Nicotinamide Riboside and Phycocyanin Oligopeptides Affect Stress Susceptibility in Chronic Corticosterone-Exposed Rats.

Nicotinamide riboside (NR) is an NAD+ precursor capable of regulating mammalian cellular metabolism. Phycocyanin oligopeptide (PC), a phytonutrient found in blue-green algae, has antioxidant and anti-inflammatory properties. This study explored the effects of NR, PC, and their combination on the telomere length as well as inflammatory and antioxidant status of rats under chronic stress conditions (CS). Forty-nine rats were allocated into seven groups: control, chronic stress (CS), CS with NR (26.44 mg/kg), a low dose of 2.64 mg/kg of PC (PC-LD), or a high dose of 26.44 mg/kg PC (PC-HD), NR + PC-LD, and NR + PC-HF. The rats were given daily corticosterone injections (40 mg/kg) to induce stress conditions, or NR and PC were orally administered for 21 days. NR and PC supplementation, particularly NR plus PC, increased the serum antioxidant enzyme activities, hepatic nicotinamide adenine (NAD+) content, and telomere length (p < 0.001 for all) compared to the CS group. The levels of serum malondialdehyde (MDA), liver interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), IL-1ß, and IL-8 were reduced under the CS condition (p < 0.001). In addition, CS decreased the levels of hepatic telomere-related proteins and sirtuins (SIRT1 and 3), whereas administration of NR and PC or their combination to CS-exposed rats increased the levels of telomere-related proteins (e.g., POT1b, TRF1 and TRF2), SIRT3 and NAMPT (p < 0.05). In conclusion, NR and PC, especially their combination, can alleviate metabolic abnormalities by enhancing hepatic cytokines, SIRT3, NAMPT, and NAD+ levels in CS-exposed rats. More research is needed to further elucidate the potential health effects of the combination of NR and PC in humans.

Evaluation of pea/rice and amylopectin/chromium as an alternative protein source to improve muscle protein synthesis in rats.

BACKGROUND: A preclinical study reported that the combination of an amylopectin/chromium complex (ACr) of branched-chain amino acids (BCAA) significantly enhanced muscle protein synthesis (MPS). This study was conducted to determine the effects of the addition of ACr complex to a pea/rice (PR) protein on MPS, insulin, muslin levels, and the mTOR pathway in exercised rats. METHODS: Twenty-four rats were divided into three groups: (i) exercise (Ex); (ii) Ex + PR 1:1 blend (0.465 g/kg BW); (iii) Ex + PR + ACr (0.155 g/kg BW). On the day of single-dose administration, after the animals were exercised at 26/m/min for 2 h, the supplement was given by oral gavage. The rats were injected with a bolus dose (250 mg/kg BW, 25 g/L) of deuterium-labeled phenylalanine to determine the protein fractional synthesis rate (FSR) one h after consuming the study product. RESULTS: The combination of PR and ACr enhanced MPS by 42.55% compared to the Ex group, while Ex + PR alone increased MPS by 30.2% over the Ex group (p < 0.0001) in exercised rats. Ex + PR plus ACr significantly enhanced phosphorylation of mTOR and S6K1 (p < 0.0001), and 4E-BP1 (p < 0.001) compared to the Ex (p < 0.0001). PR to ACr also significantly increased insulin and musclin levels (p < 0.0001) in exercised rats. Additionally, compared to Ex + PR alone, Ex + PR + ACr enhanced mTOR (p < 0.0001) and S6K1 (p < 0.0001) levels. CONCLUSION: These data suggested that PR + ACr may provide an alternative to animal proteins for remodeling and repairing muscle by stimulating MPS and mTOR signaling pathways in post-exercised rats. More preclinical and clinical human studies on combining pea/rice and amylopectin/chromium complex are required.

Effects of a Combination of Arginine Silicate Inositol Complex and a Novel Form of Biotin on Hair and Nail Growth in a Rodent Model.

