content, using a commercial or laboratory sourdough, that could be appropriate for patients afflicted with wheat allergy, hypertension and pancreatic malfunctions. A reference sample (no sourdough) was prepared alongside wheat and wheat-rye bread samples-produced with either commercial or laboratory sourdough (L. plantarum BS, L. brevis 1269, L. sanfranciscensis 20663). We measured the QQQPP allergen content (ELISA) in bread extracts digested in vitro and determined how these extracted components affect the level of active angiotensin and alpha amylase (spectrophotometry). We then elucidated how these properties changed when physiological digestion conditions (pH and pancreatin activity) were disturbed to mimic gastric hyperacidity, hypochlorhydria or exocrine pancreatic insufficiency. The key finding was that every tested type of bread produced with laboratory sourdough exhibited pronounced angiotensin-converting enzyme inhibition. The effect was preserved even in dysregulated digestive conditions. The use of laboratory sourdough prevented an increase in allergenicity when pancreatin was restricted as opposed to the commercial sourdough, which surpassed the reference sample reading at 50% pancreatin. No statistically consistent link was reported when the inhibition of alpha amylase was assayed. In conclusion, functional bread manufactured with sourdough composed of L. plantarum BS, L. brevis 1269, and L. sanfranciscensis 20663 was shown to be potentially capable of contributing to the treatment against hypertension as evidenced by in vitro research. It was also moderately safer with regard to its allergenicity.

Allergenic Biomarkers in the Molecular Diagnosis of IgE-Mediated Wheat Allergy.

IgE-mediated wheat allergy can take on various forms, including childhood food allergy to wheat, wheat-dependent exercise-induced anaphylaxis in young adults, baker's respiratory allergy/asthma in workers exposed to wheat flour inhalation, and contact urticaria that is caused by hydrolyzed wheat proteins in some cosmetics, and that is sometimes associated with a food allergy. Singleplex and multiplex immunoassays detect specific IgE antibodies to wheat allergenic molecular biomarkers such as omega-5 gliadin Tri a 19, lipid transfer protein Tri a 14, and alpha-amylase inhibitors. The fluorescence enzyme immunoassay with capsulated cellulose polymer solid-phase coupled allergens is a commonly used singleplex assay. Multiplex methods include the ELISA-based macroarray immunoassay using nano-bead technology and a microarray immunoassay on polymer-coated slides. Another promising diagnostic tool is the basophil activation test performed with omega-5 gliadin and other wheat protein types. Detailed comprehension of the structural and immunological features of the numerous wheat allergens significant in clinical settings is imperative for advancing diagnostic biomarkers for IgE-mediated wheat allergies.

Synthesis, bioactivity, and molecular docking of pyrazole bearing Schiff-bases as prospective dual alpha-amylase and alpha-glucosidase inhibitors with antioxidant activity

A series of pyrazole-Schiff base derivatives, 3a-i, were synthesized by reacting arylamines 2a-i with pyrazole aldehyde 1, utilizing two catalysts: ammonium chloride (catalystA) or acetic acid (catalystB). The compounds were analyzed using spectroscopic methods, including 1H and 13C NMR, along with high-resolution mass spectrometry. Their antidiabetic and antioxidant activities were assessed through various in vitro assays, encompassing evaluation of inhibitory effects on α-glucosidase, α-amylase enzymes and determination of reducing power, free radical scavenging activity. The most promising in vitro antidiabetic results were also observed with analogs 3c (α-amylase IC50 = 19.57 ± 0.07 µM, α-glucosidase IC50 = 17.13 ± 0.28 µM) and 3h (α-amylase IC50 = 22.50 ± 0.06 µM, α-glucosidase IC50 = 20.75 ± 0.17 µM). Both products 3c and 3h revealed activity near to the standard acarbose (IC50 (α-amylase) =16.28 ± 0.24 µM, IC50 (α-glucosidase) =13.19 ± 0.26 µM). Among all compounds, 3c and 3h exhibited the highest transition metal reducing activity at levels of 75.27 ± 1.99 and 78.42 ± 0.58 µM Trolox equivalents (TE), respectively, along with the most significant free radical scavenging effects at levels of 73.79 ± 0.11 and 72.98 ± 0.33 µM TE, respectively. The antioxidant results of the current set of pyrazole-Schiff base derivatives 3a–i indicated their potential benefits as free radical scavenging and metal-reducing agents, thus proving their antioxidant capability. Their higher antidiabetic and antioxidant activities compared to other compounds might be explained by the presence of a free phenolic hydroxy group in 3c and a benzothiazole motif in 3h. These findings also lend support to the multifaceted biological functions associated with their antidiabetic activity, including their antioxidant activity. In silico molecular docking studies confirm the antihyperglycemic impact, elucidating the nature of interactions between 3c and 3h and HPA/HLAG catalytic sites.

