Niacinamide and undenatured type II collagen modulates the inflammatory response in rats with monoiodoacetate-induced osteoarthritis.

The current work aimed to examine the properties of oral supplementation of niacinamide and undenatured type II collagen (UCII) on the inflammation and joint pain behavior of rats with osteoarthritis (OA). Forty-nine Wistar rats were allocated into seven groups; control (no MIA), MIA as a non-supplemental group with monosodium iodoacetate (MIA)-induced knee osteoarthritis, MIA + undenatured type II collagen (UCII) at 4 mg/kg BW, MIA + Niacinamide at 40 mg/kg BW (NA40), MIA + Niacinamide at 200 mg/kg BW (NA200), MIA + UCII + NA40 and MIA + UCII + NA200. Serum IL-1ß, IL-6, TNF-α, COMP, and CRP increased in rats with OA and decreased in UCII and NA groups (p < 0.05). Rats with osteoarthritis had greater serum MDA and knee joint MMP-3, NF-κB, and TGß protein levels and decreased in treated groups with UCII and NA (p < 0.05). The rats with OA also bore elevated joint diameters with joint pain behavior measured as decreased the stride lengths, the paw areas, and the paw widths, and increased the Kellgren-Lawrence and the Mankin scores (p < 0.05) and decreased in UCII treated groups. These results suggest the combinations with the UCII + NA supplementation as being most effective and reduce the inflammation responses for most OA symptoms in rats.

Lutein/zeaxanthin isomers regulate neurotrophic factors and synaptic plasticity in trained rats

Background/aim: This study was conducted to elucidate the effects of lutein/zeaxanthin isomers (L/Zi) on lipid metabolism, oxidative stress, NF-κB/Nrf2 pathways, and synaptic plasticity proteins in trained rats. Materials and methods: Wistar rats were distributed into four groups: 1) control, 2) L/Zi: rats received L/Zi at the dose of 100 mg/kg by oral gavage, 3) exercise, 4) exercise+L/Zi: rats exercised and received L/Zi (100 mg/kg) by oral gavage. The duration of the study was eight weeks. Results: Exercise combined with L/Zi reduced lipid peroxidation and improved antioxidant enzyme activities of muscle and cerebral cortex in rats (p < 0.001). In the Exercise + L/Zi group, muscle and cerebral cortex Nrf2 and HO-1 levels increased, while NF-κB levels decreased (p <0.001). Also, L/Zi improved BDNF, synapsin I, SYP, and GAP-43 levels of the cerebral cortex of trained rats (p < 0.001). The highest levels of BDNF, synapsin SYP, and GAP-43 in the cerebral cortex were determined in the Exercise+L/Zi group. Conclusion: These results suggested that exercise combined with L/Zi supplementation might be effective to reduce neurodegeneration via improving neurotrophic factors and synaptic proteins, and oxidative capacity in the cerebral cortex.

Mango ginger (curcuma amada) inhibits collagen-induced arthritis by modulating inflammatory cytokine levels in rats

Background/aim: Mango ginger (MG: curcuma amada) has antioxidant and antiinflammatory activities. The aim was to evaluate the antiarthritic potential efficacy of MG on collagen-induced arthritis. Materials and methods: Twenty-one female Wistar-albino rats were divided into three groups. Arthritis was induced by intradermal injections of type II collagen and Freund's adjuvant. MG extract was orally administered starting from the first collagen injection. TNF-α, IL-6, IL-17, obestatin, sclerostin, and DKK-1 serum levels were determined, and perisynovial inflammation and cartilage-bone destruction in the paws were histologically evaluated. Moreover, joint tissue TNF-α, IL-17, NF-κB, and COX-2 levels were analyzed. Results: TNF-α, IL-17, IL-6, and DKK-1 serum levels were increased, and obestatin and sclerostin serum levels were decreased in the arthritis group compared to the control group. However, MG supplements decreased TNF-α, IL-17, IL-6, and DKK-1 serum levels and increased obestatin and sclerostin serum levels. Similarly, while collagen injection increased tissue TNF-α, IL-17, NF-κB, and COX-2 levels, MG decreased TNF-α, IL-17, and NF-κB levels. Moreover, MG ameliorated perisynovial inflammation and cartilage-bone destruction in the paws. Conclusion: MG ameliorates arthritis via actions on inflammatory ways and wingless (Wnt) signaling pathway. These results suggest that MG may have a considerable potential efficacy for the treatment of rheumatoid arthritis.