The purpose of this study was to examine the effects of a combination of inositol-stabilized arginine silicate complex (ASI) and magnesium biotinate (MgB) on hair and nail growth in an animal model. Twenty-eight female Sprague-Dawley rats (8 weeks old) were randomized into one of the following groups: (i) group (control), shaved; (ii) group (ASI), shaved + ASI (4.14 mg/rat/day); (iii) group (ASI + MgB I), shaved + ASI (4.14 mg/rat/day) + MgB (48.7 µg/rat/day); and (iv) group (ASI + MgB II), shaved + ASI (4.14 mg/rat/day) + MgB (325 µg/rat/day). On day 42, compared with the control group, while hair density (p < 0.05, p < 0.01, and p < 0.0001, respectively) and anagen ratio (p < 0.01, p < 0.01, and p < 0.001) increased in the ASI, ASI + MgB I, and ASI + MgB II groups, telogen ratio decreased (p < 0.01, p < 0.01, and p < 0.001, respectively). In the molecular analysis, VEGF, HGF, and KGF-2 increased in the ASI (p < 0.01, p < 0.01, and p < 0.05, respectively), ASI + MgB I (p < 0.0001 for all), and ASI + MgB II (p < 0.0001 for all) groups when compared to the control group. FGF-2 (p < 0.01) and IGF-1 (p < 0.001) were found to be increased in the ASI + MgB I and ASI + MgB II groups. SIRT-1 and ß-catenin increased in the ASI (p < 0.05 and p < 0.01), ASI + MgB I (p < 0.001 for both), and ASI + MgB II (p < 0.0001 for both) groups. Wnt-1 increased in the ASI + MgB I (p < 0.001) and ASI + MgB II (p < 0.0001) groups. In conclusion, the combination of ASI and MgB could promote hair growth by regulating IGF-1, FGF, KGF, HGF, VEGF, SIRT-1, Wnt, and ß-catenin signal pathways. It was also established that ASI did not affect nail growth, whereas the MgB combination was effective using a higher dose of biotin.

A Novel Theanine Complex, Mg-L-Theanine Improves Sleep Quality via Regulating Brain Electrochemical Activity.

L-Theanine is commonly used to improve sleep quality through inhibitory neurotransmitters. On the other hand, Mg2+, a natural NMDA antagonist and GABA agonist, has a critical role in sleep regulation. Using the caffeine-induced brain electrical activity model, here we investigated the potency of L-theanine and two novel Mg-L-theanine compounds with different magnesium concentrations on electrocorticography (ECoG) patterns, GABAergic and serotonergic receptor expressions, dopamine, serotonin, and melatonin levels. Furthermore, we evaluated the sleep latency and duration in the pentobarbital induced sleep model. We herein showed that L-theanine, particularly its various complexes with magnesium increases the expression of GABAergic, serotonergic, and glutamatergic receptors, which were associated with decreased ECoG frequency, increased amplitude, and enhanced delta wave powers. Besides increased dopamine, serotonin, and melatonin; decreased MDA and increased antioxidant enzyme levels were also observed particularly with Mg-complexes. Protein expression analyses also showed that Mg-L-theanine complexes decrease inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) levels significantly. In accordance with these results, Mg complexes improved the sleep latency and duration even after caffeine administration. As a result, our data indicate that Mg-L-theanine compounds potentiate the effect of L-theanine on sleep by boosting slow-brain waves, regulating brain electrical activity, and increasing neurotransmitter and GABA receptor levels.

Effects of magnesium picolinate, zinc picolinate, and selenomethionine co-supplementation on reproductive hormones, and glucose and lipid metabolism-related protein expressions in male rats fed a high-fat diet.