Studying the Anti-microbial and Alpha Amylase Inhibition Activity of Cerium Oxide Nanoparticles for Biomedical Applications

Cerium oxide nanoparticles (CNP) have been produced using a wet chemical technique. The therapeutic capacities of cerium oxide nanoparticles are determined based on the analysis of their anti-diabetic and antibacterial activities. The study below demonstrated the antibacterial characteristics of cerium oxide nanoparticles (CNP) against several bacteria. Specifically, the inhibition zones observed for Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Enterococcus gergovae were 14.5mm, 11mm, 17mm, and 15mm, respectively. The results obtained indicate that CNP has the potential to address the urgent problem of hospital-acquired microbial infections, particularly those caused by antibiotic-resistant microorganisms. Additionally, the anti-diabetic property of CNP was evaluated and found to have a 66% alpha amylase inhibition, which suggests a significant reduction in glucose levels. Therefore, it has the potential to be utilized as an antidiabetic medication as well. The study has produced a compound with potent biological capabilities that can be enhanced through a synthesis technique and utilized in the pharmaceutical industry.

In Silico Investigation against Inhibitors of Alpha-Amylase Using Structure-based Screening, Molecular Docking, and Molecular Simulations Studies.

Type-II diabetes mellitus is a chronic disorder that results from fluctuations in the glucose level leading to hyperglycemia with severe adverse effects increasing worldwide. Alpha-Amylase is the key enzyme involved in the mechanism of glucose formation therefore Alpha-Amylase inhibitors have become a therapeutic target in the development of new leads as they have the potential to suppress glucose levels. Existing drugs targeting Alpha-Amylase highlight major drawbacks in terms of poor absorption rate that causes several gastrointestinal issues. So, this research is aimed to develop novel inhibitors interacting with Alpha-Amylase's active site using structural-based screening, binding pattern analysis, and molecular dynamic simulation. Hence, to search for a potential lead, we analyzed a total of 133 valiolamine derivatives and 535 desoxynojirimycin derivatives that exhibited drug-like properties screened through Lipinski filters. Virtual screening followed by binding interaction analysis we identified ten compounds that exhibited better binding energy scores compared to the standard drugs voglibose and miglitol, used in our study. The docking analysis, ADMET and metabolic site prediction estimated the best top two compounds with good drug profiles. Further, top compounds VG9 and VG15 were promoted to simulation study using the Biovia Discovery study to access the stability at a time interval of 100 ns. MD simulation results revealed that our compound VG9 possesses better conformational stability in the complex to the active site residues of Alpha-Amylase target protein than standard drug voglibose. Thus, our investigation revealed that compound VG9 also exhibits the best pharmacokinetic as well as binding affinity results and could act as a potential lead compound targeting Alpha-Amylase for Type II diabetes.

Molecular Mechanisms Underlying the Therapeutic Potential of Plant-Based α-Amylase Inhibitors for Hyperglycemic Control in Diabetes.

