Potential Antidiabetic Activity Research Articles

Potential antidiabetic activity of probiotic and Garcinia kola-yoghurt and its role in regulation of male fertility-stimulating hormones in high-fat diet/low dose streptozotocin-treated rats

Garcinia kola Heckel seed is widely used in the African traditional medicine as a aphrodisiac and male fertility enhancer. Probiotics can reestablish glucose homeostasis and improve blood lipid profiles by altering the composition of the intestinal flora. The study was planned to assess the efficacy of co-administration of Garcinia kola seed aqueous infusion and probiotic yoghurt in the management of diabetes and associated male fertility-stimulating hormones abnormalities. G. kola seed infusion was prepared, assessed for radical scavenging capacity, total phenolic content and phenolic profile using HPLC. Fermented yoghurt was prepared and inoculated with probiotic mixture. Rats were given a high-fat diet for four weeks and received an intraperitoneal injection of streptozotocin (30 mg/kg) to induce type 2 diabetes. Diabetic rats were received 200 mg/kg freeze-dried infusion of G. kola seed, probiotics yoghurt, and probiotic yoghurt mixed with G. kola once a day for four weeks. The levels of glucose, insulin, testosterone, follicle-stimulating hormone, luteinizing hormone, inflammatory indicators, oxidative markers, lipid profiles and liver as well as kidney biochemical indicators were measured. The administration of G. kola seed, probiotic yoghurt, or their combination to diabetic rats demonstrated potential anti-diabetic effects as evidenced by the down-regulation in glucose, insulin, lipid profile, oxidative markers, and inflammatory markers simultaneously with an up-regulation in testosterone, FSH, and LH levels compared to diabetic rats. G. kola seed, probiotic yoghurt, or their combination increased testosterone, FSH, and LH levels and are thought to have therapeutic promise for T2DM and its related oxidative stress.Graphical

Synthesis, Computational Study, and In Vitro α-Glucosidase Inhibitory Action of Thiourea Derivatives Based on 3-Aminopyridin-2(1H)-Ones

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

Metabolic profiling and enzyme inhibitory activity of the essential oil of citrus aurantium fruit peel

BackgroundBitter orange (Citrus aurantium) is a fruiting shrub native to tropical and subtropical countries around the world and cultivated in many regions due to its nutraceutical value. The current study investigated the metabolic profiling and enzyme inhibitory activities of volatile constituents derived from the C. aurantium peel cultivated in Egypt by three different extraction methods.MethodsThe volatile chemical constituents of the peel of C. aurantium were isolated using three methods; steam distillation (SD), hydrodistillation (HD), and microwave-assisted hydrodistillation (MAHD), and then were investigated by GC-MS. The antioxidant potential was evaluated by different assays such as DPPH, ABTS, FRAP, CUPRAC, and phosphomolybdenum and metal chelating potential. Moreover, the effect of enzyme inhibition of the three essential oils was tested using BChE, AChE, tyrosinase, glucosidase, as well as amylase assays.ResultsA total of six compounds were detected by GC/MS analysis. The major constituent obtained by all three extraction methods was limonene (98.86% by SD, 98.68% by HD, and 99.23% by MAHD). Differences in the composition of the compounds of the three oils were observed. The hydrodistillation technique has yielded the highest number of compounds, notably two oxygenated monoterpenes: linalool (0.12%) and α-terpineol acetate (0.1%).ConclusionIn our study differences in the extraction methods of C. aurantium peel oils resulted in differences in the oils’ chemical composition. Citrus essential oils and their components showed potential antioxidant, anticholinesterase, antimelanogenesis, and antidiabetic activities. The presence of linalool and α-terpineol acetate may explain the superior activity observed for the oil isolated by HD in both radical scavenging and AChE inhibition assays, as well as in the enzyme inhibition assays.

