Multitargeted inhibition of key enzymes associated with diabetes and Alzheimer's disease by 1,3,4-oxadiazole derivatives: Synthesis, in vitro screening, and computational studies.

A library of 22 derivatives of 1,3,4-oxadiazole-2-thiol was synthesized, structurally characterized, and assessed for its potential to inhibit α-amylase, α-glucosidase, acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and antioxidant activities. Most of the tested compounds demonstrated good to moderate inhibition potential; however, their activity was lower than that of the standard acarbose. Significantly, compound 3f exhibited the highest inhibition potential against α-glucosidase and α-amylase enzymes, with IC50 values of 18.52 ± 0.09 and 20.25 ± 1.05 µM, respectively, in comparison to the standard acarbose (12.29 ± 0.26; 15.98 ± 0.14 µM). Compounds also demonstrated varying degrees of inhibitory potential against AChE (IC50 = 9.25 ± 0.19 to 36.15 ± 0.12 µM) and BChE (IC50 = 10.06 ± 0.43 to 35.13 ± 0.12 µM) enzymes compared to the standard donepezil (IC50 = 2.01 ± 0.12; 3.12 ± 0.06 µM), as well as DPPH (IC50 = 20.98 ± 0.06 to 52.83 ± 0.12 µM) and ABTS radical scavenging activities (IC50 = 22.29 ± 0.18 to 47.98 ± 0.03 µM) in comparison to the standard ascorbic acid (IC50 = 18.12 ± 0.15; 19.19 ± 0.72). The kinetic investigations have demonstrated that the compounds exhibit competitive-type inhibition for α-amylase, noncompetitive-type inhibition for α-glucosidase and AChE, and mixed-type inhibition for BChE. Additionally, a molecular docking study was performed on all synthetic oxadiazoles to explore the interaction details of these compounds with the active sites of the enzymes.

Bioevaluation of synthetic pyridones as dual inhibitors of α-amylase and α-glucosidase enzymes and potential antioxidants.

Herein, a library of novel pyridone derivatives 1-34 was designed, synthesized, and evaluated for α-amylase and α-glucosidase inhibitory as well as antioxidant activities. Pyridone derivatives 1-34 were synthesized via a one-pot multi-component reaction of variously substituted aromatic aldehydes, acetophenone, ethyl cyanoacetate, and ammonium acetate in absolute ethanol. Synthetic compounds 1-34 were structurally characterized by different spectroscopic techniques. Most of the tested compounds showed more promising inhibition potential than the standard acarbose (IC50 = 14.87 ± 0.16 µM) but compounds 13 and 12 were found to be the most potent compounds with IC50 values of 9.20 ± 0.14 µM and 3.05 ± 0.18 µM against α-amylase and α-glucosidase enzymes, respectively. Compounds 1-34 also displayed moderate antioxidant potential in the range of IC50 = 96.50 ± 0.45 to 189.98 ± 1.00 µM in comparison to the control butylated hydroxytoluene (BHT) (IC50 = 66.50 ± 0.36 µM), in DPPH radical scavenging activities. Additionally, all synthetic derivatives were subjected to a molecular docking study to investigate the interaction details of compounds 1-34 (ligands) with the active site of enzymes (receptors). These results indicate that the newly synthesized pyridone class may serve as promising lead candidates for controlling diabetes mellitus and as antioxidants.

Indole Derivatives: Unveiling New Frontiers in Medicinal and Synthetic Organic Chemistry.

In recent years, significant attention has been given to indoles, a diverse group of heterocyclic compounds widely found in nature that play a crucial role in various bioactive natural and synthetic substances [...].

Application of Synergistic Phenomena for Enhanced Production of Alpha 1,4 D- Glucan Glucanohydrolase Using Submerged Fermentation.

The study revealed enhanced production of α 1, 4 D glucan glucanohydrolase utilizing the synergistic phenomena of bacterial hetero-culture. For this purpose, 101 hetero-cultures were screened qualitatively and quantitatively. The bacterial hetero-culture showing the highest amylolytic potential was identified as Bacillus subtilis and Bacillus amyloliquefeciens by 16S rDNA sequencing technique. Different fermentation media were evaluated and M 5 gave maximum GGH production. Different physicochemical parameters like incubation time, temperature, initial pH and inoculum size was optimized. The optimal enzyme production was obtained at 24 h, 37oC, pH 7.0 and 3% inoculum size. Glucose (3%), ammonium sulphate (1.5%) and yeast extract (2.0%) was selected as best carbon and nitrogen source, respectively. The novelty of the present piece of research was the application of the hetero-culture technique for enhanced GGH production using submerged fermentation which was not experienced before with these strains.

