Beneficial effects of a novel polyherbal formulation on the skeletal muscle antioxidant status, inflammation, and muscle-signaling proteins in exercised rats.

Background/aim: Exhausting exercise can damage muscle tissue due to free radical interactions. It is hypothesized that the increase in free radicals following muscle injury, either due to oxidative damage to biomolecules or the activation of inflammatory cytokines, may lead to secondary muscle damage. This study investigated the effects of a novel joint health formula (JHF) containing bisdemethoxycurcumin-enriched curcumin, 3-O-Acetyl-11-keto-beta-boswellic acid-enriched Boswellia (AKBA), and Ashwagandha on exhaustion time, grip strength, antioxidant status, and muscle-signaling proteins in exhaustively exercised rats. Materials and methods: Twenty-eight rats were divided into four groups: Control (C), exercise (E), E + JHF 100 (100 mg/kg), and E + JHF 200 (200 mg/kg). Results: An increase in time to exhaustion and grip strength was recorded with JHF supplementation in a dose-dependent manner (p < 0.0001). In addition, serum and muscle lactate dehydrogenase, malondialdehyde, myoglobin, creatine kinase, and lactic acid concentrations were decreased in the groups supplemented with JHF, particularly at the high dose of JHF (200 mg/kg) (p < 0.0001 for all). JHF supplementation also increased antioxidant enzyme activities and suppressed the production of inflammatory cytokines compared to the exercise group (p < 0.0001). Moreover, JHF reduced the levels of PGC-1α, p-70S6K1, MAFbx, MuRF1, and p-mTOR proteins in muscle tissue compared to the exercise group (p < 0.05), being more effective at high doses. Conclusion: These findings show that JHF might reduce muscle damage by modulating antiinflammatory, antioxidant, and muscle mass regulatory pathways in exhausted training rats. At the same time, JHF improved exercise performance and grip strength.

A highly bioavailable curcumin formulation ameliorates inflammation cytokines and neurotrophic factors in mice with traumatic brain injury.

A novel curcumin formulation increases 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. This study aimed to investigate the impact of a novel formulation of curcumin 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). Mice (adult, male, C57BL/6j) were randomly divided into three groups as follows: TBI group (TBI-induced mice); TBI + CUR group (TBI mice were injected i.p. curcumin just after TBI); TBI+ CurcuWIN® group (TBI mice were injected i.p. CurcuWIN® just after TBI). Brain injury was induced using a cold injury model. Injured brain tissue was stained with Cresyl violet to evaluate infarct volume and brain swelling, analyzed, and measured using ImageJ by Bethesda (MD, USA). Western blot analysis was performed to determine the protein levels related to injury. While standard curcumin significantly reduced brain injury, CurcuWIN® showed an even greater reduction associated with reductions in glial activation, NF-κB, and the inflammatory cytokines IL-1ß and IL-6. Additionally, both standard curcumin and CurcuWIN® led to increased BDNF, GAP-43, ICAM-1, and Nrf2 expression. Notably, CurcuWIN® enhanced their expression more than standard curcumin. This data suggests that highly bioavailable curcumin formulation has a beneficial effect on the traumatic brain in mice.

Effects of Whey Protein Combined with Amylopectin/Chromium on the Muscle Protein Synthesis and mTOR Phosphorylation in Exercised Rats.

This study aimed to examine the impact of varying doses of whey protein (WP) and amylopectin/chromium complex (ACr) supplementation on muscle protein synthesis (MPS), amino acid and insulin levels, and the rapamycin (mTOR) signaling pathways in exercised rats. A total of 72 rats were randomly divided into nine groups: (1) Exercise (Ex), (2) Ex + WPI to (5) Ex + WPIV with various oral doses of whey protein (0.465, 1.55, 2.33, and 3.1 g/kg) and (6) Ex + WPI + ACr to (9) Ex + WPIV + ACr with various doses of whey protein combined with 0.155 g/kg ACr. On the day of single-dose administration, the products were given by oral gavage after exercise. To measure the protein fractional synthesis rate (FSR), a bolus dose of deuterium-labeled phenylalanine was given, and its effects were evaluated 1 h after supplementation. Rats that received 3.1 g/kg of whey protein (WP) combined with ACr exhibited the most significant increase in muscle protein synthesis (MPS) compared to the Ex group (115.7%, p < 0.0001). In comparison to rats that received the same dose of WP alone, those given the combination of WP and ACr at the same dosage showed a 14.3% increase in MPS (p < 0.0001). Furthermore, the WP (3.1 g/kg) + ACr group exhibited the highest elevation in serum insulin levels when compared to the Ex group (111.9%, p < 0.0001). Among the different groups, the WP (2.33 g/kg) + ACr group demonstrated the greatest increase in mTOR levels (224.2%, p < 0.0001). Additionally, the combination of WP (2.33 g/kg) and ACr resulted in a 169.8% increase in 4E-BP1 levels (p < 0.0001), while S6K1 levels rose by 141.2% in the WP (2.33 g/kg) + ACr group (p < 0.0001). Overall, supplementation with various doses of WP combined with ACr increased MPS and enhanced the mTOR signaling pathway compared to WP alone and the Ex group.