Metabolic profiling and enzyme inhibitory activity of the essential oil of citrus aurantium fruit peel

BackgroundBitter orange (Citrus aurantium) is a fruiting shrub native to tropical and subtropical countries around the world and cultivated in many regions due to its nutraceutical value. The current study investigated the metabolic profiling and enzyme inhibitory activities of volatile constituents derived from the C. aurantium peel cultivated in Egypt by three different extraction methods.MethodsThe volatile chemical constituents of the peel of C. aurantium were isolated using three methods; steam distillation (SD), hydrodistillation (HD), and microwave-assisted hydrodistillation (MAHD), and then were investigated by GC-MS. The antioxidant potential was evaluated by different assays such as DPPH, ABTS, FRAP, CUPRAC, and phosphomolybdenum and metal chelating potential. Moreover, the effect of enzyme inhibition of the three essential oils was tested using BChE, AChE, tyrosinase, glucosidase, as well as amylase assays.ResultsA total of six compounds were detected by GC/MS analysis. The major constituent obtained by all three extraction methods was limonene (98.86% by SD, 98.68% by HD, and 99.23% by MAHD). Differences in the composition of the compounds of the three oils were observed. The hydrodistillation technique has yielded the highest number of compounds, notably two oxygenated monoterpenes: linalool (0.12%) and α-terpineol acetate (0.1%).ConclusionIn our study differences in the extraction methods of C. aurantium peel oils resulted in differences in the oils’ chemical composition. Citrus essential oils and their components showed potential antioxidant, anticholinesterase, antimelanogenesis, and antidiabetic activities. The presence of linalool and α-terpineol acetate may explain the superior activity observed for the oil isolated by HD in both radical scavenging and AChE inhibition assays, as well as in the enzyme inhibition assays.

In Vitro Analysis of Camellia sinensis Leaf Extract Against Diabetes Mellitus.

Diabetes mellitus (DM) poses a significant global health challenge, with its prevalence steadily increasing. Natural compounds derived from plants have garnered attention for their potential therapeutic effects in managing this metabolic disorder. Camellia sinensis, commonly known as tea, is rich in bioactive compounds exhibiting various pharmacological properties. This study investigates the potential anti-diabetic activity of C. sinensis leaf extract through in vitro analysis. Camella sinensisleaf extract was prepared by grinding the plant's leaf into a powder, mixing it with distilled water, and heating. The antidiabetic activity was assessed through α-Amylase and α-Glucosidase inhibitory assays, employing varying concentrations of the plant extract. Molecular docking analysis utilized Autodock 1.5.6 software (The Scripps Research Institute, California, US)to predict ligand-receptor interactions, guiding subsequent experimental validation. Camella sinensisleaf extract exhibited high phenolic content, suggesting potential in managing hyperglycemia. Tannins may aid glucose absorption and inhibit adipogenesis, making them promising for non-insulin-dependent DM (NIDDM). Terpenoids, with antioxidant activity, inhibit advanced glycation. Saponins and steroids were absent. Molecular docking revealed residues like IR, IRS1, and AS160 with significant impact on α-Amylase and α-Glucosidase, comparable to metformin. The findings of this study highlight the promising potential of C. sinensis leaf extract in managing hyperglycemia associated with DM. The high phenolic content aids in glucose regulation. Specifically, the presence of tannins suggests a potential role in modulating glucose absorption and inhibiting adipogenesis, which could be particularly beneficial for individuals with NIDDM.These findings provide valuable insights into the molecular mechanisms underlying the potential therapeutic efficacy of C. sinensis leaf extract against DM, paving the way for further research and development of novel therapeutic interventions in diabetes management.

Labdanum Resin from Cistus ladanifer L. as a Source of Compounds with Anti-Diabetic, Neuroprotective and Anti-Proliferative Activity.