Effects of allyl isothiocyanate on insulin resistance, oxidative stress status, and transcription factors in high-fat diet/streptozotocin-induced type 2 diabetes mellitus in rats.

Allyl isothiocyanate (AITC), a dietary phytochemical found in some cruciferous vegetables, is commonly used as an antimicrobial, anticancer, and antioxidant agent. In the present study, we investigated the effects of AITC on insulin resistance and transcription factors in a diabetic rat model. A total of 42 Wistar rats were divided into six groups and orally treated for 12 weeks as follows: (i) control; (ii) AITC (100 mg/kg body weight [BW]); (iii) high fat diet (HFD); (iv) HFD + AITC (100 mg/kg BW); (v) HFD + streptozotocin (STZ, 40 mg/kg BW); and (vi) HFD + STZ + AITC. Administration of AITC reduced blood glucose, total cholesterol, triglycerides, and creatinine levels, but increased (P < 0.001) total antioxidant capacity. In AITC-treated rats, the glucose transporter-2, peroxisome proliferator-activated receptor gamma, p-insulin receptor substrate-1, and nuclear factor erythroid-derived 2 in the liver and kidney were increased while nuclear factor-kappa B was downregulated (P < 0.05). In conclusion, AITC possesses antidiabetic, antioxidant, and anti-inflammatory activities in HFD/STZ-induced T2DM in rats. These findings may further justify the importance of AITC in phytomedicine.

(3R, 3'R)-zeaxanthin protects the retina from photo-oxidative damage via modulating the inflammation and visual health molecular markers.

PURPOSE: Zeaxanthin protects the macula from ocular damage due to light or radiation by scavenging harmful reactive oxygen species. In the present study, zeaxanthin product (OmniXan®; OMX), derived from paprika pods (Capsicum annum; Family-Solanaceae), was tested for its efficacy in the rat retina against photooxidation. METHODS: Forty-two male 8-week-old Wistar rats exposed to 12L/12D, 16L/8D and 24L/0D hours of intense light conditions were orally administrated either 0 or 100 mg/kg BW of zeaxanthin concentration. Retinal morphology was analyzed by histopathology, and target gene expressions were detected with real-time polymerase chain reaction methods. RESULTS: OMX treatment significantly increased the serum zeaxanthin concentration (p < 0.001) and ameliorated oxidative damage by increasing the antioxidant enzyme activities in the retina induced by light (p < 0.001). OMX administration significantly upregulated the expression of genes, including Rhodopsin (Rho), Rod arrestin (SAG), Gα Transducin 1 (GNAT-1), neural cell adhesion molecule (NCAM), growth-associated protein 43 (GAP43), nuclear factor-(erythroid-derived 2)-like 2 (Nrf2) and heme oxygenase (HO-1) and decreased the expression of nuclear factor-κB (NF- κB) and GFAP by OMX treatment rats. The histologic findings confirmed the antioxidant and gene expression data. CONCLUSIONS: This study suggests that OMX is a potent substance that can be used to protect photoreceptor cell degeneration in the retina exposed to intense light.

MAT, a Novel Polyherbal Aphrodisiac Formulation, Enhances Sexual Function and Nrf2/HO-1 Pathway While Reducing Oxidative Damage in Male Rats.

Mucuna pruriens, Ashwagandha, and Tribulus terrestris are known as the enhancers for sexual health, functional activities, vitality, and longevity. These herbs had been widely used in the Ayurveda medicine as aphrodisiacs through the ages, and their efficacy was also verified separately in our previous publication. Therefore, the aim of this study was to determine the effects of Mucuna, Ashwagandha, and Tribulus complexes on sexual function in rats. Twenty-eight male rats allocated to four groups as follows: (i) negative control (C); (ii) positive control or sildenafil citrate treated group (5 mg/kg) (S); (iii) MAT1 (combination of 10 mg Mucuna (M) + 10 mg Ashwagandha (A) + 10 mg Tribulus (T)/kg BW); (iv) MAT 2 (20 mg Mucuna + 20 mg Ashwagandha + 20 mg Tribulus/kg BW). There was no significant difference found between the MAT1 and MAT2 groups while they showed significantly increased testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels when compared to the negative control. Significant increases in Nrf2/HO1 levels and decreases in NF-κB were detected in MAT groups similar to the decrease in serum and testis malondialdehyde (MDA) levels as compared to both controls. The sperm motility, count, and rate also significantly improved in both MAT groups, while ALT, AST, creatinine, ALP, and urea levels did not change in any of the groups. Oral consumption of MATs combination in male rats resulted in inhibition of NF-κB and MDA and also increased sex hormones with Nrf2-mediated HO-1 induction. MAT combinations may improve sexual functions by increasing levels of sexual hormones and regulation of NF-κB and Nrf2/HO-1 signaling pathways.

