Background and objectives In the present article, we explore a novel strategy of selenium nanoparticles (Se-NPs) for the treatment of type 2 diabetes mellitus (T2DM) by investigating the effect of Se-NPs alone and in combination with standard anti-diabetic drug metformin (MET) in high-fat diet/streptozotocin (HFD/STZ)-induced T2DM. Methods HFD was supplemented daily to experimental rats for 8 weeks, followed by a single low dose injection of 35 mg/kg of STZ to induce T2DM. The synergistic effect of the different therapeutic strategies on diabetic complications was evaluated after the Se-NPs and MET administration for 8 weeks. Molecular and biochemical analyses were conducted to figure out the effectiveness of our treatment on insulin sensitivity, oxidative mediators and inflammatory markers. Results Our observations demonstrated that HFD/STZ-induced rats have a toxic effect on serum and hepatic tissues resulted in inducing remarkable oxidative damage and hyper-inflammation with a significant disturbance in the insulin signaling pathway. Experimental animals either treated with mono-therapeutic-two doses Se-NPs (0.1 and 0.4 mg/kg) and/or MET (100 mg/kg) alone as well as the combined therapy resulted in a remarkable protective anti-diabetic effect illustrated by significant decreases in fasting blood glucose and insulin levels after 8 weeks treatment. At the same time, the levels of active insulin signaling proteins pIRS1/pAKT/pGSK-3β/pAMPK were significantly improved. Moreover, Se-NPs exhibited an anti-inflammatory effect by the mitigation of cytokine expression and a balance between oxidative stress and antioxidant status was restored. Furthermore, the anti-diabetic drug MET administration also exhibited a significant improvement in diabetic complications after the treatment period. Conclusion This study provides mightily the mechanism of action of combined Se-NPs and MET as a promising therapeutic alternative that synergistically alleviates most of diabetic complications and insulin resistance.

Background and objectivesInsulin resistance of the brain is a specific form of type2-diabetes mellitus (T2DM) and the active insulin-signaling pathway plays a neuroprotective role against damaging conditions and Alzheimer’s progression. The present study identifies the mediated emerging effects of the Nigella sativa oil (NSO) on the memory enhancing process, its anti-oxidative, acetylcholinestrase (AChE) inhibition, anti-brain insulin resistance and anti-amyloidogenic activities. In addition, the possible role of some anti-diabetic drugs in the neuro-protection processes and their effect in combination with NSO and/or the insulin receptor inhibitor IOMe-AG538 were investigated.MethodsT2DM-induced rats were orally and daily administrated 2.0 ml NSO, 100 mg metformin (MT), 0.8 mg glimepiride (GI) and different combinations (100 mg MT & 2.0 ml NSO, 0.8 mg GI & 2.0 ml NSO and 2.0 ml NSO & intraperitoneal injection of 1/100 LD50 of IOMe-AG538) per kg body weight for 21 days.ResultsA significant increase in the brain lipid peroxidation and decrease in the antioxidant status with peripheral and central production of pro-inflammatory mediators were observed in diabetes-induced rats. The brain AChE was activated and associated with diminished brain glucose level and cholinergic function. In addition, the brain insulin resistance and the attenuated insulin signaling pathway (p-IRS/ p-AKT/p-GSK-3β) were accompanied by an augmentation in GSK-3β level, which in turn may contribute in the extensive alterations of Tau phosphorylation along with changes in PP2A level. Furthermore, neuronal loss and elevation in Aβ-42 plaque formation were observed due to a low IDE formation and an increased expression of p53, BACE1 and APP with diminished ADAM10, SIRT1 and BDNF levels. The expression profile of AD-related miRNAs in sera and brain tissues displayed its neuro-protection role. The treatment of diabetes-induced rats with NSO and the anti-diabetic drugs alone and/or in combination have the potential to suppress the oxidative stress, the pro-inflammatory mediators and amyloidogenic pathway. Moreover, it lowers the insulin receptor inhibitory effect of IOMe-AG538 and modifies the insulin-signaling pathway. Therefore, it prevents the neurotoxicity, amyloid plaque formation and Tau hyper-phosphorylation and restores AD-related miRNA normal levels.ConclusionThese data suggest that NSO or its combined treatments with anti-diabetic drugs have a possible benefit as disease modifying agents for the insulin resistance in the brain through enhancing brain insulin signaling pathway.

