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Scope This study was carried out to investigate the efficacy of a new combination of root extracts of the Lepidium meyenii (maca) plant, known for its nutritional and energizing features as well as its antioxidant properties, on nutrient digestibility and nutrient transporters expression. Methods and results A total of 28 Sprague‐Dawley rats (8‐week‐old) were divided into four groups: (i) control, (ii) Lepidium m., (iii) high‐fat diet (HFD), and (iv) HFD+Lepidium m. Maca was given to the rats as a powdered combination of the plant roots with a daily dose of 40 mg per kg BW. Maca administration significantly increased the digestibility of dry matter (DM), organic matter (OM), crude protein (CP), and ether extract (EE), and some nutrient transporter (Pept1/2, Fatp1, Glut1/2, and Sglt1)‐expressions compared with non‐treated control and HFD groups in the jejunum and ileum tissues (p, Maca supplementation to the basal and HFD diets of the rats improved digestibility of DM, OM, CP, and EE along with the enhancement of Pept1/2, Fatp1, Glut1/2, and Sglt1 expressions in the jejunum and ileum of the rats.

Background/aim Numerous studies show that cancer risk is reduced by consumption of soy-based foods containing genistein, but its effects on the glycogen synthase kinase-3 pathway (GSK-3) in ovarian cancer is unknown. Therefore, we tested the properties of genistein on inflammatory biomarkers and GSK-3 signaling pathways in the ovaries of old laying hens with ovarian cancer. Materials and methods A total of 300 laying hens were distributed into three groups as follows: group 1, animals fed a standard diet (comprising 22.39 mg of genistein/kg of diet); groups 2 and 3, animals fed a standard diet reconstituted with supplementation of 400 mg or 800 mg of genistein/kg of diet, respectively. Results Genistein modulated the inflammatory biomarkers by decreasing serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL- 6), interleukin-8 (IL-8), and vascular endothelial growth factor (VEGF) compared with control (p < 0.001). Moreover, it upregulated insulin receptor substrate-1 (p-IRS-1) and protein kinase B (p-AKT), but downregulated GSK-3α and β after treatment. It acts in a dose-dependent manner. Conclusion Genistein exhibited an anticancer effect by reducing proinflammatory biomarkers levels and inhibiting GSK-3 expression in the ovaries of old laying hens. It is a potential candidate in the chemoprevention and/or treatment of ovarian cancer.

This study investigated the effects of marine phytoplankton supplementation on 1) perceived recovery and ground reaction forces in humans following a non-functional overreaching resistance-training program and 2) myogenic molecular markers associated with muscle cell recovery in a rat model. In the human trial, a 5-week resistance-training program with intentional overreaching on weeks 2 and 5 was implemented. Results indicate that marine phytoplankton prompted positive changes in perceived recovery at post-testing and, while both marine phytoplankton and placebo conditions demonstrated decreased peak and mean rate of force development following the overreaching weeks, placebo remained decreased at post-testing while marine phytoplankton returned to baseline levels. In the rat model, rats were divided into four conditions: (i) control, (ii) exercise, (iii) exercise + marine phytoplankton 2.55 mg·d-1, or (iv) exercise+marine phytoplankton 5.1 mg·d-1. Rats in exercising conditions performed treadmill exercise 5 d·wk-1 for 6 weeks. Marine phytoplankton in exercising rats increased positive and decrease negative myogenic factors regulating satellite cell proliferation. Taken together, marine phytoplankton improved perceptual and functional indices of exercise recovery in an overreaching human model and, mechanistically, this could be driven through cell cycle regulation and a potential to improve protein turnover.

Curcumin positively affects performance during exercise and subsequent recovery. However, curcumin has limited bioavailability unless consumed in larger doses. In the current study, we examined the impact of a new formulation of curcumin, Next-Generation Ultrasol Curcumin (NGUC), which is relatively more bioavailable than natural curcumin on exhaustion time, grip strength, muscle damage parameters, and serum and muscle proteins. A total of 28 rats were randomly grouped as control (C, non-supplemented), exercise (E, non-supplemented), E+NGUC100 (supplemented with 100 mg/kg BW NGUC), and E+NGUC200 (supplemented with 200 mg/kg NGUC). Grip strength and exhaustion time were increased with NGUC supplementation (p &lt, 0.0001). Creatine kinase (CK), lactate dehydrogenase (LDH), lactic acid (LA), myoglobin, malondialdehyde (MDA) concentrations were reduced in serum, and muscle tissue in NGUC supplemented groups (p &lt, 0.05). In contrast, NGUC supplementation elevated the antioxidant enzyme levels compared to the non-supplemented exercise group (p &lt, 0.01). Additionally, inflammatory cytokines were inhibited with NGUC administration (p &lt, 0.05). NGUC decreased PGC-1α, p-4E-BP1, p-mTOR, MAFbx, and MuRF1 proteins in muscle tissue (p &lt, 0.05). These results indicate that NGUC boosts exercise performance while reducing muscle damage by targeting antioxidant, anti-inflammatory, and muscle mass regulatory pathways.

Magnesium (Mg) deficiency may affect bone metabolism by increasing osteoclasts, decreasing osteoblasts, promoting inflammation/oxidative stress, and result in subsequent bone loss. The objective of the present study was to identify the molecular mechanism underlying the bone protective effect of different forms of Mg (inorganic magnesium oxide (MgO) versus organic magnesium picolinate (MgPic) compound) in rats fed with a high-fat diet (HFD). Forty-two Wistar albino male rats were divided into six group (n = 7): (i) control, (ii) MgO, (iii) MgPic, (iv) HFD, (v) HFD + MgO, and (vi) HFD + MgPic. Bone mineral density (BMD) increased in the Mg supplemented groups, especially MgPic, as compared with the HFD group (p &lt, 0.001). As compared with the HFD + MgO group, the HFD + MgPic group had higher bone P (p &lt, 0.05) and Mg levels (p &lt, 0.001). In addition, as compared to MgO, MgPic improved bone formation by increasing the levels of osteogenetic proteins (COL1A1 (p &lt, 0.001), BMP2 (p &lt, 0.001), Runx2 (p &lt, 0.001), OPG (p &lt, 0.05), and OCN (p &lt, 0.001), IGF-1 (p &lt, 0.001)), while prevented bone resorption by reducing the levels of RANK and RANKL (p &lt, 0.001). In conclusion, the present data showed that the MgPic could increase osteogenic protein levels in bone more effectively than MgO, prevent bone loss, and contribute to bone formation in HFD rats.

WOS: 000471268100003 The clinical use of cisplatin, which is a first-line anticancer agent, is highly restricted due to its adverse effects on kidneys that lead to nephrotoxicity. Therefore, some potential reno-protective substances have been used in combination with cisplatin to cope with nephrotoxicity. Due to its high antitumor activity and oxygen-carrying capacity, we investigated the molecular effects of squalene against cisplatin-induced oxidative stress and kidney damage in mice. Single dose of cisplatin (7 mg/kg) was given to male Balb/c mice. Squalene (100 mg/kg/day) was administered orogastrically to mice for 10 days. Following sacrification, molecular alterations were investigated as analysis of the levels of oxidative stress index (OSI), inflammatory cytokines and cell survival-related proteins in addition to histopathological examinations in mice kidney tissue. The level OSI and Interferon-gamma (IFN-gamma) decreased in the cisplatin and squalene cotreated mice compared to cisplatin-treated mice. Squalene treatment also increased the activation of protein kinase B (AKT). Furthermore, cisplatin-induced inactivation of mammalian target of rapamycin (mTOR) and histopathological damages were reversed by squalene. It may be suggested that squalene ameliorated the cisplatin-induced histopathological damages in the kidney through activation of AKT/mTOR signaling pathway by regulating the balance of the redox system due to its antioxidative effect.