Labdanum resin or "gum" can be obtained from Cistus ladanifer L. by two different extraction methods: the Zamorean and the Andalusian processes. Although its main use is in the fragrance and perfumery sectors, ethnobotanical reports describe its use for medicinal purposes in managing hyperglycemia and mental illnesses. However, data concerning the bioactivities and pharmacological applications are scarce. In this work, it was found that the yield of labdanum resin extracted by the Andalusian process was 25-fold higher than the Zamorean one. Both resins were purified as absolutes, and the Andalusian absolute was purified into diterpenoid and flavonoid fractions. GC-EI-MS analysis confirmed the presence of phenylpropanoids, labdane-type diterpenoids, and methylated flavonoids, which are already described in the literature, but revealed other compounds, and showed that the different extracts presented distinct chemical profile. The potential antidiabetic activity, by inhibition of α-amylase and α-glucosidase, and the potential neuroprotective activity, by inhibition of acetylcholinesterase, were investigated. Diterpenoid fraction produced the higher α-amylase inhibitory effect (~30% and ~40% at 0.5 and 1 mg/mL, respectively). Zamorean absolute showed the highest α-glucosidase inhibitory effect (~14% and ~24%, at 0.5 and 1 mg/mL, respectively). Andalusian absolute showed the highest acetylcholinesterase inhibitory effect (~70% and ~75%, at 0.5 and 1 mg/mL, respectively). Using Caco-2 and HepG2 cell lines, Andalusian absolute and its purified fractions showed moderate cytotoxic/anti-proliferative activity at 24 h exposure (IC50 = 45-70 µg/mL, for Caco-2; IC50 = 60-80 µg/mL, for HepG2), whereas Zamorean absolute did not produce cytotoxicity (IC50 ≥ 200.00 µg/mL). Here we show, for the first time, that labdanum resin obtained by the Andalusian process, and its fractions, are composed of phytochemicals with anti-diabetic, neuroprotective and anti-proliferative potential, which are worth investigating for the pharmaceutical industry. However, toxic side-effects must also be addressed when using these products by ingestion, as done traditionally.

Improvement of phenolic profile and biological activities of wild mustard sprouts

The current study aimed to assess the effect of the germination process of wild mustard seeds on the phenolic profile, antioxidant, antibacterial, and antidiabetic properties, and some relevant enzyme activities. The total phenolic and flavonoid contents increased 5- and 10-fold, respectively, and were maximized on 5-days sprouts. One new phenolic compound was identified on 5-days sprout extract using HPLC. The concentrations of the identified phenolic compounds increased 1.5–4.3 folds on 5-days sprouts compared with dry seeds. The total antioxidant activity multiplied 17- and 21-fold on 5-days sprouts using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) assays, respectively. The activity of carbohydrate-cleaving, phenolic-synthesizing and antioxidant enzymes also increased during germination. On 5-days sprouts, there was a substantial correlation between the highest β-glucosidase and peroxidase activities with highest phenolic and flavonoid levels and maximum antioxidant activity. The phenolic extract of 5-days sprouts exhibited antimicrobial activities against Escherichia coli and Staphylococcus aureus and showed potent antidiabetic activity established by its inhibitory effect against α-amylase and α-glucosidase compared to dry seeds.

Characterization and evaluation of the in vitro and in vivo anti-diabetic activities of camel milk protein hydrolysates derived with different protease digestions

The study aimed to determine the potential anti-diabetic activities of the hydrolysates of camel milk proteins (CMPH). Camel milk proteins were hydrolyzed independently by using 11 proteases, and their anti-diabetic activities were analyzed by in vitro, and in vivo. The results showed that CMPH-Flavourzyme exhibited the best α-glucosidase and dipeptidyl peptidase-IV inhibitory activity, while CMPH-Papain exhibited the highest α-amylase inhibitory activity, and best proliferative effect on streptozotocin-induced NIT-1 cells in vitro. Furthermore, CMPH-Papain exhibited the most effect in decreasing the serum levels of fasting blood glucose, oral glucose tolerance test, pro-inflammatory factors (IL-1β, IL-6) and triglyceride, as well as increasing insulin levels on in vivo streptozotocin-induced diabetic mice. Peptides identification followed with molecular docking and network pharmacology analysis also found the potential anti-diabetic peptides from CMPH-Flavourzyme and CMPH-Papain. Our results indicated the type of protease used for the treatment significantly influences the anti-diabetic activities of the resulting CMPH.