Biology-oriented drug synthesis and evaluation of secnidazole esters as novel enzyme inhibitors.

The identification of novel compounds that can inhibit physiologically and metabolically important drug targets or enzymes has prime importance in medicinal chemistry. With this aim, a range of secnidazole esters 1-30 were synthesized under the heading of biology-oriented drug synthesis by the 1,1'-carbonyldiimidazole-mediated coupling reaction between secnidazole and varyingly benzoic acid derivatives. All compounds were screened for inhibitory activity against human carbonic anhydrase (hCA) I and II, acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and α-glucosidase. The results indicate that all the synthesized compounds showed potent inhibitory activities against all targets, as compared to the standard inhibitors, revealed by IC50 values. Ki values of the secnidazole derivatives 1-30 for hCA I, hCA II, AChE, BChE, and α-glucosidase enzymes were obtained in the ranges of 47.37-190.74, 44.38-198.21, 12.14-68.37, 8.04-61.53, and 7.78-45.91 nM, respectively. To assess the enzyme-ligand interactions, the optimized most active compounds 2, 3, 8, 9, 14, 17, and 23 were subjected to molecular docking studies with modeled AChE, BChE, hCA I, hCA II, and α-glucosidase enzymes, where several important and key interactions were monitored with amino acid residues of each target enzyme.

Isatin thiazoles as antidiabetic: Synthesis, in vitro enzyme inhibitory activities, kinetics, and in silico studies.

Diabetes mellitus is one of the most prevalent diseases nowadays. Several marketed drugs are available for the cure and treatment of diabetes, but there is still a dire need of introducing compatible drug molecules with lesser side effects. The current study is based on the synthesis of isatin thiazole derivatives 4-30 via the Hantzsch reaction. The synthetic compounds were characterized using different spectroscopic techniques and evaluated for their α-amylase and α-glucosidase inhibition potential. Of 27 isatin thiazoles, five (4, 5, 10, 12, and 16) displayed good activities against the α-amylase enzyme with IC50 values in the range of 22.22 ± 0.02-27.01 ± 0.06 µM, and for α-glucosidase, the IC50 values of these compounds were in the range of 20.76 ± 0.17-27.76 ± 0.17 µM, respectively. The binding interactions of the active molecules within the active site of enzymes were studied with the help of molecular docking studies. In addition, kinetic studies were carried out to examine the mechanism of action of the synthetic molecules as well. Compounds 3a, 4, 5, 10, 12, and 16 were also examined for their cytotoxic effect and were found to be noncytotoxic. Thus, several molecules were identified as good antihyperglycemic agents, which can be further modified to enhance inhibition ability and to find the lead molecule that can act as a potential antidiabetic agent.

Virtual Screening, Synthesis and Biological Evaluation of Streptococcus mutans Mediated Biofilm Inhibitors.

Dental caries, a global oral health concern, is a biofilm-mediated disease. Streptococcus mutans, the most prevalent oral microbiota, produces extracellular enzymes, including glycosyltransferases responsible for sucrose polymerization. In bacterial communities, the biofilm matrix confers resistance to host immune responses and antibiotics. Thus, in cases of chronic dental caries, inhibiting bacterial biofilm assembly should prevent demineralization of tooth enamel, thereby preventing tooth decay. A high throughput screening was performed in the present study to identify small molecule inhibitors of S. mutans glycosyltransferases. Multiple pharmacophore models were developed, validated with multiple datasets, and used for virtual screening against large chemical databases. Over 3000 drug-like hits were obtained that were analyzed to explore their binding mode. Finally, six compounds that showed good binding affinities were further analyzed for ADME (absorption, distribution, metabolism, and excretion) properties. The obtained in silico hits were evaluated for in vitro biofilm formation. The compounds displayed excellent antibiofilm activities with minimum inhibitory concentration (MIC) values of 15.26-250 µg/mL.

Synthesis of azachalcones, their α-amylase, α-glucosidase inhibitory activities, kinetics, and molecular docking studies.