Previous studies revealed that oxidative stress and inflammation are the main contributors to secondary injury after traumatic brain injury (TBI). In an earlier study, we reported that lutein/zeaxanthin isomers (L/Zi) exert antioxidative and anti-inflammatory effects by activating the nuclear factor-kappa B (NF-kappa B) and nuclear factor-erythroid 2-related factor 2 (Nrf2) pathways. However, its precise role and underlying mechanisms were largely unknown after TBI. This study was conducted to investigate the potential mechanism of L/Zi isomers in a TBI model induced by a cold injury model in mice. To investigate the effects of L/Zi, male C57BL/6j mice-induced brain injury using the cold trauma model was allocated into two groups (n = 7): (i) TBI + vehicle group and (ii) TBI + L/Zi group (20 mg/kg BW). Brain samples were collected 24 h later for analyses. L/Zi given immediately after the injury decreased infarct volume and blood-brain barrier (BBB) permeability; L/Zi treatment also significantly reduced proinflammatory cytokines, including interleukin1 beta (IL-1 beta), interleukin 6 (IL-6), and NF-kappa B levels and increased growth-associated protein 43 (GAP-43), neural cell adhesion molecule (NCAM), brain-derived neurotrophic factor (BDNF), and Nrf2 levels compared with vehicle control. These data suggest that L/Zi improves mitochondrial function in TBI models, possibly decreasing inflammation and activating the Nrf2 pathway. OmniActive Health Technologies, NJ, USA ; Turkish Academy of Sciences

Osteoarthritis (OA) is an age-related joint disease that includes gradual disruption of the articular cartilage and the resulting pain. The present study was designed to test the effects of undenatured type II collagen (UC-II®) on joint inflammation in the monoiodoacetate (MIA) OA model. We also investigated possible mechanisms underlying these effects. Female Wistar rats were divided into three groups: (i) Control; (ii) MIA-induced rats treated with vehicle; (iii) MIA-induced rats treated with UC-II (4 mg/kg BW). OA was induced in rats by intra-articular injection of MIA (1 mg) after seven days of UC-II treatment. UC-II reduced MIA-induced Kellgren-Lawrence scoring (53.3%, P < 0.05). The serum levels of inflammatory cytokines [IL-1β (7.8%), IL-6 (18.0%), TNF-α (25.9%), COMP (16.4%), CRP (32.4%)] were reduced in UC-II supplemented group (P < 0.0001). In the articular cartilage, UC-II inhibited the production of PGE2 (19.6%) and the expression of IL-1β, IL-6, TNF-a, COX-2, MCP-1, NF-κB, MMP-3, RANKL (P < 0.001). The COL-1 and OPG levels were increased, and MDA decreased in UC-II supplemented rats (P < 0.001). UC-II could be useful to alleviate joint inflammation and pain in OA joints by reducing the expression of inflammatory mediators.

The current study aimed to investigate the effect of exercise combined with undenatured type II collagen (UCII) administration on endurance capacity, lipid metabolism, inflammation, and antioxidant status in rats. Twenty-one male Wistar albino rats were divided into three groups as follows: (1) Sedentary control, (2) Exercise (E), (3) Exercise + UCII (4 mg/kg BW/day, E + UCII). The findings showed that the exhaustive running time in the UCII group was significantly prolonged compared to that of the non-supplemented group (p &lt, 0.001). When compared to the control group, total serum cholesterol (TC, p &lt, 0.05) and triglyceride (TG, p &lt, 0.05) levels decreased, while creatinine kinase (CK) levels increased in the E group (p &lt, 0.001). Serum creatinine kinase levels were reduced in the E + UCII group compared to the E group (p &lt, 0.01). Serum lactate, myoglobin (p &lt, 0.01), and osteocalcin levels (p &lt, 0.01) increased significantly in exercised rats compared to sedentary control rats, while serum lactate (p &lt, 0.01) and myoglobin (p &lt, 0.0001) levels decreased in the E + UCII group compared to control. Additionally, UCII supplementation caused significant increases in antioxidant enzyme activities [SOD (p &lt, 0.01) and GSH-Px (p &lt, 0.05)] and decreases in malondialdehyde (MDA) and tumor necrosis factor (TNF-α) levels (p &lt, 0.001). Muscle lipogenic protein (SREBP-1c, ACLY, LXR, and FAS) levels were lower in the E + UCII group than in other groups. In addition, UCII supplementation decreased muscle MAFbx, MuRF-1, myostatin and increased MyoD levels in exercised rats. Moreover, the E + UCII group had lower muscle inflammatory markers [TNF-α (p &lt, 0.0001) and IL-1β (p &lt, 0.01)] than the control group. These results suggest exercise combined with UCII (4 mg/kg BW/day) modulates lipid, muscle, and antioxidant status in rats.

[Purpose] This study investigated the effects of marine phytoplankton supplementation (Oceanix®, Tetraselmis chuii ) on 1) maximal isometric strength and immune function in healthy humans following a one-week high-intensity resistance-training program and 2) the proinflammatory cytokine response to exercise in a rat model. [Methods] In the human trial, 22 healthy male and female participants were randomly divided into marine phytoplankton and placebo groups. Following baseline testing, participants underwent a 14-day supplement loading phase before completing five consecutive days of intense resistance training. In the rat model, rats were randomly divided into four groups (n=7 per condi tion): (i) control, (ii) exercise, (iii) exercise + marine phy toplankton (2.55 mg/kg/day), or (iv) exercise + marine phytoplankton (5.1 mg/kg/day). Rats in the exercising groups performed treadmill exercise 5 days per week for 6 weeks. [Results] In the human model, marine phytoplankton prevented significant declines in the isometric peak rate of force development compared to placebo. Additional ly, salivary immunoglobulin A concentration was signifi cantly lower following the resistance training protocol in the placebo group but not in the marine phytoplankton group. Marine phytoplankton in exercising rats de creased intramuscular levels and serum concentrations of tumor necrosis factor-alpha (TNF-α) and interleu kin-1 beta (IL-1β) and intramuscular concentrations of malondialdehyde. [Conclusion] Marine phytoplankton prevented dec rements in indices of functional exercise recovery and immune function. Mechanistically, these outcomes could be prompted by modulating the oxidative stress and proinflammatory cytokine response to exercise.

Here, we demonstrate that the two distinct formulations of our anti-sepsis drug candidate Rejuveinix (RJX) have a very favorable safety profile in Wistar Albino rats at dose levels comparable to the projected clinical dose levels. 14-day treatment with RJX-P or RJX-B similarly elevated the day 15 tissue levels of the antioxidant enzyme superoxide dismutase (SOD) as well as ascorbic acid in both the lungs and liver in a dose-dependent fashion. The activity of SOD and ascorbic acid levels were significantly higher in tissues of RJX-P or RJX-B treated rats than vehicle-treated control rats (p p >0.05). The observed elevations of the SOD and ascorbic acid levels were transient and were no longer detectable on day 28 following a 14-day recovery period. These results demonstrate that RJX-P and RJX-B are bioequivalent relative to their pharmacodynamic effects on tissue SOD and ascorbic acid levels.

Here, we demonstrate that the two distinct formulations of our anti-sepsis drug candidate Rejuveinix (RJX), have a very favorable safety profile in Wistar Albino rats at dose levels comparable to the projected clinical dose levels. 14-day treatment with RJX-P (RJX PPP.18.1051) or RJX-B (RJX-B200702-CLN) similarly elevated the day 15 tissue levels of the antioxidant enzyme superoxide dismutase (SOD) as well as ascorbic acid in both the lungs and liver in a dose-dependent fashion. The activity of SOD and ascorbic acid levels were significantly higher in tissues of RJX-P or RJX-B treated rats than vehicle-treated control rats (p 0.05). The observed elevations of the SOD and ascorbic acid levels were transient and were no longer detectable on day 28 following a 14-day recovery period. These results demonstrate that RJX-P and RJX-B are bioequivalent relative to their pharmacodynamic effects on tissue SOD and ascorbic acid levels. Furthermore, both formulations showed profound protective activity in a mouse model of sepsis. In agreement with the PD evaluations in rats and their proposed mechanism of action, both RJX-P and RJX-B exhibited near-identical potent and dose-dependent anti-oxidant and anti-inflammatory activity in the LPS-GalN model of ARDS and multi-organ failure in mice.