Exploring the pharmacological significance of Murraya koenigii (L.) Spreng: Insights from North-East India

Murraya koenigii (L.) Spreng., is a renowned medicinal and aromatic plant having antimicrobial and broad biological activities. In the present study, the essential oil chemical profile of the leaf and floral part were analysed using GC-FID and GC-MS, and the antimicrobial activities were determined by disk diffusion assay. The scientific analysis revealed α-pinene (40.41%) was the major compound of leaf essential oil (MKL) followed by sabinene (29.66%), β-pinene (7.92%), caryophyllene (4.24%), limonene (3.39%), terpinen-4-ol (3.25%), γ-terpinene (2.63%), terpinolene (1.58%), linalool (1.32%), along with other trace components. The floral part (MKF) contains the compounds α-pinene (74.02%) as the major compound followed by β-pinene (7.17%), sabinene (5.72%), limonene (4.19%), β-myrcene (1.98%), γ-terpinene (1.47%) and terpinen-4-ol (1.41%) along with other trace compounds. The MIC result revealed essential oil showed effectiveness against Escherichia coli (40 μg/mL), Micrococcus luteus (80 μg/mL), Aspergillus fumigatus (60 μg/mL) and Aspergillus brasiliensis (80 μg/mL) for MKL while MKF did not exhibit potent antimicrobial activities. The essential oils revealed potent antioxidant potential as determined by DPPH method with IC50 values of 14.02 μL/mL (MKL) and 5.45 μL/mL (MKF) and the ABTS method with IC50 values of 5.07 μL/mL and 8.38 μL/mL in MKL and MKF respectively as compared to that of the standards. The essential oils revealed potent antidiabetic activity with 6.02 μL/mL (MKL) and 8.18 μL/mL (MKF) as that of the standard. However, both MKL and MKF were not much effective in protease inhibitory activity and anti-tyrosinase activity. The study results exhibited a potent bioactivity profile and revealed many new utilization aspects of this essential oil.

LC-ESI-MS/MS-Based Comparative Metabolomic Study, Antioxidant and Antidiabetic Activities of Three Lobelia Species: Molecular Modeling and ADMET Study.

The hydroethanol (70%) extracts of three Lobelia species (L. nicotianifolia, L. sessilifolia, and L. chinensis) were analyzed using LC-ESI-MS/MS. Forty-five metabolites were identified, including different flavonoids, coumarin, polyacetylenes, and alkaloids, which were the most abundant class. By applying Principal Component Analysis (PCA) and Hierarchical Cluster Analysis (HCA) based on LC-ESI-MS/MS analysis, the three species were completely segregated from each other. In addition, the three Lobelia extracts were tested for their antioxidant activities using a DPPH assay and as antidiabetic agents against α-glycosidase and α-amylase enzymes. L. chinensis extract demonstrated significant antioxidant activity with an IC50 value of 1.111 mg/mL, while L. nicotianifolia showed mild suppressing activity on the α-glycosidase activity with an IC50 value of 270.8 μg/mL. A molecular simulation study was performed on the main compounds to predict their potential antidiabetic activity and pharmacokinetic properties. The molecular docking results confirmed the α-glycosidase inhibitory activity of the tested compounds, as seen in their binding mode to the key amino acid residues at the binding site compared to that of the standard drug acarbose. Furthermore, the predictive ADMET results revealed good pharmacokinetic properties of almost all of the tested compounds. The biological evaluation results demonstrated the promising activity of the tested compounds, aligned with the in silico results.

