scholarly journals Multitargeted Effects of Vitexin and Isovitexin on Diabetes Mellitus and Its Complications

2021 ◽  
Vol 2021 ◽  
pp. 1-20
Author(s):  
Ibrahim Luru Abdulai ◽  
Samuel Kojo Kwofie ◽  
Winfred Seth Gbewonyo ◽  
Daniel Boison ◽  
Joshua Buer Puplampu ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Metabolic Pathways ◽  
Clinical Manifestations ◽  
In Vivo Studies ◽  
Technological Advancement ◽  
Application Research ◽  
One Stop ◽  
Product Chemistry

Background. Till date, there is no known antidote to cure diabetes mellitus despite the discovery and development of diverse pharmacotherapeutic agents many years ago. Technological advancement in natural product chemistry has led to the isolation of analogs of vitexin and isovitexin found in diverse bioresources. These compounds have been extensively studied to explore their pharmacological relevance in diabetes mellitus. Aim of the Study. The present review was to compile results from in vitro and in vivo studies performed with vitexin and isovitexin derivatives relating to diabetes mellitus and its complications. A systematic online literature query was executed to collect all relevant articles published up to March 2020. Results. In this piece, we have collected data and presented it in a one-stop document to support the multitargeted mechanistic actions of vitexin and isovitexin in controlling diabetes mellitus and its complications. Conclusion. Data collected hint that vitexin and isovitexin work by targeting diverse pathophysiological and metabolic pathways and molecular drug points involved in the clinical manifestations of diabetes mellitus. This is expected to provide a deeper understanding of its actions and also serve as a catapult for clinical trials and application research.

scholarly journals Pan-American Lancehead Pit-Vipers: Coagulotoxic Venom Effects and Antivenom Neutralisation of Bothrops asper and B. atrox Geographical Variants

Toxins ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 78
Author(s):  
Lachlan A. Bourke ◽  
Christina N. Zdenek ◽  
Edgar Neri-Castro ◽  
Melisa Bénard-Valle ◽  
Alejandro Alagón ◽  
...  
Keyword(s):  
Evolutionary Biology ◽  
Current Knowledge ◽  
Clinical Manifestations ◽  
In Vivo Studies ◽  
Factor X ◽  
Clotting Factors ◽  
Bothrops Asper ◽  
Species Specific

The toxin composition of snake venoms and, thus, their functional activity, can vary between and within species. Intraspecific venom variation across a species’ geographic range is a major concern for antivenom treatment of envenomations, particularly for countries like French Guiana that lack a locally produced antivenom. Bothrops asper and Bothrops atrox are the most medically significant species of snakes in Latin America, both producing a variety of clinical manifestations, including systemic bleeding. These pathophysiological actions are due to the activation by the venom of the blood clotting factors Factor X and prothrombin, thereby causing severe consumptive coagulopathy. Both species are extremely wide-ranging, and previous studies have shown their venoms to exhibit regional venom variation. In this study, we investigate the differential coagulotoxic effects on human plasma of six venoms (four B. asper and two B. atrox samples) from different geographic locations, spanning from Mexico to Peru. We assessed how the venom variation of these venom samples affects neutralisation by five regionally available antivenoms: Antivipmyn, Antivipmyn-Tri, PoliVal-ICP, Bothrofav, and Soro Antibotrópico (SAB). The results revealed both inter- and intraspecific variations in the clotting activity of the venoms. These variations in turn resulted in significant variation in antivenom efficacy against the coagulotoxic effects of these venoms. Due to variations in the venoms used in the antivenom production process, antivenoms differed in their species-specific or geographical neutralisation capacity. Some antivenoms (PoliVal-ICP, Bothrofav, and SAB) showed species-specific patterns of neutralisation, while another antivenom (Antivipmyn) showed geographic-specific patterns of neutralisation. This study adds to current knowledge of Bothrops venoms and also illustrates the importance of considering evolutionary biology when developing antivenoms. Therefore, these results have tangible, real-world implications by aiding evidence-based design of antivenoms for treatment of the envenomed patient. We stress that these in vitro studies must be backed by future in vivo studies and clinical trials before therapeutic guidelines are issued regarding specific antivenom use in a clinical setting.

scholarly journals Assessment of biosafety and toxicity of hydrophilic gel for implantation in experimental in vitro and in vivo models 

