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Chapter 13: Computational screening of phytochemicals for antidiabetic drug discovery
Abstract
Diabetes is one of the most common chronic and progressive diseases around the world and the number of people with diabetes is projected to rise in the next few years. Although many synthetic drugs are effective in controlling diabetes, their long-term usage has undesirable side effects. Hence, there is a growing scientific interest to replace synthetic drugs with natural drugs from medicinal plants. However, understanding the role of molecules and their interaction are necessary for the effective anti-diabetic drug discovery. Over the years, computational biology methods, such as molecular docking, simulations of biomolecules, computer-aided drug design (CADD), and multi-scale biological modeling have been developed in the drug discovery process. Therefore, the present chapter aimed to understand the characteristics of diabetes, the role of phytochemicals from natural sources in controlling diabetes, and the anti-diabetic mechanism of phytochemicals. The chapter also covers the computational screening techniques using phytochemicals in anti-diabetic drug discovery. Many phytochemicals from natural sources showed potential anti-diabetic properties. The use of CADD will speed up the drug discovery process, mitigate risk, and help to identify well-established targets with more innovative drugs in the future.
... Numerous biological processes involving fatty acids, such as their anti-inflammatory characteristics, help organisms defend themselves [30]. According to the findings of a number of studies, Fagonia indica can both aid in the prevention of bacterial and fungal diseases, and speed up the body's recovery from their effects [31]. those of recognized compounds in the library of the National Institute of Standards and Technology (NIST) [25]. ...
... Numerous biological processes involving fatty acids, such as their anti-inflammatory characteristics, help organisms defend themselves [30]. According to the findings of a number of studies, Fagonia indica can both aid in the prevention of bacterial and fungal diseases, and speed up the body's recovery from their effects [31]. ...
The Aja and Salma mountains in the Hail region are home to a variety of indigenous
wild plants, some of which are used in Bedouin folk medicine to treat various ailments. The purpose of the current study was to unveil the chemical, antioxidant and antibacterial properties of Fagonia indica (Showeka) grown widely in these mountains, as data on the biological activities of this plant in this remote area are scarce. XRF spectrometry indicated the presence of some essential elements, which were in the order of Ca > S > K > AL > CL > Si > P > Fe > Mg > Na > Ti > Sr > Zn > Mn. Qualitative chemical screening revealed the presence of saponins, terpenes, flavonoids, tannins, phenols and cardiac glycosides in the methanolic extract (80% v/v). GC–MS showed the presence of 2-chloropropanoic acid 18.5%, tetrahydro-2-methylfuran 20.1%, tridecanoic acid 12-methyl-, methyl ester 2.2%, hexadecanoic acid, methyl ester 8.6%, methyl 3-(3,5-di-tert-butyl4-hydroxyphenyl) propionate 13.4%, methyl linoleate 7.0%, petroselinic acid methyl ester 15%,
erucylamide 6.7% and diosgenin 8.5%. Total phenols, total tannins, flavonoids, DPPH, reducing power, -carotene and ABTS IC50 (mg/mL) scavenging activity were used to measure the antioxidant capabilities of Fagonia indica, which exhibited prominent antioxidant properties at low concentrations when compared to ascorbic acid, butylate hydroxytoluene and beta-carotene. The antibacterial investigation revealed significant inhibitory effects against Bacillus subtilis MTCC121
and Pseudomona aeruginosa MTCC 741 with inhibition zones of 15.00 ± 1.5 and 12.0 ± 1.0 mm, respectively. The MIC (minimum inhibitory concentration) and MBC (minimum bactericidal concentration) ranged between 125 to 500 µg/mL. The MBC/MIC ratio indicated possible bactericidal efficacy against Bacillus subtilis and bacteriostatic activity against Pseudomona aeruginosa. The study also showed that this plant has anti-biofilm formation activity.
Diabetes mellitus (DM) is a group of metabolic disorders characterized by hyperglycemia, insulin insufficiency or insulin resistance, and many issues, including vascular complications, glycative stress and lipid metabolism dysregulation. Natural products from plants with antihyperglycemic, hypolipidemic, pancreatic protective, antioxidative, and insulin-like properties complement conventional treatments. Throughout this review, we summarize the current status of knowledge of plants from the Caribbean basin traditionally used to manage DM and treat its sequelae. Seven plants were chosen due to their use in Caribbean folk medicine. We summarize the antidiabetic properties of each species, exploring the pharmacological mechanisms related to their antidiabetic effect reported in vitro and in vivo. We propose the Caribbean flora as a source of innovative bioactive phytocompounds to treat and prevent DM and DM-associated complications.
Computer-Aided Drug Design (CADD): From Ligand-Based Methods to Structure-Based Approaches outlines the basic theoretical principles, methodologies and applications of different fundamental and advanced CADD approaches and techniques. Including information on current protocols as well as recent developments in the computational methods, tools and techniques used for rational drug design, the book explains the fundamental aspects of CADD, combining this with a practical understanding of the various in silico approaches used in modern drug discovery processes to assess the field in a comprehensive and systematic manner.
Providing up-to-date, information and guidance for scientists, researchers, students and teachers, the book helps readers address specific academic and research related problems using illustrative explanations, examples and case studies, which are systematically reviewed.
Highlights in silico approaches to drug design and discovery using computational tools and techniques
Details ligand-based and structure-based drug design in a comprehensive and systematic approach
Summarizes recent developments in computational drug design strategy as novel approaches of rational drug designing
Background: Diabetes is a complex disease requiring a multidisciplinary approach. However, the dynamics of this collaboration and the involvement of healthcare providers remain unclear. Aim(s): To explore the composition, the division of roles/tasks, and the collaboration in a diabetes team. Methods: A qualitative, explorative study with six focus groups was conducted, of which four focus groups were with healthcare providers (n = 34) and two with informal caregivers and persons with diabetes (n = 13). In addition, two in-depth interviews with doctors were performed. An iterative process of data analysis took place, guided by the Qualitative Analysis Guide of Leuven (QUAGOL). Results: All participants confirm the importance of patient empowerment and the fact that the person with diabetes should have a central role within the team. However, this has not been achieved yet. This research gives a clear insight into the dynamics of a diabetes team. Roles and tasks are allocated according to the specific expertise and knowledge of the different healthcare providers. Interprofessional collaboration is the ultimate goal. However, the diabetes team is often formed ad hoc depending on the needs of the person with diabetes and the preferences for collaboration of the healthcare providers. Furthermore, this study revealed some important bottlenecks with regard to the knowledge of healthcare providers, persons with diabetes and their informal caregivers, the regulation and reimbursement. Discussion: Our study uncovers the dynamics of a diabetes team and its members. Healthcare providers work mainly alone, except in hospitals, where they can consult other healthcare providers briefly if necessary. Although collaboration proves to be difficult, all healthcare providers ask for a more intensive interprofessional collaboration. Conclusion: In order to improve quality of diabetes care, patient-centered care and the satisfaction of patients, informal caregivers, and healthcare providers, efforts have to be made to facilitate interprofessional collaboration. This can be achieved by sharing information via electronic shared patient records, coordination, overview, local task agreements, simplified legal regulations, and an adjusted financing system.