This study aimed to investigate the properties of Salacia chinensis (Celastraceae, SC) and its molecular mechanism in the type 2 diabetic rats. Forty-two Wistar rats were divided into six groups (n = 7): control, SC (100 mg/kg, per os), high-fat diet (HFD), HFD + SC (100 mg/kg), HFD + streptozotocin (STZ, 40 mg/kg, i.p.), and HFD + STZ+SC. SC decreased serum glucose, insulin, triglycerides, free fatty acid, and malondialdehyde levels, but increased serum total antioxidant capacity (0.33 ± 0.02 versus. 0.79 ± 0.03), compared with the untreated group (p < .001). Additionally, SC elevated the expression of glucose-regulated proteins GLUT2, PPAR-ɣ, p-IRS, and Nrf2, but downregulated NF-κB in the liver and kidney (p < .001). In conclusion, SC could improve insulin resistance by modulation of glucose-regulated proteins and transcription factors in diabetic rats. PRACTICAL APPLICATIONS: Present data has contributed to the current ethnomedicinal benefits of SC, through which the SC intake regulated the carbohydrate metabolism and increased the antioxidant capacity. The balance of transcription factors can mediate these efficacies partially and various key proteins involved in energy metabolism, along with oxidative stress and insulin sensitivity.

The objective of this work is to investigate the effects of Carnipure® Tartrate (CT) supplementation with or without exercise on endurance capacity, recovery, and fatigue by assessing time to exhaustion as well as body weight and composition in rats. In addition, antioxidant capacity has been evaluated by measuring malondialdehyde (MDA) levels and antioxidant enzyme (superoxide dismutase, SOD, catalase, CAT, glutathioneperoxidase, GSHPx) activities. Fifty-six male Wistar rats were divided into eight groups including seven rats each. A control group did not receive CT nor exercise. Another control group received 200 mg/kg CT without exercise. The other six groups of rats went through an exercise regimen consisting of a 5-day training period with incremental exercise capacity, which was followed by 6 weeks of the run at 25 m/min for 45 min every day. CT was supplemented at 0, 25, 50, 100, 200, and 400 mg/kg per day during the 6 weeks. Rats submitted to exercise and supplemented with CT had a significant and dose-dependent increase in time to exhaustion and this effect seems to be independent of exercise (p &lt, 0.05). Additionally, recovery and fatigue were improved, as shown by a significant and dose-dependent decrease in myoglobin and lactic acid plasma levels, which are two markers of muscle recovery. CT supplementation led to a dose-response decrease in body weight and visceral fat. These effects become significant at 200 and 400 mg/kg doses (p &lt, 0.05). Additionally, the antioxidant capacity was improved, as shown by a significant and dose-dependent increase in SOD, CAT, and GSHPx. Serum MDA concentrations decreased in exercising rats with CT supplementation. CT supplementation led to a decrease in serum glucose, triglycerides, and total cholesterol concentrations with the lowest levels observed at 400 mg/kg dose (p &lt, 0.05). These effects correlated with a significant dose-dependent increase in serum total L-carnitine, free L-carnitine, and acetyl-carnitine, which linked the observed efficacy to CT supplementation. These results demonstrate that CT supplementation during exercise provides benefits on exercise performance, recovery, and fatigue as well as improved the lipid profile and antioxidant capacity. The lowest dose leads to some of these effects seen in rats where 25 mg/kg corresponds to 250 mg/day as a human equivalent.

This study was conducted to examine the effects of dietary taurine supplementation on productive performance, nutrient digestibility, antioxidant status, and the gene expression of ileal nutrient transporters in laying quails reared under heat stress (HS). One hundred and eighty laying Japanese quails (Coturnix coturnix japonica) were fed a basal diet or basal diet supplemented with either 2.5 or 5 g of taurine per kg of diet, and reared at either 22 ± 2 °C for 24 h/d (thermoneutral, TN) or 34 ± 2 °C for 8 h/d (HS) for 12 weeks. The quails reared under HS consumed less feed, produced less egg, and had lower dry matter, organic matter and crude protein apparent digestibilities compared with the quails reared under the TN condition (P = 0.001). However, increasing taurine concentrations in the diet improved feed intake and egg production (P = 0.001), but also the apparent digestibilities (P ≤ 0.027) in quails reared under HS. The greater doses (5 g/kg) of taurine resulted in more responses. The quails reared under HS had greater serum and liver MDA concentrations (P = 0.0001) which decreased with dietary taurine supplementations, particularly greater doses. The gene expressions of ileal PEPT1, EAAT3, CAT1, CAT2, SGLT1, SGLT5, GLUT2, and GLUT5 decreased under HS conditions (P = 0.001). However, supplementing taurine, in a dose-dependent fashion, to the diet of quails reared under HS resulted in increases in the gene expressions of the transporters (P 0.05) except for CAT1. The results of the present work showed that taurine supplementation, particularly with greater doses (5 g/kg), to the diet of laying quails kept under HS acts as alleviating negative effects of HS, resulting in improvements in productive performance and nutrient digestion, and also upregulation of ileal nutrient transporters.

Simple Summary Osteoarthritis (OA), the most common joint disease affecting humans and animals, is a painful, degenerative, and inflammatory disease that affects synovial joints and ultimately leads to loss of mobility. Non-pharmacological preventive approaches, several pharmaceutical therapeutic agents, and some medicines may reduce the progression of OA in animals. Many clinical and experimental studies have revealed that the undenatured form of type II collagen (UC-II) offers common health benefits to patients with OA. Abstract OA is quite common in companion animals, especially in large breed dogs and horses. Collagen, the most abundant protein of mammals, has specific connective tissue types for skin, bones, reticulate, basal lamina, bones, cell surfaces, while type II collagen (UC-II) forms the main structure of cartilage tissue. Even at the smaller dosages, UC-II has also been reported to be more effective than the glucosamine and chondroitin sulfate supplements, which are the supplements most frequently used in the market. In this review, we summarize the effects of UC-II on joint health and function in health and disease conditions in companion animals.

Objectives: We tested the chemopreventive effect of WHI-P131 in side by side evaluation with the standard anti-breast cancer drug paclitaxel in the well-established 7,12‐dimethylbenz(a)anthracene (...

PubMed: 29355388, 2-s2.0-85042231716, 1. The objective of this study was to determine muscle structure and gene expression in pectoralis major (p. major) muscle of broilers in response to deep pectoral myopathy (DPM) induction. 2. A total of 160 chickens from slow-and fast-growing broilers were raised under same conditions. Half of the broilers from each strain were encouraged to wing flap when they reached 2800 g body weight. Pectoralis minor (p. minor) muscle of the broilers was inspected for the occurrence of DPM and p. major samples were collected from broilers with or without DPM. The muscle fibre area and number, capillary number and the signalling pathways of vascular development (vascular endothelial growth factor A, VEGFA) and muscle contraction regulation (actin alpha 1, ACTA1; myosin light chain kinase 2, MYLK2 and ATPase Ca+2 transporting gene 1, ATP2A1) were studied in p. major muscle. 3. DPM induction increased fibre area of p. major muscle with a greater rate in the slow-growing strain compared with fast-growing line. Although the capillary number was higher in slow-growing compared with fast-growing broilers, in the case of DPM induction, the number of capillaries was similar between strains. 4. Expression of VEGFA, MYLK2 and ATP2A1 was greater in slow-than in fast-growing broilers. DPM induction increased expression of ACTA1, VEGFA and ATP2A1 in p. major muscle of broilers from both strains; however, MYLK2 expression was downregulated. 5. Changes in capillary density and expression of VEGFA found in the p. major muscle of broilers with DPM suggest increased blood flow to increase oxygen availability. The upregulation of ATP2A1 by DPM induction could be attributable to alterations in calcium ion transportation from the cytoplasm into the sarcoplasmic reticulum. 6. The results are evidence of changes in muscle structure and gene expression pathways in p. major muscle of broilers with DPM. © 2018 British Poultry Science Ltd., Türkiye Bilimsel ve Teknolojik Araştirma Kurumu, TÜBITAK: 115O434, This work was supported by The Scientific and Technological Research Council of Turkey [115O434].