The effects of Mucuna pruriens on the renal oxidative stress and transcription factors in high-fructose-fed rats.

In the present study, we evaluated the effects of M. pruriens administration on metabolic parameters, oxidative stress and kidney nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling pathways in high-fructose fed rats. Male rats (n = 28) were divided into 4 groups as control, M. pruriens, fructose, and M. pruriens plus fructose. All rats were fed a standard diet supplemented or no supplemented with M. pruriens (200 mg/kg/d by gavage). Fructose was given in drinking water for 8 weeks. High fructose consumption led to an increase in the serum level of glucose, triglyceride, urea and renal malondialdehyde (MDA) levels. Although M. pruriens treatment reduced triglyceride and MDA levels, it did not affect other parameters. M. pruriens supplementation significantly decreased the expression of NF-Ò¡B and decreased expression of Nrf2 and HO-1 proteins in the kidney. This study showed that the adverse effects of high fructose were alleviated by M. pruriens supplementation via modulation of the expression of kidney nuclear transcription factors in rats fed high fructose diet.

Cinnamon Polyphenol Extract Exerts Neuroprotective Activity in Traumatic Brain Injury in Male Mice.

BACKGROUND: Cinnamon polyphenol extract is a traditional spice commonly used in different areas of the world for the treatment of different disease conditions which are associated with inflammation and oxidative stress. Despite many preclinical studies showing the anti-oxidative and antiinflammatory effects of cinnamon, the underlying mechanisms in signaling pathways via which cinnamon protects the brain after brain trauma remained largely unknown. However, there is still no preclinical study delineating the possible molecular mechanism of neuroprotective effects cinnamon polyphenol extract in Traumatic Brain Injury (TBI). The primary aim of the current study was to test the hypothesis that cinnamon polyphenol extract administration would improve the histopathological outcomes and exert neuroprotective activity through its antioxidative and anti-inflammatory properties following TBI. METHODS: To investigate the effects of cinnamon, we induced brain injury using a cold trauma model in male mice that were treated with cinnamon polyphenol extract (10 mg/kg) or vehicle via intraperitoneal administration just after TBI. Mice were divided into two groups: TBI+vehicle group and TBI+ cinnamon polyphenol extract group. Brain samples were collected 24 h later for analysis. RESULTS: We have shown that cinnamon polyphenol extract effectively reduced infarct and edema formation which were associated with significant alterations in inflammatory and oxidative parameters, including nuclear factor-κB, interleukin 1-beta, interleukin 6, nuclear factor erythroid 2-related factor 2, glial fibrillary acidic protein, neural cell adhesion molecule, malondialdehyde, superoxide dismutase, catalase and glutathione peroxidase. CONCLUSION: Our results identify an important neuroprotective role of cinnamon polyphenol extract in TBI which is mediated by its capability to suppress the inflammation and oxidative injury. Further, specially designed experimental studies to understand the molecular cross-talk between signaling pathways would provide valuable evidence for the therapeutic role of cinnamon in TBI and other TBI related conditions.

Mesozeaxanthin protects the liver and reduces cardio-metabolic risk factors in an insulin resistant rodent model.