Citation: Prasad, M.; Jayaraman, S.; Eladl, M.A.; El-Sherbiny, M.; Abdelrahman, M.A.E.; Veeraraghavan, V.P.; Vengadassalapathy, S.; Umapathy, V.R.; Jaffer Hussain, S.F.; Krishnamoorthy, K.; et al. A Comprehensive Review on
Natural products in the form of functional foods have become increasingly popular due to their protective effects against life-threatening diseases, low risk of adverse effects, affordability, and accessibility. Plant components such as phytosterol, in particular, have drawn a lot of press recently due to a link between their consumption and a modest incidence of global problems, such as Type 2 Diabetes mellitus (T2DM), cancer, and cardiovascular disease. In the management of diet-related metabolic diseases, such as T2DM and cardiovascular disorders, these plant-based functional foods and nutritional supplements have unquestionably led the market in terms of cost-effectiveness, therapeutic efficacy, and safety. Diabetes mellitus is a metabolic disorder categoriszed by high blood sugar and insulin resistance, which influence major metabolic organs, such as the liver, adipose tissue, and skeletal muscle. These chronic hyperglycemia fallouts result in decreased glucose consumption by body cells, increased fat mobilisation from fat storage cells, and protein depletion in human tissues, keeping the tissues in a state of crisis. In addition, functional foods such as phytosterols improve the body’s healing process from these crises by promoting a proper physiological metabolism and cellular activities. They are plant-derived steroid molecules having structure and function similar to cholesterol, which is found in vegetables, grains, nuts, olive oil, wood pulp, legumes, cereals, and leaves, and are abundant in nature, along with phytosterol derivatives. The most copious phytosterols seen in the human diet are sitosterol, stigmasterol, and campesterol, which can be found in free form, as fatty acid/cinnamic acid esters or as glycosides processed by pancreatic enzymes. Accumulating evidence reveals that phytosterols and diets enriched with them can control glucose and lipid metabolism, as well as insulin resistance. Despite this, few studies on the advantages of sterol control in diabetes care have been published. As a basis, the primary objective of this review is to convey extensive updated information on the possibility of managing diabetes and associated complications with sterol-rich foods in molecular aspects.
Intellectual property rights (IPR) are intellectual privileges that allow authors and inventors to defend their original inventions from misuse or theft. With the assistance of algorithms, clinical science has taken on a different level in recent years. Various advanced tools can be used to investigate pharmacokinetics profiling, in silico experiments, receptor simulations, drug synergistic effects, and so on. Computational scientists are making continuous efforts to figure out how to connect business models in pharmacology. However, software theft and security rights remain major concerns for all. In order to avoid such violations, IPR compliance for R&D as well as promoting machine applications is critical. This compilation will illustrate diverse software concepts, the latest patent data structures, copyright management laws for software, trade secrets, compliance rights, software patenting and contracts, artificial technology priorities and problems, licenses, and case studies relating to IPR violations in pharmaceutical and other fields.
The burden of diabetes is high and increasing globally, and in developing economies like India, mainly fueled by the increasing prevalence of overweight/obesity and unhealthy lifestyles. The estimates in 2019 showed that 77 million individuals had diabetes in India, which is expected to rise to over 134 million by 2045. Approximately 57% of these individuals remain undiagnosed. Type 2 diabetes, which accounts for majority of the cases, can lead to multiorgan complications, broadly divided into microvascular and macrovascular complications. These complications are a significant cause for increased premature morbidity and mortality among individuals with diabetes, leading to reduced life expectancy and financial and other costs of diabetes leading to profound economic burden on the Indian health care system. The risk for diabetes is largely influence by ethnicity, age, obesity and physical inactivity, unhealthy diet, and behavioral habits in addition to genetics and family history. Good control of blood sugar blood pressure and blood lipid levels can prevent and/or delay the onset of diabetes complications. The prevention and management of diabetes and associated complications is a huge challenge in India due to several issues and barriers, including lack of multisectoral approach, surveillance data, awareness regarding diabetes, its risk factors and complications, access to health care settings, access to affordable medicines, etc. Thus, effective health promotion and primary prevention, at both, individual and population levels are the need of the hour to curb the diabetes epidemic and reduce diabetes-related complications in India.
Homeostatic trafficking of immune cells by CC chemokine receptor 7 (CCR7) keeps immune responses and tolerance in a balance. The involvement of this protein in lymph node metastasis in cancer marks CCR7 as a penitential drug target. Using the crystal structure of CCR7, herein, a comprehensive virtual screening study is presented to filter novel strong CCR7 binding phytochemicals from Saudi medicinal plants that have a higher binding affinity for the intracellular allosteric binding pocket. By doing so, three small natural molecules named as Hit-1 (1,8,10-trihydroxy-3-methoxy-6-methylanthracen-9(4H)-one), Hit-2 (4-(3,4-dimethoxybenzyl)-3-(4-hydroxy-3-methoxybenzyl)dihydrofuran-2(3H)-one), and Hit-3 (10-methyl-12,13-dihydro-[1,2]dioxolo[3,4,5-de]furo[3,2-g]isochromeno[4,3-b]chromen-8-ol) are predicted showing strong binding potential for the CC chemokine receptor 7 allosteric pocket. During molecular dynamics simulations, the compounds were observed in the formation of several chemical bonding of short bond distances. Additionally, the molecules remained in strong contact with the active pocket residues and experienced small conformation changes that seemed to be mediated by the CCR7 loops to properly engage the ligands. Two types of binding energy methods (MM/GBPBSA and WaterSwap) were additionally applied to further validate docking and simulation findings. Both analyses complement the good affinity of compounds for CCR7, the electrostatic and van der Waals energies being the most dominant in intermolecular interactions. The active pocket residue’s role in compounds binding was further evaluated via alanine scanning, which highlighted their importance in natural compounds binding. Additionally, the compounds fulfilled all drug-like rules: Lipinski, Ghose, Veber, Egan, and Muegge passed many safety parameters, making them excellent anti-cancer candidates for experimental testing.
Background
: SARS-CoV-2 infection or COVID-19 is a major global public health issue which requires urgent attention in term of drug development. Transmembrane Protease Serine 2 (TMPRSS2) is a good drug target against SARS-CoV-2 because of the role it plays during the viral entry into the cell. Virtual screening of phytochemicals as potential inhibitors of TMPRSS2 can lead to the discovery of drug candidates for the treatment of COVID-19.
Purpose
: The study was designed to screen 132 phytochemicals from three medicinal plants traditionally used as antivirals; Zingiber officinalis Roscoe (Zingiberaceae), Artemisia annua L. (Asteraceae), and Moringa oleifera Lam. (Moringaceae), as potential inhibitors of TMPRSS2 for the purpose of finding therapeutic options to treat COVID-19.