Probing benzenesulfonamide–thiazolidinone hybrids as multitarget directed ligands for efficient control of type 2 diabetes mellitus through targeting the enzymes: α-glucosidase and carbonic anhydrase II

Diabetes mellitus is a chronic metabolic disorder characterized by improper expression/function of a number of key enzymes that can be regarded as targets for anti-diabetic drug design. Herein, we report the design, synthesis, and biological assessment of two series of thiazolidinone-based sulfonamides 4a-l and 5a-c as multitarget directed ligands (MTDLs) with potential anti-diabetic activity through targeting the enzymes: α-glucosidase and human carbonic anhydrase (hCA) II. The synthesized sulfonamides were evaluated for their inhibitory activity against α-glucosidase where most of the compounds showed good to potent activities. Compounds 4d and 4e showed potent inhibitory activities (IC50 = 0.440 and 0.3456 μM), comparable with that of the positive control (acarbose; IC50 = 0.420 μM). All the synthesized derivatives were also tested for their inhibitory activities against hCA I, II, IX, and XII. They exhibited different levels of inhibition against these isoforms. Compound 4d outstood as the most potent one against hCA II with Ki equals to 7.0 nM, more potent than the reference standard (acetazolamide; Ki = 12.0 nM). In silico studies for the most active compounds within the active sites of α-glucosidase and hCA II revealed good binding modes that can explain their biological activities. MM-GBSA refinements and molecular dynamic simulations were performed on the top-ranking docking pose of the most potent compound 4d to confirm the formation of stable complex with both targets. Compound 4d was screened for its in vivo antihyperglycemic efficacy by using the oral glucose tolerance test. Compound 4d decreased blood glucose level to 217 mg/dl, better than the standard acarbose (234 mg/dl). Hence, this revealed its synergistic mode of action on post prandial hyperglycemia and hepatic gluconeogenesis. Thus, these benzenesulfonamide thiazolidinone hybrids could be considered as promising multi-target candidates for the treatment of type II diabetes mellitus.

Green Synthesis and Anti-Diabetic Potential of Berberis vulgaris Silver Nanoparticles: A Promising Approach for Natural Therapeutics

This study reports the green synthesis of Berberis vulgaris root water-mediated silver nanoparticles (BvAgNPs) showcasing high purity, size-controlled morphology, and potential anti-diabetic activity. Characterization techniques confirmed the successful synthesis of predominantly spherical BvAgNPs within the 15–70 nm range, coated with organic moieties from the extract. Remarkably, BvAgNPs exhibited significantly enhanced α-amylase and α-glucosidase inhibitory activity compared to the extract alone, with inhibition higher for α-amylase. This superior anti-diabetic activity, even comparable to the standard drug Acarbose for α-amylase inhibition, highlights the potential of BvAgNPs as natural and potentially less-toxic alternatives in diabetes management. Further research on their mechanisms and in vivo efficiency is warranted to pave the way for their future application as promising anti-diabetic therapeutics.

Phytochemical Screening and Antidiabetic Activity of Aqueous Extract of Evolvulus Alsinoides Leaves: An In Vitro and In Silico Study.

Nowadays, diabetes mellitus has become common worldwide due to changes in lifestyle, sedentary life, alterations in food habits, and other genetic and environmental factors. It is necessary to create awareness about the growing pandemic. To evaluate the antidiabetic potential of Evolvulus alsinoides. In vitro α-amylase inhibition and α-glucosidase inhibition activity. Molecular docking analysis. The plant is rich in naturally occurring phytocompound. The results of the study showed that E. alsinoides has the potential to inhibit the activity of alpha-amylase and alpha-glucosidase. Moreover, this result was validated using in silico molecular docking studies that showed a good binding affinity of one of the major phytocompound, caffeic acid, with molecules in the insulin signaling cascade. E. alsinoides has a potent antidiabetic activity and can be further employed in animal and human studies.

An Update on Pharmacological and Phytochemical Aspects of Costus pictus D. Don - A Promising Anti-diabetic Plant.