Eucalyptol regulates Nrf2 and NF-kB signaling and alleviates gentamicin-induced kidney injury in rats by downregulating oxidative stress, oxidative DNA damage, inflammation, and apoptosis.

Gentamicin, an aminoglycoside antibiotic, is nowadays widely used in the treatment of gram-negative microorganisms. The antimicrobial, anti-inflammatory, and antioxidant activities of eucalyptol, a type of saturated monoterpene, have been reported in many studies. The aim of this study was to examine the possible effects of eucalyptol on gentamicin-induced renal toxicity. A total of 32 rats were divided into 4 groups; Control (C), Eucalyptol (EUC), Gentamicin (GEN), and Gentamicin + Eucalyptol (GEN + EUC). In order to induce renal toxicity, 100 mg/kg gentamicin was administered intraperitoneally (i.p.) for 10 consecutive days in the GEN and GEN + EUC groups. EUC and GEN + EUC groups were given 100 mg/kg orally of eucalyptol for 10 consecutive days. Afterwards, rats were euthanized and samples were taken and subjected to histopathological, biochemical, immunohistochemical, and real-time PCR examinations. The blood urea nitrogen (BUN) and creatinine (CRE) levels were significantly decreased in the GEN + EUC group (0.76 and 0.69-fold, respectively) compared to the GEN group. The glutathione peroxidase (GPx) and catalase (CAT) activities were significantly increased in the GEN + EUC group (1.35 and 2.67-fold, respectively) compared to the GEN group. In GEN group, Nuclear factor kappa B (NF-kB), Interleukin 1-beta (IL-1ß), Inducible nitric oxide synthase (iNOS), Tumor necrosis factor-α (TNF-α), Caspase-3, 8-Hydroxy-2'-deoxyguanosine (8-OHdG) and Nuclear factor erythroid 2-related factor (Nrf2) expression levels were found to be quite irregular. GEN + EUC group decreased the expressions of NF-kB, IL-1ß, iNOS, TNF-α, Caspase-3, and 8-OHdG (0.55, 0.67, 0.54, 0.54, 0.63 and 0.67-fold, respectively), while it caused increased expression of Nrf2 (3.1 fold). In addition, eucalyptol treatment ameliorated the histopathological changes that occurred with gentamicin. The results of our study show that eucalyptol has anti-inflammatory, antioxidative, antiapoptotic, nephroprotective, and curative effects on gentamicin-induced nephrotoxicity.

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.

Mango ginger (Curcuma amada Roxb.) may alleviate the effect of high-fat diet/streptozotocin-induced diabetes by activation of the GSK-3ß/Fyn/Nrf2 pathway.

Mango ginger (MG) exhibits antioxidant, anti-inflammatory, and antihyperglycemic effects; however, the exact mechanism of action of MG extract in relation to its antidiabetic properties remains unclear. To investigate the potential antidiabetic effect of MG extract, we used a high-fat diet (HFD)/low-dose streptozotocin (STZ)-induced type 2 diabetic rat model. A total of 28 male Wistar rats were randomly divided into four groups: (i) Control, (ii) MG (50 mg/kg/day of MG extract), (iii) HFD + STZ (40 mg/kg i.p.), and (iv) HFD + STZ + MG. Following a 12-week administration of MG extract, significant reductions were observed in serum glucose, insulin, free fatty acid, cholesterol, and triglyceride levels in diabetic rats (p < .0001 for all). MG extract supplementation led to an increase in the total antioxidant capacity of the serum and a decrease in malondialdehyde (MDA) levels in both the serum and liver (p < .0001). Furthermore, hepatocellular fat accumulation was partially attenuated in the HFD + STZ + MG group. Notably, MG extract inhibited glycogen synthase kinase-3ß (GSK-3ß) in the liver (p < .01) and downregulated Fyn expression, resulting in elevated nuclear factor erythroid 2-related factor 2 (Nrf2) activity in the HFD + STZ + MG group compared to the HFD + STZ group (p < .05). The increased activity of Nrf2 in the HFD + STZ + MG group likely promoted the upregulation of heme oxygenase 1 (HO-1) in the liver (p < .0001). In conclusion, MG extract may exert antidiabetic effects by augmenting the antioxidant defense system through the regulation of GSK-3ß/Fyn/Nrf2 in a rat model of type 2 diabetes.