Methods
: Homology model of TMPRSS2 was built using the ProMod3 3.1.1 program of the SWISS-MODEL. Binding affinities and interaction between compounds and TMPRSS2 model was examined using molecular docking and molecular dynamics simulation. The drug-likeness and ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties of potential inhibitors of TMPRSS2 were also assessed using admetSAR web tool.
Results
: Three compounds, namely, niazirin, quercetin, and moringyne from M. oleifera demonstrated better molecular interactions with binding affinities ranging from -7.1 to -8.0 kcal/mol compared to -7.0 kcal/mol obtained for camostat mesylate (a known TMPRSS2 inhibitor), which served as a control. All the three compounds exhibited good drug-like properties by not violating the Lipinski rule of 5. Niazirin and moringyne possessed good ADMET properties and were stable in their interactions with the TMPRSS2 based on the molecular dynamics simulation. However, the ADMET tool predicted the potential hepatotoxic and mutagenic effects of quercetin.
Conclusion
: This study demonstrated the potentials of niazirin, quercetin, and moringyne from M. oleifera, to inhibit the activities of human TMPRSS2, thus probably being good candidates for further development as new drugs for the treatment or management of COVID-19.
Background
Medicinal plants are used to treat various disorders, including diabetes, globally in a range of formulations. While attention has mainly been on the aerial plant parts, there are only a few review studies to date that are focused on the natural constituents present in the plant roots with health benefits. Thus, the present study was performed to review in vivo studies investigating the antidiabetic potential of the natural compounds in plant roots.
Methods
We sorted relevant data in 2001–2019 from scientific databases and search engines, including Web of Knowledge, PubMed, ScienceDirect, Medline, Reaxys, and Google Scholar. The class of phytochemicals, plant families, major compounds, active constituents, effective dosages, type of extracts, time of experiments, and type of diabetic induction were described.
Results
In our literature review, we found 104 plants with determined antidiabetic activity in their root extracts. The biosynthesis pathways and mechanism of actions of the most frequent class of compounds were also proposed. The results of this review indicated that flavonoids, phenolic compounds, alkaloids, and phytosteroids are the most abundant natural compounds in plant roots with antidiabetic activity. Phytochemicals in plant roots possess different mechanisms of action to control diabetes, including inhibition of α -amylase and α -glucosidase enzymes, oxidative stress reduction, secretion of insulin, improvement of diabetic retinopathy/nephropathy, slow the starch digestion, and contribution against hyperglycemia.
Conclusion
This review concludes that plant roots are a promising source of bioactive compounds which can be explored to develop against diabetes and diabetes-related complications.
Graphical abstract
Preparation of Phytopharmaceuticals for the Management of Disorders presents a comprehensive coverage on the essentials and important recent advances in phytopharmaceuticals, nutraceuticals, traditional and alternative systems of medicines. The introductory section presents chapters that explain the concepts of phytopharmaceuticals, the history and the current highlights in phytomedicine. Also included are herbal remedy and toxicity, traditional and alternative system of medicines, nanotechnology applications, and herbal cosmeticology. The next section presents chapters on the applications of microbiology and biotechnology in drug discovery, while the concluding section details the health benefits of nutraceuticals. Preparation of Phytopharmaceuticals for the Management of Disorders provides introduces key frameworks and information for everyone interested in drug discovery including medicinal chemists, nutritionists, biochemists, toxicologists, drug developers, and health care professionals. Students, professors, and researchers working in the area of pharmaceutical sciences and beyond will find the book useful.
Background
Chronic conditions are a leading cause of death and disability worldwide. Low-income and middle-income countries such as India bear a significant proportion of this global burden. Redesigning primary care from an acute-care model to a model that facilitates chronic care is a challenge and requires interventions at multiple levels.
Objectives
In this intervention study, we aimed to strengthen primary care for diabetes and hypertension at publicly funded primary healthcare centres (PHCs) in rural South India.
Design and methods
The complexities of transforming the delivery of primary care motivated us to use a ‘theory of change’ approach to design, implement and evaluate the interventions. We used both quantitative and qualitative data collection methods. Data from patient records regarding processes of care, glycaemic and blood pressure control, interviews with patients, observations and field notes were used to analyse what changes occurred and why.
Interventions
We implemented the interventions for 9 months at three PHCs: (1) rationalise workflow to include essential tasks like counselling and measurement of blood pressure/blood glucose at each visit; (2) distribute clinical tasks among staff; (3) retain clinical records at the health facility and (4) capacity building of staff.
Results
We found that interventions were implemented at all three PHCs for the first 4 months but did not continue at two of the PHCs. This fadeout was most likely the result of staff transfers and a doctor’s reluctance to share tasks. The availability of an additional staff member in the role of a coordinator most likely influenced the relative success of implementation at one PHC.
Conclusion
These findings draw attention to the need for building teams in primary care for managing chronic conditions. The role of a coordinator emerged as an important consideration, as did the need for a stable core of staff to provide continuity of care.
The strategy of reducing carbohydrate digestibility by controlling the activity of two hydrolyzing enzymes (α‐amylase and α‐glucosidase) to control postprandial hyperglycemia is considered as a viable prophylactic treatment of type 2 diabetes mellitus (T2DM). Thus, the consumption of foods rich in hydrolyzing enzyme inhibitors is recommended for diet therapy of diabetes. Whole cereal products have gained increasing interests for plasma glucose‐reducing effects. However, the mechanisms for whole cereal benefits in relation to T2DM are not yet fully understood, but most likely involve bioactive components. Cereal‐derived phenolic compounds, peptides, nonstarch polysaccharides, and lipids have been shown to inhibit α‐amylase and α‐glucosidase activities. These hydrolyzing enzyme inhibitors seem to make whole cereals become nutritional strategies in managing postmeal glucose for T2DM. This review presents an updated overview on the effects provided by cereal‐derived ingredients on carbohydrate digestibility. It suggests that there is some evidence for whole cereal intake to be beneficial in amelioration of T2DM through inhibiting α‐glucosidase and α‐amylase activities. The cereal‐derived α‐amylase and/or α‐glucosidase inhibitor could be targeted for developing valuable whole cereal foods in T2DM dietary managements.
Diabetes is a major threat to people's health and has become a burden worldwide. Current drugs for diabetes have limitations, such as different drug responses among individuals, failure to achieve glycemic control, and adverse effects. Exploring more effective therapeutic strategies for patients with diabetes is crucial. Currently pharmacogenomics has provided potential for individualized drug therapy based on genetic and genomic information of patients, and has made precision medicine possible. Responses and adverse effects to antidiabetic drugs are significantly associated with gene polymorphisms in patients. Many new targets for diabetes also have been discovered and developed, and even entered clinical trial phases. This review summarizes pharmacogenomic evidence of some current antidiabetic agents applied in clinical settings, and highlights potential drugs with new targets for diabetes, which represent a more effective treatment in the future.