Colostrum is a nutrient-dense fluid secreted by female mammals for the first few days following birth. Colostrum can be supplemented to poultry diets as a feed additive due to its nutritious and performance-enhancing properties. This study was conducted to determine the effect of dietary colostrum powder (CL-P, Alpha Lipid Lifeline Colostrum, New Zealand) on growing performance, carcass weight and yield, organ weights, serum vitamins and malondialdehyde (MDA) levels in quails (Coturnix coturnix japonica). A total of 90 birds, one day old, were divided into 3 groups consisting of 6 replicate cages, 5 birds per cage. Birds were randomly fed on one of three diets: basal diet and basal diet supplemented with 2.5% or 5% of CL-P. At the end of the period of 42 days, CL-P supplementation increased final body weight (P

The goals of the present study were to define the anticancer activity of LFM-A13 (α-cyano-β-hydroxy-β-methyl-N-(2,5-dibromophenyl)-propenamide), a potent inhibitor of Polo-like kinase (PLK), in a mouse mammary cancer model induced by 7,12-dimethylbenz(a)anthracene (DMBA) in vivo and explore its anticancer mechanism(s). We also examined whether the inhibition of PLK by LFM-A13 would improve the efficiency of paclitaxel in breast cancer growth in vivo. To do this, female BALB/c mice received 1 mg of DMBA once a week for 6 weeks with oral gavage. LFM-A13 (50 mg/kg body weight) was administered intraperitoneally with DMBA administration and continued for 25 weeks. We found that LFM-A13, paclitaxel, and their combination have a significant effect on the DMBA-induced breast tumor incidence, mean tumor numbers, average tumor weight, and size. At the molecular level, the administration of LFM-A13 hindered mammary gland carcinoma development by regulating the expression of PLK1, cell cycle-regulating proteins cyclin D1, cyclin dependent kinase-4 (CDK-4), and the CDK inhibitor, p21. Moreover, LFM-A13 treatment upregulated the levels of IκB, the pro-apoptotic proteins Bax, and caspase-3, and down-regulated p53 and the antiapoptotic protein Bcl-2 in mammary tumors. The combination of LFM-A13 with paclitaxel was found to be more effective compared with either agent alone. Collectively, these results suggest that LFM-A13 has an anti-proliferative activity against breast cancer in vivo and that LFM-A13 and paclitaxel combination could be a strategy for the treatment of breast cancer.

Kazim Sahin,1 Cemal Orhan,1 Mehmet Tuzcu,2 Nurhan Sahin,1 Oguzhan Ozdemir,2 Vijaya Juturu3 1Department of Animal Nutrition, Veterinary Faculty, Firat University, Elazig, Turkey; 2Department of Biology, Faculty of Science, Firat University, Elazig, Turkey; 3Scientific and Clinical Affairs, Research and Development, OmniActive Health Technologies, Inc., Morristown, NJ, USA Objective: Capsaicinoids (CAPs), most commonly found in chili peppers, have a multitude of pharmacological and physiological effects, such as anti-inflammation, antioxidant, and anticancer effects. In the present study, we set out to investigate the hypothesis that CAPs mitigate obesity in rats and the possible mechanisms thereof.Materials and methods: Rats were divided into six groups, including control (±10 mg CAPs/kg body weight [BW]), low-fat–high-sucrose diet (±10 mg CAPs/kg BW), and high-fat diet (±10 mg CAPs/kg BW). Blood samples and liver and aortic tissues were taken at the end of the study.Results: CAPs supplementation significantly reduced hyperglycemia and hyperlipidemia (P

In this study, the effect of the supplemental organic chromium (Cr) forms on the expression of ovarian orexin(hypocretin), glucose transporters (GLUTs), heat shock proteins (HSPs) andnuclear factor-kappaB (NF-κB)were investigated in laying hens (HS). Laying hens (n=1800; 16-wk-old; Lohmann LSL-Lite) were allocated to 6 random groups according to a 2"‰í—"‰3 factorial trial scheme with two different environmental temperatures [Thermoneutral (TN groups; at either 22±2 °C 24 h/d) and heat stress (HS groups; at 34±2 °C for 8 h/d, 08:00 to 17:00 h, followed by 22°C for 16 h for a period of 12 wks)], andhens reared under both environmental conditions were fed either a basal diet or the basal diet supplemented with 1.600 mg of chromium-picolinate (CrPic, 12.43% Cr) and 0.788 mg of chromium-histidinate (CrHis, 25.22% Cr) per kg of diet, delivering 200 µg elemental Cr per kg diet. HS groups showed decreased levels of orexin and GLUTs(GLUT1, GLUT4), and increased NFκB, HSP60, HSP70 and HSP90 levels compared to the TN groups in ovarian tissue of hens (P < 0.0001 for all).However, dietary chromium supplementation (CrPic–CrHis) increasedorexin and GLUTs levels and significantly reduced the NF-κB and HSPs levels making them closer to those of thermoneutral group (P < 0.0001).In conclusion, CrPic and CrHis showed supported the relief and treatment of stress complications.

Epigallocatechin 3-gallate (EGCG) is a polyphenol that has been shown to have antioxidant and anti-inflammatory effects. In this study, collagen-induced arthritis (CIA) model, in Wistar albino rats, was used to elucidate the effect of EGCG on pathogenetic pathways in inflammatory arthritis. The levels of serum TNF-α, IL-17, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx); the expression levels of tissue heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf2); histopathologically, perisynovial inflammation and cartilage-bone destruction were examined. In the sham group, serum TNF-α, IL-17, and MDA levels increased, while SOD, CAT, GPx levels, and the expressions of Nrf2 and HO-1 decreased. On the other hand, in the EGCG administered groups, serum TNF-α, IL-17, and MDA levels improved, while SOD, CAT, GPx levels and the expressions of Nrf2 and HO-1 increased. Moreover, histopathological analysis has shown that perisynovial inflammation and cartilage-bone destruction decreased in the EGCG administered groups. These results suggest that EGCG has an antiarthritic effect by regulating the oxidative-antioxidant balance and cytokine levels in the CIA model, which is a surrogate experimental model of rheumatoid arthritis.

OBJECTIVES: Curcumin, extracted from the rhizome Curcuma longa, has been shown to be beneficial for neuroprotection in previous studies. In a recent study, a novel formulation of curcumin resulted in an increased relative absorption by 46 times (CurcuWIN®) of the total curcuminoids over the unformulated standard curcumin form. However, the exact mechanisms by which curcumin demonstrates its neuroprotective effects are not fully understood. The present study aimed to investigate the effects of curcumin supplementation on the expression of brain-derived neurotrophic factor (BDNF), glial fibrillary acidic protein (GFAP), a main component of the glial scar, and growth-associated protein-43 (GAP-43), a signaling molecule in traumatic brain injury (TBI). METHODS: Brain injury was induced using a cold trauma model in male mice that were treated with curcumin (50 mg/kg) or vehicle via intraperitoneal administration just after TBI. Mice were divided into two groups: TBI + vehicle group and TBI + curcumin (CurcuWIN) group. RESULTS: The results show that curcumin treatment reduced the infarct volume in the brain. TBI induction increased inflammatory cytokines (IL-1β and IL-6), nuclear factor-κB (NF-κB) and GFAP, and reduced BDNF, GAP-43, neural cell adhesion molecule (ICAM) and nuclear factor erythroid 2-related factor 2 (Nrf2) levels in the brain. Interestingly, curcumin decreased the levels of NF-κB, IL-1β, IL-6, and GFAP, and increased BDNF, GAP-43, ICAM and Nrf2 levels in the brain. CONCLUSIONS: In conclusion, these results showed that curcumin could increase the levels of BDNF, GAP-43, ICAM, and Nrf2 and attenuate brain injury in the model of TBI. FUNDING SOURCES: This study was supported by OmniActive Health Technologies Inc. (NJ, USA). This work was also supported in part by the Turkish Academy of Sciences. SUPPORTING TABLES, IMAGES AND/OR GRAPHS

Background Retina photoreceptor cells are specially adapted for functioning over comprehensive ambient light conditions. Lutein and Zeaxanthin isomers (L/Zi) can protect photoreceptor cells against excessive light degeneration. Efficacy of L/Zi has been assessed on some G protein-coupled receptors (GPCRs), transcription and neurotrophic factors in the retina of rats exposed to incremental intense light emitting diode (LED) illumination conditions. Methods Forty-two male rats (age: 8 weeks) were randomly assigned to six treatment groups, 7 rats each. The rats with a 3x2 factorial design were kept under 3 intense light conditions (12hL/12hD, 16hL/8hD, 24hL/0hD) and received two levels of L/Zi (0 or 100 mg/kg BW) for two months. Increased nuclear factor-kappa B (NF-κB), glial fibrillary acid protein (GFAP), and decreased Rhodopsin (Rho), Rod arrestin (Sag), G Protein Subunit Alpha Transducin1 (Gnat1), neural cell adhesion molecule (NCAM), growth-associated protein-43 (GAP43), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), and heme oxygenase 1 (HO-1) were observed in 24 h light intensity adaptation followed by 16 h IL and 8 h D. Results L/Zi administration significantly improved antioxidant capacity and retinal Rho, Rod-arrestin (Sag), Gnat1, NCAM, GAP43, BDNF, NGF, IGF1, Nrf2, and HO-1 levels. However, the levels of NF-κB and GFAP levels were decreased by administration of L/Zi. Conclusions According to these results, L/Zi may be assumed as an adjunct therapy to prevent early photoreceptor cell degeneration and neutralize free radicals derived from oxidative stress.