Background: Mesozeaxanthin (MZ) is a macular carotenoid which has been reported to have a number of pharmacological properties, including the antioxidant, and anticarcinogenic property, and has been stated to decrease the hepatocyte lipid content. Objective: In this study, we investigated the effect of MZ on cardio-metabolic health risk (CMHR) and its probable mechanisms of action in rats fed a high-fat diet (HFD). Design: Rats were randomly divided into four groups consisting of (i) Control, (ii) MZ, (iii) HFD, and (iv) HFD+MZ. Results: MZ treatment increased the antioxidant enzyme activities and helped improve the liver function. The treatment alleviated CMHR and decreased the level of nuclear factor kappa B (NF-κB p65) and tumor necrosis factor-alpha (TNF-α). The levels of hepatic peroxisome proliferator-activated receptor gamma (PPAR-γ), phosphorylated insulin receptor substrate 1 (p-IRS-1), ß,ß-carotene 9',10'-oxygenase 2 (BCO2) and nuclear factor erythroid 2-related factor 2 (Nrf2), which decrease in HFD rats, were found to be significantly higher in MZ supplemented animals. Conclusion: MZ has antioxidant and anti-inflammatory properties and can is reported in this study toprotect against fatty liver and cardio-metabolic syndrome, possibly through regulation of PPAR-γ, IRS-1, Nrf2 and NF-κB proteins, in an insulin-resistant rodent model.

Lutein and zeaxanthin isomers modulates lipid metabolism and the inflammatory state of retina in obesity-induced high-fat diet rodent model.

BACKGROUND: Several studies associated high-fat intakes with a high incidence of age-related macular degeneration (AMD). Lutein and Zeaxanthin isomers (L/Zi) may counteract reactive oxygen species produced by oxidative stress. The present study was conducted to determine the possible effects of L/Zi administration on lipid profile, protein genes associated with oxidative stress and inflammation pathways in the obesity induced by a high-fat diet (HFD) in rodents. METHODS: Twenty-eight male Wistar rats were allocated into four groups as follows: (i) Control, (ii) Control + L/Zi, (iii) High Fat Diet (HFD), and (iv) HFD+ L/Z. L/Zi was administrated for 8 weeks at a daily dose of 100 mg/kg BW. RESULTS: L/Zi administration significantly reduced insulin and free fatty acid (FFA) levels (P < 0.001) and ameliorated the oxidative damage by reducing malondialdehyde (MDA) concentration and increasing antioxidant enzymes activities of retina induced by HFD. In addition, supplementation decreased the levels of vascular endothelial growth factor (VEGF), inducible nitric oxide synthase (iNOS), nuclear factor-kappa B (NF-κB) and intercellular adhesion molecule-1 (ICAM) (P < 0.001, respectively) and improved nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) gene proteins in retinal tissues (P < 0.001). CONCLUSION: Rats fed with HFD exhibited increased oxidative stress and upregulation of inflammatory indicators. However, L/Zi supplementation modulates genes involved oxidative stress and inflammation including NF-κB and Nrf2 signaling pathways in the retina which may contribute to ameliorating retinal damage induced by HFD.

Cinnamon Polyphenol Extract Inhibits Hyperlipidemia and Inflammation by Modulation of Transcription Factors in High-Fat Diet-Fed Rats.

We evaluated the effects of cinnamon polyphenol extract on hepatic transcription factors expressions including SREBP-1c and LXR-α in rats fed high fat diet (HFD). Twenty-eight Wistar rats were allocated into four groups: (i) normal control: animals fed with normal chow; (ii) cinnamon: animals supplemented with cinnamon polyphenol; (iii) HFD: animals fed a high-fat diet; and (iv) HFD + cinnamon: animals fed a high-fat diet and treated with cinnamon polyphenol. Obesity was linked to hyperglycemia, hyperlipidemia, and oxidative stress as imitated by elevated serum glucose, lipid profile, and serum and liver malondialdehyde (MDA) concentrations. Cinnamon polyphenol decreased body weight, visceral fat, liver weight and serum glucose and insulin concentrations, liver antioxidant enzymes, and lipid profile (P < 0.05) and reduced serum and liver MDA concentration compared to HFD rats (P < 0.05). Cinnamon polyphenol also suppressed the hepatic SREBP-1c, LXR-α, ACLY, FAS, and NF-κB p65 expressions and enhanced the PPAR-α, IRS-1, Nrf2, and HO-1 expressions in the HFD rat livers (P < 0.05). In conclusion, cinnamon polyphenol reduces the hyperlipidemia, inflammation, and oxidative stress through activating transcription factors and antioxidative defense signaling pathway in HFD rat liver.

Salacia Extract Improves Postprandial Glucose and Insulin Response: A Randomized Double-Blind, Placebo Controlled, Crossover Study in Healthy Volunteers.