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Purpose A novel coronavirus (COVID-19) that has not been previously identified in humans and has no specific treatment has recently spread. Treatment trials using antiviral and immune-modulating drugs such as hydroxychloroquine (HCQ) were used to control this viral outbreak however several side effects have emerged. Berberine (BER) is an alkaloid that has been reported to reveal some pharmacological properties including antioxidant and antimicrobial activities. Additionally, Zinc oxide nanoparticles (ZnO-NPs) possess potent antioxidant and anti-inflammatory properties. Therefore, this study was undertaken to estimate the efficiency of both BER and synthetic ZnO/BER complex as an anti-COVID-19 therapy. Methods First, the ZnO/BER complex was prepared by the facile mixing method. Then in vitro studies on the two compounds were conducted including VeroE6 toxicity, anti-COVID-19 activity, determination of inhibitory activity towards papain-like proteinase (PL pro) and spike protein- and receptor- binding domain (RBD) as well as assessment of drug toxicity on RBCs. Results The results showed that ZnO/BER complex acts as an anti-COVID-19 by inhibiting spike protein binding with angiotensin-converting enzyme II (ACE II), PL pro activity, spike protein and E protein levels, and expression of both E-gene and RNA dependent RNA polymerase (RdRp) at a concentration lower than that of BER or ZnO-NPs alone. Furthermore, ZnO/BER complex had antioxidant and antimicrobial properties where it prevents the auto oxidation of 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and the culture of lower respiratory system bacteria that affected Covid 19 patients. The ZnO/BER complex prevented as well the HCQ cytotoxic effect on both RBC and WBC (in vitro) and hepatotoxicity, nephrotoxicity and anemia that occurred after HCQ long administration in vivo. Conclusion The ZnO/BER complex can be accounted as promising anti-COVID 19 candidate because it inhibited the virus entry, replication, and assembly. Furthermore, it could be used to treat a second bacterial infection that took place in hospitalized COVID 19 patients. Moreover, ZnO/BER complex was found to eliminate the toxicity of long-term administration of HCQ in vivo .

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Introduction: Oxidative stress is a key contributor to aging and age-related diseases. In the present study, we examine the protective effects of PFT, a novel kefir product, against age-associated oxidative stress using aged (10-month-old) mice. Methods: Mice were treated with PFT orally at a daily dose of 2 mg/kg body weight over 6 weeks, and antioxidant status, protein oxidation, and lipid peroxidation were studied in the brain, liver, and blood. Results: PFT supplementation significantly reduced the oxidative stress biomarkers malondialdehyde (MDA) and nitric oxide; reversed the reductions in glutathione (GSH) levels, total antioxidant capacity (TAC), and anti-hydroxyl radical (AHR) content; enhanced the antioxidant enzyme activities of glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD); inhibited the liver enzyme levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT); significantly reduced triglyceride (TG), total cholesterol (TC), and low density lipoprotein (LDL) levels; and significantly elevated high density lipoprotein (HDL) levels. Interestingly, PFT supplementation reversed the oxidative changes associated with aging, thus bringing levels to within the limits of the young control mice in the brain, liver, and blood. We also note that PFT affects the redox homeostasis of young mice and that it is corrected post-treatment with PFT. Conclusion: Our findings show the effectiveness of dietary PFT supplementation in modulating age-associated oxidative stress in mice and motivate further studies of PFT’s effects in reducing age-associated disorders where free radicals and oxidative stress are the major cause.

The present study was carried out to investigate the therapeutic effect of synthesized naturally compounds, curcumin nanoparticles (CurNPs) and metal oxide, zinc oxide nanoparticles (ZnONPs) on a high-fat diet (HFD)/streptozotocin (STZ)-induced hepatic and pancreatic pathophysiology in type 2 diabetes mellitus (T2DM) via measuring AKT pathway and MAPK pathway. T2DM rats were intraperitoneally injected with a low dose of 35 mg/kg STZ after being fed by HFD for 8 weeks. Then the rats have orally received treatments for 6 weeks. HFD/STZ-induced hepatic inflammation, reflected by increased phosphorylation of p38-MAPK pathway’s molecules, was significantly decreased after nanoparticle supplementation. In addition, both nanoparticles significantly alleviated the decreased phosphorylation of AKT pathway. Further, administration of ZnONPs, CurNPs, conventional curcumin, and ZnSO4 (zinc sulfate), as well as metformin, effectively counteracted diabetes-induced oxidative stress and inflammation in the internal hepatic and pancreatic tissues. Based on the results of the current study, ZnONPs and CurNPs could be explored as a therapeutic adjuvant against complications associated with T2DM. Both nanoparticles could effectively delay the progression of several complications by activating AKT pathway and down-regulating MAPK pathway. Our findings may provide an experimental basis for the application of nanoparticles in the treatment of T2DM with low toxicity.

Numerous epidemiological findings have repeatedly established associations between Type 2 Diabetes Mellitus (T2DM) and Alzheimer’s disease. Targeting different pathways in the brain with T2DM-therapy offers a novel and appealing strategy to treat diabetes-related neuronal alterations. Therefore, here we investigated the capability of a natural compound, curcumin nanoparticle (CurNP), and a biomedical metal, zinc oxide nanoparticle (ZnONP), to alleviate hippocampal modifications in T2DM-induced rats. The diabetes model was induced in male Wistar rats by feeding a high-fat diet (HFD) for eight weeks followed by intraperitoneal injection of streptozotocin (STZ). Then model groups were treated orally with curcumin, zinc sulfate, two doses of CurNP and ZnONP, as well as metformin, for six weeks. HFD/STZ-induced rats exhibited numerous biochemical and molecular changes besides behavioral impairment. Compared with model rats, CurNP and ZnONP boosted learning and memory function, improved redox and inflammation status, lowered Bax, and upregulated Bcl2 expressions in the hippocampus. In addition, the phosphorylation level of the MAPK/ERK pathway was downregulated significantly. The expression of amyloidogenic-related genes and amyloid-beta accumulation, along with tau hyperphosphorylation, were lessened considerably. In addition, both nanoparticles significantly improved histological lesions in the hippocampus. Based on our findings, CurNP and ZnONP appear to be potential neuroprotective agents to mitigate diabetic complications-associated hippocampal toxicity.