Ginger (Zingiberaceae family) containing gingerols, shogaols, zingerone and volatile oils active compounds, exerts anti-inflammatory, antioxidant, antiplatelet, fat loss, prevention of cardiovascul...

Background/aim: The polypeptide hormone insulin is essential for the maintenance of whole-body fuel homeostasis, and defects in insulin secretion and/or action are associated with the development of type 1 and type 2 diabetes. The aim of this study was to assess the role of some G-protein coupled receptors (GPCRs), GPR54, GPR56, and GPR75, and cannabinoid receptors CB1R and CB2R, in the regulation of pancreatic ß-cell function.Materials and methods: Insulin secretion from mouse insulinoma ß-cell line (MIN6) monolayers was assessed via insulin radioimmu-noassay (RIA). Reverse transcription-polymerase chain reaction (RT-PCR) was used to assess the expression of some specific GPCRs and the other receptors by MIN6 pancreatic ß-cells. Results: The agonists were not found to be toxic for the MIN6 pancreatic ß-cells within the range of the doses used in this study, whereas insulin secretion altered depending on the ligands and receptors. In addition, arachidonyl-2'-chloroethylamide (ACEA), carbachol, chemokine (C-C motif ) ligand-5 (CCL5), and exendin as well as phorbol myristate acetate (PMA) ligands showed significant increases in the insulin secretion of MIN6 pancreatic ß-cells.Conclusion: Understanding the normal ß-cell function and identifying the defects in ß-cell function that lead to the development of diabetes will generate new therapeutic targets.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been responsible for one of the worst pandemics in modern history. Several prevention and treatment strategies have been designed and evaluated in recent months either through the repurposing of existing treatments or the development of new drugs and vaccines. In this study, we show that L-carnitine tartrate supplementation in humans and rodents led to significant decreases of key host dependency factors, notably angiotensin-converting enzyme 2 (ACE2), transmembrane protease serine 2 (TMPRSS2), and Furin, which are responsible for viral attachment, viral spike S-protein cleavage, and priming for viral fusion and entry. Interestingly, pre-treatment of Calu-3, human lung epithelial cells, with L-carnitine tartrate led to a significant and dose-dependent inhibition of the infection by SARS-CoV-2. Infection inhibition coincided with a significant decrease in ACE2 mRNA expression levels. These data suggest that L-carnitine tartrate should be tested with appropriate trials in humans for the possibility to limit SARS-CoV-2 infection.

Curcumin, derived from Curcuma longa, exerts antioxidant, antibacterial, anticancer and immunomodulatory properties. This study was conducted to determine the effect of dietary water-soluble curcumin (0, 200 or 400 mg kg−1) on growth performance and antioxidant status in rainbow trout (Oncorhynchus mykiss, Walbaum) rearing under normal (20 kg m−3) or high (100 kg m−3) stocking density conditions. A significant increase in body weight (FBW), feed intake (FI) and weight gain (BWG) was observed in fish fed with curcumin-supplemented diet at 200 mg kg−1 of diet levels of high stocking density conditions (P

Kazim Sahin,1Ragip Pala,2Mehmet Tuzcu,3 Oguzhan Ozdemir,3 Cemal Orhan,1 Nurhan Sahin,1 Vijaya Juturu4 1Department of Animal Nutrition, Faculty of Veterinary Medicine, 2Department of Movement and Training Science, 3Department of Biology, Firat University, Elazig, Turkey; 4OmniActive Health Technologies Inc., Morristown, NJ, USA Purpose: Exercise (Ex) increases reactive oxygen species and impairs antioxidant defense systems. Recent data suggest that curcumin (CW) possesses peroxisome proliferator-activated receptor gamma activity and anti-inflammatory properties. Therefore, this study was designed to investigate the effects of CW supplementation on Ex performance, endurance, and changes in serum and muscle proteins in rats after exhaustive Ex.Materials and methods: Twenty-eight (28) male Wistar rats (age: 8weeks and body weight: 180±20g) were divided into four treatment groups: 1) control (C; no Ex), 2) C + CW (no Ex + CW), 3) C + Ex, and 4) C + Ex + CW (Ex + CW). CW was administered as 100mg/kg CurcuWin®, providing 20mg of curcuminoids daily for 6weeks. A motor-driven rodent treadmill was used to carry out the Ex protocols. During a 5-day period, animals in chronic Ex groups were put through different regimens: day 1, 10m/min for 10minutes; day 2, 20m/min for 10minutes; day 3, 25m/min for 10minutes; day 4, 25m/min for 20minutes; and day 5, 25m/min for 30minutes. Animals were exercised at 25m/min for 45min/d for 5d/wk for 6weeks. Blood and muscle samples were analyzed for muscle markers, oxidative stress, and antioxidant markers.Results: Lactate and muscle malondialdehyde levels decreased in the CW-treated groups (P

This study was conducted to evaluate the effects of dietary lycopene supplementation on growth performance, antioxidant status, and muscle nuclear transcription factor [Kelch like-ECH-associated protein 1 (Keap1) and (erythroid-derived 2)-like 2 (Nrf2)] expressions in broiler chickens exposed to heat stress (HS). A total of 180 one-day-old male broiler chicks (Ross 308) were assigned randomly to one of 2×3 factorially arranged treatments: two housing temperatures (22°C for 24 h/d; thermoneutral, TN or 34°C for 8 h/d HS) and three dietary lycopene levels (0, 200, or 400 mg/kg). Each treatment consisted of three replicates of 10 birds. Birds were reared to 42 d of age. Heat stress caused reductions in feed intake and weight gain by 12.2 and 20.7% and increased feed efficiency by 10.8% (P

The purpose of this study was to investigate the impact of antioxidant-rich marine phytoplankton supplementation (Oceanix, OCX) on performance and muscle damage following a cross-training event in endurance-trained subjects. Additionally, an animal model was carried out to assess the effects of varying dosages of OCX, with exercise, on intramuscular antioxidant capacity. Methods: In the human trial, endurance-trained subjects (average running distance = 29.5 ± 2.6 miles × week−1) were randomly divided into placebo (PLA) and OCX (25 mg) conditions for 14 days. The subjects were pre-tested on a one-mile uphill run, maximal isometric strength, countermovement jump (CMJ) and squat jump (SJ) power, and for muscle damage (creatine kinase (CK)). On Day 12, the subjects underwent a strenuous cross-training event. Measures were reassessed on Day 13 and 14 (24 h and 48 h Post event). In the animal model, Wistar rats were divided into four groups (n = 7): (i) Control (no exercise and placebo (CON)), (ii) Exercise (E), (iii) Exercise + OCX 1 (Oceanix, 2.55 mg/day, (iv) Exercise + OCX 2 (5.1 mg/day). The rats performed treadmill exercise five days a week for 6 weeks. Intramuscular antioxidant capacity (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px)) and muscle damage (CK and myoglobin (MYOB) were collected. The data were analyzed using repeated measures ANOVA and t-test for select variables. The alpha value was set at p < 0.05. Results: For the human trial, SJ power lowered in PLA relative to OCX at 24 h Post (−15%, p < 0.05). Decrements in isometric strength from Pre to 48 h Post were greater in the PLA group (−12%, p < 0.05) than in the OCX. Serum CK levels were greater in the PLA compared to the OCX (+14%, p < 0.05). For the animal trial, the intramuscular antioxidant capacity was increased in a general dose-dependent manner (E + Oc2 > E + Oc1 > E > CON). Additionally, CK and MYOB were lower in supplemented compared to E alone. Conclusions: Phytoplankton supplementation (Oceanix) sustains performance and lowers muscle damage across repeated exercise bouts. The ingredient appears to operate through an elevating oxidative capacity in skeletal muscle.