Diabetes being a chronic metabolic disorder have attracted the attention of medicinal chemists and biologists. The introduction of new and potential drug candidates for the cure and treatment of diabetes has become a major concern due to its increased prevelance worldwide. In the current study, twenty-seven azachalcone derivatives 3-29 were synthesized and evaluated for their antihyperglycemic activities by inhibiting α-amylase and α-glucosidase enzymes. Five compounds 3 (IC50 = 23.08 ± 0.03 µM), (IC50 = 26.08 ± 0.43 µM), 5 (IC50 = 24.57 ± 0.07 µM), (IC50 = 27.57 ± 0.07 µM), 6 (IC50 = 24.94 ± 0.12 µM), (IC50 = 27.13 ± 0.08 µM), 16 (IC50 = 27.57 ± 0.07 µM), (IC50 = 29.13 ± 0.18 µM), and 28 (IC50 = 26.94 ± 0.12 µM) (IC50 = 27.99 ± 0.09 µM) demonstrated good inhibitory activities against α-amylase and α-glucosidase enzymes, respectively. Acarbose was used as the standard in this study. Structure-activity relationship was established by considering the parent skeleton and different substitutions on aryl ring. The compounds were also subjected for kinetic studies to study their mechanism of action and they showed competitive mode of inhibition against both enzymes. The molecular docking studies have supported the results and showed that these compounds have been involved in various binding interactions within the active site of enzyme.

Indole acrylonitriles as potential anti-hyperglycemic agents: Synthesis, α-glucosidase inhibitory activity and molecular docking studies.

One of the most prevailing metabolic disorder diabetes mellitus has become the global health issue that has to be addressed and cured. Different marketed drugs have been made available for the treatment of diabetes but there is still a need of introducing new therapeutic agents that are economical and have lesser or no side effects. The current study deals with the synthesis of indole acrylonitriles (3-23) and the evaluation of these compounds for their potential for α-glucosidase inhibition. The structures of these synthetic molecules were deduced by using different spectroscopic techniques. Acarbose (IC50 = 2.91 ± 0.02 µM) was used as standard in this study and the synthetic molecules (3-23) have shown promising α-glucosidase inhibitory activity. Compounds 4, 8, 10, 11, 14, 18, and 21 displayed superior inhibition of α-glucosidase enzyme in the range of (IC50 = 0.53 ± 0.01-1.36 ± 0.04 µM) as compared to the standard acarbose. Compound 10 (IC50 = 0.53 ± 0.01 µM) was the most effective inhibitor of this library and displayed many folds enhanced activity in contrast to the standard. Molecular docking of synthetic compounds was performed to verify the binding interactions of ligand with the active site of enzyme. This study had identified a number of potential α-glucosidase inhibitors that can be used for further research to identify a potent therapeutic agent against diabetes.

Association of hepatocyte growth factor gene polymorphisms with primary angle closure glaucoma from Lahore, Pakistan.

OBJECTIVE: To determine the association of hepatocyte growth factor gene single nucleotide polymorphismsrs 5745718 and rs17427817 with primary angle closure glaucoma.. METHODS: This case-control study was conducted at the Department of Biotechnology, Lahore College for Women University, Lahore, Pakistan, from August 2016 to September 2017. In this study seventy sporadic cases of primary angle closure glaucoma and sixty healthy controls were enrolled from different hospitals of the Lahore, Punjab. Blood samples were obtained from all the subjects. Genomic deoxyribonucleic acid was extracted by non-organic method. Two single nucleotide polymorphism (SNPs) rs5745718 and rs17427817 in Hepatocytes Growth Factor (HFG) gene were genotyped in patients and ethnically same healthy controls by using polymerase chain reaction restriction fragment length polymorphism (RFLP) assay. Data was analysed using SPSS (version20). RESULTS: Of the 130 subjects, 70(54%) were cases and 60(46%) controls. The mean age of the cases was 54±17 years (range: 13-85 years). The differences in genotype distribution were statistically significant for rs 5745718 (p=0.005 and p=0.009), while results were not significant for rs 17427817 (p=0.06 and p=0.09) between the cases and the controls. CONCLUSIONS: AC alleles were found to be protective while CC alleles were a risk factor for primary angle closure glaucoma in rs5745718 single nucleotide polymorphism.

Multiple upstream start codons (AUG) in 5' untranslated region enhance translation efficiency of cry2Ac11 without helper protein.

