Differentiated Effects of Allyl Isothiocyanate in Diabetic Rats: From Toxic to Beneficial Action

Allyl isothiocyanate (AITC), a constituent of Brassica family plants, has been reported to possess a high bioactivity in animal and human cells, showing ambiguous properties from adverse to beneficial ones. It was reported its genotoxic, carcinogenic, goitrogenic effects. On the other side, AITC has shown anti-cancer, cardioprotective, neuroprotective, and lately anti-obesity abilities. So far, its anti-diabetic effects are poorly explored. We tried to assess AITC action on carbohydrate, lipid and hormonal disorders in high fat diet-fed/streptozotocin diabetic rats. In this report, diabetic rats were treated intragastrically at doses 2.5, 5 and 25 mg/kg b.w./day of AITC for 2 weeks. Irrespectively of doses, AITC considerably lowered thyroid hormones (fT4, fT3), increased liver TG content, and also caused robust LDL-cholesterol and direct bilirubin concentration enhancement. Moreover, AITC at the highest dose caused pancreatic amylase and lipase drops and thyroid gland hypertrophy. AITC at 2.5 and 5 mg significantly reduced blood glucose levels along with robust beta-hydroxybutyric acid drop. Additionally, AITC at 5 mg improved insulin sensitivity (HOMA-IR index) in spite of reduced blood insulin. To conclude, despite amelioration of diabetic hyperglycemia by AITC, the adverse lipids and hormonal effects may exclude its use as a health-promoting compound in terms of anti-diabetic properties.

Tranilast treats cold-related hypertension by reducing the expression of NLRP3 inflammasome

Objective Cold exposure is associated with increased prevalence of hypertension and the related severe cardiovascular events. Aberrant activation of the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome plays an important role in the development of hypertension. Tranilast (TR), an inhibitor of NLRP3, provides a useful pharmacological probe for exploring the role of NLRP3 in pathogenesis associated with inflammation and its potential application as a therapeutic agent. This study was designed to examine the effects of TR on NLRP3 and hypertension in rats exposed to cold environment to simulate the frigid-zone conditions. Methods and results Sprague Dawley (SD) rats were exposed to moderate cold temperature (4±1°C), and then were randomized to receive TR or vehicle for 3 weeks, while the control group was raised under rat room temperature (RT, 23±1°C). We found that cold exposure substantially increased blood pressure, NLRP3 inflammasome level, and fibrosis in aorta, which were reversed by TR. Conclusion TR has an anti-hypertensive property in cold environment, and this beneficial action is likely conferred by its inhibitory effects on inflammation and fibrosis. These findings suggest TR as a potential drug for the treatment of cold-induced hypertension.

Beneficial Effect of Saharan Propolis on Glucose Metabolism in Streptozotocin-induced Diabetic Rats

Aims: The aim of the study was to evaluate the antihyperglycemic activity of propolis from Saharan region of Morocco. Background: Propolis is known from ancient times for its beneficial action on health. Objective: The study aimed to evaluate the effect of Moroccan propolis aqueous extract from the desert region on glycemia and lipid metabolism. Methods: The antihyperglycemic and antidyslipidemic activities of Moroccan propolis aqueous extract were evaluated in streptozotocin-induced diabetic rats. Glycemia was monitored during acute (6h) and subchronic treatments. Histopathological analysis of the liver and the serum lipid profile was also evaluated in addition to the glucose tolerance. Results: This work demonstrated that the aqueous extract of Moroccan propolis exhibited a significant antihyperglycemic effect in diabetic rats. Histopathological data demonstrated that propolis acts positively on the liver of diabetic rats. In addition, the preliminary phytochemical screening revealed that Moroccan propolis contains several phytochemicals. Finally, Moroccan propolis had a potent antioxidant activity which may be due to the richness in polyphenols content (90.91 mg EAG/1 g of extract). Conclusion: The present study shows that Moroccan propolis from the hot desert region possesses a potent antihyperglycemic effect.