This study aimed to examine the impacts of the magnesium picolinate (MgPic), zinc picolinate (ZnPic), and selenomethionine (SeMet) alone or as a combination on blood metabolites, oxidative enzymes, reproductive hormones, and glucose and lipid metabolism-related protein expressions in Wistar rats fed a high-fed diet (HFD). The rats were fed either a control, HFD, or HFD supplemented with a single (MgPic, ZnPic, SeMet) or two or three organic mineral combinations. Body weights, visceral fat, serum glucose, insulin, total cholesterol, triglycerides, leptin, malondialdehyde (MDA) concentrations as well as liver sterol regulatory element-binding protein-1c (SREBP-1c), liver X receptor alpha (LXRα), ATP citrate lyase (ACLY), fatty acid synthase (FAS), and nuclear factor kappa B (NF-κB) levels increased, while serum testosterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), sex hormone-binding globulin (SHBG), and insulin-like growth factor (IGF-1) concentrations along with liver nuclear factor erythroid 2-related factor 2 (Nrf2) levels declined in HFD rats (P < 0.05). Supplementing each organic mineral, but particularly the combination of HFD + MgPic + ZnPic + SeMet reversed the responses with various degrees. None of the organic elements alone or as a combination of two exerted a prominent effect on parameters measured. Although not additive or synergistic, the combination of all organic minerals added to HFD (HFD + MgPic + ZnPic + SeMet) provided the greatest responses.

Therapeutic Effects of a Novel Form of Biotin on Propionic Acid-Induced Autistic Features in Rats.

Magnesium biotinate (MgB) is a novel biotin complex with superior absorption and anti-inflammatory effects in the brain than D-Biotin. This study aimed to investigate the impact of different doses of MgB on social behavior deficits, learning and memory alteration, and inflammatory markers in propionic acid (PPA)-exposed rats. In this case, 35 Wistar rats (3 weeks old) were distributed into five groups: 1, Control; 2, PPA treated group; 3, PPA+MgBI (10 mg, HED); 4, PPA+MgBII (100 mg, HED); 5, PPA+MgBIII (500 mg, HED). PPA was given subcutaneously at 500 mg/kg/day for five days, followed by MgB for two weeks. PPA-exposed rats showed poor sociability and a high level of anxiety-like behaviors and cognitive impairments (p < 0.001). In a dose-dependent manner, behavioral and learning-memory disorders were significantly improved by MgB supplementation (p < 0.05). PPA decreased both the numbers and the sizes of Purkinje cells in the cerebellum. However, MgB administration increased the sizes and the densities of Purkinje cells. MgB improved the brain and serum Mg, biotin, serotonin, and dopamine concentrations, as well as antioxidant enzymes (CAT, SOD, GPx, and GSH) (p < 0.05). In addition, MgB treatment significantly regulated the neurotoxicity-related cytokines and neurotransmission-related markers. For instance, MgB significantly decreased the expression level of TNF-α, IL-6, IL-17, CCL-3, CCL-5, and CXCL-16 in the brain, compared to the control group (p < 0.05). These data demonstrate that MgB may ameliorate dysfunctions in social behavior, learning and memory and reduce the oxidative stress and inflammation indexes of the brain in a rat model.

Maca could improve endurance capacity possibly by increasing mitochondrial biogenesis pathways and antioxidant response in exercised rats.

The objective of this study was to shed light on the effect of a novel Lepidium peruvianum (Maca) blend on anti-fatigue capacities in exercised rats. Twenty-eight male albino rats were allocated into four groups (n = 7) at random: (i) Control (vehicle), (ii) Maca: (40 mg/kg/BW), (iii) WL-FST: weight-loaded forced swimming test group, and (iv) WL-FST + Maca group. Maca supplementation increased swimming time to exhaustion (p < .01), while decreased serum lactate and liver glycogen concentrations. Maca addition resulted in lower levels of serum, liver, and muscle MDA (p < .05). Muscle GPx activity increased in both Maca groups (p < .001). Moreover, NF-κB levels were less in the WL-FST + Maca compared to the WL-FST group (p < .001). Nrf1, Nrf2, PGC-1α, SIRT1, and TFAM levels were augmented in the WL-FST + Maca compared to the WL-FST (p < .05). Consequently, our Maca blend increased endurance capacity and prevented exercise-induced oxidative stress and lactic acid buildup. PRACTICAL APPLICATIONS: The brassica species Lepidium peruvianum (maca) has been consumed in Peru for centuries to enhance mood, libido, and energy. Although the positive effects of this plant on energy metabolism are accredited, the underlying molecular mechanisms of these effects have not been sufficiently elucidated. The current study's findings suggest that this innovative, exclusive maca powder blend can boost endurance while preventing oxidative stress and lactic acid buildup during acute exercise. The mechanism of this efficacy is thought to be caused by maca's regulatory properties on energy metabolism signaling receptors and strong antioxidant scavenging effects on the free radicals that are produced by prolonged exhaustive exercise periods.