2021 ◽  
Author(s):  
Natalia Bezdieniezhnykh ◽  
Alexandra Lykhova ◽  
Tamara Kozak ◽  
Taras Zadvornyi ◽  
Olena Voronina ◽  
...  
Keyword(s):  
Human Peripheral Blood ◽  
Clinical Manifestations ◽  
Peripheral Blood Lymphocytes ◽  
Model Systems ◽  
In Vivo Studies ◽  
In Vivo Models ◽  
Pharmacologically Active ◽  
Hydrophilic Gel

Abstract Background: The assessment of biosafety of pharmacologically active substances is crucial for determining the feasibility of their medical use. There are controversial issues regarding the use of substances of different origins as implants. Methods: We have conducted the comprehensive studies to determine the in vivo toxicity and in vitro genotoxicity of new generation of hydrophilic gel for implantation (production name of the substance "Activegel") to detail its characteristics and assess its biosafety. Results: In vivo studies have shown the absence of clinical manifestations of intoxication in animals and no abnormalities in their physiological condition, general and biochemical blood tests. Evaluation of the site of the gel application showed no inflammatory reaction and evidenced on normal state of tissues of animal skin. The results of the genotoxicity test indicated that the gel did not affect the parameters of DNA comets and, accordingly, had no genotoxic effect on human peripheral blood lymphocytes. When studying the effect of the gel on malignantly transformed cells in vitro, it was found that the gel for implantation did not change the proliferative activity and viability of human breast cancer cells. Conclusions: Comprehensive in vitro and in vivo study using various experimental model systems showed that the hydrophilic gel for implantation "Activegel" is non-toxic.

scholarly journals The Pleiotropic Effects of Vitamin D in Gynaecological and Obstetric Diseases: An Overview on a Hot Topic

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Francesca Colonese ◽  
Antonio Simone Laganà ◽  
Elisabetta Colonese ◽  
Vincenza Sofo ◽  
Francesca Maria Salmeri ◽  
...  
Keyword(s):  
Vitamin D ◽  
Metabolic Pathways ◽  
Polycystic Ovary ◽  
Serum Levels ◽  
In Vivo Studies ◽  
Vitamin D Metabolites ◽  
Vitamin D Metabolism ◽  
Vitamin D Levels

The traditionally recognized role of vitamin D consists in the regulation of bone metabolism and calcium-phosphorus homeostasis but recently a lot of in vitro and in vivo studies recognized several “noncalcemic” effects of vitamin D metabolites. Accumulating evidence suggests that the metabolic pathways of this vitamin may play a key role in the developing of gynaecological/obstetric diseases. VDR-mediated signalling pathways and vitamin D levels seem to (deeply) affect the risk of several gynaecological diseases, such as polycystic ovary syndrome (PCOS), endometriosis, and ovarian and even breast cancer. On the other hand, since also the maternal-fetal unit is under the influence of vitamin D, a breakdown in its homeostasis may underlie infertility, preeclampsia, and gestational diabetes mellitus (GDM). According to our literature review, the relationship between vitamin D and gynaecological/obstetric diseases must be replicated in future studies which could clarify the molecular machineries behind their development. We suggest that further investigation should take into account the different serum levels of this vitamin, the several actions which arise from the binding between it and its receptor (taking into account its possible polymorphism), and finally the interplay between vitamin D metabolism and other hormonal and metabolic pathways.

scholarly journals New Insights into the Hypotensins from Tityus serrulatus Venom: Pro-Inflammatory and Vasopeptidases Modulation Activities

Toxins ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 846
Author(s):  
Bruno Duzzi ◽  
Cristiane Castilho Fernandes Silva ◽  
Roberto Tadashi Kodama ◽  
Daniela Cajado-Carvalho ◽  
Carla Cristina Squaiella-Baptistão ◽  
...  
Keyword(s):  
Phagocytic Activity ◽  
Clinical Manifestations ◽  
Direct Interaction ◽  
Kinetic Studies ◽  
Pressure Control ◽  
In Vivo Studies ◽  
Hypotensive Activity ◽  
Tityus Serrulatus