Garlic Exosomes Promote Hair Growth Through the Wnt/ß-catenin Pathway and Growth Factors.

Background Exosomes are membrane-derived nanovesicles produced by cells and play an important role in intercellular communication. Objectives This study aimed to investigate the effects of garlic exosome (GE) on hair growth. Methods Forty-two Sprague-Dawley/Wistar albino rats were randomly divided into six groups: non-shaved control, shaved control, topical control, GE 2 mg, GE 4 mg, and topical GE. At the end of the experiment, the number of hair follicles, follicle diameter, and subcutaneous tissue thicknesses were measured histopathologically. The Wnt-1, ß-catenin, platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), transforming growth factor-ß1 (TGF-ß1), and collagen I levels were measured by the Western Blot method. Results The anagen follicle counts of the GE 2 mg, 4 mg, and topical GE groups were 66.57±15.49, 105.71±25.06, and 55.29±6.72, and were significantly higher than the control groups (p<0.01, p<0.001 and p<0.05, respectively). The follicle diameter of the GE 4 mg group was higher than the others (p<0.05). The Wnt-1, PDGF, VEGF, TGF-ß1, and collagen I levels of all GE groups, and the ß-catenin levels of the GE 4 mg and topical GE groups were significantly higher than the control groups (p<0.05). Conclusion GE induces hair growth in rats via the Wnt-1, ß-catenin, VEGF, PDGF, and TGF-ß1 signaling pathways.

Phytochemical Profiling and Biological Activity of Achillea sintenisii Hub.-Mor.

Achillea (Asteraceae) species have been traditionally used for their different therapeutical properties. In this study, phytochemical composition of aerial parts of A. sintenisii which is endemic in Turkey was determined with Liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS). To evaluate the wound healing potential, the cream formulation prepared from A. sintenisii was tested on the linear incision wound model in mice. In vitro enzyme inhibitory activity tests were performed on elastase, hyaluronidase, and collagenase. In the histopathological examination, angiogenesis and granulation tissue formation were significantly increased in A. sintenisii treatment groups compared to the negative control group. As a result of this study, it is thought that the enzyme inhibition and antioxidant activity of the plant may contribute to the wound healing process. According to LC/MS/MS analysis result, quinic acid (24.261 µg/mg extract) and chlorogenic acid (14.97 µg/mg extract) were identified as main constituents of the extract.

The effects of melatonin against atherosclerosis-induced endothelial dysfunction and inflammation in hypercholesterolemic rats.

The aim of this study was to investigate the effects of melatonin on the serum asymmetric dimethylarginine (ADMA) levels and the expressions of vaspin, visfatin, dimethylarginine dimethylaminohydrolase (DDAH), and signal transducer and activator of transcription-3 (STAT-3) for evaluation of endothelial function and inflammation in the hypercholesterolemic rats. Rats were divided into 5 groups: (1) control, (2) hypercholesterolaemia, (3) melatonin administrated concurrently with cholesterol diet, (4) melatonin administrated only last 2 weeks and fed with cholesterol diet, (5) atorvastatin administered only last 2 weeks fed with cholesterol diet. Although an increase was observed in the expressions of visfatin and STAT-3 and the serum ADMA levels, the vaspin and DDAH protein expressions were found to decrease with hypercholesterolemic diets. Melatonin was determined to restore all the parameters to the normal levels. In conclusion, melatonin may have protective and therapeutic effects on hypercholesterolaemia by regulating vaspin, STAT-3, DDAH, and ADMA signalling pathways and create similar effects with atorvastatin.

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.