Anthocyanins are a class of water-soluble flavonoids widely present in fruits and vegetables. Dietary sources of anthocyanins include red and purple berries, grapes, apples, plums, cabbage, or foods containing high levels of natural colorants. Cyanidin, delphinidin, malvidin, peonidin, petunidin, and pelargonidin are the six common anthocyanidins. Following consumption, anthocyanin, absorption occurs along the gastrointestinal tract, the distal lower bowel being the place where most of the absorption and metabolism occurs. In the intestine, anthocyanins first undergo extensive microbial catabolism followed by absorption and human phase II metabolism. This produces hybrid microbial–human metabolites which are absorbed and subsequently increase the bioavailability of anthocyanins. Health benefits of anthocyanins have been widely described, especially in the prevention of diseases associated with oxidative stress, such as cardiovascular and neurodegenerative diseases. Furthermore, recent evidence suggests that health-promoting effects attributed to anthocyanins may also be related to modulation of gut microbiota. In this paper we attempt to provide a comprehensive view of the state-of-the-art literature on anthocyanins, summarizing recent findings on their chemistry, biosynthesis, nutritional value and on their effects on human health.
With sustained growth of diabetes numbers, sustained
patient engagement is essential. Using nationally available
data, we have shown that the higher mortality associated
with a diagnosis of T1DM/T2DM could produces loss of
6.4 million future life years in the current UK population.
In the model, the ‘average’ person with T1DM (age
42.8 years) has a life expectancy from now of 32.6 years,
compared to 40.2 years in the equivalent age non diabetes
mellitus population, corresponding to lost life years (LLYs)
of 7.6 years/average person. The ‘average’ person with
T2DM (age 65.4 years) has a life expectancy from now of
18.6 years compared to the 20.3 years for the equivalent
non diabetes mellitus population, corresponding to LLY of
1.7 years/average person. We estimate that for both T1DM
and T2DM, one year with HbA1c >58 mmol/mol loses
around 100 life days. Linking glycaemic control to mortality
has the potential to focus minds on effective engagement
with therapy and lifestyle recommendation adherence.
(Cardiovascular Endocrinology & Metabolism)
In silico methodologies have opened new avenues of research to understanding and predicting drug resistance, a pressing health issue that keeps rising at alarming pace. Sequence-based interpretation systems are routinely applied in clinical context in an attempt to predict mutation-based drug resistance and thus aid the choice of the most adequate antibiotic and antiviral therapy. An important limitation of approaches based on genotypic data exclusively is that mutations are not considered in the context of the three-dimensional (3D) structure of the target. Structure-based in silico methodologies are inherently more suitable to interpreting and predicting the impact of mutations on target-drug interactions, at the cost of higher computational and time demands when compared with sequence-based approaches. Herein, we present a fast, computationally inexpensive, sequence-to-structure-based approach to drug resistance prediction, which makes use of 3D protein structures encoded by input target sequences to draw binding-site comparisons with susceptible templates. Rather than performing atom-by-atom comparisons between input target and template structures, our workflow generates and compares Molecular Interaction Fields (MIFs) that map the areas of energetically favorable interactions between several chemical probe types and the target binding site. Quantitative, pairwise dissimilarity measurements between the target and the template binding sites are thus produced. The method is particularly suited to understanding changes to the 3D structure and the physicochemical environment introduced by mutations into the target binding site. Furthermore, the workflow relies exclusively on freeware, making it accessible to anyone. Using four datasets of known HIV-1 protease sequences as a case-study, we show that our approach is capable of correctly classifying resistant and susceptible sequences given as input. Guided by ROC curve analyses, we fined-tuned a dissimilarity threshold of classification that results in remarkable discriminatory performance (accuracy ≈ ROC AUC ≈ 0.99), illustrating the high potential of sequence-to-structure-, MIF-based approaches in the context of drug resistance prediction. We discuss the complementarity of the proposed methodology to existing prediction algorithms based on genotypic data. The present work represents a new step toward a more comprehensive and structurally-informed interpretation of the impact of genetic variability on the response to HIV-1 therapies.
Diabetes mellitus type 2 (T2DM) is a metabolic disorder develops due to the overproduction of free radicals where oxidative stress could contribute it. Possible factors are defective insulin signals, glucose oxidation, and degradation of glycated proteins as well as alteration in glutathione metabolism which induced hyperglycemia. Previous studies revealed a link between T2DM with oxidative stress, inflammation and insulin resistance which are assumed to be regulated by numerous cellular networks such as NF-κB, PI3K/Akt, MAPK, GSK3 and PPARγ. Flavonoids are ubiquitously present in the nature and classified according to their chemical structures for example , flavonols, flavones, flavan-3-ols, anthocyanidins, flavanones, and isoflavones. Flavonoids indicate poor bioavailability which could be improved by employing various nano-delivery systems against the occurrences of T2DM. These bioactive compounds exert versatile anti-diabetic activities via modulating targeted cellular sig-naling networks, thereby, improving glucose metabolism, α-glycosidase, and glucose transport or aldose re-ductase by carbohydrate metabolic pathway in pancreatic β-cells, hepatocytes, adipocytes and skeletal myo-fibres. Moreover, anti-diabetic properties of flavonoids also encounter diabetic related complications. This review article has designed to shed light on the anti-diabetic potential of flavonoids, contribution of oxidative stress, evidence of efficacy in clinical, cellular and animal studies and nano-delivery approaches to enhance their therapeutic efficacy. This article might give some new insights for therapeutic intervention against T2DM in near future.
Simple physico-chemical properties, like logD, solubility, or melting point, can reveal a great deal about how a compound under development might later behave. These data are typically measured for most compounds in drug discovery projects in a medium throughput fashion. Collecting and assembling all the Bayer in-house data related to these properties allowed us to apply powerful machine learning techniques to predict the outcome of those assays for new compounds. In this paper, we report our finding that, especially for predicting physicochemical ADMET endpoints, a multitask graph convolutional approach appears a highly competitive choice. For seven endpoints of interest, we compared the performance of that approach to fully connected neural networks and different single task models. The new model shows increased predictive performance compared to previous modeling methods and will allow early prioritization of compounds even before they are synthesized. In addition, our model follows the generalized solubility equation without being explicitly trained under this constraint.
Survivin (IAP proteins) is considered as a significant target for anticancer drug research owing to its upregulation in tumor cells to mediate resistance to apoptotic stimulus. The current study aimed to investigate phytochemicals as inhibitors of survivin with caspases to reactivate the functioning of caspases through molecular docking. The compounds namely 2(R), 4(R)-dihydroxypyrrolidine, 4-hydroxy-2-(4-methoxyphenyl)-1,1-dioxo-3,4-dihydrothieno[3,2-e]thiazine-6-sulfonamide, 2,3-Diketo-L-gulonic acid, (3-hydroxy-2-octadeca-9,12-dienoyloxypropyl) octadecanoate, 2-[[4-[[4-[(4-formamido-1-methylimidazole-2-carbonyl)amino]-1-methylimidazole-2-carbonyl]amino]-1-methylimidazole-2-carbonyl]amino]ethyl-dimethylazanium, Picolinic acid and (2-Hydroxy-5-nitrophenyl) dihydrogen phosphate successfully bind inside the pocket of survivin. ADMETsar was used to evaluate the anticancer potential of selected compounds. These compounds can be proposed as effective inhibitors, disrupting the survivin-caspases interaction and reactivating the caspases function of apoptosis. The study might facilitate the development of cost-effective and natural drugs against cancer. However, further validation is essential for confirmation of its drug efficacy and bio-compatibility.