The Tityus serrulatus scorpion is considered the most dangerous of the Brazilian fauna due to the severe clinical manifestations in injured victims. Despite being abundant components of the venom, few linear peptides have been characterized so far, such as hypotensins. In vivo studies have demonstrated that hypotensin I (TsHpt-I) exerts hypotensive activity, with an angiotensin-converting enzyme (ACE)-independent mechanism of action. Since experiments have not yet been carried out to analyze the direct interaction of hypotensins with ACE, and to deepen the knowledge about these peptides, hypotensins I and II (TsHpt-II) were studied regarding their modulatory action over the activities of ACE and neprilysin (NEP), which are the peptidases involved in blood pressure control. Aiming to search for indications of possible pro-inflammatory action, hypotensins were also analyzed for their role in murine macrophage viability, the release of interleukins and phagocytic activity. TsHpt-I and -II were used in kinetic studies with the metallopeptidases ACE and NEP, and both hypotensins were able to increase the activity of ACE. TsHpt-I presented itself as an inhibitor of NEP, whereas TsHpt-II showed weak inhibition of the enzyme. The mechanism of inhibition of TsHpt-I in relation to NEP was defined as non-competitive, with an inhibition constant (Ki) of 4.35 μM. Concerning the analysis of cell viability and modulation of interleukin levels and phagocytic activity, BALB/c mice’s naïve macrophages were used, and an increase in TNF production in the presence of TsHpt-I and -II was observed, as well as an increase in IL-6 production in the presence of TsHpt-II only. Both hypotensins were able to increase the phagocytic activity of murine macrophages in vitro. The difference between TsHpt-I and -II is the residue at position 15, with a glutamine in TsHpt-I and a glutamic acid in TsHpt-II. Despite this, kinetic analyzes and cell assays indicated different actions of TsHpt-I and -II. Taken together, these results suggest a new mechanism for the hypotensive effects of TsHpt-I and -II. Furthermore, the release of some interleukins also suggests a role for these peptides in the venom inflammatory response. Even though these molecules have been well studied, the present results suggest a new mechanism for the hypotensive effects of TsHpt-I

scholarly journals In vitro and in vivo studies of anti diabetic effect of khaya senegalensis leaves and bark extracts

2019 ◽  
Vol 7 (1) ◽  
pp. 12
Author(s):  
Marvit Osman Widdat Allah ◽  
Ayat Ahmed Alrasheid ◽  
Eltayeb Suliman Elamin
Keyword(s):  
Diabetes Mellitus ◽  
In Vitro Models ◽  
In Vivo Studies ◽  
Health Concern ◽  
Bark Extract ◽  
Diabetes Model ◽  
Ic50 Value ◽  
Khaya Senegalensis

Diabetes mellitus in Sudan is one of public health concern since it causes significant mortality and complications for long term. Though conventional drugs are used in the management of diabetes mellitus they are expensive, unavailable and also have numerous side effects. Khaya senegalensis has traditionally used in the management of diabetes. The present study was conducted to examine the In vitro and In vivo anti-diabetic activity of leaves and bark extracts of Khaya senegalensis. The leaves and bark of the plant were extracted with ethanol 96%, and then tested for anti-diabetic activity in a series of in vitro models and a type 2 diabetes model of rats. In vitro bark extract of k.senegalensis showed higher inhibitory activities against the enzyme with IC50 value 226.14 µg/ml. In vivo oral administration of the extracts of the k. senegalensis exhibited decrease in blood sugar level and was found to be time dependent. Bark extract showed strong in vitro and in vivo anti diabetic activity.  

Antidiabetic Effects and Mechanisms of Rosemary (Rosmarinus officinalis L.) and its Phenolic Components

2020 ◽  
Vol 48 (06) ◽  
pp. 1353-1368
Author(s):  
Tian-Qi Bao ◽  
Yi Li ◽  
Cheng Qu ◽  
Zu-Guo Zheng ◽  
Hua Yang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Scientific Evidence ◽  
Rosmarinus Officinalis ◽  
Carnosic Acid ◽  
In Vivo Studies ◽  
Rosemary Extract ◽  
Phenolic Components ◽  
Phenolic Constituents

Diabetes mellitus is a chronic endocrine disease result from absolute or relative insulin secretion deficiency, insulin resistance, or both, and has become a major and growing public healthy menace worldwide. Currently, clinical antidiabetic drugs still have some limitations in efficacy and safety such as gastrointestinal side effects, hypoglycemia, or weight gain. Rosmarinus officinalis is an aromatic evergreen shrub used as a food additive and medicine, which has been extensively used to treat hyperglycemia, atherosclerosis, hypertension, and diabetic wounds. A great deal of pharmacological research showed that rosemary extract and its phenolic constituents, especially carnosic acid, rosmarinic acid, and carnosol, could significantly improve diabetes mellitus by regulating glucose metabolism, lipid metabolism, anti-inflammation, and anti-oxidation, exhibiting extremely high research value. Therefore, this review summarizes the pharmacological effects and underlying mechanisms of rosemary extract and its primary phenolic constituents on diabetes and relative complications both in vitro and in vivo studies from 2000 to 2020, to provide some scientific evidence and research ideas for its clinical application.

