Effect of inositol -stabilized arginine silicate on arthritis in a rat model.

The purpose of this study was to test the effects of arginine-silicate-inositol complex (ASI), compared to a combination of the individual ingredients (A+S+I) of the ASI, on inflammatory markers and joint health in a collagen-induced arthritis (CIA) rat model. A total of 28 Wistar rats were divided into four groups: (i) Control; (ii) Arthritic group, rats subjected to CIA induction by injection of bovine collagen type II (A); (iii) Arthritic group treated with equivalent doses of the separate components of the ASI complex (arginine hydrochloride, silicon, and inositol) (A+S+I); (iv) Arthritic group treated with the ASI complex. The ASI complex treatment showed improved inflammation scores and markers over the arthritic control and the A+S+I group. ASI group had also greater levels of serum and joint-tissue arginine and silicon than the A+S+I group. Joint tissue IL-6, NF-κB, COX-2, TNF-α, p38 MAPK, WISP-1, and ß-Catenin levels were lower in the ASI group compared to the other groups (P < 0.05 for all). In conclusion, these results demonstrate that the ASI complex may be effective in reducing markers of inflammation associated with joint health and that the ASI complex is more effective than a combination of the individual ingredients.

(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.

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.

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.

A novel nutritional supplement containing chromium picolinate, phosphatidylserine, docosahexaenoic acid, and boron activates the antioxidant pathway Nrf2/HO-1 and protects the brain against oxidative stress in high-fat-fed rats.

AIMS: A novel nutritional supplement complex (N21 #125) composed of four well-known compounds (chromium picolinate, phosphatidylserine, docosahexaenoic acid, and boron) was designed to improve memory function and maintain brain health. The present study evaluated the complex's potential mechanism of action and its role in reducing oxidative stress in the brain of obese rats fed a high-fat diet (HFD). METHODS: Male Wistar rats (n = 40, 8-week-old) were divided into four groups. Group I was fed a standard diet; Group II was fed a standard diet and supplemented with N21 } Group III was fed an HFD; and Group IV was fed an HFD and supplemented with N21 #125 for 12 weeks. RESULTS: Rats fed HFD had greater serum C-reactive protein (CRP) and tumor necrosis factor alpha (TNF-α) and brain malondialdehyde (MDA) concentrations than rats fed the control diet. Supplementation of N21 #125 decreased CRP, TNF-α, and MDA concentration in rats fed HFD. The levels of brain nuclear factor-E2-related factor-2 (Nrf2), heme oxygenase, extracellular signal-regulated kinases and protein kinase B were lower in rats fed the control diet than for rats fed the HFD. These parameters were increased by supplementation of N21 #125. DISCUSSION: The data indicate that N21 #125 protected the brain from oxidative damage and inflammation induced by the HFD. This effect may be through up-regulation of the transcription factor Nrf2 expression.

Chromium picolinate and chromium histidinate protects against renal dysfunction by modulation of NF-κB pathway in high-fat diet fed and Streptozotocin-induced diabetic rats.

BACKGROUND: Diabetic nephropathy is one of major complications of diabetes mellitus. Although chromium is an essential element for carbohydrate and lipid metabolism, its effects on diabetic nephropathy are not well understood. The present study was conducted to investigate the effects of chromium picolinate (CrPic) and chromium histidinate (CrHis) on nuclear factor-kappa B (NF-κB) and nuclear factor-E2-related factor-2 (Nrf2) pathway in the rat kidney. METHODS: Male Wistar rats were divided into six groups. Group I received a standard diet (8% fat) and served as a control; Group II was fed with a standard diet and received CrPic; Group III was fed with a standard diet and received CrHis; Group IV received a high fat diet (HFD, 40% fat) for 2 weeks and then were injected with streptozotocin (STZ) (HFD/STZ); Group V was treated as group IV (HFD/STZ) but supplemented with CrPic for 12 weeks. Group VI was treated as group IV (HFD/STZ) but supplemented with CrHis. RESULTS: The increased NF-κß p65 in the HFD/STZ group was inhibited by CrPic and CrHis supplementation (P < 0.05). In STZ-treated rats, a significant decrease in levels of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα) was found in kidney tissues when compared to control rats (P < 0.05). A significant increase in the levels of IκBα was observed in CrPic- and CrHis-treated rats when compared with STZ-treated rats. Renal Nrf2 levels were significantly decreased in diabetic rats compared with the control rats. There was a higher tendency for increase of kidney Nrf2 level and decrease in kidney NFκBp65 levels and 4- hydroxyl nonenal (4-HNE) protein adducts (P < 0.05) in diabetic rats. CONCLUSION: Our result show that in kidney tissue CrHis/CrPic increases Nrf2 level, parallelly decreases NF-κB and partially restores IκBα levels in HFD/STZ group, suggesting that CrPic and CrHis may play a role in antioxidant defense system via the Nrf2 pathway by reducing inflammation through NF-κß p65 inhibition. Moreover, a greater reduction in NF-κB expression and greater increases in expressions of IκBα and Nrf2 in diabetic rats supplemented with CrHis than rats supplemented with CrPic suggest that CrHis has more favorable effects than CrPic.