Computational prediction of xenobiotic metabolism can provide valuable information to guide the development of drugs, cosmetics, agrochemicals, and other chemical entities. We have previously developed FAME 2, an effective tool for predicting sites of metabolism (SoMs). In this work, we focus on the prediction of the chemical structures of metabolites, in particular metabolites of xenobiotics. To this end, we have developed a new tool, GLORY, which combines SoM prediction with FAME 2 and a new collection of rules for metabolic reactions mediated by the cytochrome P450 enzyme family. GLORY has two modes: MaxEfficiency and MaxCoverage. For MaxEfficiency mode, the use of predicted SoMs to restrict the locations in the molecule at which the reaction rules could be applied was explored. For MaxCoverage mode, the predicted SoM probabilities were instead used to develop a new scoring approach for the predicted metabolites. With this scoring approach, GLORY achieves a recall of 0.83 and can predict at least one known metabolite within the top three ranked positions for 76% of the molecules of a new, manually curated test set. GLORY is freely available as a web server at https://acm.zbh.uni-hamburg.de/glory/, and the datasets and reaction rules are provided in the Supplementary Material.
Emergence of Dengue as one of the deadliest viral diseases prompts the need for development of effective therapeutic agents. Dengue virus (DV) exists in four different serotypes and infection caused by one serotype predisposes its host to another DV serotype heterotypic re-infection. We undertook virtual ligand screening (VLS) to filter compounds against DV that may inhibit inclusively all of its serotypes. Conserved non-structural DV protein targets such as NS1, NS3/NS2B and NS5, which play crucial role in viral replication, infection cycle and host interaction, were selected for screening of vital antiviral drug leads. A dataset of plant based natural antiviral derivatives was developed. Molecular docking was performed to estimate the spatial affinity of target compounds for the active sites of DV’s NS1, NS3/NS2B and NS5 proteins. The drug likeliness of the screened compounds was followed by ADMET analysis whereas the binding behaviors were further elucidated through molecular dynamics (MD) simulation experiments. VLS screened three potential compounds including Canthin-6-one 9-O-beta-glucopyranoside, Kushenol W and Kushenol K which exhibited optimal binding with all the three conserved DV proteins. This study brings forth novel scaffolds against DV serotypes to serve as lead molecules for further optimization and drug development against all DV serotypes with equal effect against multiple disease causing DV proteins. We therefore anticipate that the insights given in the current study could be regarded valuable towards exploration and development of a broad-spectrum natural anti-dengue therapy.
Several plants have been used in ancient times as medicines to treat, manage and prevent many diseases in various traditional settings throughout the world. The effect of administration of hydro-ethanolic extract of Laportea aestuans (La) leaves at different doses in Wistar rats induced with benign prostatic hyperplasia (BPH) using antioxidant parameters and phytochemical screening data was obtained. Thirty (30) animals were randomly divided into six (6) groups (A-F) of five (5) animals each. BPH was induced in the animals by daily subcutaneous injection of testosterone propionate (TP) (3 mg/kg) in olive oil and administration of treatments for four (4) weeks were done concurrently. Group A received olive oil alone subcutaneously, group B was induced with BPH alone, groups C-E were induced with BPH but received different doses of La at 100, 200 and 400 mg/kg. Lastly, group F was induced with BPH but treated with finasteride (5 mg/kg) which serves as the positive control group. Phytochemical screening data of saponins, flavonoids (0.5010 ± 0.0009 mg/ml), alkaloids (0.528 mg/ml), phenols (0.6195 ± 0.0015 mg/ml), tannins (0.5410 ± 0.0013 mg/ml) and steroids (1.6230 ± 0.0210 mg/ml) in hydro-ethanolic extract of La. Antioxidant parameters such as superoxide dismutase, catalase and reduced glutathione data were alsoµ gotten at 400 mg/kg La (48.1 ± 4.17U/mg protein), (29.43 ± 1.38U/mg protein) and (30.60 ± 2.05 µg/ml) respectively when compared to the BPH group (35.5 ± 0.97U/mg protein), (11.36 ± 2.39U/mg protein) and (15.60 ± 1.14 µg/ml).
Abstract: Alkaloids are plant secondary metabolite. They are well known nitrogen-containing natural bioactive compounds. Cutting edge research is going on alkaloids to unravel novel therapeutic approaches. Literature reveals that alkaloids contribute multiple biological activities and some alkaloids transform into active metabolites too. In this review, we have focused on marketed and experimental alkaloids. We have summarized sources and biological activities of reported alkaloids in past decades.
Phytochemicals derived from natural plants have been used commonly for the prevention and/or treatment of different diseases due to the belief of their safety. Many plant species synthesize toxic chemicals. New natural chemicals are being discovered but their toxic effects are unknown. Phytochemicals have been regarded as possible antioxidants. But on the other hand it is suggested that various phenolic antioxidants can display pro-oxidant properties at high doses. In this review, the role of some phytochemicals (epigallocathecin gallate, carvacrol, galangin, limonene, lycopene, naringin, puerarin, terpinene, thymol and ursolic acid) on the prevention of DNA damage will be discussed.
Ferns are an important phytogenetic bridge between lower and higher plants. Historically they have been used in many ways by humans, including as ornamental plants, domestic utensils, foods, and in handicrafts. In addition, they have found uses as medicinal herbs. Ferns produce a wide array of secondary metabolites endowed with different bioactivities that could potentially be useful in the treatment of many diseases. However, there is currently relatively little information in the literature on the phytochemicals present in ferns and their pharmacological applications, and the most recent review of the literature on the occurrence, chemotaxonomy and physiological activity of fern secondary metabolites was published over 20 years ago, by Soeder (Bot Rev 51:442–536, 1985). Here, we provide an updated review of this field, covering recent findings concerning the bioactive phytochemicals and pharmacology of fern species.