Transient Receptor Potential Vanilloid Subtype 1: Potential Role in Infection, Susceptibility, Symptoms and Treatment of COVID-19

The battle against the new coronavirus that continues to kill millions of people will be still long. Novel strategies are demanded to control infection, mitigate symptoms and treatment of COVID-19. This is even more imperative given the long sequels that the disease has on the health of the infected. The discovery that S protein includes two ankyrin binding motifs (S-ARBMs) and that the transient receptor potential vanilloid subtype 1 (TRPV-1) cation channels contain these ankyrin repeat domains (TRPs-ARDs) suggest that TRPV-1, the most studied member of the TRPV channel family, can play a role in binding SARS-CoV-2. This hypothesis is strengthened by studies showing that other respiratory viruses bind the TRPV-1 on sensory nerves and epithelial cells in the airways. Furthermore, the pathophysiology in COVID-19 patients is similar to the effects generated by TRPV-1 stimulation. Lastly, treatment with agonists that down-regulate or inactivate TRPV-1 can have a beneficial action on impaired lung functions and clearance of infection. In this review, we explore the role of the TRPV-1 channel in the infection, susceptibility, pathogenesis, and treatment of COVID-19, with the aim of looking at novel strategies to control infection and mitigate symptoms, and trying to translate this knowledge into new preventive and therapeutic interventions.

Effect of virtual reality hypnosis on pain threshold, neurophysiological and autonomic biomarkers in healthy volunteers: a prospective randomized cross-over study. (Preprint)

BACKGROUND Virtual reality hypnosis (VRH) is a promising tool to reduce pain. However, VRH benefits on pain perception and on the physiological expression of pain still require further investigation. OBJECTIVE In this study, we characterized the effects of VRH on heat pain threshold in adult healthy volunteers and simultaneously monitored several physiological and autonomic functions. METHODS 60 healthy volunteers were prospectively included to receive nociceptive stimulations. The first series of thermal stimuli consisted of 20 stimulations at 60°C (duration: 500 ms) to trigger contact heat evoked potentials (CHEPs). The second series of thermal stimuli consisted of temperature ramps (1°C/sec) to determine the thermal pain thresholds of the participants. Electrocardiogram, electrodermal conduction, respiration rate as well as the analgesia nociception index were also recorded throughout the experiment. RESULTS Data from 58 participants were analysed. There was a significant increase in pain threshold in VRH compared to NoVRH (p<0.001, Wilcoxon matched-pairs signed ranks). No significant effect of VRH on CHEPs and heart rate parameters was observed. Compared to control, VRH subjects display a clear reduction in their autonomic sympathetic tone as seen by the low number of non-specific skin conductance peak responses (p = 0.0007, 2-way ANOVA) and the analgesia nociception index increase (p = 0.0005; paired t-test). CONCLUSIONS The results obtained in this study support the idea that VRH administration to healthy volunteers is effective at increasing heat pain thresholds and impacts autonomic functions. As a non-pharmacological intervention, VRH has beneficial action on acute experimental heat pain. This beneficial action will now need to be evaluated for the treatment of other types of pain including chronic pain.

Narrative Review: Bioactive Potential of Various Mushrooms as the Treasure of Versatile Therapeutic Natural Product

Mushrooms have remained an eternal part of traditional cuisines due to their beneficial health potential and have long been recognized as a folk medicine for their broad spectrum of nutraceuticals, as well as therapeutic and prophylactic uses. Nowadays, they have been extensively investigated to explain the chemical nature and mechanisms of action of their biomedicine and nutraceuticals capacity. Mushrooms belong to the astounding dominion of Fungi and are known as a macrofungus. Significant health benefits of mushrooms, including antiviral, antibacterial, anti-parasitic, antifungal, wound healing, anticancer, immunomodulating, antioxidant, radical scavenging, detoxification, hepatoprotective cardiovascular, anti-hypercholesterolemia, and anti-diabetic effects, etc., have been reported around the globe and have attracted significant interests of its further exploration in commercial sectors. They can function as functional foods, help in the treatment and therapeutic interventions of sub-optimal health states, and prevent some consequences of life-threatening diseases. Mushrooms mainly contained low and high molecular weight polysaccharides, fatty acids, lectins, and glucans responsible for their therapeutic action. Due to the large varieties of mushrooms present, it becomes challenging to identify chemical components present in them and their beneficial action. This article highlights such therapeutic activities with their active ingredients for mushrooms.