Diabetes mellitus (DM), arising from pancreatic β-cell dysfunction and disrupted alpha-amylase secretion, manifests as hyperglycemia. Synthetic inhibitors of alphaamylase like acarbose manage glucose but pose adverse effects, prompting interest in plantderived alternatives rich in antioxidants and anti-inflammatory properties. The current review investigates plant-based alpha-amylase inhibitors, exploring their potential therapeutic roles in managing DM. Focusing on their ability to modulate postprandial hyperglycemia by regulating alpha-amylase secretion, it assesses their efficacy, health benefits, and implications for diabetes treatment. This review examines plant-derived alpha-amylase inhibitors as prospective diabetic mellitus treatments using PubMed, Google Scholar, and Scopus data. Plant-derived inhibitors, including A. deliciosa, B. egyptiaca, and N. nucifera, exhibit anti-inflammatory and antioxidant properties, effectively reducing alpha-amylase levels in diabetic conditions. Such alpha-amylase inhibitors showed promising alternative treatment in managing diabetes with reduced adverse effects. The current literature concludes that plant-derived alpha-amylase inhibitors present viable therapeutic avenues for diabetes management by modulating alpha-amylase secretion by regulating inflammatory, oxidative stress, and apoptotic mechanisms involved in the pathogenesis of diabetes. Further investigation into their formulations and clinical efficacy may reveal their more comprehensive diabetes therapeutic significance, emphasizing their potential impact on glucose regulation and overall health.</p>.

Natural Diabetes Treatment with Litchi Seeds Extract In Vivo

Background: Diabetes mellitus imposes a substantial health and economic cost on societies. Novel antidiabetic medicines are necessary because the present therapies have impoverished safety and effectiveness. Traditional medicines often make use of medicinal plants, which are considered to be excellent choices. Objective: The aim of the research to investigating the potential anti-diabetic activities of extracts from Litchi chinensis seeds (LCS). Methods: The extract was prepared using an aqueous solvent and 80% ethanol. It was subsequently used in laboratory settings to investigate primary alpha amylase inhibition, with acarbose serving as the reference standard. The extract was then administered in vivo to observe the effects on STZ-mediated diabetes rats. The induction of diabetes in Long-Evans rats was achieved by administering a solitary intraperitoneal injection of streptozotocin at a dosage of 80 mg/kg. the hydroethanolic extract of litchi seed were used at different concentrations (100 and 200 mg/kg BW) to treat rats with diabetes. The finding analyzed various biochemical and histological parameters in diabetic rats over a period of 28 day, using established protocols. Results: The results showed significant improvements in plasma glucose (p &lt; 0.001) and considerable increased in body weight (p &lt; 0.0001). The LCS extract (200 mg/kg BW) showed significant ameliorative effects on glycemic markers, lipid profile, and renal functioning. Additionally, histopathological studies reveals that LCS can potentially reduce renal inflammation as well as hepatic tissue damage. Conclusions: The findings indicate that hydroethanolic litchi seed extracts may have potential therapeutic benefits in managing diabetes and reducing lipid levels.

Phytochemical estimation, evaluation of antioxidant, anti-inflammatory and antidiabetic activity of three different solvent extracts of Croton joufra leaves: A medicinal plant of Assam, India

Abstract BACKGROUND: The ancient medicinal herb known as croton joufra, which originated in northeastern India, is still used today in folk medicine to treat a wide range of illnesses. Phytochemicals are naturally occurring active compounds found in plants that provide various biological activities in humans and animals. METHODS: Soxhlet extraction was used to prepare extracts of three different solvents (chloroform, methanol, and 50% ethanol). Total alkaloid and total tannin were calculated using the simple titrimetric method. Folin and Ciocalteu’s colorimetric method was used to estimate the total phenol content. In vitro antioxidant activity was evaluated using three different methods: DPPH free radical scavenging assay, hydrogen peroxide scavenging assay, and ABTS radical scavenging assay. Heat-induced bovine serum albumin (BSA) denaturation assay was used for evaluating in vitro anti-inflammatory activity. In vitro antidiabetic activity was determined by alpha-amylase inhibition assay. RESULTS: Among these three solvent extracts, a high amount of yield was found in the hydroalcoholic extract. Based on the qualitative and quantitative tests of plant extracts, it was shown that hydroalcoholic extracts contained a higher amount of alkaloids (162.33 ± 0.96 mg/g of dry extract), phenols (205.30 ± 0.95 mg/g of dry extract of gallic acid equivalent), and tannins (214.50 ± 0.95mg/g of dry extract) compared to chloroform and methanolic extract. Among these three extracts, the hydroalcoholic extract and methanolic extract have better antioxidant, anti-inflammatory, and antidiabetic activities than standard drugs such as ascorbic acid, aspirin, and metformin. CONCLUSION: From the results of the experiment, it was concluded that among these three solvent extracts, the hydroalcoholic (50% ethanol) extract contains substantial amounts of secondary metabolites such as alkaloids, phenols, and tannins. The hydroalcoholic extract also has promising pharmacological properties. So the hydroalcoholic extract of Croton joufra leaves may be used as a raw material for drug development.