Cry2Ac11, a 65 kDa insecticidal protein produced by Bacillus thuringiensis, shows toxicity against dipteran and lepidopteran larvae. It is encoded by cry2Ac11 gene ( orf3), which is part of an operon comprising orf1, orf2, and orf3. Orf2, a helper protein, helps in proper folding and prevents aberrant aggregation of newly produced molecules. In this study, we have elucidated the effect of different mutations in translation initiation region (TIR), particularly the ribosomal binding site and the start codon (RBS-ATG) on cry2Ac11 gene expression without helper protein. All recombinant constructs were expressed in acrystalliferous B. thuringiensis subsp israelensis 4Q7 under the control of strong chimeric promoter cyt1AP/STAB. Of all the mutants, mut/RBS2, with two consecutive AUGs after the spacer region in TIR, exhibited 89- and 2246-fold higher transcript levels compared with 4Q7-operSalI/RBS ( cry2Ac11 operon) and 4Q7-w-RBS ( cry2Ac11 gene), respectively. The analysis of mut/RBS2 messenger RNA (mRNA) structure in the RBS-AUG region showed the presence of RBS in the single-stranded part of the moderately stable hairpin loop. The high expression efficiency of Cry2Ac11 mutant without helper protein is a cumulative and cooperative result of chimeric promoter cyt1AP/STAB-SD with the optimal context of RBS-AUG region provided by multiple AUGs and stabilizer sequence at 3' ends.

Influence of medium composition and physical factors on enhanced production of endoglucanase by locally isolated fungal strain in solid state fermentation.

Endoglucanase is one of the most important enzymes of the cellulase group.  Endoglucanase are involved in the catalytic hydrolysis of cellulose and plays a pivotal role in different sectors like pharmaceutical, textile, detergent, and food processing as well as paper and pulp industry. With consumers getting more and more aware of environmental issues, industries find enzymes as a better option over other chemical catalysts. In the current research different thermophilic fungal strains were isolated from the different sources. Qualitative screening was carried out on the basis of cellulose hydrolysis zone. The quantitative screening was carried out employing solid state fermentation.  The fungal culture, showing highest EG potential was selected identified and assigned the code Aspergillus fumigatus BBT2. Different fermentation media were evaluated and M 2 containing wheat bran gave maximum EG production. The maximal enzyme productivity was recorded in 72 hours, 40°C, pH 5, inoculum size 1.5ml, and moisture content (1:1). Glucose (1%) and peptone (1%) were optimized as best carbon and nitrogen sources, respectively.

Drug Non-Adherence In Type 2 Diabetes Mellitus; Predictors And Associations.

BACKGROUND: Diabetes being a serious health issue faced by developing countries with drug adherence having pivot role for recommended glycaemic target. This study aims to determine drug non-adherence in type 2 diabetics and its predictors and associations. METHODS: This cross sectional study was conducted after ethical approval at Medicine Dept. Rawal Institute of Health Sciences Islamabad over 10 months duration. Demographic details, duration of diabetes, education, socioeconomic class, glycaemic control, mode of anti-diabetic therapy, number of medications and other modes of therapy documented. Michigan Diabetes Knowledge Questionnaire applied with outcome as good, acceptable and poor knowledge. Drug adherence was assessed by Morisky Medication Adherence Scale (non-adherence at <6 points). Data analysed via SPSS version 17 with significant p-value <0.05. RESULTS: Among 183 diabetics there were 43 (23.5%) males and 140 (76.5%) females. Mean age was 56.6±10.6 years and mean duration of diabetes 8.4±6.57 years. One hundred and fourteen (62%) cases were non-adherent. Diabetes knowledge was poor in 76 (41.5 %), acceptable in 76 (41.5 %) and good in 31 (16.9%). Un-satisfactory glycaemic control present in 149 (81.4%). Non-adherence was found to be associated with poor glycaemic control, poor dietary adherence, poly-pharmacy, illiteracy, practicing other modes of therapy and poor diabetes knowledge (p<0.05). CONCLUSIONS: Nonadherence to medication in type 2 diabetics needs to be addressed. Suggested contributory factors are illiteracy, practicing other modes of therapy, poor diabetes knowledge and poly-pharmacy. Public awareness programs, self-monitoring of blood sugars, regular follow-up visits with focus at patient education may improve glycaemic control and diabetes related complications.

Contribution of GLC3A locus to Primary Congenital Glaucoma in Pakistani population.