Effects of a Novel Magnesium Complex on Metabolic and Cognitive Functions and the Expression of Synapse-Associated Proteins in Rats Fed a High-Fat Diet.

This study was conducted to compare the effects of a novel form of magnesium, Mg picolinate (MgPic), to magnesium oxide (MgO) on metabolic and cognitive functions and the expression of genes associated with these functions in rats fed a high-fat diet (HFD). Forty-two Wistar rats were divided into six groups: control, MgO, MgPic, HFD, HFD + MgO, and HFD + MgPic. Mg was supplemented at 500 mg of elemental Mg/kg diet for 8 weeks. MgPic and MgO supplementation decreased visceral fat, serum glucose, insulin, leptin, TC, TG, FFA, testosterone, FSH, LH, SHBG, IGF-1, and MDA levels, but increased brain SOD, CAT, and GSH-Px activities in HFD rats. Inflammation and cognitive-related markers (presynaptic synapsin PSD95, postsynaptic PSD93, postsynaptic GluR1, and GluR2) were improved in HFD rats administered Mg, with more significant effects seen in the MgPic group. MgPic also decreased brain NF-κB but elevated brain Nrf2 levels, compared with the HFD group. The phosphorylation levels of Akt (Thr308), Akt (Ser473), PI3K try 458/199, and Ser9-GSK-3 in the brain were improved after Mg treatment in HFD rats, with more potent effects seen from MgPic supplementation. MgPic has a higher bioavailability and is more effective in improving metabolic parameters and enhancing memory than MgO. The pro-cognitive effects of MgO and MgPic could be mediated via modulation of the AMPA-type glutamate receptor and activation of the PI3K-Akt-GSK-3ß signaling pathway. These findings further support the use of MgPic in the management of metabolic and cognitive disorders.

The Protective Effects of a Combination of an Arginine Silicate Complex and Magnesium Biotinate Against UV-Induced Skin Damage in Rats.

The purpose of this study was to observe the effects of a novel combination of inositol-stabilized arginine silicate complex (ASI) and magnesium biotinate (MgB) on the prevention of skin damage after UVB exposure in rats. Forty-nine Sprague-Dawley rats were randomized into one of the following groups: (1) NC, normal control, (2) SC, shaved control, (3) UVB (exposed to UVB radiation), (4) ASI+MgB-L (Low Dose), (5) ASI+MgB-H (High Dose), (6) ASI+MgB-L+MgB cream, (7) ASI+MgB-H+MgB cream. The results showed that ASI+MgB treatment alleviated the macroscopic and histopathological damages in the skin of rats caused by UVB exposure. Skin elasticity evaluation showed a similar trend. ASI+MgB increased serum Mg, Fe, Zn, Cu, Si, biotin, and arginine concentrations and skin hydroxyproline and biotinidase levels while decreasing skin elastase activity (p < 0.05) and malondialdehyde (MDA) concentration (p < 0.001). Moreover, ASI+MgB treatment increased skin levels of biotin-dependent carboxylases (ACC1, ACC2, PC, PCC, MCC) and decreased mammalian target of rapamycin (mTOR) pathways and matrix metalloproteinase protein levels by the regulation of the activator protein 1 (AP-1), and mitogen activated protein kinases (MAPKs) signaling pathways. In addition, ASI+MgB caused lower levels of inflammatory factors, including TNF-α, NFκB, IL-6, IL-8, and COX-2 in the skin samples (p < 0.05). The levels of Bax and caspase-3 were increased, while anti-apoptotic protein Bcl-2 was decreased by UVB exposure, which was reversed by ASI+MgB treatment. These results show that treatment with ASI and MgB protects against skin damage by improving skin appearance, elasticity, inflammation, apoptosis, and overall health.

