In silico interaction of hesperidin with some immunomodulatory targets: A docking analysis

Forms eternal era, plant, mineral and animal products are used as drugs for the treatment of various diseases. The use of medicinal plants for immunomodulation has a long history. The modern medicinal compounds find their leads in natural products. Immunomodulation amends the immune system of an individual by prying with its usual functions. Discovery of immunomodulators from natural sources has been comprehensively made to modulate the immune system to prevent diseases. Hesperidin has been investigated for its potential anti-inflammatory effects. Hesperidin demonstrated analgesic effects in experimental animals. The present study is focused on exploring the in silico interaction of hesperidin with some chemokines and inflammatory targets. In this study, hesperidin was docked with TNF-α, IL-1β, IL-6, and NOs. Docking studies revealed the excellent interaction of hesperidin with these targets. The result of this work provided an insight into the discovery of novel molecules for immunomodulation and treatment of inflammatory disorders. Additional studies on hesperidin and associated flavonoids are necessary to establish its safety. Hesperidin, can, therefore, can be considered as a candidate for development of an immunomodulatory agent

Effect of Nucleus Basalis Magnocellularis Lesions on Memory and Hippocampal Brain-Derived Neurotrophic Factor, IL-1β, Glucose, and Corticosterone Levels in Adult Rats

   Background: The nucleus basalis magnocellularis (NBM) sends projections to the hippocampus that are implicated in learning and memory formation. Despite ample evidence proposing that cognitive function impairment related to neurodegeneration, it may result from alteration of biochemical substances. We aimed to investigate the effects of NBM lesions on the hippocampal interleukin-1beta (IL-1β), brain-derived neurotrophic factor (BDNF), and corticosterone levels, as inflammation markers, and hallmarks of neurodegeneration, stress, and metabolic status. Methods: Thirty-six male Wistar rats were randomly put in control, sham, and NBM-lesioned groups. After inducing the lesion using an intra-NBM injection of 10 μg ibotenic acid (5 μg/μL, each side) in rats, memory was estimated using the passive avoidance test. Moreover, serum and hippocampal IL-1β levels, as well as the hippocampal corticosterone, BDNF, and glucose levels were measured after 42 days. Results: Findings indicated a significant impairment of retention at different intervals in the NBM-lesioned group. BDNF decreased whereas corticosterone, glucose, and IL-1β levels increased in the hippocampus. Also, the levels of serum IL-1β, hippocampal BDNF, corticosterone, and glucose had significant correlations with hippocampal IL-1β levels. Conclusion: The synchronous alterations of some hippocampal factors, including BDNF, corticosterone, IL-1β, and glucose, caused by NBM lesion suggest that their interaction might play a significant role in neurodegeneration and relevant learning and memory impairments

Type 2 diabetes mellitus alters cardiac mitochondrial content and function in a non-obese mice model

Type 2 diabetes mellitus (T2DM) is associated with an increase of premature appearance of several disorders such as cardiac complications. Thus, we test the hypothesis that a combination of a high fat diet (HFD) and low doses of streptozotocin (STZ) recapitulate a suitable mice model of T2DM to study the cardiac mitochondrial disturbances induced by this disease. Animals were divided in 2 groups: the T2DM group was given a HFD and injected with 2 low doses of STZ, while the CNTRL group was given a standard chow and a buffer solution. The combination of HFD and STZ recapitulate the T2DM metabolic profile showing higher blood glucose levels in T2DM mice when compared to CNTRL, and also, insulin resistance. The kidney structure/function was preserved. Regarding cardiac mitochondrial function, in all phosphorylative states, the cardiac mitochondria from T2DM mice presented reduced oxygen fluxes when compared to CNTRL mice. Also, mitochondria from T2DM mice showed decreased citrate synthase activity and lower protein content of mitochondrial complexes. Our results show that in this non-obese T2DM model, which recapitulates the classical metabolic alterations, mitochondrial function is impaired and provides a useful model to deepen study the mechanisms underlying these alterations.This study was supported by Coordenacao de aperfeicoamento de pessoal de nivel superior (CAPES), Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) and Fundacao de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ)

Possible Role of Interleukin-1β in Type 2 Diabetes Onset and Implications for Anti-inflammatory Therapy Strategies

<div><p>Increasing evidence of a role of chronic inflammation in type 2 diabetes progression has led to the development of therapies targeting the immune system. We develop a model of interleukin-1β dynamics in order to explain principles of disease onset. The parameters in the model are derived from <i>in vitro</i> experiments and patient data. In the framework of this model, an IL-1β switch is sufficient and necessary to account for type 2 diabetes onset. The model suggests that treatments targeting glucose bear the potential of stopping progression from pre-diabetes to overt type 2 diabetes. However, once in overt type 2 diabetes, these treatments have to be complemented by adjuvant anti-inflammatory therapies in order to stop or decelerate disease progression. Moreover, the model suggests that while glucose-lowering therapy needs to be continued all the way, dose and duration of the anti-inflammatory therapy needs to be specifically controlled. The model proposes a framework for the discussion of clinical trial outcomes.</p></div

Effets aigus de la chaleur sur la fonction cardiométabolique dans le diabète de type 2 et la maladie coronarienne.