Integral membrane proteins in the G Protein-Coupled Receptor (GPCR) class are attractive drug development targets. However, computational methods applicable to ligand discovery for many GPCR targets are restricted by limited numbers of known ligands. Pharmacophore models can be developed using variously sized training sets and applied in database mining to prioritize candidate ligands for subsequent validation. This in silico study assessed the impact of key pharmacophore modeling decisions that arise when known ligand numbers for a target of interest are low. GPCR included in this study are the adrenergic alpha-1A, 1D and 2A, adrenergic beta 2 and 3, kappa, delta and mu opioid, serotonin 1A and 2A, and the muscarinic 1 and 2 receptors, all of which have rich ligand data sets suitable to assess the performance of protocols intended for application to GPCR with limited ligand data availability. Impact of ligand function, potency and structural diversity in training set selection was assessed to define when pharmacophore modeling targeting GPCR with limited known ligands becomes viable. Pharmacophore elements and pharmacophore model selection criteria were also assessed. Pharmacophore model assessment was based on percent pharmacophore model generation failure, as well as Güner-Henry enrichment and goodness-of-hit scores. Three of seven pharmacophore element schemes evaluated in MOE 2018.0101, Unified, PCHD, and CHD, showed substantially lower failure rates and higher enrichment scores than the others. Enrichment and GH scores were used to compare construction protocol for pharmacophore models of varying purposes— such as function specific versus nonspecific ligand identification. Notably, pharmacophore models constructed from ligands of mixed functions (agonists and antagonists) were capable of enriching hitlists with active compounds, and therefore can be used when available sets of known ligands are limited in number.
A well-structured in silico workflow is here reported for disclosing structure-based pharmacophore models against bromodomain-containing protein 9 (BRD9), accelerating virtual screening campaigns and facilitating the identification of novel binders. Specifically, starting from 23 known ligands co-crystallized with BRD9, three-dimensional pharmacophore models, namely placed in a reference protein structure, were developed. Specifically, we here introduce a fragment-related pharmacophore model, useful for the identification of new promising small chemical probes targeting the protein region responsible of the acetyllysine recognition, and two further pharmacophore models useful for the selection of compounds featuring drug-like properties. A pharmacophore-driven virtual screening campaign was then performed to facilitate the selection of new selective BRD9 ligands, starting from a large library of commercially available molecules. The identification of a promising BRD9 binder (7) prompted us to re-iterate this computational workflow on a second focused in-house built library of synthesizable compounds and, eventually, three further novel BRD9 binders were disclosed (8-10). Moreover, all these compounds were tested among a panel comprising other nine bromodomains, showing a high selectivity for BRD9. Preclinical bioscreens for potential anticancer activity highlighted compound 7 as that showing the most promising biological effects, proving the reliability of this in silico pipeline and confirming the applicability of the here introduced structure-based three-dimensional pharmacophore models as straightforward tools for the selection of new BRD9 ligands.
Tea, one of the most widely consumed beverages, is prepared from the leaves of the Camellia sinensis. The promising health recompenses of tea have been linked to its different phenolic components, which have diverse biological characteristics. Tea also contains several flavonoids, alkaloids, phenolic, theanine, etc., which are associated with anti-oxidant characteristics and a variety of health benefits. It can also lower the pervasiveness of neurological disorders as well as prevent different types of cancer, metabolic syndromes, cardiovascular diseases, urinary stone, obesity, type 2 diabetes. Keeping in mind that tea helps to improve health and prevents many diseases, its consumption has been regarded as a “health-promoting habit” and current medical investigators have established the scientific basis for this concept over time. The current review provides new updated information and perspectives on the tea phytochemicals and their overall health benefits based on molecular processes, experimental studies, and clinical trials.
A methylene chloride extract of Myoporum insulare R. Br. (Scrophulariaceae) root material was investigated by dual high-resolution PTP1B/α-glucosidase inhibition profiling and LC-PDA-HRMS. Subsequent analytical-scale separation of the crude extract afforded serrulatanes 1-9 of which 2 ((1R,11S,18R)-5,18-epoxyserrulat-3,14-dien-8,18-diol or myoporulatane A), 6 ((1R,4S,11S)-8-hydroxy-serrulat-14-en-18,5-olide or myoporulatane B), 7 ((1R,4S,11S)-serrulat-14-en-5,8,18-trione or myoporulatane C), and 9 ((1S, 2R,4S,11S)-2β-hydroxy-serrulat-14-ene or myoporulatane D) are previously unreported. The structures of all isolated compounds were established by HRMS as well as 1D and 2D NMR analysis. Relative configurations were determined from combined analyses of chemical shifts, J-coupling constants and ROESY correlations, and absolute configurations were tentatively assigned by comparison to previous studies and from biosynthetic arguments. Compounds correlated with PTP1B inhibitory activity in the high-resolution inhibition profile were tested after isolation. However, the pure compounds exhibited weak or essentially no inhibitory activity against PTP1B with IC50 values of 97.4 μM for 2, 3.0 mM for 4, and > 100 μM for 7. This is the first study of the root chemistry of M. insulare.
The American Society for Pharmacology and Experimental Therapeutics has revised the Instructions to Authors for Drug Metabolism and Disposition, Journal of Pharmacology and Experimental Therapeutics, and Molecular Pharmacology These revisions relate to data analysis (including statistical analysis) and reporting but do not tell investigators how to design and perform their experiments. Their overall focus is on greater granularity in the description of what has been done and found. Key recommendations include the need to differentiate between preplanned, hypothesis-testing, and exploratory experiments or studies; explanations of whether key elements of study design, such as sample size and choice of specific statistical tests, had been specified before any data were obtained or adapted thereafter; and explanations of whether any outliers (data points or entire experiments) were eliminated and when the rules for doing so had been defined. Variability should be described by S.D. or interquartile range, and precision should be described by confidence intervals; S.E. should not be used. P values should be used sparingly; in most cases, reporting differences or ratios (effect sizes) with their confidence intervals will be preferred. Depiction of data in figures should provide as much granularity as possible, e.g., by replacing bar graphs with scatter plots wherever feasible and violin or box-and-whisker plots when not. This editorial explains the revisions and the underlying scientific rationale. We believe that these revised guidelines will lead to a less biased and more transparent reporting of research findings.
The American Society for Pharmacology and Experimental Therapeutics has revised the Instructions to Authors for Drug Metabolism and Disposition, Journal of Pharmacology and Experimental Therapeutics, and Molecular Pharmacology These revisions relate to data analysis (including statistical analysis) and reporting but do not tell investigators how to design and perform their experiments. Their overall focus is on greater granularity in the description of what has been done and found. Key recommendations include the need to differentiate between preplanned, hypothesis-testing, and exploratory experiments or studies; explanations of whether key elements of study design, such as sample size and choice of specific statistical tests, had been specified before any data were obtained or adapted thereafter; and explanations of whether any outliers (data points or entire experiments) were eliminated and when the rules for doing so had been defined. Variability should be described by S.D. or interquartile range, and precision should be described by confidence intervals; S.E. should not be used. P values should be used sparingly; in most cases, reporting differences or ratios (effect sizes) with their confidence intervals will be preferred. Depiction of data in figures should provide as much granularity as possible, e.g., by replacing bar graphs with scatter plots wherever feasible and violin or box-and-whisker plots when not. This editorial explains the revisions and the underlying scientific rationale. We believe that these revised guidelines will lead to a less biased and more transparent reporting of research findings.