Pre-treatment of the beta3-adrenergic receptor agonist BRL37344 reduces in vivo myocardial ischemia/reperfusion injury by improving AMPK and SIRT1 activity and by suppressing mTOR and p70S6K signaling pathways

Abstract This study aimed to investigate the role and signaling pathways of β3-AR in myocardial ischemia/reperfusion (I/R) injury, which is one of the leading causes of death worldwide. 47 male rats were randomly divided into two main groups to evaluate infarct size and molecular parameters. Rats in both groups were randomly divided into 4 groups. Control (sham), I/R (30 min ischemia/120 min reperfusion), BRL37344 (BRL) (A) (5 µg/kg single-dose pre-treatment (preT) before I/R) and BRL (B) (5 µg/kg/day preT for 10 days before I/R). Infarct size was determined with triphenyltetrazolium chloride staining and analyzed with ImageJ program. The levels of AMPK, SIRT1, mTOR, and p70SK6 responsible for cellular energy and autophagy were evaluated by western blot. Infarct size increased in the I/R group (44.84 ± 1.47%) and reduced in the single-dose and 10-day BRL-treated groups (32.22 ± 1.57%, 29.65 ± 0.55%; respectively). AMPK and SIRT1 levels were decreased by I/R but improved in the treatment groups. While mTOR and p70S6K levels increased in the I/R group, they decreased with BRL preT. BRL preT protects the heart against I/R injury. These beneficial effects are mediated in part by activation of AMPK and SIRT1, inhibition of mTOR and p70S6K, and consequently protected autophagy.

RJX Improves Wound Healing in Diabetic Rats.

Background: We recently reported the clinical safety profile of RJX, a well-defined intravenous GMP-grade pharmaceutical formulation of anti-oxidant and anti-inflammatory vitamins as active ingredients, in a Phase 1 study in healthy volunteers (ClinicalTrials.gov Identifier: NCT03680105) (Uckun et al., Front. Pharmacol. 11, 594321. 10.3389/fphar.2020.594321). The primary objective of the present study was to examine the effects of GMP-grade RJX on wound and burn injury healing in diabetic rats. Methods: In the present study, a rat model of T2DM was used that employs HFD in combination with a single injection of STZ intraperitoneally (i.p) at a moderate dose level (45 mg/kg). Anesthetized diabetic rats underwent full-thickness skin excision on the back or were subjected to burn injury via a heated brass probe and then started on treatments with normal saline (NS = vehicle) or RJX administered via intraperitoneal injections for three weeks. Findings: Notably, diabetic rats treated with the 1.25 mL/kg or 2.5 mL/kg RJX (DM+RJX groups) rapidly healed their wounds as fast as non-diabetic control rats. Inflammatory cell infiltration in the dermis along with fibrin and cell debris on the epithelial layer persisted for up to 14 days in the DM+NS group but not in RJX-treated groups. The histopathological score of wound healing on days 7 and 14 was better in diabetic rats treated with RJX than diabetic rats treated with NS and comparable to the scores for non-diabetic healthy rats consistent with an accelerated healing process. The residual wound area of RJX-treated rats was significantly smaller than that of NS-treated diabetic rats at each evaluation time point (P<0.001). The accelerating effect of RJX on diabetic wound healing was dose-dependent. We obtained similar results in the burn injury model. Our results demonstrate that RJX - at a dose level >10-fold lower than its clinical maximum tolerated dose (MTD) - accelerates the healing of excision wounds as well burn injury in diabetic rats.

Protective effect of a novel polyherbal formulation on experimentally induced osteoarthritis in a rat model.

Osteoarthritis (OA) is a musculoskeletal disorder mainly found in elderly individuals. Modern treatment of OA, like nonsteroidal anti-inflammatory drugs, corticosteroids, hyaluronic acid injections, etc., is linked to long-term side effects. We evaluated the anti-osteoarthritic properties of a novel joint health formula (JHF) containing Bisdemethoxycurcumin enriched curcumin, 3-O-Acetyl-11-keto-beta-Boswellic acid-enriched Boswellia, and Ashwagandha in monosodium iodoacetate (MIA)-induced knee OA in rats. Twenty-eight female rats were distributed into four groups: Control, OA, OA + JHF (100 mg/kg), and OA + JHF (200 mg/kg). JHF decreased the right joint diameters but increased the paw area and stride length compared to the OA group with no treatment. JHF significantly reduced the arthritic conditions after four weeks of supplementation (p < 0.05). JHF significantly decreased TNF-α, IL-1ß, IL-10, COMP, and CRP in the serum of osteoarthritic rats (p < 0.0001). We observed reduced lipid peroxidation but increased SOD, GSH-Px, and CAT activities in response to JHF treatment in OA animals. JHF down-regulated MMP-3, COX-2, and LOX-5 and improved the histological structure of the knee joint of osteoarthritic rats. JHF demonstrated a protective effect against osteoarthritis, possibly due to anti-inflammatory and antioxidant activity in experimentally induced osteoarthritis in rats, and could be an effective option in the management of OA.