Alpha-Amylase and Glucoamylase Inhibitory Assessment of Methanol Extract of Fagonia Indica and its GC-MS analysis

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.

In Silico and In Vitro Alpha-amylase Activities of Previously Synthesized Pyridazine Derivatives

Diabetes mellitus is one of the fastest-growing metabolic disorders. Worldwide, one out of 10 people suffer from diabetes mellitus. In this manuscript, we establish the antidiabetic potential of previously synthesized pyridazine derivatives using in silico and in vitro experiments. Molecular docking studies of pyridazine derivatives with pullulanase Amy12, isomaltase, and alpha-amylase receptors revealed that Molecules 45, 46, and 29 showed good docking interaction scores. ADMET analysis of the top three docked pyridazine derivatives (45, 46, and 29) showed lesser solubility and poor distribution behavior. Molecules 45, 46, and 29 maintained drug-like properties with good oral bioavailability. Molecules 45 and 29 showed reproductive toxicity without any sign of mutagenicity, tumorigenicity, or other irritancy. Molecule 46 emerged as a nontoxic molecule in all aspects. In vitro alpha-amylase inhibition data of molecules 45, 46, 29, and acarbose showed IC50 values of 8.67, 8.46, 8.83, and 66.65 μg/mL, respectively. The antidiabetic activity of pyridazine derivatives is increased with the presence of phenothiazine coupled with a biphenyl group, indole with a biphenyl group, and phenothiazine with an ethylphenyl group. Establishing these pyridazine derivatives using in vivo experiments could be beneficial in managing diabetes.

LC-MS metabolomics and molecular docking approaches to identify antihyperglycemic and antioxidant compounds from Melastoma malabathricum L. Leaf

The dried leaves of Melastoma malabathricum L., locally named Karamunting or Senduduk, is traditionally consumed in many regions in Indonesia as herbal tea to cure different illnesses, including diabetes. To date, information on the compounds responsible for their antidiabetic activity is still very rare. The study aimed to identify bioactive compounds of M. malabathricum L. leaves using LC-MS based metabolomics and molecular docking approaches. The leaves brewed with different methods were subjected to LC−MS measurements and several bioactivity tests (in vivo and in vitro antihyperglycemic, and in vitro antioxidant). LC−MS data were linked to the activity data using multivariate data analysis. Molecular docking using alpha-glucosidase, alpha-amylase, and insulin receptor as protein targets was used to verify the results and study the interaction between the identified compound and protein targets. As results, isoquercetin and myricitrin were identified as compounds strongly associated with alpha-amylase inhibitors, while rutin and epicatechin were identified as alpha-glucosidase inhibitors. Quercitrin, citric acid, quercetin, epicatechin, isoquercitrin, and 7-hydroxycoumarine were strongly correlated with both antihyperglycemic and antioxidant activities. The results of metabolomics were confirmed with molecular docking studies, which showed that some of these compounds acted as competitive inhibitors, while others acted as non-competitive ones. Possible synergism between epicatechin and citric acid in their interaction with IR was detected. Metabolomics combined with molecular docking efficiently identified and confirmed several antihyperglycemic and antioxidant compounds from M. malabathricum L., leaf. This study provides scientific evidence for the traditional use of M. malabathricum L. as an antidiabetic herbal.