OBJECTIVES: The retinal pigment epithelium (RPE) regulates the transport of nutrients and waste products to and from the retina and protects against light and oxidative stress. Structural or physiological dysfunction of RPE leads to retinal conditions such as age-related eye disease (ARED). It is well-established that artificial and natural light is an important factor in the progression of ARED as it can induce oxidative damage and photochemical lesions. Recently, the use of LED in general lighting has raised concerns regarding the effects of this light source on the RPE. The goal was to investigate whether beta-cryptoxanthin, an efficient pro-vitamin A carotenoid can exert protective effects against LED-induced RPE cell damage. METHODS: Rats were fed with BCX for 4 weeks at a dose of 2 and 4 mg/kg body weight followed by retinal damage by exposing the eye to bright LED light for 48 hrs. Commercially available white LED sources, which are widely used in rat housing studies was used to induce retinal damage. Animals were sacrificed at the end of the study and retinal tissue and blood samples were collected and evaluated for retinal damage and markers of oxidative stress. RESULTS: BCX supplementation significantly reduced retinal damage as demonstrated by histopathology measurements including total retinal thickness, outer nuclear layer thickness, and swelling. Similarly, markers of oxidative stress including serum and retinal tissue levels of malondialdehyde, superoxide dismutase, glutathione peroxidase, and catalase were beneficially modulated by BCX supplementation. In parallel, BCX supplementation reduced inflammatory markers (IL-1β, IL-6, NF-κB), angiogenic factor VEGF, apoptotic proteins (Caspase-3, GAP43, GFAP, NCAM, HO-1) and mitochondrial stress markers (ATF4, ATF6, Grp78, Grp97) in retinal tissue. CONCLUSIONS: Our study supports that oral supplementation of BCX dose-dependently exerts a protective effect against retinal damage induced by high-intensity light in a rat model by reducing oxidative stress, inflammation, angigogenesis and protection against mitochondrial DNA damage. BCX dietary intakes and supplementation throughout all stages of life can help protect against ARED that may start early in life. FUNDING SOURCES: OmniActive Health Technologies.

WOS: 000462022300026 PubMed ID: 30406889 Traumatic brain injury (TBI) is the leading cause of mortality and morbidity in young adults and children in the industrialized countries; however, there are presently no FDA approved therapies. TBI results in oxidative stress due to the overproduction of reactive oxygen species and overwhelming of the endogenous antioxidant mechanisms. Recently, it has been reported that antioxidants including phytochemicals have a protective role against oxidative damage and inflammation after TBI. To analyze the effects of a naturally occurring antioxidant molecule, allyl isothiocyanate (AITC), on the nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor kappa B (NF-kappa B) signaling pathways in TBI, a cryogenic injury model was induced in mice. Here, we showed that AITC administered immediately after the injury significantly decreased infarct volume and blood-brain barrier (BBB) permeability. Protein levels of proinflammatory cytokines interleukin-1 beta (IL1 beta) and interleukin-6 (IL6), glial fibrillary acidic protein (GFAP) and NF-kappa B were decreased, while Nrf2, growth-associated protein 43 (GAP43) and neural cell adhesion molecule levels were increased with AITC when compared with vehicle control. Our results demonstrated that the antioxidant molecule AITC, when applied immediately after TBI, provided beneficial effects on inflammatory processes while improving infarct volume and BBB permeability. Increased levels of plasticity markers, as well as an antioxidant gene regulator, Nrf2, by AITC, suggest that future studies are warranted to assess the protective activities of dietary or medicinal AITC in clinical studies. OmniActive Health Technologies Inc.; Turkish Academy of Sciences This study was supported by OmniActive Health Technologies Inc. (NJ, USA). This work was also supported in part by the Turkish Academy of Sciences.

WOS: 000439207700001, PubMed: 30020350, Objective: In this study, we aimed to histologically and immunologically evaluate the effect of diode laser treatment when applied adjunctive to scaling and root planing (SRP) in an experimental periodontitis model. Materials and methods: We used Wistar-Albino rats (n=60) with average weight of 230 g. Experimental periodontitis was induced by ligature at the right and left first mandibular molar teeth in all rats. After 11 days, the ligature was removed and rats were divided into two groups. The control group (n=30) received only SRP treatment, while the laser group (n=30) received a diode laser (GaAlAs, 810 nm, 1 W, 10 J, 20 s) treatment adjunctive to SRP. Ten rats in each group were sacrificed after 7, 15, and 30 days. Histopathological examination was performed in the left mandible of rats. Myeloperoxidase (MPO) was evaluated by western blot in the gingival specimens from the right mandible. Results: MPO levels in the laser group were statistically significantly lower compared with the control group (p 0.05). MPO levels in the laser group at the 7th day were statistically significantly higher compared to the 15th (p, Scientific Research Support Foundation of Inonu University, Malatya, Turkey [2013/90], This study was financially supported by the Scientific Research Support Foundation of Inonu University, Malatya, Turkey, under project number 2013/90. The authors kindly thank Mehmet Tuzcu, Department of Molecular Biology, Firat University, Elazig, Turkey, for technical support in laboratory procedures. The authors declare that they have no conflict of interest related to this study.

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.

Wound healing is an orderly process driven by numerous cellular mediators that aim to accelerate it. In skin conditions such as leprosy and psoriasis, Centella asiatica, which contains high amounts of triterpenoid saponins (TSs), has been reported to have beneficial effects. This study examined the effects of TS fraction of the herb on tissue regeneration and excision wound repair in rat skin. Briefly, TS fraction was prepared from C. Asiatica and applied on the wound area for 7 consecutive days. The IL-1β, NF-κB, and other biochemical parameters were then estimated, followed by examination of inflammatory cell infiltration, epithelialization, angiogenesis, and general morphology of granulation (wound) tissue by histopathology. Treatment decreased the IL-1β and NF-κB, increased epithelialization and collagen synthesis, and decreased matrix metalloproteinases. Asiatic acid, the active ingredient in the fraction, increased cell viability and inhibited nitrite production in macrophage culture. Taken together, TSs augmented wound healing, which could be due to their effect on cellular mediators involved in the process, thus creating a microenvironment that could promote tissue repair and favor tissue remodeling. The fraction, in addition to its effect on excision wounds in rat skin, is speculated to have a similar role in accidental, surgical, and diabetic wounds.

Renal cell carcinoma (RCC) is the most frequent upper urinary tract cancer in humans and accounts for 80–85% of malignant renal tumors. Eker rat represents a unique animal model to study RCC since these rats develop spontaneous renal tumors and leiomyoma, which may be due to tuberous sclerosis 2 (TSC2) mutation resulting in the activation of the mammalian target of rapamycin (mTOR) pathway. This study examines the role of a lycopene-rich diet in the development of RCC in the TSC2 mutant Eker rat model. Ten-week old female Eker rats (n = 90) were assigned in equal numbers to receive 0,100 or 200 mg/kg of lycopene as part of their daily diet. After 18 months the rats were sacrificed and the kidneys were removed. Immunohistochemical staining with antibodies against mTOR, phospho-S6 and EGFR were performed, as well as hematoxylin–eosin staining for histologic examination of the tumors. Tumors were counted and measured in individual kidneys. Presence of tumor decreased from 94% in control animals to 65% in the experimental group, but the difference was not statistically significant (P< 0.12). However, mean numbers of renal carcinomas were statistically significantly decreased in the lycopene-treated rats (P< 0.008) when compared to untreated controls. In the lycopene group, tumor numbers decreased (P< 0.002) and the numbers tended to decrease linearly (P< 0.003) as supplemental lycopene increased from 0 to 200. Control rats fed only basal diet had a greater length of tumors (23.98 mm) than rats fed lycopene supplement groups (12.90 mm and 11.07 mm) (P