Les maladies cardiométaboliques sont les principales causes de décès dans le monde, et au Canada elles sont responsables d'environ 700 000 décès par année. Le diabète de type 2 et la maladie coronarienne sont les maladies cardiométaboliques les plus répandues. Malgré des avancées pharmacologiques, la prévalence de ces maladies demeure élevée, ce qui souligne l'importance des thérapies complémentaires qui améliorent le contrôle glycémique ainsi que la fonction vasculaire afin de prévenir les complications liées à ces maladies. Depuis quelques années, l’exposition à la chaleur reçoit une attention accrue pour son potentiel thérapeutique. En outre, des études scientifiques suggèrent que l’exposition à la chaleur pourrait diminuer la glycémie et améliorer la fonction vasculaire. Cependant, le potentiel thérapeutique de l'exposition à la chaleur demeure sous-étudié chez les personnes atteintes du diabète de type 2 ou de la maladie coronarienne. L’objectif général de cette thèse était d’évaluer les effets aigus de l’exposition à la chaleur sur des marqueurs de la fonction cardiométabolique auprès de gens ayant un diabète de type 2 ou une maladie coronarienne. L’article 1 a déterminé l’effet aigu d’une immersion en eau chaude sur la sensibilité à l’insuline, la fonction vasculaire, les concentrations des protéines de choc thermique plasmatique (eHSP70/90) et intracellulaire (iHSP70/90), les marqueurs inflammatoires (IL-6, IL1-RA, NFKB) ainsi que sur les médiateurs de l'action de l'insuline (IRS-1, GLP-1) comparativement à une immersion thermoneutre au sein d’une population ayant le diabète de type 2. Les résultats démontrent qu’une immersion en eau chaude n’améliore pas la sensibilité à l’insuline, ni la fonction vasculaire et elle n’affecte pas les concentrations de HSP70 / 90 et les marqueurs inflammatoires. L’article 2 a déterminé l’effet aigu d’une exposition dans un sauna Finlandais sur la fonction vasculaire, des marqueurs de dysfonction endothéliale (VCAM-1, ICAM-1) et des marqueurs inflammatoires (IL-6, IL-10, TNF-α, IL-1β, CRP) auprès de personnes ayant une maladie coronarienne. Les résultats démontrent qu’une séance de sauna Finlandais améliore la fonction endothéliale et augmente la concentration circulante d’IL-6 sans affecter d’autres marqueurs inflammatoires (IL-10, TNF-α, IL-1β, CRP) ainsi que des marqueurs de dysfonction endothéliale. Combinées, les deux études de cette thèse démontrent que l’exposition passive à la chaleur n’améliore pas de façon aiguë les marqueurs cardiométaboliques chez les personnes diabétiques de type 2. Par contre, la chaleur exerce un effet bénéfique sur la fonction endothéliale chez les personnes ayant une maladie coronarienne.Cardiometabolic diseases are the leading cause of death globally, and in Canada they are responsible for approximately 700 000 deaths each year. Type 2 diabetes and coronary artery disease are the most prevalent cardiometabolic diseases. Despite advancements in pharmacological treatments, the prevalence of these diseases remains high which underlines the importance of complementary therapies to prevent complications related to these diseases. In recent years, heat exposure has received attention for its therapeutic potential. Studies have demonstrated that heat exposure could be an effective method to decrease glycemia and improve vascular function. However, the therapeutic potential of heat exposure remains understudied in people with type 2 diabetes or coronary artery disease. The general objective of this thesis was to evaluate the acute effects of heat exposure on cardiometabolic markers in people with type 2 diabetes and coronary artery disease. The first article of this thesis determined the acute effect of hot water immersion on insulin sensitivity, vascular function, plasma (eHSP70 / 90) and intracellular (iHSP70 / 90) heat shock protein concentrations, inflammatory markers (IL- 6, IL1-RA, NFKB) as well as mediators of insulin action (IRS-1, GLP-1) compared to thermoneutral water immersion in a population with type 2 diabetes. Findings from this study demonstrate that acute hot water immersion does not improve insulin sensitivity, vascular function or affect HSP70 / 90 concentrations and inflammatory markers. The second article of this thesis determined the acute effects of Finnish sauna bathing on vascular function, markers of endothelial dysfunction (VCAM-1, ICAM-1) and inflammatory markers (IL-6, IL-10, TNF- α, IL-1β, CRP) in older adults with coronary artery disease. Results from this study demonstrate that one bout of Finnish sauna bathing improves endothelial function and increases the circulating concentration of IL-6 without affecting other markers of inflammation (IL-10, TNF-α IL-1β, CRP) or endothelial dysfunction. Combined, these results show that acute heat exposure does not acutely improve cardiometabolic markers in people with type 2 diabetes. On the other hand, heat exposure has a beneficial effect on endothelial function in people with coronary artery disease