Sodium pentaborate pentahydrate promotes hair growth through the Wnt/ß-catenin pathway and growth factors.

BACKGROUND: Boron (B) is an element involved in many physiological processes in humans and accelerates wound healing and increases angiogenesis. This study aimed to evaluate the possible effects of sodium pentaborate pentahydrate (NaB) on hair growth and reveal its effects on Wnt-1, ß-catenin, vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and transforming growth factor-ß1 (TGF-ß1) signaling pathways, which are important molecular mechanisms involved in hair growth. METHODS: Thirty-five Sprague-Dawley/Wistar albino rats were randomly divided into five groups: non-shaved control, shaved control, NaB 1 mg (shaved + NaB 1 mg elemental B/kg CA), NaB 2 mg (shaved + NaB 2 mg elemental B/kg CA), and NaB 4 mg (shaved + NaB 4 mg elemental B/kg CA). Hair density was measured using the trichoscopy method. Dorsal skin samples were examined histopathologically at the end of the 42nd day, and follicle count, follicle diameter, and subcutaneous tissue thickness were recorded. Wnt-1, ß-catenin, PDGF, VEGF, TGF-ß1, and collagen I levels were analyzed with the Western blot method. RESULTS: In trichoscopy measurements, hair density increased in the NaB 4 mg group (90.9%). In histopathological examination, anagen follicles were observed to increase in the NaB 1 mg and 2 mg groups (p < 0.05). Follicle diameter increased in all NaB groups (p < 0.05). The Wnt-1, ß-catenin, PDGF, VEGF, TGF-ß1, and collagen I level increased in the NaB 1 mg and 2 mg groups (p < 0.05), but they were similar in the NaB 4 mg group compared to the control groups (p > 0.05). CONCLUSION: NaB 1 and 2 mg B/kg supplementation induces the anagen phase in rats via Wnt-1, ß-catenin, VEGF, PDGF, and TGF-ß1 signaling pathways. NaB 4 mg B/kg suppresses these pathways and adversely affects hair growth.

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.

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.

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.

Erratum: Sharp et al. Phytoplankton Supplementation Lowers Muscle Damage and Sustains Performance across Repeated Exercise Bouts in Humans and Improves Antioxidant Capacity in a Mechanistic Animal. Nutrients 2020, 12, 1990.

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Protective Effect of Allyl Isothiocyanate in an Experimentally Induced Rat Model for Dry Eye Syndrome.

PURPOSE: Growing evidence emphasizes the role of inflammation and oxidative stress in the pathogenesis of Dry Eye Syndrome (DES). Concordantly, the importance of agents targeting the inflammatory cascade and oxidative stress in the treatment is also progressively increasing. Herein, the study has investigated the protective effects and underlying mechanism of allyl isothiocyanate (AITC) on the ocular surface in a benzalkonium chloride (BAC)-induced dry eye rat model. METHODS: A total of twenty-one Wistar albino rats were used to form the following three groups: Control, BAC, BAC + AITC. DES was established by topical application of BAC (four times daily for two weeks) in two groups, of which one group was treated with AITC (10 mg/kg BW daily oral dosage) for four weeks. Rats were monitored by dry eye diagnostic tests during the study period, and eventually, corneal tissues were used to evaluate for histopathologic analyzes and inflammatory and oxidative status. RESULTS: A significant improvement was observed in various histopathologic and ophthalmologic findings, including tear volume, tear film integrity, ocular surface damage, ocular inflammatory signs, corneal thickness, and edema through AITC supplementation. AITC prominently balanced the inflammatory status and oxidative stress by lowering key proinflammatory mediators (NF-κB, TNF-α, IL-1ß, IL-6, and IL-8) and increasing the activities of antioxidant enzymes (SOD, GSH-Px). Also, levels of protective tear proteins, including Muc1, Muc4, and Muc5 were recovered with AITC supplementation. CONCLUSION: AITC alleviates clinical and histopathologic signs related to DES. Antioxidative and anti-inflammatory properties of AITC play a significant role in the mechanism of action.