OBJECTIVES: To check the contribution of GLC3A locus to primary congenital glaucoma in the Pakistani population. METHODS: We enrolled twenty-nine sporadic cases and three families with multiple individuals affected with recessive primary congenital glaucoma in the year 2013. It was a genetic linkage study accomplished jointly in Department of Biotechnology of Lahore College for Women University and School of Biological Sciences, University of the Punjab, Lahore. Samples from all affected individuals were checked for homozygosity for alleles of microsatellite markers spanning CYP1B1 at GLC3A locus. Genotyping was performed with fluorescently labeled primers by capillary electrophoresis. For familial cases, linkage was evaluated by checking the co-segregation of the phenotype with the genotypes. Two-point LOD score was calculated for each microsatellite marker with MLINK. RESULTS: Our study revealed that GLCA3 may contribute to glaucoma in 17% of the sporadic cases and patients in 2 of the 3 families. CONCLUSIONS: This data suggests that the GLC3A may make an important contribution to autosomal recessive primary congenital glaucoma in the Pakistani population. Genotyping and Sequencing of more families will be helpful to identify the common mutations in CYP1B1 in future.

Evaluating the impact of technological innovation and energy efficiency on load capacity factor: empirical analysis of India.

The determinants of environmental degradation have been investigated many times by utilizing carbon dioxide emissions and/or ecological footprint. However, these traditional environmental degradation indicators do not consider the supply side of environmental problems. Therefore, this study focuses on the dynamic influence of financial development, energy efficiency, economic growth, and technological innovation on environmental degradation in India through the load capacity factor, including both the supply and demand sides of environmental problems. For that purpose, the recently developed dynamically simulated autoregressive distributed lag (ARDL) method is employed using the annual time-series data extending from 1980-2020. The dynamically simulated ARDL results demonstrate that financial development, economic growth, and technological innovation have a dynamic adverse impact on the load capacity factor, whereas energy efficiency has a positive dynamic influence on environmental quality. In addition, the results support the validity of the environmental Kuznets curve hypothesis as the negative effect of economic growth on environmental quality decreases over time. Based on the study findings, policy recommendations are provided for India. Finally, this study utilizing load capacity factor as an indicator for environmental quality will provide new topics in exploring the determinants of environmental degradation.

Comprehensive bioinformatics-based annotation and functional characterization of bovine chymosin protein revealed novel biological insights.

Chymosin, an aspartic protease present in the stomachs of young ruminants like cows (bovine), causes milk coagulation and cheese production through the breakdown of κ-casein peptide bonds at the Met105-Phe106 site. Bovine chymosin is first synthesized as a pre-prochymosin that is cleaved to produce the mature chymosin protein. Despite significant strides in research, our understanding of this crucial enzyme remains incomplete. The purpose of this work was to perform in silico evolutionary and functional analysis and to gain unique insights into the structure of this protein. For this, the sequence of Bos taurus chymosin from UniProt database was subjected to various bioinformatics analyses. We found that bovine chymosin is a low molecular weight and hydrophilic protein that has homologs in other Bovidae species. Two active sites of aspartic peptidases, along with a functional domain, were identified. Gene Ontology analysis further confirmed chymosin's involvement in proteolysis and aspartic endopeptidase activity. Potential disordered residues and post-translational modification sites were also uncovered. It was revealed that the secondary structure of bovine chymosin is comprised of beta strands (44.27%), coils (43.65%), and alpha helices (12.07%). A highly optimized 3D structure was also obtained. Moreover, crucial protein-protein interactions were unveiled. Altogether, these findings provide valuable insights that could guide future research on bovine chymosin and its biological roles.

Phytochemical and antimicrobial properties of different plants and in silico investigation of their bioactive compounds in wound healing and rheumatism.