The genus Costus is the largest genus in the family Costaceae and encompasses about 150 known species. Among these, Costus pictus D. Don (Synonym: Costus mexicanus) is a traditional medicinal herb used to treat diabetes and other ailments. Currently, available treatment options in modern medicine have several adverse effects. Herbal medicines are gaining importance as they are cost-effective and display improved therapeutic effects with fewer side effects. Scientists have been seeking therapeutic compounds in plants, and various in vitro and in vivo studies report Costus pictus D. Don as a potential source in treating various diseases. Phytochemicals with various pharmacological properties of Costus pictus D. Don, viz. anti-cancer, anti-oxidant, diuretic, analgesic, and anti-microbial have been worked out and reported in the literature. The aim of the review is to categorize and summarize the available information on phytochemicals and pharmacological properties of Costus pictus D. Don and suggest outlooks for future research. This review combined scientific data regarding the use of Costus pictus D. Don plant for the management of diabetes and other ailments. A systematic search was performed on Costus pictus plant with anti-diabetic, anti-cancer, anti-microbial, anti-oxidant, and other pharmacological properties using several search engines such as Google Scholar, PubMed, Science Direct, Sci-Finder, other online journals and books for detailed analysis. Research data compilation and critical review of the information would be beneficial for further exploration of its pharmacological and phytochemical aspects and, consequently, new drug development. Bioactivity-guided fractionation, isolation, and purification of new chemical entities from the plant as well as pharmacological evaluation of the same will lead to the search for safe and effective novel drugs for better healthcare. This review critically summarizes the reports on natural compounds, and different extract of Costus pictus D. Don with their potent anti-diabetic activity along with other pharmacological activity. Since this review has been presented in a very interactive manner showing the geographical region of availability, parts of plant used, mechanism of action and phytoconstituents in different extracts of Costus pictus responsible for particular action, it will be of great importance to the interested readers to focus on the development of the new drug leads for the treatment of diseases.

Efficacy of Quercetin and Kaempferol from Methanolic Extracts of Adiantum lunulatum Burm. F. and Polystichum acrostichoides as Antidiabetic Activity

In present investigation, the aerial parts of two fern species viz. Polystichum acrostichoides (PA) and Adiantum lunulatum (AL) were used to evaluate the potent antidiabetic activity. Methanol solvent was used for extraction by soxhlation method followed by LC-MS analysis to identify the presence of compounds in both the extracts. Further, isolation of the major compounds was carried out and characterized by IR, mass and NMR techniques. Thereafter, in vitro α-amylase inhibitory activity for both the extracts was determined by comparing with acarbose as standard. Thereafter, α-glucosidase inhibition activity followed by glucose uptake was studied using L6 cell line study. Practical yield for both the fern extracts was calculated and observed A. lunulatum extract showed more yield (7 g) than P. acrostichoides (3 g). Based on the analytical data, isolated compound was identified as quercetin and kaempferol from the A. lunulatum and P. acrostichoides extracts, respectively. A. lunulatum extract even showed better dose dependent α-amylase inhibition and α-glucosidase inhibition activity than P. acrostichoides furthermore, L6 cell line study showed increased glucose uptake by A. lunulatum extract than P. acrostichoides extract when compared with standard insulin. Based on the findings, it appears that the both A. lunulatum and P. acrostichoides have the potential to be used as antidiabetic drugs due to presence of major isolated flavonoids i.e. quercetin and kaempferol as among the bioactive compounds. Antidiabetic efficacy was dosage dependent and A. lunulatum extract was more effective in inhibiting glucose uptake than P. acrostichoides extract.