Abstract P313: Over-expression Of Serine Threonine Kinase 35 Improves Cardiac Function In Streptozotocin Induced Diabetic Mice

Diabetic cardiomyopathy is a common complication in patients with diabetes and is associatedwith impaired responsiveness of ischemic myocardium to proangiogenic factors, subsequentlyleading to heart failure. STK35, a novel kinase that binds to nuclear actin, has been shown toregulate important cellular functions such as cell migration, proliferation, survival, andangiogenesis. Currently, the contribution of altered STK35 expression in human diseases remainsunexplored. In initial studies, we observed that human cardiac biopsies from diabetic patientsshowed a significant decrease in STK35 expression as compared to non-diabetic control hearts.Intriguingly, in a STZ-induced mouse model of diabetes, i.v . injection of rAAV9-STK35 to expressconstitutive STK35 in heart in FVB/N male mice promoted neovascularization and lowered cardiacfibrosis, leading to improved cardiac function of diabetic heart. Our in vitro studies observed highglucose decreased STK35 expression in mouse cardiac endothelial cells (MCEC), whereasSTK35 overexpression increased MCEC migration and vascular tube formation, and upregulatedMCEC to expression of multiple pro-angiogenic proteins. Taken together, our results demonstratethat cardiac-targeted STK35 gene therapy exerts a marked beneficial action by attenuating bothcardiac remodeling and cardiac function in a mouse model of diabetes mellitus. Mechanistically,the beneficial effect may be attributed, at least partially, to enhanced neovascularization in heart.

Metformin treatment for 8 days impacts multiple intestinal parameters in high-fat high-sucrose fed mice

Although the mechanism of action of the antidiabetic drug metformin is still a matter of discussions, it is well accepted that the gut plays an important role. To gain more insights into the mechanisms occurring in the different regions of the intestine, adult male mice were fed a high-fat-high sucrose (HFS) diet for 8 days and treated with metformin by gavage (300 mg/day/kg body weight) during the HFS diet. Metformin counteracted HFS diet-induced overexpression of a network of genes involved in the transport of glucose and fatty acids in the different regions of the small intestine. It also induced beneficial modification of secondary bile acid profile in the caecum, with a reduction of deoxycholic acid and lithocholic acid levels and increased abundance of ursodeoxycholic acid and tauroursodeoxycholic acid, potentially leading to FRX inhibition. In parallel, metformin treatment was associated with specific changes of the microbiota composition in the lumen of the different regions of the intestine. Metformin induced a marked increase in the abundance of Akkermansia muciniphila in the lumen all along the gut and counteracted the effects of HFS diet on the abundances of some bacterial groups generally associated with metabolic disturbances (f-Lachnospiraceae, f-Petostreptococcaceae, g-Clostidium). Therefore, the present work clearly emphasises the role of all the regions of the intestinal tract in the beneficial action of the antidiabetic drug metformin in a prediabetic mouse model.

Effects of a New Combination of Natural Extracts on Glaucoma-Related Retinal Degeneration

Background: Glaucoma is currently the leading cause of irreversible blindness; it is a neuropathy characterized by structural alterations of the optic nerve, leading to visual impairments. The aim of this work is to develop a new oral formulation able to counteract the early changes connected to glaucomatous degeneration. The composition is based on gastrodin and vitamin D3 combined with vitamin C, blackcurrant, and lycopene. Methods: Cells and tissues of the retina were used to study biological mechanisms involved in glaucoma, to slow down the progression of the disease. Experiments mimicking the conditions of glaucoma were carried out to examine the etiology of retinal degeneration. Results: Our results show a significant ability to restore glaucoma-induced damage, by counteracting ROS production and promoting cell survival by inhibiting apoptosis. These effects were confirmed by the intracellular mechanism that was activated following administration of the compound, either before or after the glaucoma induction. In particular, the main results were obtained as a preventive action of glaucoma, showing a beneficial action on all selected markers, both on cells and on eyecup preparations. It is therefore possible to hypothesize both the preventive and therapeutic use of this formulation, in the presence of risk factors, and due to its ability to inhibit the apoptotic cycle and to stimulate cell survival mechanisms, respectively. Conclusion: This formulation has exhibited an active role in the prevention or restoration of glaucoma damage for the first time.

Sensing Organophosphorus Compounds with SWCNT Films

Promising electrical properties of single-walled carbon nanotubes (SWCNTs) open a spectrum of applications for this material. As the SWCNT electronic characteristics respond well to the presence of various analytes, this makes them highly sensitive sensors. In this contribution, selected organophosphorus compounds were detected by studying their impact on the electronic properties of the nanocarbon network. The goal was to untangle the n-doping mechanism behind the beneficial effect of organic phosphine derivatives on the electrical conductivity of SWCNT networks. The highest sensitivity was obtained in the case of the application of 1,6-Bis(diphenylphoshpino)hexane. Consequently, free-standing SWCNT films experienced a four-fold improvement to the electrical conductivity from 272 ± 21 to 1010 ± 44 S/cm and an order of magnitude increase in the power factor. This was ascribed to the beneficial action of electron-rich phenyl moieties linked with a long alkyl chain, making the dopant interact well with SWCNTs.