scholarly journals Morpholine derivatives as potential agents for neurological manifestations of nervous system diseases

2020 ◽  
Vol 2 (1) ◽  
pp. 16-35
Author(s):  
Veronika A. Prikhodko ◽  
Yuriy I. Sysoev ◽  
Sergey Okovityi
Keyword(s):  
Nervous System ◽  
Social Impact ◽  
Neurological Diseases ◽  
Clinical Manifestations ◽  
Biologically Active ◽  
New Drugs ◽  
In Vivo Studies ◽  
Morpholine Derivatives

Diseases of the nervous system, especially those of vascular, traumatic, and neurodegenerative nature, are characterized by high prevalence, disability and mortality rates, and therefore have a particularly big medical and social impact. Currently, pharmacotherapy options for these diseases are limited to a relatively small number of clinically proven drugs, which is largely due to the difficulties associated with the translation of preclinical studies results. This explains the essential importance of discovering and developing new drugs, both effective and safe, that could be used to reduce clinical manifestations of neurological disorders. The present review is aimed to give a detailed account of several biologically active derivatives of morpholine, a six-membered heterocyclic compound. As demonstrated by a number of in vitro and in vivo studies using cell and animal models, morpholine derivatives should be considered viable drug candidates for a broad range of neurological diseases.

In vivo toxic effects of halothane on canine cerebral metabolic pathways

1975 ◽  
Vol 229 (4) ◽  
pp. 1050-1055 ◽  
Author(s):  
JD Michenfelder ◽  
RA Theye
Keyword(s):  
Oxidative Phosphorylation ◽  
Metabolic Pathways ◽  
Cerebral Metabolism ◽  
Systemic Circulation ◽  
Metabolic Effects ◽  
In Vivo Studies ◽  
Blood Levels ◽  
High Concentrations

The effects of high concentrations of halothane on cerebral metabolism were examined in dogs with the aid of an extracorporeal circuit to support the systemic circulation. At blood levels exceeding those representing equilibration with 2.3% halothane, a dose-related decrease in cerebral oxygen consumption (CMR02) occurred that was unrelated to the presence or absence of an active electroencephalogram. In this circumstance, despite adequate oxygen delivery, a dose-related alteration in oxidative phosphorylation also occurred as evidenced by progressive decreases in cerebral concentrations of ATP and phosphocreatine and concomitant increases in cerebral lactate and lactate/pyruvate ratio. These effects were totally reversible, except for persistence of increased of increased CMR02, after return to low halothane concentrations. It is concluded that the mechanisms of the cerebral metabolic effects of halothane differ from those of thiopental and, at high concentrations, are at least in part related to interference with oxidative phosphorylation. These in vivo studies confirm the potentially detrimental effects of high halothane concentrations on cerebral metabolic pathways as demonstrated by others in vitro.

Analyzing Phytochemicals as Inhibitors of Diabetes Mellitus 2 Causing Proteins based on Computer-Aided Drug Discovery Protocols

2020 ◽  
Vol 10 ◽  
Author(s):  
Sobia Nazir Chaudry ◽  
Waqar Hussain ◽  
Nouman Rasool
Keyword(s):  
Diabetes Mellitus ◽  
Molecular Docking ◽  
Diabetes Mellitus Type 2 ◽  
Multidrug Resistant ◽  
Diabetes Mellitus Type ◽  
In Vivo Studies ◽  
Fructose 1,6 Bisphosphate

Background: Diabetes Mellitus type 2 is one of the complex diseases, affecting people both in developed and developing countries. Plant extracted compounds known as phytochemicals are worthy because they have various medicinal properties. Objective: The present study aims at the in silico discovery of novel potent inhibitors against Diabetes Mellitus type 2. Methods: A total of 2750 phytochemicals from various medicinal important plants were collected for this study. Origin of these plants was Pakistan and India. The ADMET, molecular docking approaches were used to determine the binding and reactivity of these phytochemicals as Diabetes Mellitus type 2 inhibitors. Results: The ADMET analysis and molecular docking resulted in the selection of 42 phytochemicals (3 against Glucokinase receptor, 22 against Fructose 1,6 Bisphosphate protein and 17 for multidrug-resistant protein) showing high binding affinity as compared to the previously reported inhibitors of Diabetes Mellitus type 2. Conclusions: These 42 phytochemicals can be considered novel inhibitors against Diabetes Mellitus type 2 and can be selected for additional in vitro and in vivo studies to develop a suitable drug against diabetes.

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