Oral glucose tolerance assay of extract from Mangifera foetida l. and Pandanus amaryllifolius roxb. leaves

This study examines the potential antidiabetic activity of a combination of Mangifera foetida L. and Pandanus amaryllifolius Roxb. leaves. Mangifera leaves contain a compound called mangiferin, which acts as an antidiabetic and antioxidant. On the other hand, Pandanus leaves, are rich in terpenoids and steroids that also possess anti-diabetic effects. An Oral Glucose Tolerance Test (OGTT) was conducted on male mice of the Babl/c strain to assess the antidiabetic effects. The test involved administering a combination of ethanolic leaf extracts from Mangifera foetida L. and Pandanus amaryllifolius Roxb. in a 1:1 ratio. The study followed a pre-test design with a control group, comprising six treatment groups, each consisting of four male mice. The groups were described as follows: Group 1 was served as the normal group without any treatment. Groups II-IV received single extracts or combinations of extracts at doses of 62.5 mg/200g BW, 125 mg/200g BW, and 250 mg/200g BW. Group V acted as the positive control and was given oral glucose and glibenclamide at a dose of 0.09 mg/200g BW. Group VI was served as the negative control, receiving oral glucose and distilled water. The group that exhibited the highest percentage of decreased blood sugar levels was the one given oral glucose at a dose of 0.078g/20g BW of mice, along with the combination of Mangifera foetida L. and Pandanus amaryllifolius Roxb. leaves extract (1:1) at a dose of 35 mg/20g BW. This group demonstrated a decrease of 71.985 ± 4.858 in blood glucose levels. The ANOVA analysis confirmed that the percentage decrease in blood sugar levels was significantly different from the positive control, indicating a higher effectiveness of the combination treatment in reducing blood glucose levels than the positive control.

Potential Antidiabetic Activity of Apis mellifera Propolis Extraction Obtained with Ultrasound.

Recent studies have linked phenolic compounds to the inhibition of digestive enzymes. Propolis extract is consumed or applied as a traditional treatment for some diseases. More than 500 chemical compounds have been identified in propolis composition worldwide. This research aimed to determine Mexican propolis extracts' total phenolic content, total flavonoid content, antioxidant activity, and digestive enzyme inhibitory activity (ɑ-amylase and ɑ-glucosidase). In vitro assays measured the possible effect on bioactive compounds after digestion. Four samples of propolis from different regions of the state of Oaxaca (Mexico) were tested (Eloxochitlán (PE), Teotitlán (PT), San Pedro (PSP), and San Jerónimo (PSJ)). Ethanol extractions were performed using ultrasound. The extract with the highest phenolic content was PE with 15,362.4 ± 225 mg GAE/100 g. Regarding the flavonoid content, the highest amount was found in PT with 8084.6 ± 19 mg QE/100 g. ABTS•+ and DPPH• radicals were evaluated. The extract with the best inhibition concentration was PE with 33,307.1 ± 567 mg ET/100 g. After simulated digestion, phenolics, flavonoids, and antioxidant activity decreased by 96%. In contrast, antidiabetic activity, quantified as inhibition of ɑ-amylase and ɑ-glucosidase, showed a mean decrease in enzyme activity of approximately 50% after the intestinal phase. Therefore, it is concluded that propolis extracts could be a natural alternative for treating diabetes, and it would be necessary to develop a protective mechanism to incorporate them into foods.

Identification and molecular docking of a novel antidiabetic peptide from protamex-camel milk protein hydrolysates against α-amylase and DPP-IV

Antidiabetic peptides were identified from camel milk protein hydrolysates, and their inhibitory activities against α-amylase and dipeptidyl peptidase-IV (DPP-IV) were determined. The possible binding mechanism between the enzymes and the peptide was elucidated through molecular docking. Camel milk proteins were hydrolyzed using protamex, and the hydrolysates were divided into three fractions (>10, 3–10, and <3 kDa) through ultrafiltration. Fraction <3 kDa was more effective at inhibiting α-amylase and DPP-IV and was purified through gel chromatography and identified through LC-MS/MS. In total, 20 peptides were considered as potential bioactive peptides, mainly derived from β-casein. The novel peptide QEPVPDPVRGL exhibited the most potent antidiabetic activity and spontaneously interacted with α-amylase and DPP-IV through hydrogen bonds, salt bridges, and pi–alkyl, thereby occupying their active cavities. This study indicated that camel milk protein hydrolysates are good sources of peptides with antidiabetic potential.

