Chromium (Cr) is an essential trace element that has garnered interest for use as a weight loss aid, but its molecular mechanism in obesity is not clear. In this study, an attempt has been made to investigate the effects of chromium histidinate (CrHis) on glucose transporter-2 (GLUT-2), nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), nuclear factor-kappa B (NF-κB p65) and the oxidative stress marker 4-hydroxynonenal adducts (HNE) expressions in liver of rats fed high fat diet (HFD).Male Wistar rats (n = 40, 8 wk-old) were divided into four groups. Group I was fed a standard diet (12% of calories as fat); Group II was fed a standard diet and supplemented with 110 μg CrHis/kg BW/d; Group III was fed a HFD (40% of calories as fat); Group IV was fed HFD and supplemented with 110 μg CrHis/kg BW/d.Rats fed HFD possessed greater serum insulin (40 vs.33 pmol/L) and glucose (158 vs. 143 mg/dL) concentration and less liver Cr (44 vs.82 μg/g) concentration than rats fed the control diet. However, rats supplemented with CrHis had greater liver Cr and serum insulin and lower glucose concentration in rats fed HFD (P < 0.05). The hepatic nuclear factor-kappa B (NF-κB p65) and HNE were increased in high fat group compared to control group, but reduced by the CrHis administration (P < 0.05). The levels of hepatic Nrf2 and HO-1 were increased by supplementation of CrHis (P < 0.05).These findings demonstrate that supplementation of CrHis is protective against obesity, at least in part, through Nrf2-mediated induction of HO-1 in rats fed high fat diet.
This study aimed to examine the impacts of the magnesium picolinate (MgPic), zinc picolinate (ZnPic), and selenomethionine (SeMet) alone or as a combination on blood metabolites, oxidative enzymes, reproductive hormones, and glucose and lipid metabolism-related protein expressions in Wistar rats fed a high-fed diet (HFD). The rats were fed either a control, HFD, or HFD supplemented with a single (MgPic, ZnPic, SeMet) or two or three organic mineral combinations. Body weights, visceral fat, serum glucose, insulin, total cholesterol, triglycerides, leptin, malondialdehyde (MDA) concentrations as well as liver sterol regulatory element-binding protein-1c (SREBP-1c), liver X receptor alpha (LXRα), ATP citrate lyase (ACLY), fatty acid synthase (FAS), and nuclear factor kappa B (NF-κB) levels increased, while serum testosterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), sex hormone-binding globulin (SHBG), and insulin-like growth factor (IGF-1) concentrations along with liver nuclear factor erythroid 2-related factor 2 (Nrf2) levels declined in HFD rats (P < 0.05). Supplementing each organic mineral, but particularly the combination of HFD + MgPic + ZnPic + SeMet reversed the responses with various degrees. None of the organic elements alone or as a combination of two exerted a prominent effect on parameters measured. Although not additive or synergistic, the combination of all organic minerals added to HFD (HFD + MgPic + ZnPic + SeMet) provided the greatest responses.
An experiment utilizing Cobb-500 male broilers was conducted to evaluate the effects of vitamin E (d1--to- copheryl acetate) supplementation at various concentrations (0, 62.5, 125, 250, or 500 mg/kg of diet) on performance and serum concentrations of Triiodothyronine (T3), Thyroxin (T4), Adrenocorticotropine Hormone (ACTH), and some metabolites and minerals in broilers reared under heat stress (32°C). One day-old 150 male broilers were randomly assigned to 5 treatment groups, 3 replicates of 10 birds each. The birds received either a basal diet or basal diet supplemented with vitamin E at 62.5, 125, 250, or 500 mg/kg of diet. Increased supplemental vitamin E linearly increased feed intake (P = 0.01), live weight gain (P = 0.01), and improved feed efficiency linearly (P = 0.001). Increasing dietary vitamin E supplementation also resulted in linear increases in serum T3 and T4 concentrations (P = 0.01) but, linear decreases in ACTH concentration (P = 0.01). Serum glucose, uric acid, triglycerides, and cholesterol concentrations decreased linearly (P = 0.001) while, protein and albumin concentrations increased linearly (P = 0.001) when dietary vitamin E supplementation increased. Serum activities of Serum Glutamic Oxalate Transaminase (SGOT) and Serum Glutamic Pyruvate Transaminase (SGPT) were not influenced by dietary vitamin E supplementation (P > 0.10). However, serum activity of Alkaline Phosphatase (AP) increased linearly (P = 0.001) with increasing dietary vitamin E supplementation. Increasing dietary vitamin E supplementation also caused linear increases (P = 0.001) in serum concentrations of Ca and P. Results of the present study conclude that a 250 mg/kg of vitamin E provides an optimal performance in broiler chicks reared under heat stress, and vitamin E supplementation at such a level can be considered as a protective management practice in a broiler diet, reducing the negative effects of heat stress.