An experiment was conducted to evaluate the effects of a histidine complex of chromium (chromium histidinate, CrHis) on egg production, lipid peroxidation and the expression of hepatic nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and heat-shock proteins (HSPs) in Japanese quails (Coturnix coturnix japonica) exposed to heat stress (HS). A total of 180 5-week-old female quails were reared either at 22°C for 24 h/d (thermoneutral, TN) or 34°C for 8 h/d (heat stress, HS) for 12 weeks. Birds in both environments were randomly given one of three diets: basal diet and basal diet supplemented with 400 or 800 µg of elemental Cr as CrHis per kg of diet. Blood, egg yolk and liver samples collected at the end of the trial were analysed to determine concentrations of cholesterol and malondialdehyde (MDA) and expressions of transcription and heat-shock proteins. Exposure to HS caused reductions in feed intake (-8.1%) and egg production (-15.8%), elevations in serum (14.8%) and egg-yolk (29.0%) cholesterol concentrations, decreases in serum (113%) and egg-yolk (73.0%) MDA concentrations and increases in the expressions of hepatic NF-κB (52.3%) and HSPs (averaging 53.6%). The effects of increasing supplemental CrHis on the response variables were more notable in the HS environment than in the TN environment. There were considerable improvements in feed intake and egg production, decreases in serum and egg-yolk cholesterol concentrations and suppressions in the expressions of hepatic nuclear protein and HSPs in response to increasing supplemental CrHis concentration in the diet of quails reared under the HS environment. In conclusion, supplemental CrHis improves productivity through alleviating oxidative stress and modulating the expressions of hepatic NF-κB and HSPs in heat-stressed quails.

Background Dietary intake of lycopene has been associated with a reduced risk of ovarian cancer, suggesting its chemopreventive potential against ovarian carcinogenesis. Lycopene's molecular mechanisms of action in ovarian cancer have not been fully understood. Therefore, in the present study, we investigated the effects of lycopene on the ovarian cancer formation using the laying hen model, a biologically relevant animal model of spontaneous ovarian carcinogenesis due to high incidence rates similar to humans. Methods In this study, a total of 150 laying hens at age of 102 weeks were randomized into groups of 50: a control group (0 mg of lycopene per kg of diet) and two treatment groups (200 mg or 400 mg of lycopene per kg of diet, or ~26 and 52 mg/d/hen, respectively). At the end of 12 months, blood, ovarian tissues and tumors were collected. Results We observed that lycopene supplementation significantly reduced the overall ovarian tumor incidence (P < 0.01) as well as the number and the size of the tumors (P < 0.004 and P < 0.005, respectively). Lycopene also significantly decreased the rate of adenocarcinoma, including serous and mucinous subtypes (P < 0.006). Moreover, we also found that the serum level of oxidative stress marker malondialdehyde was significantly lower in lycopene-fed hens compared to control birds (P < 0.001). Molecular analysis of the ovarian tumors revealed that lycopene reduced the expression of NF-κB while increasing the expression of nuclear factor erythroid 2 and its major target protein, heme oxygenase 1. In addition, lycopene supplementation decreased the expression of STAT3 by inducing the protein inhibitor of activated STAT3 expression in the ovarian tissues. Conclusions Taken together, our findings strongly support the potential of lycopene in the chemoprevention of ovarian cancer through antioxidant and anti-inflammatory mechanisms.

BACKGROUND: Chromium histidinate (CrHis) and biotin are micronutrients commonly used to improve health by athletes and control glycaemia by patients with diabetes. This study investigates the effects of 8-week regular exercise training in rats together with dietary CrHis and biotin supplementation on glucose, lipids and transaminases levels, as well as protein expression levels of peroxisome proliferator-activated receptor gamma (PPAR-γ), insulin receptor substrate-1 (IRS-1) and nuclear transcription factor kappa B (NF-κB). METHODS: A total of 56 male Wistar rats were randomly divided into 8 groups of 7 animals each and treated as follows: Control, CrHis, Biotin, CrHis+Biotin, Exercise, CrHis+Exercise, Biotin+Exercise, and CrHis+Biotin+Exercise. The doses of CrHis and biotin were 400 μg/kg and 6 mg/kg of diet, respectively. The training program consisted of running at 30 m/min for 30 min/day at 0% grade level, 5 days per week, once a day for 6 weeks. Serum glucose, total cholesterol (TC), high-density lipoprotein cholesterol (HDL), triglycerides (TG), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were measured with an automatic biochemical analyzer. Muscle and liver PPAR-γ, IRS-1 and NF-κB expressions were detected with real-time polymerase chain reaction. RESULTS: Regular exercise significantly (p 0.05). CrHis/biotin improves the proteins expression levels of IRS-1, PPAR-γ, and NF-κB (effect size: large for all) in the liver and muscle of sedentary and regular exercise-trained rats (p

In this chapter, the role of lycopene in protecting the liver against oxidative stress-induced damage has been discussed. Lycopene, which is a very potent antioxidant, provides defense against cellular damage caused by reactive oxygen species (ROS). Both conjugated and nonconjugated double bonds of lycopene make it highly reactive against oxidative stress-induced damage. A lycopene-rich diet is recommended for patients with liver diseases because numerous epidemiological studies have validated the protective effects of lycopene on the liver. Lycopene has been reported to exert its effects through pleiotropic molecular mechanisms, including transcriptional regulation, cell cycle control, apoptosis, hormonal balance, inflammation, angiogenesis, and metastasis. Molecular studies have indicated that lycopene modulates cellular processes by acting on molecular targets, such as NF-κB (nuclear factor-kappa B), Nrf2 (nuclear factor erythroid 2-related factor 2), PI3K/AKT (phosphoinositide 3-kinase/AKT), VEGF (vascular endothelial growth factor), ROS-producing enzymes (CYP-P450 enzymes, NADPH oxidase, iNOS, COX-2, and 5-LOX), leading to inhibition of liver diseases, including nonalcoholic fatty liver disease (NAFLD) and liver cancer. Here, we summarize the recent data from in vitro and in vivo studies as well as clinical trials to assess the protective effects of lycopene on oxidative stress in liver.

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.

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-ҡB 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.

The aim of this experiment was to determine the effects of β-cryptoxanthin (BCX) on the cardiometabolic health risk factors and NF-κB and Nrf2 pathway in insulin resistance induced by high-fat diet (HFD) in rodents. Twenty-eight Sprague-Dawley rats were allocated into four groups: (1) Control, rats fed a standard diet for 12 weeks; (2) BCX, rats fed a standard diet and supplemented with BCX (2.5 mg/kg BW) for 12 weeks; (3) HFD, rats fed a HFD for 12 weeks, (4) HFD + BCX, rats fed a HFD and supplemented with BCX for 12 weeks. BCX reduced cardio-metabolic health markers and decreased inflammatory markers (P < 0.001). Rats fed a HFD had the lower total antioxidant capacity and antioxidant enzymes activities and higher MDA concentration than control rats (P < 0.001 for all). Comparing with the HFD group, BCX in combination with HFD inhibited liver NF-κB and TNF-α expression by 22% and 14% and enhanced liver Nrf2, HO-1, PPAR-α, and p-IRS-1 by 1.43, 1.41, 3.53, and 1.33 fold, respectively (P < 0.001). Furthermore, in adipose tissue, BCX up-regulated Nrf2, HO-1, PPAR-α, and p-IRS-1 expression, whereas, down-regulated NF-κB and TNF-α expression. In conclusion, BCX decreased visceral fat and cardiometabolic health risk factors through modulating expressions of nuclear transcription factors.