Peptic Ulcer Disease (PUD) is the most common disorder of the stomach and duodenum, which is associated with Helicobacter pylori infection. PUD occurs due to an imbalance between offensive and defensive factors and Proton Pump Inhibitors (PPI), Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) and antibiotics are frequently used for the treatment. Recently, medicinal plants have emerged as efficacious, safe and widely available alternative therapies for PUD. The aim of this review was to study the medicinal plants and phytochemicals, which have been used for PUD treatment to evaluate the potential role of natural compounds to develop herbal remedies for PUD. Information was obtained using a literature search of electronic databases, such as Web of Science, Google Scholar, PubMed, Sci Finder, Reaxys and Cochrane. Common and scientific names of the plants and keywords such as ‘peptic ulcer’, ‘gastric ulcer’, ‘stomach ulcer’ and ‘duodenal ulcer’ were used for search. Eventually, 279 plants from 89 families were identified and information on the plant families, part of the plant used, chemical constituents, extracts, ulcer model used and dosage were abstracted. The results indicated that most of the anti-PUD plants were from Asteraceae (7.1%) and Fabaceae (6.8%) families while flavonoids (49%), tannins (13%), saponins (10%) and alkaloids (9%) were the most common natural compounds in plants with anti-PUD activity.
The present study was designed to review the antidiabetic potential of anthraquinones (AQs) with emphasis on the extent of blood glucose reduction, the half maximal inhibitory concentration values (in vitro studies), the proposed mechanisms of action, and the structure activity relationship studies. We sourced relevant data from the major scientific databases (Pubmed, Science Direct, Medline, and Google Scholar). According to our search, 25 AQs have shown variable antidiabetic potential, whereas one AQ (morindone‐6‐O‐β‐D‐primeveroside) showed no blood glucose‐lowering ability. Emodin and rhein showed the most promising antidiabetic potential in various models. The proposed mechanisms of antidiabetic action include upregulation of insulin receptor substrates‐1, phosphoinositide‐3‐kinase, and Akt‐ser473 expression and elevation of glucagon‐like peptide‐1 level in diabetic animal models linked to the potent protein tyrosine phosphatase 1B and dipeptidyl peptidase‐4 inhibitions. In addition, activation of peroxisome proliferator‐activated receptors gamma and inhibition of α‐glucosidase activity are other possible targets proposed as the mechanism of AQs antidiabetic action. The position and the number of hydroxyl group showed great influence on the overall antidiabetic potential of AQs. AQs hold promising antidiabetic activity despite scanty information. We hope that the present study will serve as a template to further explore the antidiabetic potential of AQs and subsequent antidiabetic drug development.
Diabetes mellitus, a chronic metabolic disease, characterized by elevated levels of blood glucose and insufficiency in production and action of insulin is the seventh leading cause of death worldwide. Numerous studies have shown that diabetes mellitus is associated with increased formation of free radicals and decrease in antioxidant potential. In the patients with diabetes mellitus, the levels of antioxidant parameters are found to decrease, hence in many studies phytochemicals which can exert antioxidant and free radical scavenging activities, are suggested to improve the insulin sensitivity. Several phytoactive compounds such as flavonoids, lignans, prophenylphenols, are also found to combat the complications of diabetes. This chapter mainly focuses on the relationship between diabetes mellitus and preventive roles of various phytochemicals on diabetes via their antioxidant properties.
Background
One class of phytochemicals are phenols with (OH) group bounded to aromatic hydrocarbon group. The aim of this study was to review the anti-diabetic and anti-oxidant properties of important phenols.
Methods
This is a review study with ethic number (95s108) from AJUMS. About 450 articles (original, review,etc) been screened; 40 of them in the range of (1992–2017) were used due to their correlation to the study purpose. 28 of them were indexed by “Web of science (ISI)”, 24 of them indexed by pubmed and also 29 of them were indexed by scopus data center.
Findings
Phenols affect diabetes in different ways. CGA suppress hepatic gluconeogenesis through the inhibition of G6Pase and is also an insulin sensitizer that potentiates insulin action. Curcumin reduce insulin resistance so decrease AGE's products in diabetes mellitus. Hydroxytyrosol regulates the calcium channels which plays key role in insulin secretion. Resveratrol increase the stimulation of glucose uptake and insulin secretion. CGA has similar antioxidant activity as vitamin E and ellagic acid maybe is even more potent than vitamin E. curcumin inhibits lipid peroxidation and scavenge superoxide anion and hydroxyl radicals. The antioxidant activity of hydroxytyrosol protects pancreatic cells from damage and death. Treatment with resveratrol significantly decreases the level of glucosylated hemoglobin.
Conclusion
All these phytochemicals have potent antidiabetic and antioxidant effects in different ways beside their other effects like anti-inflammatory and anti-carcinogenic properties in ellagic acid, or like anti-angiogenic and apoptogenic activities in curcumin. So we suggest further studies in the field of diabetes and antioxidation.
Ocimum sanctum Linn. commonly known as Holy Basil or Tulsi is an Ayurvedic herb of Southeast Asia with a long history of traditional use. The culinary, medicinal and industrial importance of this plant led to explore its chemical and pharmacological properties. Here, we provide a comprehensive review on scientific findings of O. sanctum chemical constituents and their related anticancer, antioxidant, anti-inflammatory, antistress, γ-irradiation protection, antidiabetic and antileishmanicidal activities. More than 60 chemical compounds have been reported from O. sanctum, including phenolics, flavonoids, phenyl propanoids, terpenoids, fatty acid derivatives, essential oil, fixed oil, and steroids. The pharmacological activities of O. sanctum compounds reflect their medicinal importance and in the standardization of medicinal products. This compilation will be helpful in the development of new active principle and nutraceuticals in the area of drug resistance and emerging chronic disease vectors.
Abstract
Alkaloids are plant secondary metabolite. They are well known nitrogen-containing natural bioactive compounds. Cutting edge research is going on alkaloids to unravel novel therapeutic approaches. Literature reveals that alkaloids contribute multiple biological activities and some alkaloids transform into active metabolites too. In this review, we have focused on marketed and experimental alkaloids. We have summarized sources and biological activities of reported alkaloids in past decades.
Type 2 diabetes is associated with elevated levels of triglycerides and small, dense low-density lipoprotein particles, in addition to low levels of high-density lipoprotein cholesterol. Clinical trials have demonstrated the clear cardiovascular benefit of use of statin therapy in patients with diabetes. Additional lipid-modifying agents are typically guided by the presence of additional lipid abnormalities. The optimal use of existing lipid agents and the potential for novel therapies in patients with diabetes is reviewed.