Thirty-five healthy subjects were randomly assigned to different doses of Salacia chinensis extract (200 mg, 300 mg, and 500 mg SCE) capsules and compared with placebo. It is a placebo controlled randomized crossover design study. Subjects were given oral sucrose solution along with capsules and plasma glucose and insulin responses were analyzed. Blood samples were collected at 0, 30, 60, 90, 120, and 180 minutes after administration. AUC insulin significantly lowered after ingestion of SCE. No significant adverse events were observed. Reducing glucose and insulin is very important in reducing postprandial hyperglycemia.

Overall skin tone and skin-lightening-improving effects with oral supplementation of lutein and zeaxanthin isomers: a double-blind, placebo-controlled clinical trial.

PURPOSE: Carotenoids, especially lutein and zeaxanthin isomers (L/Zi), filter blue light and protect skin from environmental factors including high-energy sources. These carotenoids may be able to block the formation of melanin pathways, decrease cytokines, and increase antioxidants. SUBJECTS AND METHODS: This is a randomized, double-blind, placebo-controlled clinical trial over a 12-week supplementation period. Fifty healthy people (50 healthy subjects were recruited and 46 subjects completed the study) (males and females, age: 18-45 years) with mild-to-moderate dry skin were included in this study. Skin type of the subjects was classified as Fitzpatrick skin type II-IV scale. Subjects were administered with either an oral dietary supplement containing 10 mg lutein (L) and 2 mg zeaxanthin isomers (Zi) (L/Zi: RR-zeaxanthin and RS (meso)-zeaxanthin) or a placebo daily for 12 weeks. The minimal erythemal dose and skin lightening (L*) were measured via the Chromameter®. The individual typological angle was calculated. Subjective assessments were also recorded. RESULTS: Overall skin tone was significantly improved in the L/Zi group compared to placebo (P<0.0237), and luminance (L*) values were significantly increased in the L/Zi group. Mean minimal erythemal dose was increased with L/Zi supplementation after 12 weeks of supplementation. L/Zi supplementation significantly increased the individual typological angle. CONCLUSION: L/Zi supplementation lightens and improves skin conditions.

Comparative evaluation of the sexual functions and NF-κB and Nrf2 pathways of some aphrodisiac herbal extracts in male rats.

BACKGROUND: Mucuna pruriens, Tribulus terrestris and Ashwagandha (Withania somnifera) are widely known as antioxidant effective herbals and have been reported to possess aphrodisiac activities in traditional usages. In this study, we determined the effects of these herbals on sexual functions, serum biochemical parameters, oxidative stress and levels of NF-κB, Nrf2, and HO-1 in reproductive tissues. METHODS: Thirty-five male rats were divided into five groups: the control group, sildenafil-treated group (5 mg/kg/d), Mucuna, Tribulus and Ashwagandha groups. The extract groups were treated orally either with Mucuna, Tribulus or Ashwagandha (300 mg/kg b.w.) for 8 weeks. RESULTS: All of the extracts were found to be significantly effective in sexual functioning and antioxidant capacity and Tribulus showed the highest effectiveness. Serum testosterone levels significantly increased in Tribulus and Ashwagandha groups in comparison to control group. Tribulus was able to reduce the levels of NF-κB and increase the levels of Nrf2 and HO-1 to a much greater extent than Mucuna and Ashwagandha. CONCLUSIONS: These results demonstrate for the first time that Mucuna, Tribulus and Ashwagandha supplementation improves sexual function in male rats via activating Nrf2/ HO-1 pathway while inhibiting the NF-κB levels. Moreover, Tribulus terrestris extract was found to be more bioavailable from Ashwagandha extract followed by Mucuna extract. Schematic representation of the mode of action of some aphrodisiac herbal extracts to improve sexual functions.

Mesozeaxanthin Protects Retina from Oxidative Stress in a Rat Model.