Inhibitory effects of combination of lycopene and genistein on 7,12- dimethyl benz(a)anthracene-induced breast cancer in rats.

Breast cancer is one of the most common cancers in women. Carotenoids and soy isoflavones have been postulated to have breast cancer preventive effects. We investigated the potential preventive effects of lycopene and genistein, alone and in combination, on breast cancer development in female Wistar rats treated with 7,12-dimethylbenz[a]anthracene (DMBA), a carcinogen known to induce breast tumors. Mammary carcinogenesis was initiated by a single, oral gavage of DMBA (80 mg/kg body weight) at 55 days of animal age. Fifty female Wistar rats were divided into 5 experimental groups having 10 animals per group: Group 1 (normal control), Group 2 (DMBA control), Group 3 (DMBA + lycopene), Group 4 (DMBA + genistein), and Group 5 (DMBA + lycopene and genistein). Rats were fed either lycopene (20 mg /kg bw) or genistein (2 mg /kg bw) by oral gavage (3 times per week) starting 2 wk prior to DMBA injection. Treatment was continued for 20 wk. Rats treated with DMBA developed mammary tumors with 100% tumor incidence during the 20-wk study. Inhibition of mammary cancer incidence by lycopene (70%), genistein (60%) and their combination (40%) was observed. Tumor weight decreased by 48%, 61%, and 67%, and mean tumor volume decreased by 18%, 35%, and 65% with lycopene, genistein, and lycopene + genistein, respectively (P < 0.01 for the combination). The proportions of adenocarcinoma masses decreased with lycopene and genistein combination (P < 0.05). Administration of lycopene and genistein combination suppressed breast cancer development and was associated with a decrease in MDA, 8-isoprostane, and 8-OhdG levels and with an increase in serum lycopene and genistein levels. Animals administered DMBA developed breast cancer, which was associated with increased expression of Bcl-2 and decreased expression of Bax, caspase 3, and caspase 9 in mammary tissues. Administration of genistein and lycopene in combination was more effective in inhibiting DMBA-induced breast tumors and modulating the expression of apoptosis associated proteins than the administration of each agent alone. Our results suggest that lycopene and genistein are potent antioxidants and, when given in combination, offer maximum protection against DMBA-induced mammary carcinogenesis.

Impact of chromium histidinate on high fat diet induced obesity in rats.

BACKGROUND: 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). METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Chemoprevention of fibroid tumors by [-]-epigallocatechin-3-gallate in quail.

Spontaneous leiomyomas of the oviduct are common tumors of the Japanese quail (Coturnix coturnix japonica), and fibroid tumors in the laying hen are similar to human fibroid tumors with respect to estrogen and progesterone receptors. This makes the quail a good animal model for screening potential agents for that aid in the prevention and treatment of human myoma uteri. We have previously reported a decreased incidence of leiomyomas in the oviduct of Japanese quail with antioxidant supplementation, for example, lycopene and soy isoflavones. Most of the health benefits associated with green tea consumption is attributed to EGCG, one of 4 major catechins found in green tea. This study investigated the effects of epigallocatechin-3-gallate supplementation on the development of leiomyomas in the oviduct of Japanese quail. We also measured serum and tissue levels of malondialdehyde and TNF-alpha. One hundred eighty quail (8 months old) were assigned to 3 treatment groups consisting of 6 replicates of 10 quail in each group. Animals were fed either a basal diet (control group) or the basal diet supplemented with 200 or 400 mg of EGCG/kg of diet. The animals were euthanized at the end of the 12-month study period, and the tumors were characterized. Epigallocatechin gallate supplementation significantly decreased the number of leiomyomas as compared with the controls (P = .001). The tumors in the EGCG fed birds were smaller than those found in the control birds (P = .001). Serum and liver malondialdehyde and TNF-alpha concentrations decreased (P = .001) with EGCG supplementation. The results indicate that dietary supplementation with EGCG reduces the incidence and size of spontaneously occurring leiomyoma of the oviduct in Japanese quail. Clinical trials should be conducted to investigate the efficacy of EGCG supplementation in the prevention and treatment of uterine leiomyoma in humans.