Wine polymeric material (WPM), which includes polysaccharides, proteins, and polyphenolic compounds, interacts with anthocyanins. To determine the contribution of polysaccharides in these interactions, the diffusion performance of anthocyanins along a dialysis membrane was determined in the presence and absence of isolated mannoproteins (MP) and arabinogalactans (AG) from WPM. Furthermore, to estimate the extent of the interaction between WPM and polyphenolic compounds, the activation energy (Ea) required for their diffusion in the presence of WPM was determined. AG, generally more abundant than MP in wine, interact in a greater extent with anthocyanins, showing their relevant contribution for WPM/anthocyanins interactions. The Ea for the diffusion of polyphenolic compounds in presence of WPM indicated the occurrence of interactions with relative weak to strong intensities (2.6–50.8 kJ/mol). As not all polyphenolic compounds were able to be released from WPM, stronger interactions, possibly by covalent linkages, are involved, providing new insights on WPM/polyphenolic compounds relationships.
Diabetes, one of the most common metabolic disorders, is no longer a disease of affluent nations. The prevalence rates of diabetes are rising steeply in low and middle-income nations that have rapidly improved their economy and adopted a ‘westernized’ life style. The worldwide explosion of diabetes also increases the propensity for developing both micro and macro vascular complications and this result in a huge burden due to mobility and mortality in addition to increasing the costs of therapy. As both micro and macrovascular complications share common pathophysiological mechanisms, several studies have shown a strong association between the various vascular complications. Thus, screening for all diabetic complications simultaneously is recommended. If the burden due to diabetes and its complications is to be reduced, there is need for a multi-prolonged strategy involving early diagnosis of diabetes, screening for its complications and offering optimal therapy at all levels of care. Luckily, effective interventions are available, making such efforts justifiable.
Background
Dietary flavonoids, which occur in many plant foods, are considered as the most active constituents among the plant-derived ones in vitro and in vivo. To date, many studies have addressed the anti-inflammatory activity of flavonoids. However, their considerable structural diversity and in vivo bioavailability make them able to modulate different signaling pathways.
Scope and Approach
The present review attempted to summarize and highlight a broad range of inflammation-associated signaling pathways modulated by flavonoids. Finally, based on the current scientist's literature, structure-activity relationships were concluded. hain.
Key Findings and Conclusions
Dietary flavonoids have the ability to attenuate inflammation by targeting different intracellular signaling pathways triggered by NF-κB, AP-1, PPAR, Nrf2, and MAPKs. Identification of the main structural features required for the modulation of these inflammation-related pathways (hydroxylation pattern, C2 = C3 double bond) have an important role to play in the development of new anti-inflammatory drugs.
Seeds of Securigera securidaca (Fabaceae) are used in Iranian folk medicine as an antidiabetic treatment. In this study, the antihyperglycemic activity of chloroform and methanol fractions (CF and MF) from S. securidaca seed extract was investigated and their bioactive constituents were identified. The antidiabetic effects of fractions were assessed by streptozocin-induced diabetic Naval Medical Research Institute mice. The hypoglycemic activity of MF at 100 mg/kg and CF at 400 mg/kg was comparable with glibenclamide (3 mg/kg). MF at 400 mg/kg and CF at 600 mg/kg showed equal hypoglycemic responses to 12.5 IU/kg insulin (P > 0.05). Three cardiac glycosides were isolated as active constituents responsible for the hypoglycemic activity. Securigenin-3- O -β-glucopyranosyl-(1 → 4)-β-xylopyranoside (1) was a major compound in seeds. Securigenin-3- O -inositol-(1 → 3)-β-glucopyranosyl-(1 → 4)-β-xylopyranoside (2) and securigenin-3- O -α-rhamnopyranosyl-(1 → 4)-α-glucopyranoside (3) were found as new natural products. When 1-3 were tested at 10 mg/kg there was a significant reduction of blood glucose levels in diabetic mice, comparable to that of 3 mg/kg glibenclamide (P > 0.05). The hypoglycemic effect was due to an increase in insulin secretion; the insulin levels in the diabetic mice significantly improved and were comparable with those in healthy animals (P > 0.05). Compounds responsible for the hypoglycemic properties of S. securidaca seeds were identified as cardiac glycosides and were found to act via an increase of insulin levels in a diabetic mouse model.
Cardiac glycosides, the cardiotonic steroids such as digitalis have been in use as heart ailment remedy since ages. They manipulate the renin-angiotensin axis to improve cardiac output. However; their safety and efficacy have come under scrutiny in recent times, as poisoning and accidental mortalities have been observed. In order to better understand and exploit them as cardiac ionotropes, studies are being pursued using different cardiac glycosides such as digitoxin, digoxin, ouabain, oleandrin etc. Several cardiac glycosides as peruvoside have shown promise in cancer control, especially ovary cancer and leukemia. Functional variability of these glycosides has revealed that not all cardiac glycosides are alike. Apart from their specific affinity to sodium-potassium ATPase, their therapeutic dosage and behavior in poly-morbidity conditions needs to be considered. This review presents a concise account of the key findings in recent years with adequate elaboration of the mechanisms. This compilation is expected to contribute towards management of cardiac, cancer, even viral ailments.
Berberine is the principal component of many popular medicinal plants (e.g. the genus Berberis, Coptis and Hydrastis among others) with a history of thousands of years of usage in traditional medicine. The numerous pharmacological activities of berberine reported in the last two decades have been attracting high level interests both within the scientific community, clinicians and the public at large. Despite enormous amount of efforts have been placed to show its therapeutic value for inflammatory bowel diseases (IBD), however, comprehensive up-to-date review article in this field is not yet available. In this communication, literature data from in vitro and in vivo experiments were scrutinised and concisely presented to demonstrate its anti-IBD potential. Beyond the known general antioxidant and anti-inflammatory effects of berberine, IBD-specific effects including gut epithelial barrier pathology, T cells as emerging targets, antinociceptive and other effects are discussed.
The dramatic increase in modern lifestyle diseases such as cancer, cardiovascular diseases and diabetes has renewed researchers' interest to explore nature as a source of novel therapeutic agents. Flavonoids are a large group of polyphenols that are widely present in the human diet. They have shown promising therapeutic activities against a wide variety of ailments. One of the most widely distributed and most extensively studied flavonoid is the flavonol quercetin. Its powerful antioxidant and anti-inflammatory activities are well documented and are thought to play a role in treating and protecting against diseases including diabetes, cancer, neurodegenerative and cardiovascular diseases. The purpose of this review is to shed light on quercetin therapeutic potential as an antidiabetic agent. Quercetin was reported to interact with many molecular targets in small intestine, pancreas, skeletal muscle, adipose tissue and liver to control whole-body glucose homeostasis. Mechanisms of action of quercetin are pleiotropic and involve the inhibition of intestinal glucose absorption, insulin secretory and insulin-sensitizing activities as well as improved glucose utilization in peripheral tissues. Initial studies suggested poor bioavailability of quercetin. However, recent reports have shown that quercetin was detected in the plasma after food or supplements consumption and has a long half-life in human body. Despite the wealth of in vitro and in vivo results supporting the antidiabetic potential of quercetin, its efficacy in diabetic human subjects is yet to be explored.