PURPOSE: Mesozeaxanthin (MZ) is able to protect against chronic and cumulative eye damage and neutralize free radicals produced by oxidative stress. The objective of the present study was to evaluate the protective potential of MZ against retinal oxidative damage and growth and transcription factors of the retina in rats fed with high-fat diet (HFD). METHODS: Twenty-eight Sprague Dawley rats were randomly divided into the following 4 groups: (1) Control, (2) MZ (100 mg/kg bw/d), (3) HFD (42% of calories as fat), and (4) HFD+MZ (100 mg/kg bw/d) group rats were administered daily as supplement for 12 weeks. RESULTS: Consumption of HFD was associated with hyperglycemia and oxidative stress as reflected by increased serum MDA concentration (P < 0.001). No measurable zeaxanthin (Z)+MZ and lutein (L) could be detected in the serum of control and HFD rats, whereas they were observed in the serum of MZ-administered rats. Retinal antioxidant enzyme [superoxide dismutase (SOD) and catalase (CAT)] activities were significantly decreased in the HFD group compared to the normal group (P < 0.01). However, retinal antioxidant enzymes were restored close to normal levels in HFD+MZ-treated rats (P < 0.05). The retina of rats fed with HFD had increased levels of vascular endothelial growth factor (VEGF), inducible nitric oxide (iNOS), intercellular adhesion molecule-1 (ICAM-1), and nuclear factor-kappa B (NF-κB) levels and decreased nuclear factor erythroid 2-related factor 2 (Nrf2) and heme-oxygenase 1(HO-1) levels compared to the healthy rat retina (P < 0.001). Rats treated with MZ partially alleviated the inflammation as reflected by suppressed VEGF, iNOS, ICAM, and NF-κB levels and increased Nrf2 and HO-1 levels in the retina of rats fed (P < 0.05). CONCLUSIONS: Results from the present study suggest that MZ has protective effects on the retina and the ability to modulate oxidative stress of retina in rats fed an HFD by suppressing retinal lipid peroxidation and regulating growth and transcription factors.

Safety evaluation of zeaxanthin concentrate (OmniXan™): acute, subchronic toxicity and mutagenicity studies.

The available evidence suggests a beneficial effect of zeaxanthin against the progression of age-related macular degeneration (AMD). The objective of the present study was to investigate potential adverse effects of OmniXan™, a RR-zeaxanthin (65%) enriched product obtained from paprika (Capsicum annum fruits) in subchronic toxicity and mutagenicity studies. The oral LD50 of OmniXan(TM) in rats was greater than 2000 mg/kgbody weight (bw)/day. For the subchronic toxicity study, Wistar rats (10/sex/group) were gavaged daily with zeaxanthin concentrate at doses of 0, 4, 40 and 400 mg/kg bw/day for 90-days. No treatment related clinical signs and mortalities observed. Similarly, no treatment related toxicologically significant changes in body weight, feed consumption; ophthalmoscopic examination, neurological examination, hematology, urine analysis and organ weights were observed. Statistically significant changes observed in some clinical chemistry parameters were considered toxicologically and biologically insignificant and nonadverse. Macroscopic and microscopic examinations did not reveal treatment-related abnormalities. The results of mutagenicity testing using Salmonella typhimurium did not reveal any genotoxicity. The no observed-adverse-effect level (NOAEL) for zeaxanthin concentrate (OmniXan(TM)) was determined as 400 mg/kg bw/day, the highest dose tested. The findings of this subchronic toxicity and mutagenicity studies support safety of zeaxanthin concentrate.

An evidence-based systematic review of active hexose correlated compound (AHCC) by the Natural Standard Research Collaboration.

An evidence-based systematic review of active hexose correlated compound (AHCC) by the Natural Standard Research Collaboration consolidates the safety and efficacy data available in the scientific literature using a validated, reproducible grading rationale. This article includes written and statistical analysis of clinical trials, plus a compilation of expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing.

Anti-diabetic activity of chromium picolinate and biotin in rats with type 2 diabetes induced by high-fat diet and streptozotocin.