Aim: Our main objectives were to compare the effects of Rejuveinix (RJX), dexamethasone (DEX) and their combination on the severity of sepsis and survival outcome in an animal model of fatal sepsis. Methods: We used the LPS plus D-galactosamine mouse model of sepsis to compare the anti-inflammatory activities of RJX, dexamethasone and a combination of RJX plus DEX. Additionally, we examined the clinical feasibility and tolerability of combining RJX with DEX in COVID-19 patients in a clinical phase I study. Data were analyzed using standard methods. Results & conclusion: RJX exhibited potent anti-inflammatory activity in the murine sepsis model. The combination of RJX plus DEX was more effective than either agent alone, decreased the inflammatory cytokine responses and associated organ damage, and improved the survival outcome in mice. In the phase I clinical study, RJX plus DEX was well tolerated by COVID-19 patients.
There has been an increasing interest in the usage of natural products for the prevention and treatment of chronic diseases such as cardiovascular disease (CVD). Regular consumption of fruits, vegetables and whole grains has been shown to be negatively correlated with the risk of CVDs. These foods provide a diversity of nutrients and different bioactive compounds including phytochemicals, vitamins, minerals and fibers which play critical roles in the sustainability of optimal cardiovascular health. Plant-based foods or a nutritional cure are gradually being integrated into medical practice for CVD management partly due to the supporting experimental studies, clinical trials and epidemiological studies. These products have anti-oxidant, anti-inflammatory, hypoglycemic, hypolipidemic, hypotensive, anti-atherosclerotic, anti-thrombotic and hypocholesterolemic effects, depending on the dosage in cell and tissue cultures, animal models as well as in humans. The present review considers some novel ideas on some major phytochemicals which have been suggested to have protective and therapeutic potential in CVD. The data presented in this work have been compiled from studies that have mostly been carried out in recent years. Keywords: Cardiovascular disease, cardiovascular pharmacology, molecular pharmacology, natural compound, phytochemical.
We recently reported the clinical safety profile of RJX, a well-defined intravenous GMP-grade pharmaceutical formulation of anti-oxidant and anti-inflammatory vitamins as active ingredients, in a Phase 1 study in healthy volunteers (ClinicalTrials.gov Identifier: NCT03680105) (Uckun et al., Front. Pharmacol. 11, 594321. 10.3389/fphar.2020.594321). The primary objective of the present study was to examine the effects of GMP-grade RJX on wound and burn injury healing in diabetic rats.In the present study, a rat model of T2DM was used that employs HFD in combination with a single injection of STZ intraperitoneally (i.p) at a moderate dose level (45 mg/kg). Anesthetized diabetic rats underwent full-thickness skin excision on the back or were subjected to burn injury via a heated brass probe and then started on treatments with normal saline (NS = vehicle) or RJX administered via intraperitoneal injections for three weeks.Notably, diabetic rats treated with the 1.25 mL/kg or 2.5 mL/kg RJX (DM+RJX groups) rapidly healed their wounds as fast as non-diabetic control rats. Inflammatory cell infiltration in the dermis along with fibrin and cell debris on the epithelial layer persisted for up to 14 days in the DM+NS group but not in RJX-treated groups. The histopathological score of wound healing on days 7 and 14 was better in diabetic rats treated with RJX than diabetic rats treated with NS and comparable to the scores for non-diabetic healthy rats consistent with an accelerated healing process. The residual wound area of RJX-treated rats was significantly smaller than that of NS-treated diabetic rats at each evaluation time point (P<0.001). The accelerating effect of RJX on diabetic wound healing was dose-dependent. We obtained similar results in the burn injury model. Our results demonstrate that RJX - at a dose level >10-fold lower than its clinical maximum tolerated dose (MTD) - accelerates the healing of excision wounds as well burn injury in diabetic rats.