Toxicologic evaluation of a novel, highly soluble biotin salt, magnesium biotinate.

A novel, highly soluble biotin salt, magnesium biotinate (MgB), was assessed for general and genetic toxicity using several toxicologic tests. This battery of tests included in vitro bacterial reverse mutation test, in vitro mammalian micronucleus assay, and oral acute, 14-day, and 90-day repeat-dose toxicity in Sprague-Dawley (SD) rats. The results of the in vitro studies indicate that MgB is not mutagenic, clastogenic, or aneugenic. The acute oral toxicity study established an LD50 ≥ 5000 mg MgB/kg. In the 14-day oral toxicity study, doses of MgB up to 2500 mg MgB/kg/day produced no clinical signs or mortality. In the 90-day oral toxicity study, administration of 600 mg MgB/kg/day resulted in no clinical signs and was determined to be the no-observed-adverse-effect-level (NOAEL), which equates to 39 g biotin/day for a 70 kg human. Since MgB is composed of 93% biotin, the 600 mg NOAEL equates to approximately 1.3 million times the current recommended daily allowance of 30 µg biotin/day and 3900 times supplement levels of 10 mg biotin/day. Based on the toxicologic profile and lack of findings in various in vitro and in vivo studies, MgB may be considered safe for long-term human use.

The addition of an amylopectin/chromium complex to branched-chain amino acids enhances muscle protein synthesis in rat skeletal muscle.

BACKGROUND: A previous clinical study reported that the addition of an amylopectin/chromium complex (ACr; Velositol®) to 6 g of whey protein (WP) significantly enhanced muscle protein synthesis (MPS). Branched-chain amino acids (BCAAs) are also well-known to enhance MPS. The aim of this study was to determine if the addition of ACr to BCAAs can enhance MPS and activate expression of the mammalian target of the rapamycin (mTOR) pathway compared to BCAAs and exercise alone in exercise-trained rats. METHODS: Twenty-four male Wistar rats were randomly divided into three groups (n = 8 per group): (I) Exercise control, (II) Exercise plus BCAAs (0.465 g/kg BW, a 6 g human equivalent dose (HED)), and (III) Exercise plus BCAAs (0.465 g/kg BW) and ACr (0.155 g/kg BW, a 2 g HED). All animals were trained with treadmill exercise for 10 days. On the day of the single-dose experiment, rats were exercised at 26 m/min for 2 h and then fed, via oral gavage, study product. One hour after the consumption of study product, rats were injected with a bolus dose (250 mg/kg BW, 25 g/L) of phenylalanine labeled with deuterium to measure the fractional rate of protein synthesis (FSR). Ten minutes later, muscle tissue samples were taken to determine MPS measured by FSR and the phosphorylation of proteins involved in the mTOR pathway including mTOR, S6K1, and 4E-BP1. RESULTS: ACr combined with BCAAs increased MPS by 71% compared to the exercise control group, while BCAAs alone increased MPS by 57% over control (p < 0.05). ACr plus BCAAs significantly enhanced phosphorylation of mTOR, S6K1 and 4E-BP1 compared to exercise control rats (p < 0.05). The addition of ACr to BCAAs enhanced insulin levels, mTOR and S6K1 phosphorylation compared to BCAAs alone (p < 0.05). Serum insulin concentration was positively correlated with the levels of mTOR, (r = 0.923), S6K1 (r = 0.814) and 4E-BP1 (r = 0.953). CONCLUSIONS: In conclusion, the results of this study provide evidence that the addition of ACr to BCAAs significantly enhances exercise-induced MPS, and the phosphorylation of mTOR signaling proteins, compared to BCAAs and exercise alone.

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.