The objective of the present study was to evaluate anti-diabetic effects of chromium picolinate (CrPic) and biotin supplementations in type 2 diabetic rats. The type 2 diabetic rat model was induced by high-fat diet (HFD) and low-dose streptozotocin. The rats were divided into five groups as follows: (1) non-diabetic rats fed a regular diet; (2) diabetic rats fed a HFD; (3) diabetic rats fed a HFD and supplemented with CrPic (80 µg/kg body weight (BW) per d); (4) diabetic rats fed a HFD and supplemented with biotin (300 µg/kg BW per d); (5) diabetic rats fed a HFD and supplemented with both CrPic and biotin. Circulating glucose, cortisol, total cholesterol, TAG, NEFA and malondialdehyde concentrations decreased (P< 0·05), but serum insulin concentrations increased (P< 0·05) in diabetic rats treated with biotin and CrPic, particularly with a combination of the supplements. Feeding a HFD to diabetic rats decreased PPAR-γ expression in adipose tissue and phosphorylated insulin receptor substrate 1 (p-IRS-1) expression of liver, kidney and muscle tissues, while the supplements increased (P< 0·001) PPAR-γ and p-IRS-1 expressions in relevant tissues. Expression of NF-κB in the liver and kidney was greater in diabetic rats fed a HFD, as compared with rats fed a regular diet (P< 0·01). The supplements decreased the expression of NF-κB in diabetic rats (P< 0·05). Results of the present study revealed that supplementing CrPic and biotin alone or in a combination exerts anti-diabetic activities, probably through modulation of PPAR-γ, IRS-1 and NF-κB proteins.

Chromium picolinate modulates serotonergic properties and carbohydrate metabolism in a rat model of diabetes.

Chromium picolinate (CrPic) has shown both antidepressant and antidiabetic properties. In this study, the effects of CrPic on serotonergic properties and carbohydrate metabolism in diabetic rats were evaluated. Sixty male Sprague-Dawley rats were divided into four groups. (1) The control group received only standard diet (8 % fat). (2) The CrPic group was fed standard diet and CrPic (80 µg CrPic per kilogram body mass (b.m.)/day), for 10 weeks (microgram/kilogram b.m./day). (3) The HFD/STZ group fed a high-fat diet (HFD, 40 % fat) for 2 weeks and then received streptozotocin (STZ, 40 mg/kg, i.p.) (i.v.) HFD-STZ-CrPic group treated as the previous group and then were administered CrPic. CrPic administration to HFD/STZ-treated rats increased brain chromium levels and improved all measurements of carbohydrate metabolism and serotonergic properties (P<0.001). CrPic also significantly increased levels of insulin, tryptophan, and serotonin (P<0.001) in the serum and brain, and decreased cortisol levels in the serum (P<0.01). Except chromium levels, no significant effect of CrPic supplementation was detected on the overall measured parameters in the control group. CrPic administration was well tolerated without any adverse events. The results support the use of CrPic supplementation which improves serotonergic properties of brain in diabetes.

Effects of chromium histidinate on renal function, oxidative stress, and heat-shock proteins in fat-fed and streptozotocin-treated rats.

OBJECTIVE: Chromium is an essential element for carbohydrate, fat, and protein metabolism. The therapeutic potential of chromium histidinate (CrHis) in the treatment of diabetes has been elucidated. The present study investigated the effects of CrHis on serum parameters of renal function, on oxidative stress markers (malondialdehyde [MDA] and 8-isoprostane), and on the expression of heat-shock proteins (HSPs) in rats. METHODS: Male Wistar rats (n=60, 8 weeks old) were divided into four groups. Group 1 received a standard diet (12% of calories as fat). Group 2 received a standard diet, plus CrHis. Group 3 received a high-fat diet (40% of calories as fat) for 2 weeks, and was then injected with streptozotocin (STZ) on day 14 (STZ, 40 mg/kg intraperitoneally). Group 4 was treated in the same way as group 3 (HFD/STZ), but was supplemented with 110 microg CrHis/kg/body weight/day. Oxidative stress in the kidneys of diabetic rats was evidenced by an elevation in levels of MDA and 8-isoprostane. Protein concentrations of HSP60 and HSP70 in renal tissue were determined by Western blot analyses. RESULTS: Chromium histidinate supplementation lowered kidney concentrations of MDA, 8-isoprostane levels, serum urea-N, and creatinine, and reduced the severity of renal damage in the STZ-treated group (i.e., the diabetes-induced group). The expression of HSP60 and HSP70 was lower in the STZ group that received CrHis than in the group that did not. No significant effect of CrHis supplementation was detected in regard to the overall measured parameters in the control group. CONCLUSIONS: Chromium histidinate significantly decreased lipid peroxidation levels and HSP expression in the kidneys of experimentally induced diabetic rats. This study supported the efficacy of CrHis in reducing renal risk factors and impairment because of diabetes.