Objectives: CNM (CNM) polyphenol has antioxidant and anti-inflammatory properties. Therefore, we hypothesized CNM decrease heart disease risk factors and may enhance anti- inflammatory properties in rats fed a diet containing CNM. In this study, we evaluated the effects of CNM polyphenol on insulin resistance (IR), hyperlipidemia, hepatic transcription factors expressions [sterol regulatory element-binding protein1c (SREBP-1c), liver X receptor-α (LXR-α), nuclear factor kappa B p65 (NF-κB p65), nuclear factor-E2-related factor-2 (Nrf2)] in rats fed high fat diet (HFD). Method: Twenty-eight Wistar rats were allocated into four groups; (i) normal control; animals fed with normal chow (C ) (ii) CNM (C+CNM 100 mg/kg b.wt.), (iii) HFD (42% of calories as fat, high fat diet [HFD]), and (iv) HFD + CNM for 12 weeks. Blood analysis for triglycerides (TG) and cholesterol (CHOL), glucose, insulin, malonaldehyde (MDA a marker of oxidative stress [OS]) were estimated. Body weight, visceral fat and liver weight recorded and liver MDA assessed. SREBP-1c, LXR-α, ATP-citrate lyase (ACLY), fatty acid synthase (FAS), NF-κB p65 expressions and decreased the PPAR-α, p-IRS-1, Nrf2, HO-1 proteins were evaluated by Western blotting. Results: HFD rats of the liver had increased SREBP-1c, LXR-α, ATP-citrate lyase (ACLY), fatty acid synthase (FAS), NF-κB p65 expressions and decreased the PPAR-α, p-IRS-1, Nrf2, HO-1 expressions compared to control group. CNM supplementation decreased body weight (8.4%), visceral fat (36.6%), liver weight (17.7%), serum glucose and insulin concentrations, lipid profile ( P < 0.05), and serum and liver MDA (23.3% and 25.4 %) concentration compared to HFD rats ( P < 0.05). CNM decreased hepatic SREBP-1c (18.1 %), LXRα (27.9%), ATP-citrate lyase (ACLY, 22.7 %), fatty acid synthase (FAS, 15.8 %), NF-κB p65 (23.3%) and enhanced the PPAR-α, IRS-1 (72.7 %), Nrf2 (111.7 %) and HO-1 (72.1 %) proteins in HFD rat livers ( P < 0.05). Discussion: These results suggest CNM supplementation reduces hyperlipidemia, inflammation, and oxidative stress through activating transcription factors (SREBP-1c, LXR-α, NF-κB, and Nrf2) and anti-oxidative defense signaling pathway.

The purpose of this study was to describe the effect of lycopene on antioxidant status, heat shock protein 70 (Hsp70), nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and heme-oxygenase 1(HO-1) levels in the muscle of rainbow trout ( Oncorhynchus mykiss ). The fish were kept at low (20 kg m 3 − 1 ) or high (100 kg m 3 − 1 ) stocking densities till the end of study and fed a basal diet or the basal diet supplemented with either 200 or 400 mg of lycopene kg − 1 of diet. The protein, lipid and ash contents in the muscle were not changed by the supplementation of lycopene in rainbow trout kept under high or low stocking densities. In response to increasing supplemental lycopene level, there were linear increases in lycopene levels, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities ( P P 0.001). In conclusion, lycopene supplementation to fish reduces the detrimental effects of oxidative stress and lipid peroxidation resulting from stocking densities via activating host defence system at cellular level.

OBJECTIVES: Lutein/zeaxanthin isomers (L/Zi), the major carotenoids, have demonstrated potent antioxidant and antiinflammation. This study was conducted to clarify the effects of L/Zi on brain transcription and brain-derived neurotrophic factors and synaptic proteins combined with exercise training in rats. METHODS: Wistar rats (age: 8 wks) were allocated into four groups: (i) Control: no treatments (ii) L/Zi: Rats treated with L/Zi (100 mg L/Zi/kg BW); (iii) Exercise: Rats with regular exercise only, (iv) Exercise + L/Zi: Rats with combined treatment of L/Zi (100 mg L/Zi/kg BW) and regular exercise. The exercise practice was carried out on a motor-driven rodent treadmill at 25 m/min, 45 min/day, 5 d/week for 8 wks. RESULTS: Rats with combined treatment of L/Zi (100 mg L/Zi/kg BW) and regular exercise. The exercise practice was carried out on a motor-driven rodent treadmill at 25 m/min, 45 min/day, 5 d/week for 8 wks. Brain nuclear factor (erythroid-derived 2)-like 2 (Nrf2), and heme oxygenase-1(HO-1) levels increased and nuclear factor (NF-κB) reduced in the combined group. In addition, L/Zi supplementation increased cerebral cortex brain-derived neurotrophic factor (BDNF), synapsin I, synaptophysin (SYP) and growth-associated protein-43 (GAP-43) levels both control and exercised rats (P < 0.001 for all). The highest cerebral cortex BDNF, synapsin I, SYP and GAP-43 levels were detected in the combined group. CONCLUSIONS: These results suggest that regular exercise training with L/Zi may improve brain function by regulating transcription and brain-derived neurotrophic factors and synaptic proteins in rats. FUNDING SOURCES: This study was supported by the Omniactive Health Technologies (NJ, USA) and partially supported by the Turkish Academy of Sciences (Ankara, Turkey).

Lycopene, the major carotenoid found in tomato, exhibits health beneficial effects by virtue of its antioxidant activity. As stocking density is known as a stress factor in fish, the effects of dietary lycopene supplementation (0, 200 or 400 mg kg − 1 ) on growth performance and antioxidant status in rainbow trout under normal (20 kg m 3 − 1 ) and high (100 kg m 3 − 1 ) stocking density were studied. Glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (CAT) activities were evaluated, as well as lipid peroxidation measured as malondialdehyde (MDA). Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), erythroid-derived 2-like 2 (Nrf2) and heme-oxygenase 1 (HO-1) levels were also assayed as an indicator of detoxifying/antioxidant defense mechanisms to cope with oxidative stress. Results showed that exposure to high stocking density depressed feed intake by 6.8% and body weight gain by 12.1%, increased plasma and hepatic MDA level by 88.5 and 124.3% and decreased hepatic SOD, CAT and GSH-Px activities by 22.1, 43.4 and 51.7%, respectively. In fish under crowded conditions, an expression of hepatic NF-κB was increased by 71.5%, being suppressed in Nrf2 and HO-1 by 40.6 and 42.7%, respectively. Lycopene supplementation increased linearly fish growth performance and antioxidant enzyme activity, and decreased linearly MDA concentration in both low and high stocking densities. NF-κB levels decreased hepatic Nrf2 and HO-1 levels increased linearly with lycopene supplementation at a greater extent in fish under low stocking condition. In conclusion, dietary supplementation of lycopene to fish reduces the detrimental effects of high stocking density on growth performance and modulates oxidative status via activating host defense system at cellular level. It appears that lycopene can be added up to 400 mg kg − 1 to rainbow trout diets to improve meat quality.

Aims This experiment investigated if chromium (Cr) as Cr-histidinate (CrHis) and Cr29 picolinate (CrPic) have a protective role in rats with hypoglycemia-induced brain injury, assessed by neuronal plasticity and regeneration potential. Main methods Male Sprague–Dawley rats were prospectively divided into 2 groups: control and hypoglycemic (induced by insulin administration, 15 U/kg, i.p., n = 56). Hypoglycemic rats were then received randomly 1) none, 2) dextrose (on the day of sampling), 3) CrHis, or 4) CrPic. Cr-chelates were delivered via drinking water (providing 8 μg elemental Cr per day) for one week prior to the hypoglycemia induction. The expressions of neuroplasticity markers [neural cell adhesion molecule (NCAM), growth-associated protein-43 (GAP-43), glial fibrillary acidic protein (GFAP)], glucose transporters (GLUT), and nuclear transcription proteins [nuclear factor-kappa (NF-κB), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), and 4-hydroxyl nonenal (HNE)] were determined using Western blot. Key findings Hypoglycemia caused increases in the expressions of GLUT-1, GLUT-3, GFAP, NF-κB and HNE and decreases in the expression of NCAM's, GAP-43 and Nrf2 in the hippocampus, cerebellum, and cortex. Cr-chelates suppressed expressions of GLUTs, GFAP, NF-κB and HNE expressions and enhanced expressions of NCAM, GAP-43 and Nrf2, which were more notable for CrHis than for CrPic. Significance In conclusion, hypoglycemia leads to cerebral injury and Cr-chelates, particularly CrHis have protective and regeneration potential in cerebral tissues through modulating neuroplasticity markers and nuclear transcription proteins as well as facilitating glucose transporters.