In the current study the assessment of the antimicrobial and phytochemical properties of Cassia fistula, Musa paradisiaca, Ficus religiosa and Murraya koenigii plants extracts was carried out. The antibacterial potential of these plants extracts was tested against S. aureus and E. coli. The Cassia fistula and Ficus religiosa leaves showed the larger zone of inhibition in aqueous and butanolic extract respectively against Escherichia coli. Musa paradisiaca and Murraya koenigii leaves showed larger zone of inhibition in ethanolic extract against S. aureus. Qualitative phytochemical analysis showed the presence of alkaloids, flavonoids, phenols, terpenoids, steroids, glycosides, saponins, carbohydrates, proteins and tannins in all extracts while phylobatannins, emodins, anthocyanins and leucoanthocyanins were not present in these extracts. Quantitative phytochemical analysis showed the highest alkaloid content in the Murraya koenigii leaves. Highest tannin content and flavonoid content was found in Ficus religiosa leaves, while highest phenolic content was found in case of Cassia fistula. In addition to this antioxidant potential of all the extracts was determined. Musa paradisiaca leaves showed highest antioxidant potential as compared to other plant extracts. In silico analysis of bioactive components present in plant extracts was performed by molecular docking. The rutin and Glu from Musa paradisiaca and Murraya koenigii respectively, were docked with Glycogen Synthase Kinase 3 beta (1GSK-3beta) protein. Quercetin and rutin from Cassia fistula and Ficus religiosa respectively, were docked with C- reactive protein (CRP). The tested bioactive compounds showed good binding affinity with significant number of hydrogen bonds and can be used as a good alternative of synthetic drugs to treat rheumatism and wounds.

Indenoquinoxaline-phenylacrylohydrazide hybrids as promising drug candidates for the treatment of type 2 diabetes: In vitro and in silico evaluation of enzyme inhibition and antioxidant activity.

Existing drugs that are being used to treat type-2 diabetes mellitus are associated with several side effects; thus, exploring potential drug candidates is still an utter need these days. Hybrids of indenoquinoxaline and hydrazide have never been explored as antidiabetic agents. In this study, a series of new indenoquinoxaline-phenylacrylohydrazide hybrids (1-30) were synthesized, structurally characterized, and evaluated for α-amylase and α-glucosidase inhibitory activities, as well as for their antioxidant properties. All scaffolds exhibited varying degrees of inhibitory activity against both enzymes, with IC50 values ranging from 2.34 to 61.12 µM for α-amylase and 0.42 to 54.72 µM for α-glucosidase. Particularly, compounds 10, 16, 17, 18, 24, and 25 demonstrated the highest efficacy in inhibiting α-amylase, while compounds 6, 7, 8, 10, 12, 14, 13, 16, 17, 18, 24, and 25 were the most effective α-glucosidase inhibitors, compared to standard acarbose. Moreover, most of these compounds displayed substantial antioxidant potential compared to standard butylated hydroxytoluene (BHT). Kinetics studies revealed competitive inhibition modes by compounds. Furthermore, a comprehensive in silico study and toxicity prediction were also conducted, further validating these analogs as potential drug candidates. The structured compounds demonstrated enhanced profiles, underscoring their potential as primary candidates in drug discovery.

Compliance to antipsychotic medication: a challenge for client, family and health care providers.

Compliance with anti-psychotic medications plays a significant role in managing clients with schizophrenia. It not only helps in controlling the symptoms, but also decreases the risk of relapses and ultimately improves quality of life (QoL) for the clients. However, compliance with anti-psychotic medication remains a challenge for the client, family and healthcare providers. Identification of these associated factors is vital to make appropriate plan to enhance medication compliance. In this paper, various factors are highlighted that are associated with medication compliance in clients with schizophrenia.

Prospective Nutraceutical Effects of Cinnamon Derivatives Against Insulin Resistance in Type II Diabetes Mellitus-Evidence From the Literature.

Apart from advances in pharmaceutical antidiabetic agents, efforts are being made toward hypoglycemic agents derived from natural sources. Cinnamon has been reported to have significant benefits for human health, particularly as an anti-inflammatory, antidiabetic, and anti-hypertriglyceridemic agent. The phytochemicals in cinnamon can be extracted from different parts of plant by distillation and solvent extraction. These chemicals help in decreasing insulin resistance and can act against hyperglycemia and dyslipidemia, inflammation and oxidative stress, obesity, overweight, and abnormal glycation of proteins. Cinnamon has shown to improve all of these conditions in in vitro, animal, and/or human studies. However, the mechanism of action of active ingredients found in cinnamon remains unclear. The current review presents the outstanding ability of cinnamon derivatives to control diabetes by various pathways modulating insulin release and insulin receptor signaling. It was also found that the type and dosage of cinnamon as well as subject characteristics including drug interactions are likely to affect the response to cinnamon. Future research directions based on this review include the synergistic usage of various cinnamon derivatives in managing and/or preventing diabetes and possible other relevant chronic diseases.