Innovation of 6-sulfonamide-2H-chromene derivatives as antidiabetic agents targeting α-amylase, α-glycosidase, and PPAR-γ inhibitors with in silico molecular docking simulation.

A new series of 2-imino or 2-oxo-2H-chromene-6-sulfonamide derivatives 2-9 with potential anti-diabetic activity were designed and synthesized. The new 6-sulfonamide chromenes were synthesized by reacting 3-formyl-4-hydroxybenzenesulfonyl chloride with activated methylene derivatives in the presence of ammonium acetate as a catalyst. The structure of the products was confirmed by spectroscopic analysis. All the designed derivatives 2-9 were evaluated for their activity against α-amylase and exhibited inhibitory percentage values higher than 93% at 100 μg mL-1. Additionally, the IC50 values represented a variable degree of activity with two derivatives 2 and 9 exhibiting the most promising derivative results with IC50 values of 1.76 ± 0.01 and 1.08 ± 0.02 μM, respectively, compared to Acarbose (IC50 = 0.43 ± 0.01 μM). Additionally, these derivatives showed potency against the α-glucosidase enzyme with IC50 values of 0.548 ± 0.02 and 2.44 ± 0.09 μg mL-1, compared to Acarbose (0.604 ± 0.02 μg mL-1). Moreover, the in vitro PPAR-γ transactivation assay revealed that chromene-6-sulfonamide derivatives 2 and 9 exhibited potential PPAR-γ activity with IC50 values of 3.152 ± 0.03 and 3.706 ± 0.32 μg mL-1, respectively, compared to Pioglitazone (4.884 ± 0.29 μg mL-1). This indicates that these derivatives have insulin sensitivity and glucose metabolism activity. The in silico ADMET prediction showed that these derivatives have an acceptable range of oral bioavailability, drug-likeness, and a safe toxicity profile, including being non-cytotoxic, non-mutagenic, non-immunotoxic, and non-carcinogenic. Finally, computational docking analysis demonstrated the ability of these derivatives to interact with α-amylase, α-glucosidase, and PPAR-γ enzymes, with confirmed successful placement due to good binding energy values and various interactions within the pocket.

Design, Synthesis, and Molecular Docking Studies of Integrated Benzylidenethiazolidine‐2,4‐Dione and Thieno[2,3‐d]pyrimidine‐6‐Carboxylate Derivatives as Potent Antidiabetic agents

AbstractThe present work describes the synthesis of new series of 5‐arylidene‐thiazolidine‐2,4‐dione, thieno[2,3‐d]pyrimidine‐6‐carboxylate derivatives 9 a–o. A variety of spectroscopic techniques like IR, 13CNMR, 1HNMR and LCMS were used to establish the presence of the every synthesized scaffold. The antioxidant activity of the target compounds has been studied by three different methods indicated the significant DPPH, NO and H2O2. Further, all the derivatives were evaluated for the in vitro antidiabetic potential against human pancreatic α‐amylase (PDB ID: 5NN3) and human lysosomal acid α‐glucosidase (PDB ID: 2QV4) enzymes followed by Molecular docking studies to ascertain the binding interactions of the compounds with the enzymes. The compounds 9 b and 9 g containing methoxy groups were found to exhibit potent antidiabetic and antioxidant activity. Therefore, it was rationalized that two privileged pharmacophores i. e. aryledenethiazolidine‐2,4‐dione and thieno[2,3‐d]pyrimidine‐6‐carboxylate assimilated hybrids, may be beneficial as lead template for the advance of future anti‐diabetic agents. Thus, benzylidenethiazolidine‐2,4‐dione and thieno[2,3‐d], the two preferred pharmacophores, were rationalized. Assimilation of ‐pyrimidine‐6‐carboxylate hybrids could be advantageous as a lead template for the development of new anti‐diabetic drugs.